Sample records for spontaneously occurring human

  1. Spontaneous flocking in human groups. (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete


    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Impairments of spontaneous and deliberative mentalizing co-occur, yet dissociate, in schizophrenia. (United States)

    Langdon, Robyn; Flynn, Michaela; Connaughton, Emily; Brüne, Martin


    goal-driven behaviours. These impairments were even more pronounced when participants were instructed to think of the stimuli as people, suggesting that perceiving others in social roles does not prompt people with schizophrenia to anthropomorphize about others as agents motivated by their own inner worlds. Impairments of spontaneous mentalizing were found to co-occur independently with explicit mentalizing deficits in schizophrenia, consistent with the claim that humans can access two distinct systems for understanding others' minds. Findings suggest that interventions to improve conscious deliberative mentalizing in schizophrenia may not be enough; we also need to target implicit mentalizing processes. Limitations The patient sample was chronic and only mildly symptomatic. As such, findings cannot be generalized to other stages and phases of the illness. All patients were also medicated, allowing for the possibility that automatic responses to socially salient stimuli may have been pharmacologically attenuated. Future research may examine whether unmedicated young people at ultra-high risk of psychosis show a similar profile of mentalizing impairment. Future work may also examine whether impairments of deliberative and spontaneous mentalizing associate differentially with social functioning and different cognitive domains in schizophrenia. © 2017 The British Psychological Society.

  3. Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers. (United States)

    Packer, R M A; Volk, H A; Fowkes, R C


    There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog-carer relationship. Saliva samples were obtained from sixteen dog-carer dyads in the home setting 20 and 40minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40minute post-seizure (265.1% increase), and at 20minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Spontaneous food allergy in Was-/-mice occurs independent of FcεRI-mediated mast cell activation. (United States)

    Lexmond, W S; Goettel, J A; Sallis, B F; McCann, K; Rings, E H H M; Jensen-Jarolim, E; Nurko, S; Snapper, S B; Fiebiger, E


    Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was -/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was -/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was -/- Fcer1a -/- mice. Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was -/- model. Oral administration of ovalbumin (OVA) in Was -/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was -/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was -/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. Was -/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  5. Spontaneous unscheduled DNA synthesis in human lymphocytes

    International Nuclear Information System (INIS)

    Forell, B.; Myers, L.S. Jr.; Norman, A.


    The rate of spontaneous unscheduled DNA synthesis in human lymphocytes was estimated from measurements of tritiated thymidine incorporation into double-stranded DNA (ds-DNA) during incubation of cells in vitro. The contribution of scheduled DNA synthesis to the observed incorporation was reduced by inhibiting replication with hydroxyurea and by separating freshly replicated single-stranded DNA (ss-DNA) from repaired ds-DNA by column chromatography. The residual contribution of scheduled DNA synthesis was estimated by observing effects on thymidine incorporation of: (a) increasing the rate of production of apurinic sites, and alternatively, (b) increasing the number of cells in S-phase. Corrections based on estimates of endogenous pool size were also made. The rate of spontaneous unscheduled DNA synthesis is estimated to be 490 +- 120 thymidine molecules incorporated per cell per hour. These results compare favorably with estimates made from rates of depurination and depyrimidination of DNA, measured in molecular systems if we assume thymidine is incorporated by a short patch mechanism which incorporates an average of four bases per lesion

  6. Naturally occurring flavonoids against human norovirus surrogates. (United States)

    Su, Xiaowei; D'Souza, Doris H


    Naturally occurring plant-derived flavonoids are reported to have antibacterial, antiviral, and pharmacological activities. The objectives of this study were to determine the antiviral effects of four flavonoids (myricetin, L-epicatechin, tangeretin, and naringenin) on the infectivity of food borne norovirus surrogates after 2 h at 37 °C. The lab-culturable surrogates, feline calicivirus (FCV-F9) at titers of ~7 log₁₀ PFU/ml (high titer) or ~5 log₁₀ PFU/ml (low titer) and murine norovirus (MNV-1) at ~5 log₁₀ PFU/ml, were mixed with equal volumes of myricetin, L-epicatechin, tangeretin, or naringenin at concentrations of 0.5 or 1 mM, and incubated for 2 h at 37 °C. Treatments of viruses were neutralized in cell culture medium containing 10 % heat-inactivated fetal bovine serum, serially diluted, and plaque assayed. Each treatment was replicated thrice and assayed in duplicate. FCV-F9 (low titer) was not found to be reduced by tangeretin or naringenin, but was reduced to undetectable levels by myricetin at both concentrations. Low titer FCV-F9 was also decreased by 1.40 log₁₀ PFU/ml with L-epicatechin at 0.5 mM. FCV-F9 at high titers was decreased by 3.17 and 0.72 log₁₀ PFU/ml with myricetin and L-epicatechin at 0.5 mM, and 1.73 log10 PFU/ml with myricetin at 0.25 mM, respectively. However, MNV-1 showed no significant inactivation by the four tested treatments. The antiviral effects of the tested flavonoids are dependent on the virus type, titer, and dose. Further research will focus on understanding the antiviral mechanism of myricetin and L-epicatechin.

  7. Bridging the Mechanical and the Human Mind: Spontaneous Mimicry of a Physically Present Android (United States)

    Hofree, Galit; Ruvolo, Paul; Bartlett, Marian Stewart; Winkielman, Piotr


    The spontaneous mimicry of others' emotional facial expressions constitutes a rudimentary form of empathy and facilitates social understanding. Here, we show that human participants spontaneously match facial expressions of an android physically present in the room with them. This mimicry occurs even though these participants find the android unsettling and are fully aware that it lacks intentionality. Interestingly, a video of that same android elicits weaker mimicry reactions, occurring only in participants who find the android “humanlike.” These findings suggest that spontaneous mimicry depends on the salience of humanlike features highlighted by face-to-face contact, emphasizing the role of presence in human-robot interaction. Further, the findings suggest that mimicry of androids can dissociate from knowledge of artificiality and experienced emotional unease. These findings have implications for theoretical debates about the mechanisms of imitation. They also inform creation of future robots that effectively build rapport and engagement with their human users. PMID:25036365

  8. Learning sculpts the spontaneous activity of the resting human brain


    Lewis, Christopher M.; Baldassarre, Antonello; Committeri, Giorgia; Romani, Gian Luca; Corbetta, Maurizio


    The brain is not a passive sensory-motor analyzer driven by environmental stimuli, but actively maintains ongoing representations that may be involved in the coding of expected sensory stimuli, prospective motor responses, and prior experience. Spontaneous cortical activity has been proposed to play an important part in maintaining these ongoing, internal representations, although its functional role is not well understood. One spontaneous signal being intensely investigated in the human brai...

  9. The rate of spontaneous mutations in human myeloid cells

    International Nuclear Information System (INIS)

    Araten, David J.; Krejci, Ondrej; DiTata, Kimberly; Wunderlich, Mark; Sanders, Katie J.; Zamechek, Leah; Mulloy, James C.


    Highlights: • We provide the first measurement of the mutation rate (μ) in human myeloid cells. • μ is measured to be 3.6–23 × 10 −7 per cell division. • The AML-ETO and MLL-AF9 fusions do not seem to increase μ. • Cooperating mutations in NRAS, FLT3 and p53 not seem to increase μ. • Hypermutability may be required to explain leukemogenesis. - Abstract: The mutation rate (μ) is likely to be a key parameter in leukemogenesis, but historically, it has been difficult to measure in humans. The PIG-A gene has some advantages for the detection of spontaneous mutations because it is X-linked, and therefore only one mutation is required to disrupt its function. Furthermore, the PIG-A-null phenotype is readily detected by flow cytometry. Using PIG-A, we have now provided the first in vitro measurement of μ in myeloid cells, using cultures of CD34+ cells that are transduced with either the AML-ETO or the MLL-AF9 fusion genes and expanded with cytokines. For the AML-ETO cultures, the median μ value was ∼9.4 × 10 −7 (range ∼3.6–23 × 10 −7 ) per cell division. In contrast, few spontaneous mutations were observed in the MLL-AF9 cultures. Knockdown of p53 or introduction of mutant NRAS or FLT3 alleles did not have much of an effect on μ. Based on these data, we provide a model to predict whether hypermutability must occur in the process of leukemogenesis

  10. Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs. (United States)

    Reed, S D; Fulmer, A; Buckholz, J; Zhang, B; Cutrera, J; Shiomitsu, K; Li, S


    On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

  11. Universal and uniquely human factors in spontaneous number perception. (United States)

    Ferrigno, Stephen; Jara-Ettinger, Julian; Piantadosi, Steven T; Cantlon, Jessica F


    A capacity for nonverbal numerical estimation is widespread among humans and animals. However, it is currently unclear whether numerical percepts are spontaneously extracted from the environment and whether nonverbal perception is influenced by human exposure to formal mathematics. We tested US adults and children, non-human primates, and numerate and innumerate Tsimane' adults on a quantity task in which they could choose to categorize sets of dots on the basis of number alone, surface area alone or a combination of the two. Despite differences in age, species and education, subjects are universally biased to base their judgments on number as opposed to the alternatives. Numerical biases are uniquely enhanced in humans compared to non-human primates, and correlated with degree of mathematics experience in both the US and Tsimane' groups. We conclude that humans universally and spontaneously extract numerical information, and that human nonverbal numerical perception is enhanced by symbolic numeracy.

  12. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. (United States)

    Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano


    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

  13. Uncovering intrinsic modular organization of spontaneous brain activity in humans.

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    Yong He

    Full Text Available The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz, spontaneous fluctuations of the blood oxygen level dependent (BOLD signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in

  14. Photodynamic therapy of pet animals with spontaneously occurring head and neck carcinomas (United States)

    Beck, Elsa R.; Hetzel, Fred W.


    Eleven pets with squamous cell carcinomas of the head and neck were treated with PDT using 3.0 mg/kg Photofrin II and a light dose of 300 J/cm2 at 632 nm. All tumors had measurable disease that was recurrent following at least one surgical removal. Ten of the eleven patients achieved a complete remission (CR). Of the ten animals with CR, two relapsed at 11 or 13 weeks while the other eight maintained their CR. Six animals remain disease free to the present time, with durations of 65, 56, 56, 56, 50 and 13 weeks. One died of unrelated causes at 12 weeks, and a second animal died of metastatic disease at 8 weeks. In these two cases, extensive histologic evaluation of the treated areas failed to demonstrate any evidence of residual tumor. Toxicity to the tumor bed or surrounding normal tissue was minimal. When the tumor was located adjacent to bone of the mandible or maxilla, the bone was at risk to form sequestra (in 3/5 cases). Based on these preliminary results, PDT may have applications for human patients with carcinoma of the head and neck.

  15. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    DEFF Research Database (Denmark)

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen


    , and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and pretermdeliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50......%, resp.), were identified to be higher compared to normal full-term pregnancies (푃 spontaneous abortion, spontaneous preterm...

  16. Do humans spontaneously take the perspective of others? (United States)

    Cole, Geoff G; Atkinson, Mark; Le, An T D; Smith, Daniel T


    A growing number of authors have argued that humans automatically compute the visual perspective of other individuals. Evidence for this has come from the dot perspective task in which observers are faster to judge the number of dots in a display when a human avatar has the same perspective as the observer compared to when their perspectives are different. The present experiment examined the 'spontaneous perspective taking' claim using a variant of the dot perspective paradigm in which we manipulated what the avatar could see via physical barriers that either allowed the targets to be seen by the avatar or occluded this view. We found a robust 'perspective taking' effect despite the avatar being unable to see the same stimuli as the participant. These findings do not support the notion that humans spontaneously take the perspective of others. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Spreading depolarizations occur in human ischemic stroke with high incidence

    DEFF Research Database (Denmark)

    Dohmen, C.; Sakowitz, O.W.; Fabricius, M.


    Objective: Cortical spreading depression (CSD) and periinfarct depolarization (PID) have been shown in various experimental models of stroke to cause secondary neuronal damage and infarct expansion. For decades it has been questioned whether CSD or PID occur in human ischemic stroke. Here, we...... for decompressive hernicraniectomy, an electrode strip was placed on the periinfarct region, from which four FCoG channels were acquired. Results: A total of 1,638 hours was recorded; mean monitoring time per patient was 109.2 hours. A total of 127 CSD and 42 PID events were observed. In CSD, a stereotyped slow...... frequency in this study of patients with malignant middle cerebral artery infarction. This suggests that the large volume of experimental studies of occlusive stroke that implicate spreading depolarizations in its pathophysiology can be translated, with appropriate caution, to patients and their treatment...

  18. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model. (United States)

    MacDiarmid, Jennifer A; Langova, Veronika; Bailey, Dale; Pattison, Scott T; Pattison, Stacey L; Christensen, Neil; Armstrong, Luke R; Brahmbhatt, Vatsala N; Smolarczyk, Katarzyna; Harrison, Matthew T; Costa, Marylia; Mugridge, Nancy B; Sedliarou, Ilya; Grimes, Nicholas A; Kiss, Debra L; Stillman, Bruce; Hann, Christine L; Gallia, Gary L; Graham, Robert M; Brahmbhatt, Himanshu


    Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR

  19. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model.

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    Jennifer A MacDiarmid

    Full Text Available Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers.EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT and magnetic resonance imaging (MRI. Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973. No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs.Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of

  20. Spontaneous Food Fermentations and Potential Risks for Human Health

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    Vittorio Capozzi


    Full Text Available Fermented foods and beverages are a heterogeneous class of products with a relevant worldwide significance for human economy, nutrition and health for millennia. A huge diversity of microorganisms is associated with the enormous variety in terms of raw materials, fermentative behavior and obtained products. In this wide microbiodiversity it is possible that the presence of microbial pathogens and toxic by-products of microbial origin, including mycotoxins, ethyl carbamate and biogenic amines, are aspects liable to reduce the safety of the consumed product. Together with other approaches (e.g., use of preservatives, respect of specific physico-chemical parameters, starter cultures technology has been conceived to successfully dominate indigenous microflora and to drive fermentation to foresee the desired attributes of the matrix, assuring quality and safety. Recent trends indicate a general return to spontaneous food fermentation. In this review, we point out the potential risks for human health associated with uncontrolled (uninoculated food fermentation and we discuss biotechnological approaches susceptible to conciliate fermented food safety, with instances of an enhanced contribution of microbes associated to spontaneous fermentation.

  1. Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas. (United States)

    Gillard, Marc; Cadieu, Edouard; De Brito, Clotilde; Abadie, Jérôme; Vergier, Béatrice; Devauchelle, Patrick; Degorce, Frédérique; Dréano, Stephane; Primot, Aline; Dorso, Laetitia; Lagadic, Marie; Galibert, Francis; Hédan, Benoit; Galibert, Marie-Dominique; André, Catherine


    Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Isolation of human spontaneous killer lymphocytes by bacterial adherence. (United States)

    Kleinman, R; De Boer, K P; Teodorescu, M


    Human lymphocyte subpopulations (B, T1, T2, T3, and T4 our denomination) have been identified previously by bacterial adherence and differences between them in mitogen responses and specific cytotoxic activity have been found. In this study another aspect has been investigated in order to find functions associated with these subpopulations, namely the spontaneous killing (SK) ability. Freshly isolated human peripheral blood lymphocytes (PBL) were separated into adherent and non-adherent cells following centrifugation against various bact:rial monolayers. The PBL and the resulting subpopulations of PBL were tested alone or in combination as effector cells in a 4 hr cytotoxicity assay against human lymphoblastoid cel- lines of B or T cell origin. The T3 + T4 cells or T4 cells alone showed a significantly higher SK activity against both B and T target cell lines when compared with unseparated PBL, T1 + T2, or T3 cells alone. Whe Fc portion of IgG, contain the lymphocytes responsible for SK activity and that SK cells can be purified by negative selection using bacterial adherence. PMID:7389207

  3. How much do we know about spontaneous human mutation rates

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    Crow, J.F. (Univ. of Wisconsin, Madison, WI (United States))


    The much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes on the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane in his classical study of X-linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate. The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm and may be considerably higher. The great mutation load implied by a rate of [approx] 1 per zygote can be greatly ameliorated by quasi-transition selection. Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 10[sup 2] new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known. Statistical evidence in Drosophilia shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50-100 generations. 31 refs., 3 figs., 2 tabs.

  4. Spontaneous baroreflex by sequence and power spectral methods in humans. (United States)

    Hughson, R L; Quintin, L; Annat, G; Yamamoto, Y; Gharib, C


    Beat-by-beat variations in blood pressure and RR-interval are interrelated by the actions of baroreflex and non-baroreflex responses. This study had two purposes: (1) to examine the spontaneous relationships between RR-interval and systolic blood pressure to determine the relative occurrence of baroreflex and non-baroreflex responses in humans, and (2) to compare the beat-sequence method with a cross spectral estimate of the baroreflex response slope. Eight healthy men were studied during 10 h of quiet, seated rest, and six men and three women were studied during rest, rest plus fixed pace breathing, and a cold pressor test. RR-interval and continuous, non-invasive arterial blood pressure were measured with a computerized system. A baroreflex sequence was defined by a series of at least three consecutive heart beats in which systolic pressure and the following RR-interval either both increased or both decreased. A non-baroreflex relationship was defined by sequences of at least three beats by opposite directional changes of RR-interval and systolic pressure of that beat. The results showed that there were approximately 30% as many non-baroreflex compared to baroreflex slopes. Individual subject mean baroreflex and non-baroreflex slopes were highly correlated (r = 0.72, P < 0.001). Absolute slope values were not different, and they were unaffected by time, fixed pace breathing, or cold pressor test. The data showed the relatively simple beat-by-beat sequence method to yield spontaneous baroreflex response slopes that were quantitatively similar to, and highly correlated with (r = 0.85-0.94), baroreflex response slopes calculated by spectral analysis methods.

  5. Naturally occuring nucleosome positioning signals in human exons and introns

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves


    We describe the structural implications of a periodic pattern found in human exons and introns by hidden Markov models. We show that exons (besides the reading frame) have a specific sequential structure in the form of a pattern with triplet consensus non-T(A/T)G, and a minimal periodicity...

  6. Overview of naturally occurring Earth materials and human health concerns (United States)

    Ernst, W. G.


    The biosphere and the Earth's critical zone have maintained a dynamic equilibrium for more than 3.5 billion years. Except for solar energy, almost all terrestrial substances necessary for life have been derived from near-surface portions of the land, hydrosphere, and atmosphere. If aggregate biological activities are less than the rate of nutrient supply and/or resource renewal, sustained population growth is possible. Where the replenishment rate of a life-sustaining Earth material is finite, usage may reach a condition of dynamic equilibrium in which biological consumption equals but on average cannot exceed the overall supply. Although large, most natural resources are present in finite abundances; for such commodities, excessive present-day human utilization reduces future availability, and thus the ultimate planetary carrying capacity for civilization. Intensive use of Earth materials has enhanced the quality of life, especially in the developed nations. Still, natural background levels, and Earth processes such as volcanic eruptions, as well as human activities involving agriculture, construction, and the extraction, refining, and transformation of mineral resources have led to harmful side effects involving environmental degradation and public health hazards. Among naturally and anthropogenically induced risks are bioaccessible airborne dusts and gases, soluble pollutants in agricultural, industrial, and residential waters, and toxic chemical species in foods and manufactured products. At appropriate levels of ingestion, many Earth materials are necessary for existence, but underdoses and overdoses have mild to serious consequences for human health and longevity. This overview briefly sketches several natural resource health hazards. Included are volcanic ash + aerosols + gases, mineral dusts, non-volcanic aerosols + nanoparticles, asbestos + fibrous zeolites, arsenic, fluorine, iodine, uranium + thorium + radium + radon + polonium, selenium, mercury, copper

  7. Functional structure of spontaneous sleep slow oscillation activity in humans.

    Directory of Open Access Journals (Sweden)

    Danilo Menicucci

    Full Text Available BACKGROUND: During non-rapid eye movement (NREM sleep synchronous neural oscillations between neural silence (down state and neural activity (up state occur. Sleep Slow Oscillations (SSOs events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL FINDINGS: We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. CONCLUSIONS/SIGNIFICANCE: This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.

  8. In vitro and in vivo evaluation of combined calcitriol and cisplatin in dogs with spontaneously occurring tumors (United States)

    Rassnick, Kenneth M.; Muindi, Josephia R.; Johnson, Candace S.; Balkman, Cheryl E.; Ramnath, Nithya; Yu, Wei-Dong; Engler, Kristie L.; Page, Rodney L.; Trump, Donald L.


    Purpose Calcitriol potentiates cisplatin-mediated activity in a variety of tumor models. We examine here, the effect of calcitriol and cisplatin pre-clinically and clinically in canine spontaneous tumors through in vitro studies on tumor cells and through a phase I study of calcitriol and cisplatin to identify the maximum-tolerated dosage (MTD) of this combination in dogs with cancer and to characterize the pharmacokinetic disposition of calcitriol in dogs. Methods Canine tumor cells were investigated for calcitriol/cisplatin interactions on proliferation using an MTT assay in a median-dose effect analysis; data were used to derive a combination index (CI). Cisplatin was given at a fixed dosage of 60 mg/m2. Calcitriol was given i.v. and the dosage was escalated in cohorts of three dogs until the MTD was defined. Serum calcitriol concentrations were quantified by radioimmunoassay. Results In vitro, CIs1.5 μg/kg achieved Cmax ≥ 9.8 ng/mL and dosages >1.0 μg/kg achieved AUC ≥ 45 h ng/mL. Conclusions Calcitriol and cisplatin have synergistic antiproliferative effects on multiple canine tumor cells and high-dosages of i.v. calcitriol in combination with cisplatin can be safely administered to dogs. Cmax and AUC at the MTD 3.75 μg/kg calcitriol exceed concentrations associated with antitumor activity in a murine model, indicating this combination might have significant clinical utility in dogs. PMID:18246349

  9. Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia? (United States)

    Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique


    To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

  10. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P


    Full Text Available Abstract Background The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Methods Thirty-four companion animals (27 dogs and 7 cats were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. Results The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6% the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17% experienced short lived partial responses (1-3 months duration while all the others died of progressive disease within two months. Conclusions high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of

  11. Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation. (United States)

    Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos


    To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CI<0.01%-0.7%) after a partial hydatidiform mole, and in 0/13 patients (0%; 95% CI 0%-27%) after a twin molar pregnancy. The median time to GTN diagnosis after hCG normalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CI<0.01%-0.5%; p=0.008). All patients presented with symptoms at the time of GTN diagnosis. GTN after spontaneous hCG normalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

    DEFF Research Database (Denmark)

    Thomsen, Barbara Blicher; Gredal, Hanne; Wirenfeldt, Martin


    Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human....../macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies....... stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7 years and 8 months old female neutered Rottweiler dog suffered...

  13. Comparative Analysis of Spontaneous and Stimulus-Evoked Calcium Transients in Proliferating and Fifferentiating Human Midbrain-Derived Stem Cells

    DEFF Research Database (Denmark)

    Johansen, Torben; Krabbe, Christina; Schmidt, Sissel Ida


    Spontaneous cytosolic calcium transients and oscillations have been reported in various tissues of nonhuman and human origin but not in human midbrain-derived stem cells. Using confocal microfluorimetry, we studied spontaneous calcium transients and calcium-regulating mechanisms in a human ventra...... cells that provides evidence for the mechanisms that are likely to be involved. We propose that the observed spontaneous calcium transients may contribute to mechanisms involved in cell proliferation, phenotypic differentiation, and general cell maturation....

  14. Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.

    Directory of Open Access Journals (Sweden)

    Anna Rosell

    Full Text Available BACKGROUND: Spontaneous intracerebral hemorrhage (ICH represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. METHODOLOGY/PRINCIPAL FINDINGS: Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH and the corresponding contralateral white (CW and grey (CG matter. Affymetrix GeneChip platform for analysis of over 47,000 transcripts was conducted. Microarray Analysis Suite 5.0 was used to process array images and the Ingenuity Pathway Analysis System was used to analyze biological mechanisms and functions of the genes. We identified 468 genes in the PH areas displaying a different expression pattern with a fold change between -3.74 and +5.16 when compared to the contralateral areas (291 overexpressed and 177 underexpressed. The top genes which appeared most significantly overexpressed in the PH areas codify for cytokines, chemokines, coagulation factors, cell growth and proliferation factors while the underexpressed codify for proteins involved in cell cycle or neurotrophins. Validation and replication studies at gene and protein level in brain samples confirmed microarray results. CONCLUSIONS: The genomic responses identified in this study provide valuable information about potential biomarkers and target molecules altered in the perihematomal regions.

  15. Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma. (United States)

    Barnard, Rebecca A; Wittenburg, Luke A; Amaravadi, Ravi K; Gustafson, Daniel L; Thorburn, Andrew; Thamm, Douglas H


    Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers. While pharmacologic inhibition of autophagy with hydroxychloroquine (HCQ) is currently being explored in human clinical trials, it has never been evaluated in canine cancers. Non-Hodgkin lymphoma (NHL) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL. Clinical trials in canine patients are conducted in the same way as in human patients, thus, to determine a maximum dose of HCQ that can be combined with a standard chemotherapy, a Phase I, single arm, dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic, tertiary-care veterinary teaching hospital. HCQ was administered daily by mouth throughout the trial, beginning 72 h prior to doxorubicin (DOX), which was given intravenously on a 21-d cycle. Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration. A total of 30 patients were enrolled in the trial. HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events. The overall response rate (ORR) for dogs with lymphoma was 93.3%, with median progression-free interval (PFI) of 5 mo. Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma. There was a trend that supported therapy-induced increase in LC3-II (the cleaved and lipidated form of microtubule-associated protein 1 light chain 3/LC3, which serves as a maker for autophagosomes) and SQSTM1/p62 (sequestosome 1) after treatment. The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via randomized, placebo-controlled trials in canine and human NHL.

  16. Spontaneous Recovery of Human Spatial Memory in a Virtual Water Maze (United States)

    Luna, David; Martínez, Héctor


    The occurrence of spontaneous recovery in human spatial memory was assessed using a virtual environment. In Experiment 1, spatial memory was established by training participants to locate a hidden platform in a virtual water maze using a set of four distal landmarks. In Experiment 2, after learning about the location of a hidden platform, the…

  17. Compound Stimulus Extinction Reduces Spontaneous Recovery in Humans (United States)

    Coelho, Cesar A. O.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.


    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately…

  18. Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

    DEFF Research Database (Denmark)

    Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas


    - with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

  19. Disheveled hair and ear (Dhe, a spontaneous mouse Lmna mutation modeling human laminopathies.

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    Paul R Odgren

    Full Text Available BACKGROUND: Investigations of naturally-occurring mutations in animal models provide important insights and valuable disease models. Lamins A and C, along with lamin B, are type V intermediate filament proteins which constitute the proteinaceous boundary of the nucleus. LMNA mutations in humans cause a wide range of phenotypes, collectively termed laminopathies. To identify the mutation and investigate the phenotype of a spontaneous, semi-dominant mutation that we have named Disheveled hair and ear (Dhe, which causes a sparse coat and small external ears in heterozygotes and lethality in homozygotes by postnatal day 10. FINDINGS: Genetic mapping identified a point mutation in the Lmna gene, causing a single amino acid change, L52R, in the coiled coil rod domain of lamin A and C proteins. Cranial sutures in Dhe/+ mice failed to close. Gene expression for collagen types I and III in sutures was deficient. Skulls were small and disproportionate. Skeletons of Dhe/+ mice were hypomineralized and total body fat was deficient in males. In homozygotes, skin and oral mucosae were dysplastic and ulcerated. Nuclear morphometry of cultured cells revealed gene dose-dependent blebbing and wrinkling. CONCLUSION: Dhe mice should provide a useful new model for investigations of the pathogenesis of laminopathies.

  20. Spontaneous cardiac baroreflex in humans. Comparison with drug-induced responses. (United States)

    Parlow, J; Viale, J P; Annat, G; Hughson, R; Quintin, L


    We compared two methods of assessment of baroreflex sensitivity in eight supine healthy volunteers during repeated baseline measurements and various conditions of cardiac autonomic blockade. The spontaneous baroreflex method involved computer scanning of recordings of continuous finger arterial pressure and electrocardiogram to locate sequences of three or more beats in which pressure spontaneously increased or decreased, with parallel changes in pulse intervals. The mean regression slope of all these sequences during each study condition was considered to represent the mean spontaneous baroreflex slope. In the drug-induced method, sigmoidal curves were constructed from data obtained by bolus injections of phenylephrine and nitroprusside; the tangents taken at the resting pressure of each of these curves were compared with the mean spontaneous baroreflex slopes. The two methods yielded slopes that were highly correlated (r = .96, P < .001), with significant but similar intraindividual baseline variability. Atropine virtually eliminated the baroreflex slope; subsequent addition of propranolol did not alter it further. Propranolol or clonidine alone increased average baroreflex slope to the extent that they increased resting pulse interval (r = .69 to .83). The spontaneous baroreflex method provides a reliable, noninvasive assessment of human vagal cardiac baroreflex sensitivity within its physiological operating range.

  1. Genetic regulation of recurrent spontaneous abortion in humans

    Directory of Open Access Journals (Sweden)

    Daniel Vaiman


    Full Text Available Recurrent pregnancy loss, defined as a pregnancy failure occurring before 24 weeks of gestation more than two or three times according to most definitions, is a fertility defect encountered in 1-5% of the patients. This defect is of course of multifactorial origin. Among the possible origins of recurrent pregnancy loss are uterine structural defaults, defective ploidy control of the embryo, defective immunological dialog between the embryo (or the fetus and the uterus sometimes in relation with immunological disorders (such as autoimmune diseases, thrombophilia, and free radical metabolism imbalance. Numerous studies attempted to correlate variants of genes supposed to be intervening in the different facets of the early maternal-fetal or maternal-embryonic dialog, and eventually modify the outcome of fertilization, leading to success or failure of post-implantation development. The objective of the present review is to portray the major genes and gene polymorphisms studied for their putative association with recurrent pregnancy loss. Most of these genes have been studied as candidate genes for which strong biological arguments were put forward as to their putative involvement in recurrent pregnancy loss. They were mostly studied by genetic analysis, often in various populations of different ethnic origins, throughout the world. Some of these studies were available only in English as abstracts and were nevertheless used if the information was given with enough detail. With the space being too short to depict all the available literature, different major pathways releva nt to the scientific question are presented without any attempt to hide the fact that discordant views often aroused for a given gene.

  2. Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease

    DEFF Research Database (Denmark)

    Good, David M; Zürbig, Petra; Argilés, Angel


    report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited...... the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides....

  3. Spontaneous regression of anterior mediastinal seminoma with normalization of ?-human chorionic gonadotropin levels


    Yu, Zaiqiang; Kimura, Daisuke; Tsushima, Takao; Fukuda, Ikuo


    Introduction: Although spontaneous regression (SR) of anterior mediastinal seminoma is very rare with normalization of β-human chorionic gonadotropin (β-hCG) level, video-assisted thoracic surgery (VATS) is the most effective solution for definite diagnosis of indeterminate anterior mediastinal masses. Diagnosis, therapeutic interventions, and outcomes: A rare case of an asymptomatic 37-year-old man with an anterior mediastinal mass that was detected on a routine chest X-ray is presented. ...

  4. Effect of diets containing potato protein or soya bean meal on the incidence of spontaneously-occurring subclinical necrotic enteritis and the physiological response in broiler chickens. (United States)

    Fernando, P S; Rose, S P; Mackenzie, A M; Silva, S S P


    1. An experiment was conducted to compare and explain the incidence of spontaneously occurring subclinical necrotic enteritis in broiler chickens that were fed on two practical broiler diets that differed in the major protein concentrates (soya bean meal or potato protein concentrates) and examine the relationships between the severity of the disease and the growth performance and physiological responses of the chickens. 2. A total of 840, 20-d-old birds were randomly allocated to 12 pens. Two maize-based nutritionally complete diets that either contained some potato protein or soya bean meal as the major protein supplement were fed for 16 d. Twelve birds were randomly sampled from each pen at the end of the feeding period and their blood sampled and intestinal tracts and livers dissected. 3. The birds fed on the potato protein diet had a significantly 7·7% lower feed intake and a significantly 7·8% lower growth rate compared with the birds fed on the soya-based diet. There were no significant differences in feed conversion efficiency or mortality. There were no differences in the determined apparent metabolisable energy concentrations, however, the apparent dry matter digestibility of the potato protein diet was significantly higher than that of the soya based diet and the apparent crude protein digestibility of the potato protein diet was significantly lower. 4. A significantly higher alpha toxin antibody titre was found in the birds fed on the potato protein diet compared with those fed on the soya protein diet. There was a significantly increased incidence of hepatic lesions in the birds fed on the potato protein diet compared with the birds fed on the soya diet. The mean incidence of intestinal necroses tended to be greater in the birds fed on the potato protein diet (23·6%) compared with the birds fed on the soya-based diet (15·3%). 5. There was a significant linear relationship between ileal digesta sialic acid concentration and serum alpha toxin

  5. [Expression of human spindle mitosis arrest deficiency gene in spontaneous abortion embryo tissues]. (United States)

    Cai, Yan; Wang, Jian; Yuan, Tai-Xian; Shi, Qiong; Weng, Ya-Guang; Wang, Ying-Xiong; Jiang, Hong-Yan; Liu, Zi-Jie


    To investigate the expression of human spindle mitosis arrest deficiency gene (hsMAD2) in spontaneous abortion embryos and the relationship between low expression of hsMAD2 and numerical chromosomal aberration. METHODS Spontaneous abortion embryo tissues were collected, including 23 cases of once spontaneous abortion tissue and 10 cases of twice or more spontaneous abortion tissue and induced abortion embryos (35 cases) from the Department of Gynaecology and Obstetrics of the Affiliated Hospitals of Chongqing University of Medical Science during the period of March 2006 to March 2007. FQ-PCR and western blot were used to evaluate the endogenous expression level of hsMAD2 mRNA and hsMAD2 protein; primary culturing of cells from the induced abortion embryos was conducted and 5 embryonic cells were selected by chromosomes karyotype analysis. Recombinant shRNA plasmids targeting hsMAD2 gene were constructed to inhibit the expression of endogenous hsMAD2 genes in embryonic cells which have normal karyotypes; the groups were defined as the first experimental group (transfected with pshRNA-hsMAD2-1) , the second experimental group (transfected with pshRNA-hsMAD2-2), the third experimental group (transfected with pshRNA-hsMAD2-3), the first control group (transfected with nothing), the second control group (transfected with pTZU6 + 1) and the independent group (transfected with pshRNA-N1). Interference efficiency was demonstrated by FQ-PCR and western blot; cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay; cell-cycle was assessed by flow cytometry (FCM); the chromosome numbers were calculated to analyze the variation of chromosomes. (1) The mRNA levels of hsMAD2 in the once spontaneous abortion tissue, twice or more spontaneous abortion tissue and induced abortion tissue were 0.00879 +/- 0.00035, 0.00901 +/- 0.00033 and 0.00941 +/- 0.00026 respectively, and there was no significant difference (P > 0.05) compared with each other; however, the

  6. Assessment of Anti-Tumor Cytotoxic Activity of Naturally Occurring Antibodies in Human Serum or Plasma. (United States)

    Schwartz-Albiez, Reinhard; Dill, Othmar


    A small percentage of the Western population carries antibodies in the peripheral blood, which are able to kill human tumors such as neuroblastoma or melanoma. Several observations indicate that these antibodies, preferentially of IgM isotype, belong to the class of naturally occurring antibodies. Here, we describe two screening methods for the detection and quantification of such antibodies in human blood samples: a cellular ELISA technique and a flow cytometric assay, based on intercalation of fluorescent propidium iodide into the DNA of dying or dead cells.

  7. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma. (United States)

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M


    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. © 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  8. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro. (United States)

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna


    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  9. MRI-constrained spectral imaging of benzodiazepine modulation of spontaneous neuromagnetic activity in human cortex. (United States)

    Ahveninen, Jyrki; Lin, Fa-Hsuan; Kivisaari, Reetta; Autti, Taina; Hämäläinen, Matti; Stufflebeam, Steven; Belliveau, John W; Kähkönen, Seppo


    Spontaneous electromagnetic brain rhythms have been widely used in human neuropharmacology, but their applicability is complicated by the difficulties to localize their origins in the human cortex. Here, we used a novel multi-modal non-invasive imaging approach to localize lorazepam (30 microg/kg i.v.) modulation of cortical generators of spontaneous brain rhythms. Eight healthy subjects were measured with 306-channel magnetoencephalography (MEG) in a double-blind, randomized, placebo-controlled (saline), crossover design. For anatomically realistic source modeling, wavelet-transformed MEG data were combined with high-resolution MRI to constrain the current locations to the cortical mantle, after which individual data were co-registered to surface-based coordinate system for the calculation of group statistical parametric maps of drug effects. The distributed MRI-constrained MEG source estimates demonstrated decreased alpha (10 Hz) activity in and around the parieto-occipital sulcus and in the calcarine sulcus of the occipital lobe, following from increased GABA(A)-inhibition by lorazepam. Anatomically constrained spectral imaging displays the cortical loci of drug effects on oscillatory brain activity, providing a novel tool for human pharmacological neuroimaging.

  10. Identification and safety evaluation of Bacillus species occurring in high numbers during spontaneous fermentations to produce Gergoush, a traditional Sudanese bread snack. (United States)

    Thorsen, Line; Abdelgadir, Warda S; Rønsbo, Mie H; Abban, Stephen; Hamad, Siddig H; Nielsen, Dennis S; Jakobsen, Mogens


    Gergoush is a naturally fermented Sudanese Bread snack produced in three fermentation steps (primary starter, adapted starter and final dough), followed by three baking steps for a half to one hour at above 200 °C. This study examines the microbiota of two sets of fermentations performed at a traditional production site in Khartoum, Sudan in 2006 and 2009, respectively. In 2006 four different milk/legume based primary starters (faba bean, chick pea, lentil and white bean) were sampled in order to enumerate and identify the Bacillus at species or group level. In 2009 specific focus was on the enumeration and safety evaluation of the dominant Bacillus cereus group species occurring during various Gergoush productions (including the three fermentations steps and after baking). In 2006, the primary starters contained Bacillus spp. in the order of between 7.7 and 8.1 log(10) CFU/g. Species identifications were performed by M13-PCR typing using the Escherichia coli phage M13 derived primer PM13 combined with internally transcribed 16-23S rRNA PCR, 16S rRNA gene and gyrA or gyrB gene sequencing, and selected phenotypic tests. Depending on the legume used, 40-68% of the isolates were identified as B. cereus sensu lato, 16-27% as Bacillus licheniformis, 8-32% as Bacillus subtilis and 4-20% as Bacillus sonorensis. During the second set of fermentation trials performed in 2009, the Bacillus spp. and B. cereus occurred in numbers of between 7.7-9.9 and 6.1-7.8 log(10) CFU/g, respectively, while no bacteria were detected after baking. A total of 180 B. cereus sensu lato isolates from four different primary starters, adapted starters and final doughs were further identified as B. cereus sensu stricto (118 isolates) and Bacillus thuringiensis (62 isolates). The safety of Gergoush was evaluated based on the counts and toxin gene profiles of the dominant B. cereus species. Considering that no bacteria survived the baking process, and that the cereulide synthetase gene ces

  11. Studying human respiratory disease in animals--role of induced and naturally occurring models. (United States)

    Williams, Kurt; Roman, Jesse


    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Directory of Open Access Journals (Sweden)

    Deli Liu


    Full Text Available Spontaneous canine head and neck squamous cell carcinoma (HNSCC represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling, and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  13. Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications

    Directory of Open Access Journals (Sweden)

    Zetterberg Henrik


    Full Text Available Abstract The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.

  14. Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine

    DEFF Research Database (Denmark)

    Buhl, T; Thim, L; Kofod, Hans


    Recent studies have revealed that the glucagon gene is expressed in the mammalian intestine. Here it codes for "glicentin" (proglucagon 1-69) and a glucagon-like peptide, proglucagon 78-107, recently isolated from porcine intestine. We studied the fate of the remaining COOH-terminal part of progl...... that this is the structure of the naturally occurring human peptide....... of proglucagon (proglucagon 111-160) using radioimmunoassays against proglucagon 111-123 and 126-160. Two peptides were isolated from acid ethanol extracts of porcine ileal mucosa and sequenced: one corresponding to proglucagon 126-158 and one probably corresponding to proglucagon 111-158. By comparing human...... and porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed...

  15. Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells (United States)

    Lee, Jong Ho; Shin, Yong Cheol; Jin, Oh Seong; Kang, Seok Hee; Hwang, Yu-Shik; Park, Jong-Chul; Hong, Suck Won; Han, Dong-Wook


    Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite the potential biomedical applications of graphene and its derivatives, only limited information is available regarding their osteogenic activity. This study concentrates upon the effects of reduced graphene oxide (rGO)-coated hydroxyapatite (HAp) composites on osteogenic differentiation of hMSCs. The average particle sizes of HAp and rGO were 1270 +/- 476 nm and 438 +/- 180 nm, respectively. When coated on HAp particulates, rGO synergistically enhanced spontaneous osteogenic differentiation of hMSCs, without hampering their proliferation. This result was confirmed by determining alkaline phosphatase activity and mineralization of calcium and phosphate as early and late stage markers of osteogenic differentiation. It is suggested that rGO-coated HAp composites can be effectively utilized as dental and orthopedic bone fillers since these graphene-based particulate materials have potent effects on stimulating the spontaneous differentiation of MSCs and show superior bioactivity and osteoinductive potential.Human mesenchymal stem cells (hMSCs) have great potential as cell sources for bone tissue engineering and regeneration, but the control and induction of their specific differentiation into bone cells remain challenging. Graphene-based nanomaterials are considered attractive candidates for biomedical applications such as scaffolds in tissue engineering, substrates for SC differentiation and components of implantable devices, due to their biocompatible and bioactive properties. Despite

  16. HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells.

    Directory of Open Access Journals (Sweden)

    Kyra Oswald-Richter


    Full Text Available A T-cell subset, defined as CD4(+CD25(hi (regulatory T-cells [Treg cells], was recently shown to suppress T-cell activation. We demonstrate that human Treg cells isolated from healthy donors express the HIV-coreceptor CCR5 and are highly susceptible to HIV infection and replication. Because Treg cells are present in very few numbers and are difficult to expand in vitro, we genetically modified conventional human T-cells to generate Treg cells in vitro by ectopic expression of FoxP3, a transcription factor associated with reprogramming T-cells into a Treg subset. Overexpression of FoxP3 in naïve human CD4(+ T-cells recapitulated the hyporesponsiveness and suppressive function of naturally occurring Treg cells. However, FoxP3 was less efficient in reprogramming memory T-cell subset into regulatory cells. In addition, FoxP3-transduced T-cells also became more susceptible to HIV infection. Remarkably, a portion of HIV-positive individuals with a low percentage of CD4(+ and higher levels of activated T-cells have greatly reduced levels of FoxP3(+CD4(+CD25(hi T-cells, suggesting disruption of the Treg cells during HIV infection. Targeting and disruption of the T-cell regulatory system by HIV may contribute to hyperactivation of conventional T-cells, a characteristic of HIV disease progression. Moreover, the ability to reprogram human T-cells into Treg cells in vitro will greatly aid in decoding their mechanism of suppression, their enhanced susceptibility to HIV infection, and the unique markers expressed by this subset.

  17. Naturally Occurring Asbestos in the Southern Nevada Region: Potential for Human Exposure (United States)

    Buck, B. J.; Metcalf, R. V.; Berry, D.; McLaurin, B.; Kent, D.; Januch, J.; Goossens, D.


    Naturally occurring fibrous actinolite, winchite, magnesioriebeckite, richterite, magnesiohornblende, and erionite have been found in rock, soil, and dust in southern Nevada and northwestern Arizona. The areas containing naturally occurring asbestos (NOA) include urban areas (e.g. Boulder City) and rural areas where people routinely enjoy outdoor activities including horseback riding, running, hiking, bicycling, and off-road-vehicle (ORV) recreation. A recent study showing mesothelioma in young people and women suggests some form of environmental exposure. Rock, soil, dust and clothing were analyzed using scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS); additional rock samples were analyzed using wavelength dispersive electron probe microanalysis (EPMA); additional soil samples were analyzed using PLM (polarizing light microscopy) and TEM (transmission electron microscopy) using the Fluidized Bed Asbestos Segregator preparation method. Winds have transported and mixed the Ca-amphiboles, which are primarily from Nevada, with the Na-amphiboles that are primarily from northwestern Arizona. Erionite, which has not previously been reported in this area, was a common soil component found in 5 of 6 samples. The erionite source has not yet been determined. Winds have transported the amphibole and erionite particles into the Nellis Dunes Recreation Area - an ORV recreation area located 35 km north of Boulder City that otherwise would not be geologically predicted to contain fibrous amphiboles. In Boulder City, wind directions are primarily bimodal N-NE and S-SW with the strongest winds in the spring coming from the S-SW. The arid climate in this part of the Mojave Desert greatly increases the potential for wind erosion and human exposures. These results suggest that the entire Las Vegas Basin has, at times, received these particles through wind transport. Because the most likely human exposure pathway is through inhalation of dust, the Las Vegas

  18. Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines. (United States)

    Sams, Anette; Hastrup, Sven; Andersen, Marie; Thim, Lars


    Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth.

  19. Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice. (United States)

    Wang, Xiaoli; Chen, Xiaojiao; Feng, Xuejiao; Chang, Fei; Chen, Minjian; Xia, Yankai; Chen, Ling


    Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose-dependently fetal death during GD12.5-16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo-conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS-exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis.

  20. Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells. (United States)

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana


    Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues received considerable interest in regenerative medicine, particularly in nerve regeneration owing to their embryonic origin and ease of harvest. Proliferation efficacy and differentiation capacity into diverse cell lineages propose dental MSCs as an in vitro tool for disease modeling. In this study, we investigated the spontaneous differentiation efficiency of dental MSCs obtained from human gingiva tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage 41, the morphology of hGMSCs changed from typical fibroblast-like shape into sphere-shaped cells with extending processes. Next-generation transcriptomics sequencing showed increased expression of neural progenitor markers such as NES, MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41. Immunocytochemistry results showed suppression of neurogenesis repressors TP53 and p21, whereas Western blot results revealed the expression of neurotrophic factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy of hGMSCs to differentiate into neural precursor cells over prolonged passages and that these cells may assist in producing novel in vitro disease models that are associated with neural development.

  1. Three-dimensional analysis of volumetric changes in herniated discs of the lumbar spine: does spontaneous resorption of herniated discs always occur? (United States)

    Seo, Jun-Yeong; Roh, Young-Ho; Kim, Young-Hoon; Ha, Kee-Yong


    To investigate volumetric changes in lumbar disc herniation (LDH) using three-dimensional measurements obtained by magnetic resonance imaging (MRI) and to identify possible factors affecting such changes. Between January 2004 and December 2011, 43 patients who underwent conservative treatment for LDH were enrolled. In all, 56 disc levels were investigated. MRI was performed on two or more occasions (minimally, at the initial visit and 6 months later). The volume of each herniated disc was determined. For each patient, disc migration, morphology, initial LDH size, and clinical outcome were evaluated. The mean volumes of herniated discs at the initial and follow-up visits were 1,304.57 ± 837.99 and 993.84 ± 610.04 mm(3), respectively. The mean change in volume from the initial to the follow-up visit was 310.73 ± 743.60 mm(3). Volumes decreased at 35 disc levels and increased at 21 levels. The disc containment, the extent of LDH, the initial size of the herniated disc, and the degree of intactness of the posterior longitudinal ligament were significantly correlated with disc resorption and an increase in disc volume (p = 0.01, p = 0.018, p = 0.001, and p disc volumetric change and clinical outcome. We observed that LDH is a dynamic disease and that a herniated disc is not always spontaneously resorbed, in contrast to what has been reported previously. Alleviation of clinical symptoms can be achieved via conservative treatment even if the volume of the herniated disc changes. Spinal surgeons should not only present an option of initial non-surgical treatment to LDH patients but should also inform them that the LDH may change in size during daily activity or exercise.

  2. Inhalation chemotherapy for macroscopic primary or metastatic lung tumors: proof of principle using dogs with spontaneously occurring tumors as a model. (United States)

    Hershey, A E; Kurzman, I D; Forrest, L J; Bohling, C A; Stonerook, M; Placke, M E; Imondi, A R; Vail, D M


    This study represents part of an effort to determine the safety and efficacy of inhaled antineoplastic drugs, using pet dogs with spontaneously arising primary and metastatic lung cancers (including sarcoma, carcinoma, and malignant melanoma) as a model. Dogs received new formulations of either paclitaxel (PTX) or doxorubicin (DOX) by the inhalation route every 2 weeks using a specially designed aerosol device. Response was assessed radiographically using the indices of tumor nodule number and volume measurement of discrete pulmonary nodules. Dogs experiencing progressive disease after two consecutive treatments were crossed over to receive the alternate compound. In 24 dogs, 6 (25%) responses were noted including 5 partial responses (PR) and 1 complete response. These include 4 (22.2%) of 18 responses to DOX and 2 (13.3%) of 15 responses to PTX. Responses were noted with osteosarcoma (including three dogs with metastatic osteosarcoma that had failed prior systemic chemotherapy), liposarcoma, hemangiosarcoma, and undifferentiated sarcoma. One dog with mammary carcinoma experienced a 47% reduction in volume after PTX inhalation, just shy of PR criteria. One dog with liposarcoma is experiencing a long-term (>12 months) stabilization of disease on PTX. To date, no systemic toxicities have been observed with either PTX or DOX inhalations. Local (pulmonary) toxicity was not observed with PTX; however, changes consistent with pneumonitis/fibrosis were observed in some dogs receiving DOX. Only one of these dogs showed clinical signs, which were responsive to steroid and antitussive therapy. These data represent "proof of principle" for the avoidance of systemic toxicity while delivering efficacious local drug levels by the inhalation route.

  3. Spontaneous gene transfection of human bone cells using 3D mineralized alginate-chitosan macrocapsules. (United States)

    Green, David W; Kim, Eun-Jung; Jung, Han-Sung


    The effectiveness of nonviral gene therapy remains uncertain because of low transfection efficiencies and high toxicities compared with viral-based strategies. We describe a simple system for transient transfection of continuous human cell lines, with low toxicity, using mineral-coated chitosan and alginate capsules. As proof-of-concept, we demonstrate transfection of Saos-2 and MG63 human osteosarcoma continuous cell lines with gfp, LacZ reporter genes, and a Sox-9 carrying plasmid, to illustrate expression of a functional gene with therapeutic relevance. We show that continuous cell lines transfect with significant efficiency of up to 65% possibly through the interplay between chitosan and DNA complexation and calcium/phosphate-induced translocation into cells entrapped within the 3D polysaccharide based environment, as evidenced by an absence of transfection in unmineralized and chitosan-free capsules. We demonstrated that our transfection system was equally effective at transfection of primary human bone marrow stromal cells. To illustrate, the Sox-9, DNA plasmid was spontaneously expressed in primary human bone marrow stromal cells at 7 days with up to 90% efficiency in two repeats. Mineralized polysaccharide macrocapsules are gene delivery vehicles with a number of biological and practical advantages. They are highly efficient at self-transfecting primary bone cells, with programmable spatial and temporal delivery prospects, premineralized bone-like environments, and have no cytotoxic effects, as compared with many other nonviral systems. © 2015 Wiley Periodicals, Inc.

  4. Systematic identification of the druggable interactions between human protein kinases and naturally occurring compounds in endometriosis. (United States)

    Jiang, Lai; Tang, Chaoliang; Rao, Jie; Xue, Qing; Wu, Hao; Wu, Dabao; Zhang, Aijun; Chen, Ling; Shen, Zhen; Lei, Lei


    Diverse kinase signaling pathways have been involved in the pathogenesis of endometriosis (EM), which can be modulated either by directly targeting the hub kinases or by indirectly regulating marginal members in the pathways. Here, a systematic kinase-inhibitor interaction profile was created for 8 naturally occurring compounds against 20 human protein kinases. The compounds are all non-sterid that have been reported as pharmacologically active molecular entities potential for EM therapeutics, while the kinases were curated via gene ontology terms enriched from the gene co-citation network with EM. The resulting profile was analyzed at structural, energetic and dynamic levels to identify druggable kinase-compound interactions. The compounds Gossypol, Curcumin and EGCG showed a similar interaction profile across these kinases; they can bind tightly to the top-listed kinases in gene ontology, while the compounds Marrubiin, Apigenin and DIM were predicted to exhibit generally weak affinity for the 20 curated kinases. The JNK kinase, a MAPK family member, was identified as a putative candidate of druggable target for EM therapeutics; the inhibitory activity of eight naturally occurring compounds as well as a sophisticated kinase inhibitor SP600125 against the JNK was tested using enzymatic activity analysis. As might be expected, the Gossypol and EGCG were determined to have high inhibitory activity at namomolar level (IC 50 =55 and 94nM, respectively), which are comparable with or better than the positive control SP600125 (IC 50 =76nM), while other tested compounds exhibited weak inhibition (IC 50 >100nM) or bad potency (IC 50 =n.d.) against the kinase. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Ecological and human impact assessment in the legacy enhanced and naturally occurring radiation areas - human and ecological impact assessment in the legacy enhanced and naturally occurring radiation areas

    Energy Technology Data Exchange (ETDEWEB)

    Mrdakovic Popic, Jelena [Norwegian Radiation Protection Authority, P.O. Box 55, N-1332 Oesteraas (Norway); Salbu, Brit; Skipperud, Lindis [Norwegian University of Life Sciences, Centre for Environmental radioactivity CERAD, P.O. Box 5003, 1430 Aas (Norway)


    The Fen Complex in Norway is an area well-known with its specific magmatic bedrock rich in thorium (Th), iron (Fe), niobium (Nb) and rare earth elements (REE). During several past centuries, intensive mining was conducted at sites in the area, giving rise to enhanced radioactivity levels. Previous human health studies demonstrated exposure doses among the highest in Europe. In the current work, contamination status with respect to radionuclides ({sup 232}Th, uranium ({sup 238}U)) and trace elements (arsenic (As), chromium (Cr) and lead (Pb)) and possible impact on humans and biota were investigated at legacy NORM and undisturbed surrounding NOR rich sites in the Fen Complex area. Significantly heterogeneous radionuclides ({sup 232}Th, {sup 238}U, and daughters) distribution was found in soil at both legacy NORM and undisturbed NOR rich sites. Thorium activity concentration levels exceeded screening levels for radioactive waste material given by Norwegian Pollution Control Act. Based on sequential extraction results, mobility of {sup 232}Th and trace elements were low, although higher at legacy NORM than at undisturbed NOR rich sites. Uranium was present at considerable levels (up to 50 %) in pH and redox sensitive soil fraction, as well as bound to soil organic compounds. However, no further transport towards biggest water source Norsjoe Lake was observed, as concentration levels of all investigated elements in water samples were extremely low. Long-term surveys of outdoor terrestrial gamma dose rates, thoron ({sup 220}Rn) and radon ({sup 222}Rn) concentrations in the air demonstrated elevated values (up to 9.2 μGy/h, 5000 Bq/m{sup 3} and 200 Bq/m{sup 3}, respectively) with significant seasonal variation. Calculated annual exposure doses to humans due to outdoor exposure could exceed 10 mSv, i.e., be higher than 1 mSv dose constraint given by ICRP. Roughly summarized with previously published data on indoor doses for Fen village population, total annual exposure

  6. Can human autonomic classical conditioning occur without contingency awareness? The critical importance of the trial sequence. (United States)

    Singh, Kulwinder; Dawson, Michael E; Schell, Anne M; Courtney, Christopher G; Payne, Andrew F H


    Most evidence suggests that awareness of the CS-US contingency is necessary for human autonomic conditioning. However, Schultz and Helmstetter (2010) reported unaware skin conductance conditioning using difficult-to-discriminate visual CSs. We sought to replicate these findings with procedures nearly identical to Schultz and Helmstetter among 66 participants. Results replicated the findings of significantly greater autonomic responding to CS+ than CS-; however, participants also demonstrated greater expectancy of shock to CS+ than CS- despite being classified as unaware. The differential expectancy and conditioning occurred only on trials that followed a CS+/CS- alternating sequence. On non-alternating trials, there was significantly higher expectancy and skin conductance responding to CS- compared to CS+. These results indicate that what initially appeared to be unaware differential conditioning was likely due to differential expectancy arising from a predictable trial sequence. These results underscore the critical importance of controlling for trial sequence effects in the study of learning. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. The epileptic human hippocampal cornu ammonis 2 region generates spontaneous interictal-like activity in vitro. (United States)

    Wittner, Lucia; Huberfeld, Gilles; Clémenceau, Stéphane; Eross, Loránd; Dezamis, Edouard; Entz, László; Ulbert, István; Baulac, Michel; Freund, Tamás F; Maglóczky, Zsófia; Miles, Richard


    The dentate gyrus, the cornu ammonis 2 region and the subiculum of the human hippocampal formation are resistant to the cell loss associated with temporal lobe epilepsy. The subiculum, but not the dentate gyrus, generates interictal-like activity in tissue slices from epileptic patients. In this study, we asked whether a similar population activity is generated in the cornu ammonis 2 region and examined the electrophysiological and neuroanatomical characteristics of human epileptic cornu ammonis 2 neurons that may be involved. Hippocampal slices were prepared from postoperative temporal lobe tissue derived from epileptic patients. Field potentials and multi-unit activity were recorded in vitro using multiple extracellular microelectrodes. Pyramidal cells were characterized in intra-cellular records and were filled with biocytin for subsequent anatomy. Fluorescent immunostaining was made on fixed tissue against the chloride-cation cotransporters sodium-potassium-chloride cotransporter-1 and potassium-chloride cotransporter-2. Light and electron microscopy were used to examine the parvalbumin-positive perisomatic inhibitory network. In 15 of 20 slices, the hippocampal cornu ammonis 2 region generated a spontaneous interictal-like activity, independently of population events in the subiculum. Most cornu ammonis 2 pyramidal cells fired spontaneously. All cells fired single action potentials and burst firing was evoked in three cells. Spontaneous excitatory postsynaptic potentials were recorded in all cells, but hyperpolarizing inhibitory postsynaptic potentials were detected in only 27% of the cells. Two-thirds of cornu ammonis 2 neurons showed depolarizing responses during interictal-like events, while the others were inhibited, according to the current sink in the cell body layer. Two biocytin-filled cells both showed a pyramidal-like morphology with axons projecting to the cornu ammonis 2 and cornu ammonis 3 regions. Expression of sodium

  8. Identification and safety evaluation of Bacillus species occurring in high numbers during spontaneous fermentations to produce Gergoush, a traditional Sudanese bread snack

    DEFF Research Database (Denmark)

    Thorsen, Line; Abdelgadir, Warda S.; Rønsbo, Mie Hvillum


    Gergoush is a naturally fermented Sudanese Bread snack produced in three fermentation steps (primary starter, adapted starter and final dough), followed by three baking steps for a half to one hour at above 200°C. This study examines the microbiota of two sets of fermentations performed at a trad......Gergoush is a naturally fermented Sudanese Bread snack produced in three fermentation steps (primary starter, adapted starter and final dough), followed by three baking steps for a half to one hour at above 200°C. This study examines the microbiota of two sets of fermentations performed......, the results indicate, that Gergoush produced at the traditional production site is safe for human consumption. This study is the first to identify the Bacillus of Gergoush to species level, and it is the first to perform a safety evaluation of the product, based on the dominant B. cereus species....

  9. A global downregulation of microRNAs occurs in human quiescent satellite cells during myogenesis

    NARCIS (Netherlands)

    Koning, Merel; Werker, Paul M N; van Luyn, Marja J A; Krenning, Guido; Harmsen, Martin C


    During myogenesis, human satellite cells differentiate and form multinucleated myotubes, while a fraction of the human satellite cells enter quiescence. These quiescent satellite cells are able to activate, proliferate and contribute to muscle regeneration. Post-transcriptional regulation of

  10. Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion. (United States)

    Sun, Chan; Zhang, Yuan-Yuan; Tang, Chuan-Ling; Wang, Song-Cun; Piao, Hai-Lan; Tao, Yu; Zhu, Rui; Du, Mei-Rong; Li, Da-Jin


    Spontaneous abortion is the most common complication of pregnancy. Immune activation and the subsequent inflammation-induced tissue injury are often observed at the maternal-fetal interface as the final pathological assault in recurrent spontaneous abortion. However, the precise mechanisms responsible for spontaneous abortion involving inflammation are not fully understood. Chemokine CCL28 and its receptors CCR3 and CCR10 are important regulators in inflammatory process. Here, we examined the expression of CCL28 and its receptors in decidual stromal cells (DSCs) by immunochemistry and flow cytometry (FCM), and compared their expression level in DSCs from normal pregnancy versus spontaneous abortion, and their relationship to inflammatory cytokines production by DSCs. We further analyzed regulation of the pro-inflammatory cytokines on CCL28 expression in DSCs by real-time polymerase chain reaction, In-cell Western and FCM. The effects of CCL28-CCR3/CCR10 interaction on DSC apoptosis was investigated by Annexin V staining and FCM analysis or DAPI staining and nuclear morphology. Higher levels of the inflammatory cytokines interleukin (IL)-1β, IL-17A and tumor necrosis factor-α, and increased CCR3/CCR10 expression were observed in DSCs from spontaneous abortion compared with normal pregnancy. Treatment with inflammatory cytokines differently affected CCL28 and CCR3/CCR10 expression in DSCs. Human recombinant CCL28 promoted DSC apoptosis, which was eliminated by pretreatment with neutralizing antibodies against CCR3/CCR10 and CCL28. However, CCL28 did not affect DSC growth. These results suggest that the inflammation-promoted up-regulation of CCL28 and its receptors interaction in DSCs is involved in human spontaneous abortion via inducing DSC apoptosis.

  11. Predicted congestions never occur. On the gap between transport modeling and human behavior

    Directory of Open Access Journals (Sweden)

    Harald FREY


    Full Text Available This paper presents an introduction to meso-scale transport modeling and issues of human behaviour in transport systems. Along with other examples of the human ability to learn in transport systems we look at the comparison of real life data and the prediction of modeling tools for the closure of Vienna’s inner ring road during the 2008 European Football Championship (EURO 2008. Some light is shed on the scientific question, whether currently used modeling tools are able to adequately reproduce the real-life behaviour of human beings in the transport system and should be used for transport policy decision making.

  12. Impact of Abnormal DNA Methylation of Imprinted Loci on Human Spontaneous Abortion. (United States)

    Liu, Yudong; Tang, Yan; Ye, Desheng; Ma, Weixu; Feng, Shuxian; Li, Xuelan; Zhou, Xingyu; Chen, Xin; Chen, Shiling


    Currently, there is a growing concern regarding the safety of assisted reproductive technology (ART) due to increased risk of spontaneous abortion (SA) and imprinting disorders in ART-conceived offspring. Early investigations suggested that aberrant genetic imprinting may be related to pregnancy loss; however, few studies have used human tissue specimens. Here the DNA methylation patterns of 3 imprinted genes, including maternally inherited GRB10 and the paternally inherited IGF2 and PEG3 genes, were evaluated in human chorionic villus samples by pyrosequencing and bisulfite sequencing polymerase chain reaction. The samples were divided into 4 groups: (1) SA of natural conception (NC; n = 84), (2) induced abortion of NC (n = 94), (3) SA after ART (n = 73), and (4) fetal reduction after ART (n = 86). The methylation levels and the percentages of abnormal methylation of the IGF2, GRB10, and PEG3 genes between the ART group and the NC group showed no significant difference. Both IGF2 and GRB10 genes showed higher methylation levels in the SA group compared to the non-SA group. Additionally, determining the single-nucleotide polymorphisms of 4 loci, including IGF2 rs3741205, rs3741206, rs3741211, and GRB10 rs2237457, showed that the TC+CC genotype of IGF2 rs3741211 had a 1.91-fold increased risk of SA after ART. However, there was no association between the mutant genotype of IGF2 rs3741211 and the methylation levels of IGF2 and H19, and ART might not affect the distribution of the abovementioned genotypes. It provides support for the opinion that genetic imprinting defects may be associated with SA, which might not be due to ART treatments.

  13. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

    Directory of Open Access Journals (Sweden)

    Dass Crispin R


    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  14. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant (United States)

    Sun, Shihua; Sprenger, Cynthia C.T.; Vessella, Robert L.; Haugk, Kathleen; Soriano, Kathryn; Mostaghel, Elahe A.; Page, Stephanie T.; Coleman, Ilsa M.; Nguyen, Holly M.; Sun, Huiying; Nelson, Peter S.; Plymate, Stephen R.


    Progression of prostate cancer following castration is associated with increased androgen receptor (AR) expression and signaling despite AR blockade. Recent studies suggest that these activities are due to the generation of constitutively active AR splice variants, but the mechanisms by which these splice variants could mediate such effects are not fully understood. Here we have identified what we believe to be a novel human AR splice variant in which exons 5, 6, and 7 are deleted (ARv567es) and demonstrated that this variant can contribute to cancer progression in human prostate cancer xenograft models in mice following castration. We determined that, in human prostate cancer cell lines, ARv567es functioned as a constitutively active receptor, increased expression of full-length AR (ARfl), and enhanced the transcriptional activity of AR. In human xenografts, human prostate cancer cells transfected with ARv567es cDNA formed tumors that were resistant to castration. Furthermore, the ratio of ARv567es to ARfl expression within the xenografts positively correlated with resistance to castration. Importantly, we also detected ARv567es frequently in human prostate cancer metastases. In summary, these data indicate that constitutively active AR splice variants can contribute to the development of castration-resistant prostate cancers and may serve as biomarkers for patients who are likely to suffer from early recurrence and are candidates for therapies directly targeting the AR rather than ligand. PMID:20644256

  15. CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs

    Directory of Open Access Journals (Sweden)

    Rubbo Pierre-Alain


    Full Text Available Abstract Background Transmission of human immunodeficiency virus type 1 (HIV-1 through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated. Methods The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators. Results Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7 and viremic (n = 8 women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Conclusions Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.

  16. CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs. (United States)

    Valea, Diane; Tuaillon, Edouard; Al Tabaa, Yassine; Rouet, François; Rubbo, Pierre-Alain; Meda, Nicolas; Foulongne, Vincent; Bollore, Karine; Nagot, Nicolas; Van de Perre, Philippe; Vendrell, Jean-Pierre


    Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated. The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs) from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators. Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7) and viremic (n = 8) women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.

  17. [Spontaneous models of human diseases in dogs: ichthyoses as an example]. (United States)

    André, Catherine; Grall, Anaïs; Guaguere, Éric; Thomas, Anne; Galibert, Francis


    Ichthyoses encompass a heterogeneous group of genodermatoses characterized by abnormal desquamation over the entire body due to defects of the terminal differentiation of keratinocytes and desquamation, which occur in the upper layer of the epidermis. Even though in humans more than 40 genes have already been identified, the genetic causes of several forms remain unknown and are difficult to identify in Humans. Strikingly, several purebred dogs are also affected by specific forms of ichthyoses. In the Golden retriever dog breed, an autosomal recessive form of ichthyosis, resembling human autosomal recessive congenital ichthyoses, has recently been diagnosed with a high incidence. We first characterized the disease occurring in the golden retriever breed and collected cases and controls. A genome-wide association study on 40 unrelated Golden retriever dogs, using the canine 49.000 SNPs (single nucleotide polymorphisms) array (Affymetrix v2), followed by statistical analyses and candidate gene sequencing, allowed to identify the causal mutation in the lipase coding PNPLA1 gene (patatin-like phospholipase domain-containing protein). Screening for alterations in the human ortholog gene in 10 autosomal recessive congenital ichthyoses families, for which no genetic cause has been identified thus far, allowed to identify two recessive mutations in the PNPLA1 protein in two families. This collaborative work between "human" and "canine" geneticists, practicians, histopathologists, biochemists and electron microscopy experts not only allowed to identify, in humans, an eighth gene for autosomal recessive congenital ichthyoses, but also allowed to highlight the function of this as-yet-unknown skin specific lipase in the lipid metabolism of the skin barrier. For veterinary medicine and breeding practices, a genetic test has been developed. These findings illustrate the importance of the discovery of relevant human orthologous canine genetic diseases, whose causes can be tracked

  18. Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos. (United States)

    Mio, Yasuyuki; Maeda, Kazuo


    The purpose of this study was to clarify developmental changes of early human embryos by using time-lapse cinematography (TLC). For human ova, fertilization and cleavage, development of the blastocyst, and hatching, as well as consequent changes were repeatedly photographed at intervals of 5-6 days by using an inverse microscope under stabilized temperature and pH. Photographs were taken at 30 frames per second and the movies were studied. Cinematography has increased our understanding of the morphologic mechanisms of fertilization, development, and behavior of early human embryos, and has identified the increased risk of monozygotic twin pregnancy based on prolonged incubation in vitro to the blastocyst stage. Using TLC, we observed the fertilization of an ovum by a single spermatozoon, followed by early cleavages, formation of the morula, blastocyst hatching, changes in the embryonic plates, and the development of monozygotic twins from the incubated blastocysts.

  19. Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine

    DEFF Research Database (Denmark)

    Buhl, T; Thim, L; Kofod, Hans


    and porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed...

  20. Differences in the number of micronucleated erythrocytes among young and adult animals including humans. Spontaneous micronuclei in 43 species. (United States)

    Zúñiga-González, G; Torres-Bugarín, O; Zamora-Perez, A; Gómez-Meda, B C; Ramos Ibarra, M L; Martínez-González, S; González-Rodríguez, A; Luna-Aguirre, J; Ramos-Mora, A; Ontiveros-Lira, D; Gallegos-Arreola, M P


    In our previous report we speculated about the possibility that some species had high levels of spontaneous micronucleated erythrocytes (MNE) just in a juvenile stage, this is, that the MNE diminish as the reticuloendothelial system matures. Here we show this effect in species including rat, rabbit, pig, dog, cat, gray squirrel, lion, giraffe, white-tailed deer, opossum and even human. The number of spontaneous MNE that we found in 43 species is shown, and the proportions of polychromatic and normochromatic. This is our third report on spontaneous MNE in different species. We obtained 189 peripheral blood samples of mammals, birds and reptiles. From 12 species we obtained only one sample, and 16 were reported previously, but now the size of the sample has been increased. The species with the highest spontaneous MNE were the Vietnamese potbelly pig (with the highest MNE number), Bengal tiger, capuchin monkey, puma, ferret, owl, hedgehog, squirrel monkey, pig and white-tailed deer. These species could be used as monitors for genotoxic events.

  1. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology. (United States)

    Napoli, Alessandro; Obeid, Iyad


    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  2. Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes


    O?Kell, Allison L.; Garrett, Timothy J.; Wasserfall, Clive; Atkinson, Mark A.


    While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n?=?6) and healthy (n?=?6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of k...

  3. An audit of ranulae occurring with the human immunodeficiency virus infecton. (United States)

    Butt, Fm; Chindia, Ml; Kenyanya, T; Gathece, Lw; Rana, F


    Currently, published literature has increasingly projected the ranula as a lesion that may be closely associated with exposure to the human immunodeficiency virus (HIV). In this report, we document 28 patients who presented with ranulae, among whom 19 were HIV infected. In some, this was the only lesion that was the sentinel sign of HIV infection. Most probably, this lesion could be considered as one of the clinical markers of this infection.

  4. Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes. (United States)

    O'Kell, Allison L; Garrett, Timothy J; Wasserfall, Clive; Atkinson, Mark A


    While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n = 6) and healthy (n = 6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of known and unknown metabolites. Random forest classification identified 5/6 dogs per group correctly with overall out of bag error rate = 16.7%. Diabetic dogs demonstrated significant upregulation of glycolysis/gluconeogenesis intermediates (e.g., glucose/fructose, C 6 H 12 O 6 , keto-hexose, deoxy-hexose, (P diabetic versus healthy dogs (P diabetic animals (P diabetic versus healthy dogs shared similarities with those reported in human T1D (e.g., alterations in glycolysis/gluconeogensis metabolites, bile acids, and elevated branched chain AA). Further studies are warranted to evaluate the utility of canine diabetes to provide novel mechanistic insights to the human disorder.

  5. Role of human Toll-like receptors in naturally occurring influenza A infections. (United States)

    Lee, Nelson; Wong, Chun Kwok; Hui, David S C; Lee, Sharon K W; Wong, Rity Y K; Ngai, Karry L K; Chan, Martin C W; Chu, Yi Jun; Ho, Amy W Y; Lui, Grace C Y; Wong, Bonnie C K; Wong, Sunny H; Yip, Shea Ping; Chan, Paul K S


    We investigated the roles of Toll-like receptors (TLRs) in naturally occurring influenza. A prospective, case - control study was conducted. Adults hospitalized with virologically confirmed influenza A infections (onset respiratory/cardiovascular complications. There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus strains. Higher TLR expression levels at presentation significantly correlated with lower viral loads (Spearman's rho: -0.46 to -0.69 for TLR9, TLR8, and TLR3; P-values <0.05). Multivariate regression models (adjusted for age, comorbidity, disease severity, time from onset) confirmed their independent associations. Increased signaling molecules (phospho-MAPKs, IκB) and inflammatory cytokines (IL-6, sTNFR-1, CCL2/MCP-1; CXCL10/IP-10, IFN-γ) correlated with increased TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with influenza showed significant, dynamic changes in their cytokine responses upon TLR stimulation, compared with controls. Our results suggest that TLRs play an important role in early, innate viral inhibition in naturally occurring influenza. Inflammatory cytokine responses are concomitantly induced. These findings support investigation of TLR targeting as a novel intervention approach for prophylaxis against influenza. © 2013 John Wiley & Sons Ltd.

  6. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture

    Directory of Open Access Journals (Sweden)

    Silvia Cantoni


    Full Text Available Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs. We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs from human adipose tissue (hASCs and fetal membranes of term placenta (FM-hMSCs. In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes.

  7. Telomere Attrition Occurs during Ex Vivo Expansion of Human Dental Pulp Stem Cells

    Directory of Open Access Journals (Sweden)

    Jaroslav Mokry


    Full Text Available We provide a detailed characteristic of stem cells isolated and expanded from the human dental pulp. Dental pulp stem cells express mesenchymal cell markers STRO-1, vimentin, CD29, CD44, CD73, CD90, CD166, and stem cell markers Sox2, nestin, and nucleostemin. They are multipotent as shown by their osteogenic and chondrogenic potential. We measured relative telomere length in 11 dental pulp stem cell lines at different passages by quantitative real-time PCR. Despite their large proliferative capacity, stable viability, phenotype, and genotype over prolonged cultivation, human dental pulp stem cells suffer from progressive telomere shortening over time they replicate in vitro. Relative telomere length (T/S was inversely correlated with cumulative doubling time. Our findings indicate that excessive ex vivo expansion of adult stem cells should be reduced at minimum to avoid detrimental effects on telomere maintenance and measurement of telomere length should become a standard when certificating the status and replicative age of stem cells prior therapeutic applications.

  8. Spontaneous recovery in human instrumental learning: Integration of information and recency to primacy shift. (United States)

    López-Romero, Luis Jesús; García-Barraza, Rodolfo; Vila, Javier


    This experiment was conducted to study the effect of changes in the retention interval (RI) on spontaneous recovery within an acquisition-test interference task. College students learned a reversal conditional discrimination to solve a task involving conflicting phases across two training phases. When the test was conducted immediately after training, participants' performance revealed recency, behaving according to the information received during the last phase. Performance after retention interval averaged the information received across phases, regardless of the length of the RI (1.5, 3, 24 or 48 h). These results are not in agreement with traditional theories of spontaneous recovery as they predict a recency to primacy shift effect of the RI. An interpretation of spontaneous recovery based on a temporal weighting rule (TWR) is discussed. Copyright 2010 Elsevier B.V. All rights reserved.

  9. Severity of infection and seasonal variation of non-typhoid Salmonelle occurence in humans

    DEFF Research Database (Denmark)

    Gradel, K.O.; Dethlefsen, Claus; Schønheyder, H.C.


    Non-typhoid Salmonella infections may present as severe gastroenteritis necessitatinghospitalization and some patients become septic with bacteraemia. We hypothesized that theseasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increasedseverity of infection. We...... examined the seasonal variation of non-typhoid Salmonella infections inthree patient groups with differing severity of infection: outpatients treated for gastroenteritis(n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia(n=113). The study was population......-based and included all non-typhoid Salmonella patients ina Danish county from 1994 to 2003. A periodic regression model was used to compute thepeak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4·3 [95%confidence interval (CI) 3·6–5.0] for outpatients with gastroenteritis, 3·2 (95% CI...

  10. Cryopreserved human aortic root allografts arterial wall: Structural changes occurring during thawing.

    Directory of Open Access Journals (Sweden)

    Robert Novotny

    Full Text Available The aim of our experimental work was to assess morphological changes of arterial wall that arise during different thawing protocols of a cryopreserved human aortic root allograft (CHARA arterial wall.The experiment was performed on CHARAs. Two thawing protocols were tested: 1, CHARAs were thawed at a room temperature at +23°C; 2, CHARAs were placed directly into a water bath at +37°C.After fixation, all samples were washed in distilled water for 5 min, and dehydrated in a graded ethanol series (70, 85, 95, and 100% for 5 min at each level. The tissue samples were then immersed in 100% hexamethyldisilazane for 10 minutes and air dried in an exhaust hood at room temperature. Processed samples were mounted on stainless steel stubs, coated with gold.Thawing protocol 1: All 6 (100% samples showed loss of the endothelium and damage to the subendothelial layers with randomly dispersed circular defects and micro-fractures without smooth muscle cells contractions in the tunica media. Thawing protocol 2: All 6 (100% samples showed loss of endothelium from the luminal surface, longitudinal corrugations in the direction of blood flow caused by smooth muscle cells contractions in the tunica media with frequent fractures in the subendothelial layer.All the samples thawed at the room temperature showed smaller structural damage to the CHARA arterial wall with no smooth muscle cell contraction in tunica media when compared to the samples thawed in a water bath.

  11. Flaws in current human training protocols for spontaneous Brain-Computer Interfaces: lessons learned from instructional design

    Directory of Open Access Journals (Sweden)

    Fabien eLotte


    Full Text Available While recent research on Brain-Computer Interfaces (BCI has highlighted their potential for many applications, they remain barely used outside laboratories. The main reason is their lack of robustness. Indeed, with current BCI, mental state recognition is usually slow and often incorrect. Spontaneous BCI (i.e., mental imagery-based BCI often rely on mutual learning efforts by the user and the machine, with BCI users learning to produce stable EEG patterns (spontaneous BCI control being widely acknowledged as a skill while the computer learns to automatically recognize these EEG patterns, using signal processing. Most research so far was focused on signal processing, mostly neglecting the human in the loop. However, how well the user masters the BCI skill is also a key element explaining BCI robustness. Indeed, if the user is not able to produce stable and distinct EEG patterns, then no signal processing algorithm would be able to recognize them. Unfortunately, despite the importance of BCI training protocols, they have been scarcely studied so far, and used mostly unchanged for years.In this paper, we advocate that current human training approaches for spontaneous BCI are most likely inappropriate. We notably study instructional design literature in order to identify the key requirements and guidelines for a successful training procedure that promotes a good and efficient skill learning. This literature study highlights that current spontaneous BCI user training procedures satisfy very few of these requirements and hence are likely to be suboptimal. We therefore identify the flaws in BCI training protocols according to instructional design principles, at several levels: in the instructions provided to the user, in the tasks he/she has to perform, and in the feedback provided. For each level, we propose new research directions that are theoretically expected to address some of these flaws and to help users learn the BCI skill more efficiently.

  12. Flaws in current human training protocols for spontaneous Brain-Computer Interfaces: lessons learned from instructional design. (United States)

    Lotte, Fabien; Larrue, Florian; Mühl, Christian


    While recent research on Brain-Computer Interfaces (BCI) has highlighted their potential for many applications, they remain barely used outside laboratories. The main reason is their lack of robustness. Indeed, with current BCI, mental state recognition is usually slow and often incorrect. Spontaneous BCI (i.e., mental imagery-based BCI) often rely on mutual learning efforts by the user and the machine, with BCI users learning to produce stable ElectroEncephaloGraphy (EEG) patterns (spontaneous BCI control being widely acknowledged as a skill) while the computer learns to automatically recognize these EEG patterns, using signal processing. Most research so far was focused on signal processing, mostly neglecting the human in the loop. However, how well the user masters the BCI skill is also a key element explaining BCI robustness. Indeed, if the user is not able to produce stable and distinct EEG patterns, then no signal processing algorithm would be able to recognize them. Unfortunately, despite the importance of BCI training protocols, they have been scarcely studied so far, and used mostly unchanged for years. In this paper, we advocate that current human training approaches for spontaneous BCI are most likely inappropriate. We notably study instructional design literature in order to identify the key requirements and guidelines for a successful training procedure that promotes a good and efficient skill learning. This literature study highlights that current spontaneous BCI user training procedures satisfy very few of these requirements and hence are likely to be suboptimal. We therefore identify the flaws in BCI training protocols according to instructional design principles, at several levels: in the instructions provided to the user, in the tasks he/she has to perform, and in the feedback provided. For each level, we propose new research directions that are theoretically expected to address some of these flaws and to help users learn the BCI skill more

  13. Hepatotoxic effects of fenofibrate in spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Škop, V.; Trnovská, J.; Oliyarnyk, O.; Marková, I.; Malínská, H.; Kazdová, L.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Kůdela, M.; Pravenec, Michal; Šilhavý, Jan


    Roč. 65, č. 6 (2016), s. 891-899 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT14325 Institutional support: RVO:67985823 Keywords : fenofibrate * rosuvastatin * C-reactive protein * transgenic * spontaneously hypertensive rat * inflammation * hepatotoxic Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.461, year: 2016

  14. Effect of galantamine on the human α7 neuronal nicotinic acetylcholine receptor, the Torpedo nicotinic acetylcholine receptor and spontaneous cholinergic synaptic activity (United States)

    Texidó, Laura; Ros, Esteve; Martín-Satué, Mireia; López, Susana; Aleu, Jordi; Marsal, Jordi; Solsona, Carles


    Various types of anticholinesterasic agents have been used to improve the daily activities of Alzheimer's disease patients. It was recently demonstrated that Galantamine, described as a molecule with anticholinesterasic properties, is also an allosteric enhancer of human α4β2 neuronal nicotinic receptor activity. We explored its effect on the human α7 neuronal nicotinic acetylcholine receptor (nAChR) expressed in Xenopus oocytes. Galantamine, at a concentration of 0.1 μM, increased the amplitude of acetylcholine (ACh)-induced ion currents in the human α7 nAChR expressed in Xenopus oocytes, but caused inhibition at higher concentrations. The maximum effect of galantamine, an increase of 22% in the amplitude of ACh-induced currents, was observed at a concentration of 250 μM Ach. The same enhancing effect was obtained in oocytes transplanted with Torpedo nicotinic acetylcholine receptor (AChR) isolated from the electric organ, but in this case the optimal concentration of galantamine was 1 μM. In this case, the maximum effect of galantamine, an increase of 35% in the amplitude of ACh-induced currents, occurred at a concentration of 50 μM ACh. Galantamine affects not only the activity of post-synaptic receptors but also the activity of nerve terminals. At a concentration of 1 μM, quantal spontaneous events, recorded in a cholinergic synapse, increased their amplitude, an effect which was independent of the anticholinesterasic activity associated with this compound. The anticholinesterasic effect was recorded in preparations treated with a galantamine concentration of 10 μM. In conclusion, our results show that galantamine enhances human α7 neuronal nicotinic ACh receptor activity. It also enhances muscular AChRs and the size of spontaneous cholinergic synaptic events. However, only a very narrow range of galantamine concentrations can be used for enhancing effects. PMID:15834443

  15. Detailed semantic analyses of human error incidents occurring at nuclear power plant in USA (interim report). Characteristics of human error incidents occurring in the period from 1992 to 1996

    International Nuclear Information System (INIS)

    Hirotsu, Yuko; Tsuge, Tadashi; Sano, Toshiaki; Takano, Kenichi; Gouda, Hidenori


    CRIEPI has been conducting detailed analyses of all human error incidents at domestic nuclear power plants (NPPs) collected from Japanese Licensee Event Reports (LERs) using J-HPES (Japanese version of HPES) as an analysis method. Results obtained by the analyses have been stored in J-HPES database. Since 1999, human error incidents have been selected from U.S. LERs, and they are analyzed using J-HPES. In this report, the results, which classified error action, cause, and preventive measure, are summarized for U.S. human error cases occurring in the period from 1992 to 1996. It was suggested as a result of classification that the categories of error action were almost the same as those of Japanese human error cases. Therefore, problems in the process of error action and checkpoints for preventing errors will be extracted by analyzing both U.S. and domestic human error cases. It was also suggested that the interrelations between error actions, causes, and organizational factors could be identified. While taking these suggestions into consideration, we will continue to analyze U.S. human error cases. (author)

  16. Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. (United States)

    Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L; Kusanovic, Juan Pedro; Munoz, Hernan; Honn, Kenneth V


    Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX-2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography-mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase- and lipoxygenase-pathway-derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti-inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition. © FASEB.

  17. Spontaneous vegetation succession in human-disturbed habitats: A pattern across seres

    Czech Academy of Sciences Publication Activity Database

    Prach, Karel; Pyšek, Petr; Bastl, M.


    Roč. 4, - (2001), s. 83-88 ISSN 1402-2001. [Spontanous succession in ecosystem restoration. České Budějovice, 07.09.1999-10.09.1999] R&D Projects: GA ČR GA206/94/0395 Institutional research plan: CEZ:AV0Z6005908; CEZ:MSM 123100004 Keywords : dominant * landscape character * restoration ecology Subject RIV: EF - Botanics

  18. Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro

    DEFF Research Database (Denmark)

    Rosenbaum, S.T.; Larsen, T.; Joergensen, J.C.


    Aim: To investigate the effect of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a novel SK/IK channels positive modulator, on human myometrial activity. Methods: Organ bath studies were performed on myometrial preparations obtained from women undergoing elective caesarean....... Simultaneous vehicle controls were performed for all experiments. The effects of drugs were studied on spontaneous contractions. Results: NS4591 exerted an inhibitory effect on myometrial contractions in muscle strips from non-pregnant and pregnant women. The contractility in non-pregnant and pregnant...

  19. DNA Amplification by Breakage/Fusion/Bridge Cycles Initiated by Spontaneous Telomere Loss in a Human Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Anthony W.l. Lo


    Full Text Available The development of genomic instability is an important step in generatingthe multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakagelfusionlbridge (B/F/Bcyclethatinvolvesthe repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

  20. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa. (United States)

    Kijas, James W; Cideciyan, Artur V; Aleman, Tomas S; Pianta, Michael J; Pearce-Kelling, Susan E; Miller, Brian J; Jacobson, Samuel G; Aguirre, Gustavo D; Acland, Gregory M


    Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin (RHO) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies.

  1. Where does hydrolysis of nandrolone decanoate occur in the human body after release from an oil depot? (United States)

    Kalicharan, R W; Bout, M R; Oussoren, C; Vromans, H


    Long-term therapy of nandrolone (N) is recommended to increase mineral density and muscle strength. Using a parenteral sustained release drug formulation with nandrolone decanoate (ND), therapeutic N levels can be achieved and maintained. Until now, it is unknown if hydrolysis of ND into N occurs in tissue at the injection site or after systemic absorption. Therefore, hydrolysis studies were conducted to investigate the location and rate of ND hydrolysis after its release from the oil depot. ND hydrolysis was studied in porcine tissues, to mimic the human muscular and subcutaneous tissues. Additionally, the ND hydrolysis was studied in human whole blood, plasma and serum at a concentration range of 23.3-233.3μM. ND hydrolysis only occurred in human whole blood. The hydrolysis did not start immediately, but after a lag time. The mean lag time for all studied concentrations was 34.9±2.5min. Because of a slow penetration into tissue, hydrolysis of ND is found to be very low in surrounding tissue. Therefore the local generation of the active compound is clinically irrelevant. It is argued that after injection of the oil depot, ND molecules will be transported via the lymphatic system towards lymph nodes. From here, it will enter the central circulation and within half an hour it will hydrolyse to the active N compound. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. ATP enhances spontaneous calcium activity in cultured suburothelial myofibroblasts of the human bladder.

    Directory of Open Access Journals (Sweden)

    Sheng Cheng

    Full Text Available BACKGROUND: Suburothelial myofibroblasts (sMF are located underneath the urothelium in close proximity to afferent nerves. They express purinergic receptors and show calcium transients in response to ATP. Therefore they are supposed to be involved in afferent signaling of the bladder fullness. Since ATP concentration is likely to be very low during the initial filling phase, we hypothesized that sMF Ca(2+ activity is affected even at very low ATP concentrations. We investigated ATP induced modulation of spontaneous activity, intracellular calcium response and purinergic signaling in cultured sMF. METHODOLOGY/PRINCIPAL FINDINGS: Myofibroblast cultures, established from cystectomies, were challenged by exogenous ATP in presence or absence of purinergic antagonist. Fura-2 calcium imaging was used to monitor ATP (10(-16 to 10(-4 mol/l induced alterations of calcium activity. Purinergic receptors (P2X1, P2X2, P2X3 were analysed by confocal immunofluorescence. We found spontaneous calcium activity in 55.18% ± 1.65 of the sMF (N = 48 experiments. ATP significantly increased calcium activity even at 10(-16 mol/l. The calcium transients were partially attenuated by subtype selective antagonist (TNP-ATP, 1 µM; A-317491, 1 µM, and were mimicked by the P2X1, P2X3 selective agonist α,β-methylene ATP. The expression of purinergic receptor subtypes in sMF was confirmed by immunofluorescence. CONCLUSIONS/SIGNIFICANCE: Our experiments demonstrate for the first time that ATP can modulate spontaneous activity and induce intracellular Ca(2+ response in cultured sMF at very low concentrations, most likely involving P2X receptors. These findings support the notion that sMF are able to register bladder fullness very sensitively, which predestines them for the modulation of the afferent bladder signaling in normal and pathological conditions.

  3. Somatic cell hybrids between human lymphoma lines. II. Spontaneous and induced patterns of the Epstein-Barr virus (EBV) cycle. (United States)

    Klein, G; Clements, G; Zeuthen, J; Westman, A


    The regulation of spontaneous, IUDR-induced and P3HR-1 virus-induced EA and VCA production patterns was studied in two new somatic hybrids between human lymphoma lines. The hybrid 8A was derived from the crossing of the non-producer Raji with the spontaneous producer Daudi line. The second hybrid, 83, was produced by the fusion of Raji with the EBV-genome-negative B-lymphoma line, BJAB. The studies suggest the following EBV regulation patterns: (1) the spontaneous production of EA and VCA appears to be regulated by controls that differ from the regulators of P3HR-1 virus-induced or IUDR-induced EA synthesis. While spontaneous producer status was dominant over non-producer status, the level of EA inducibility was set by one of the parental cells, Raji ATG, and could either raise (in the previously studied Raji/Namalwa hybrid, cf Nyormoi et al. 1973) or depress (in Raji/Daudi) the level of relative EA inducibility found in the partner cell. (2) Although EA production is a prerequisite for VCA synthesis, the latter is under its own restriction mechanisms, quite independent of those that regulate the level of EA synthesis. (3) Inducibility of EA synthesis by P3HR-1 virus and by IUDR appear to be under the influence of at least partially identical controls. (4) EBV-negative lymphoma cells, exemplified by BJAB, may exert a "complementation" effect on the EA inducibility of their EBV-positive fusion partner, in spite of their own restrictivity against virus-induced EA synthesis. In more general terms, it is obvious that the EBV cycle is under the influence of multiple regulatory mechanisms in the human lymphoid cell. Depending on the parental cell and viral genomes that are allowed to interact, somatic cell hybrids may display a variety of patterns. At this time, cell hybridization is one of the few pathways that permit an approach to this complex and completely unknown world.

  4. Counter-regulatory hormone responses to spontaneous hypoglycaemia during treatment with insulin Aspart or human soluble insulin

    DEFF Research Database (Denmark)

    Brock Jacobsen, I; Vind, B F; Korsholm, Lars


    examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed.......9 0.1 events per patient per week, ns), nocturnal hypoglycaemia, severe hypoglycaemic events, dosages of bolus insulin (31.8 0.4 vs. 30.0 0.6 IU day)1, ns), or NPH insulin (26.7 1.8 vs. 26.0 1.7 IU day)1, ns) or in patients satisfaction (ns). Modest differences existed in the counter......To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter-regulatory responses to spontaneous hypoglycaemia. Methods: Glycaemic control, hypoglycaemic frequency, p-insulin concentrations, insulin dosages and patients’ satisfaction were...

  5. Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas

    Directory of Open Access Journals (Sweden)

    Belen Hernandez


    Full Text Available Melanoma remains mostly an untreatable fatal disease despite advances in decoding cancer genomics and developing new therapeutic modalities. Progress in patient care would benefit from additional predictive models germane for human disease mechanisms, tumor heterogeneity, and therapeutic responses. Toward this aim, this review documents comparative aspects of human and naturally occurring canine melanomas. Clinical presentation, pathology, therapies, and genetic alterations are highlighted in the context of current basic and translational research in comparative oncology. Somewhat distinct from sun exposure-related human cutaneous melanomas, there is growing evidence that a variety of gene copy number alterations and protein structure/function mutations play roles in canine melanomas, in circumstances more analogous to human mucosal melanomas and to some extent other melanomas with murine sarcoma viral oncogene homolog B (BRAF, Neuroblastoma RAS Viral (V-Ras Oncogene Homolog (NRAS, and neurofibromin 1 tumor suppressor NF1 triple wild-type genotype. Gaps in canine genome annotation, as well as an insufficient number and depth of sequences covered, remain considerable barriers to progress and should be collectively addressed. Preclinical approaches can be designed to include canine clinical trials addressing immune modulation as well as combined-targeted inhibition of Rat Sarcoma Superfamily/Mitogen-activated protein kinase (RAS/MAPK and/or Phosphatidylinositol-3-Kinase/Protein Kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR signal transduction, pathways frequently activated in both human and canine melanomas. Future investment should be aimed towards improving understanding of canine melanoma as a predictive preclinical surrogate for human melanoma and for mutually benefiting these uniquely co-dependent species.

  6. Molecular Imprint of Exposure to Naturally Occurring Genetic Variants of Human Cytomegalovirus on the T cell Repertoire (United States)

    Smith, Corey; Gras, Stephanie; Brennan, Rebekah M.; Bird, Nicola L.; Valkenburg, Sophie A.; Twist, Kelly-Anne; Burrows, Jacqueline M.; Miles, John J.; Chambers, Daniel; Bell, Scott; Campbell, Scott; Kedzierska, Katherine; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv


    Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.

  7. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    International Nuclear Information System (INIS)

    Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.


    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  8. DNA rearrangements from γ-irradiated normal human fibroblasts preferentially occur in transcribed regions of the genome

    International Nuclear Information System (INIS)

    Forrester, H.B.; Radford, I.R.


    Full text: DNA rearrangement events leading to chromosomal aberrations are central to ionizing radiation-induced cell death. Although DNA double-strand breaks are probably the lesion that initiates formation of chromosomal aberrations, little is understood about the molecular mechanisms that generate and modulate DNA rearrangement. Examination of the sequences that flank sites of DNA rearrangement may provide information regarding the processes and enzymes involved in rearrangement events. Accordingly, we developed a method using inverse PCR that allows the detection and sequencing of putative radiation-induced DNA rearrangements in defined regions of the human genome. The method can detect single copies of a rearrangement event that has occurred in a particular region of the genome and, therefore, DNA rearrangement detection does not require survival and continued multiplication of the affected cell. Ionizing radiation-induced DNA rearrangements were detected in several different regions of the genome of human fibroblast cells that were exposed to 30 Gy of γ-irradiation and then incubated for 24 hours at 37 deg C. There was a 3- to 5-fold increase in the number of products amplified from irradiated as compared with control cells in the target regions 5' to the C-MYC, CDKN1A, RB1, and FGFR2 genes. Sequences were examined from 121 DNA rearrangements. Approximately half of the PCR products were derived from possible inter-chromosomal rearrangements and the remainder were from intra-chromosomal events. A high proportion of the sequences that rearranged with target regions were located in genes, suggesting that rearrangements may occur preferentially in transcribed regions. Eighty-four percent of the sequences examined by reverse transcriptase PCR were from transcribed sequences in IMR-90 cells. The distribution of DNA rearrangements within the target regions is non-random and homology occurs between the sequences involved in rearrangements in some cases but is not

  9. Drug-induced modification of the system properties associated with spontaneous human electroencephalographic activity (United States)

    Liley, David T.; Cadusch, Peter J.; Gray, Marcus; Nathan, Pradeep J.


    The benzodiazepine (BZ) class of minor tranquilizers are important modulators of the γ-amino butyric acid (GABAA)/BZ receptor complex that are well known to affect the spectral properties of spontaneous electroencephalographic activity. While it is experimentally well established that the BZs reduce total alpha band (8 13 Hz) power and increase total beta band (13 30 Hz) power, it is unclear what the physiological basis for this effect is. Based on a detailed theory of cortical electrorhythmogenesis it is conjectured that such an effect is explicable in terms of the modulation of GABAergic neurotransmission within locally connected populations of excitatory and inhibitory cortical neurons. Motivated by this theory, fixed order autoregressive moving average (ARMA) models were fitted to spontaneous eyes-closed electroencephalograms recorded from subjects before and approximately 2 h after the oral administration of a single 1 mg dose of the BZ alprazolam. Subsequent pole-zero analysis revealed that BZs significantly transform the dominant system pole such that its frequency and damping increase. Comparisons of ARMA derived power spectra with fast Fourier transform derived spectra indicate an enhanced ability to identify benzodiazepine induced electroencephalographic changes. This experimental result is in accord with the theoretical predictions implying that alprazolam enhances inhibition acting on inhibitory neurons more than inhibition acting on excitatory neurons. Further such a result is consistent with reported cortical neuronal distributions of the various GABAA receptor pharmacological subtypes. Therefore physiologically specified fixed order ARMA modeling is expected to become an important tool for the systematic investigation and modeling of a wide range of cortically acting compounds.

  10. La maladie de Grisel : Spontaneous atlantoaxial subluxation

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Hermens, RAEC

    Objective: "La maladie de Grisel" (Grisel's syndrome) is a spontaneously occurring atlantoaxial subluxation with torticollis. We present a case of atlantoaxial subluxation occurring in a 20-year period of pharyngoplasty surgery. The occurrence of a "spontaneous" atlantoaxial subluxation after oral

  11. An investigation of the action of Neutral Protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus. (United States)

    Palm, C A; Boston, R C; Refsal, K R; Hess, R S


    Neutral Protamine Hagedorn human analogue insulin (Humulin N) is commonly used for treatment of canine diabetes mellitus (DM). However, blood glucose and serum insulin concentrations in Humulin N-treated dogs with naturally occurring DM have not been reported. To investigate blood glucose and serum insulin concentrations in the clinical setting of client-owned Humulin N-treated dogs with naturally occurring, well-regulated DM. Ten client-owned dogs with naturally occurring, well-regulated DM. In this clinical study, blood glucose and serum insulin concentrations were measured when dogs received food and insulin (T(0)), at approximately every half hour for the next 2 hours, and then approximately every 2 hours for an additional 8 hours. Insulin duration of action was defined as the number of hours from T(0) to the lowest blood glucose concentration and until blood glucose concentration returned to an interpolated value of 70% of basal blood glucose concentration (Glucose(b)). Mean percent of insulin-induced blood glucose suppression was 49.9 +/- 17.1% (median, 46%; range, 29-78%). Insulin duration of action ranged from 4 to 10 hours. Blood glucose concentration increased initially and returned to Glucose(b) within 0.6-2.2 hours after T(0) in 5 dogs. This initial blood glucose surge then was followed by blood glucose suppression in all 5 dogs. These results suggest that Humulin N administered SC twice daily is an effective mode of treatment for dogs with naturally occurring DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs treated with Humulin N.

  12. Amyloid Plaque in the Human Brain Can Decompose from Aβ(1-40/1-42) by Spontaneous Nonenzymatic Processes. (United States)

    Lyons, Brian; Friedrich, Michael; Raftery, Mark; Truscott, Roger


    The degradation of long-lived proteins in the body is an important aspect of aging, and much of the breakdown is due to the intrinsic instability of particular amino acids. In this study, peptides were examined to discover if spontaneous nonenzymatic reactions could be responsible for the composition of Alzheimer's (AD) plaque in the human brain. The great majority of AD plaque consists of N-terminally truncated versions of Aβ(1-40/1-42), with the most abundant peptide commencing with Glu (residue 3 in Aβ1-40/1-42) that is present as pyroGlu. Several Asp residues are racemized in Aβ plaque, with residue 1 being predominantly l-isoAsp and peptide bond cleavage next to Ser 8 is also evident. In peptides, loss of the two N-terminal amino acids as a diketopiperazine was demonstrated at pH 7. For the Aβ N-terminal hexapeptide, AspAlaGluPheArgHis, this resulted in the removal of AspAla diketopiperazine and the generation of Glu as the new N-terminal residue. The Glu cyclized readily to pyroGlu. This pathway was altered significantly by zinc, which promoted pyroGlu formation but decreased AspAla diketopiperazine release. Zinc also facilitated cleavage on the N-terminal side of Ser 8. Racemization of the original N-terminal Asp to l-isoAsp was also detected and loss of one amino acid from the N-terminus. These data are therefore entirely consistent with plaque in the human brain forming from deposition of Aβ(1-40/1-42) and, over time, decomposing spontaneously. Since amyloid plaque is present in the human brain for years prior to the onset of AD, gradual spontaneous changes to the polypeptides within it will alter its properties and those of the oligomers that can diffuse from it. Such incremental changes in composition may therefore contribute to the origin of AD-associated cytotoxicity.

  13. Brain activity dynamics in human parietal regions during spontaneous switches in bistable perception. (United States)

    Megumi, Fukuda; Bahrami, Bahador; Kanai, Ryota; Rees, Geraint


    The neural mechanisms underlying conscious visual perception have been extensively investigated using bistable perception paradigms. Previous functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) studies suggest that the right anterior superior parietal (r-aSPL) and the right posterior superior parietal lobule (r-pSPL) have opposite roles in triggering perceptual reversals. It has been proposed that these two areas are part of a hierarchical network whose dynamics determine perceptual switches. However, how these two parietal regions interact with each other and with the rest of the brain during bistable perception is not known. Here, we investigated such a model by recording brain activity using fMRI while participants viewed a bistable structure-from-motion stimulus. Using dynamic causal modeling (DCM), we found that resolving such perceptual ambiguity was specifically associated with reciprocal interactions between these parietal regions and V5/MT. Strikingly, the strength of bottom-up coupling between V5/MT to r-pSPL and from r-pSPL to r-aSPL predicted individual mean dominance duration. Our findings are consistent with a hierarchical predictive coding model of parietal involvement in bistable perception and suggest that visual information processing underlying spontaneous perceptual switches can be described as changes in connectivity strength between parietal and visual cortical regions. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Age and smoking habit influence on the spontaneous and radiation induced frequencies of the micronucleus in human lymphocytes

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Nasazzi, N.; Heredia, M.L.


    Several endpoints have been used for monitoring human population that have been exposed at work or in the environment to genotoxic agents, particularly to ionizing radiation. The cytokinesis-block micronucleus (MN) assay in peripheral lymphocytes is a reliable method for evaluating radiation induced chromosomal damage (DNA breaks and mitotic spindle disturbances) and thus, a suitable dosimeter for estimating in vivo whole body exposures. A research to determine the influence of age, sex and life style factors (smoking habits) on the MN spontaneous and radiation induced frequencies was carried out in order to define the use of this assay in Biological Dosimetry. The estimation of MN frequencies was analyzed in lymphocytes cultures from 50 health donors aged between 4 and 60 years. Based on the smoking habits, they were divided into 2 groups. A fraction of the sample was irradiated in vitro with γ-rays in the range of 0.35 Gy to 4 Gy. A statistically significant influence on the spontaneous MN frequency was observed (R 2 = 0.59) when the variables age and smoking habit were analyzed, and a statistically significant influence on the radiation induced MN frequency was also obtained (R 2 = 0.86) when dose, age and smoking habit were studied. Sex did not influence significantly MN variability, but there was a greater dispersion in the results obtained from female donors, when compared to males, possibly due to the loss of X chromosomes. The comparison of the data from smoking donors to the data from non smoking donors supports the convenience of taking into account the smoking habit for estimating in vivo whole body exposure to γ-rays for doses below 2 Gy. (authors). 8 refs., 3 figs., 2 tabs

  15. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R


    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  16. Immunoglobulin V(H) gene sequence analysis of spontaneous murine immunoglobulin secreting B-cell tumours with clinical features of human disease

    NARCIS (Netherlands)

    Zhu, D.; Arkel, C. van; King, C.A.; Meirvenne, S. van; Greef, C. de; Thielemans, K.; Radl, J.; Stevenson, F.K.


    The 5T series of multiple myelomas (MM) and Waldenstrsom's macroglobulinaemia-like lymphomas (WM), which developed spontaneously in ageing mice of the C57BL/KaLwRij strain, shows clinical and biological features that closely resemble their corresponding human diseases. In order to compare the

  17. Human neural stem cell-derived cultures in three-dimensional substrates form spontaneously functional neuronal networks. (United States)

    Smith, Imogen; Silveirinha, Vasco; Stein, Jason L; de la Torre-Ubieta, Luis; Farrimond, Jonathan A; Williamson, Elizabeth M; Whalley, Benjamin J


    Differentiated human neural stem cells were cultured in an inert three-dimensional (3D) scaffold and, unlike two-dimensional (2D) but otherwise comparable monolayer cultures, formed spontaneously active, functional neuronal networks that responded reproducibly and predictably to conventional pharmacological treatments to reveal functional, glutamatergic synapses. Immunocytochemical and electron microscopy analysis revealed a neuronal and glial population, where markers of neuronal maturity were observed in the former. Oligonucleotide microarray analysis revealed substantial differences in gene expression conferred by culturing in a 3D vs a 2D environment. Notable and numerous differences were seen in genes coding for neuronal function, the extracellular matrix and cytoskeleton. In addition to producing functional networks, differentiated human neural stem cells grown in inert scaffolds offer several significant advantages over conventional 2D monolayers. These advantages include cost savings and improved physiological relevance, which make them better suited for use in the pharmacological and toxicological assays required for development of stem cell-based treatments and the reduction of animal use in medical research. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Spontaneous mutation rates and the rate-doubling dose

    International Nuclear Information System (INIS)

    Von Borstel, R.C.; Moustaccki, E.; Latarjet, R.


    The amount of radiation required to double the frequency of mutations or tumours over the rate of those that occur spontaneously is called the rate-doubling dose. An equivalent concept has been proposed for exposure to other environmental mutagens. The doubling dose concept is predicated on the assumption that all human populations have the same spontaneous mutation rate, and that this spontaneous mutation rate is known. It is now established for prokaryotes and lower eukaryotes that numerous genes control the spontaneous mutation rate, and it is likely that the same is true for human cells as well. Given that the accepted mode of evolution of human populatons is from small, isolated groups of individuals, it seems likely that each population would have a different spontaneous mutation rate. Given that a minimum of twenty genes control or affect the spontaneous mutation rate, and that each of these in turn is susceptible to spontaneously arising or environmentally induced mutations, it seems likely that every individual within a population (except for siblings from identical multiple births) will have a unique spontaneous mutation rate. If each individual in a population does have a different spontaneous mutation rate, the doubling dose concept, in rigorous terms, is fallacious. Therefore, as with other concepts of risk evaluation, the doubling dose concept is subject to criticism. Nevertheless, until we know individual spontaneous mutation rates with precision, and can evaluate risks based on this information, the doubling dose concept has a heuristic value and is needed for practical assessment of risks for defined populations. (author)

  19. Temporal expression of antioxidants in human cervicovaginal fluid associated with spontaneous labor. (United States)

    Heng, Yujing Jan; Di Quinzio, Megan Katherine Waterhouse; Permezel, Michael; Rice, Gregory Edward; Georgiou, Harry Michael


    Proteomic analysis of human cervicovaginal fluid (CVF) by 2D electrophoresis revealed significant differential expression of several major antioxidant enzymes during late pregnancy and term labor. Temporal quantitative changes of total antioxidant capacity (TAC), Cu,Zn superoxide dismutase (Cu,Zn SOD) and thioredoxin-1 (Trx-1) with impending term labor were investigated, and the potential of these biomarkers as individual and multiple predictors of labor was determined. The TAC of CVF (n = 193) was 8-fold significantly lower in labor, and approximately 2-fold significantly lower at 0-7, 8-14, 15-21, and 22-28 days, compared with >or=29 days prior to labor onset (p labor (p labor (p = 0.002). The combination of TAC and Cu,Zn SOD produced the best predictive efficacy with 74% sensitivity and 95% specificity to predict term labor within 3 days of onset. These findings suggest that labor is associated with increased oxidative stress well before its onset and is reflected in the human CVF. The biomarkers identified in this study could serve as predictors of labor and offer potential strategies for novel therapeutics.

  20. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Kirkegaard, T


    levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly......Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression...... was assessed by reverse transcription-polymerase chain reaction in HT-29 and DLD-1 cells and in CEC isolated from biopsies from IBD and control patients. Total MMP activity in the cells was measured by a functional assay, based on degradation of a fluorescent synthetic peptide containing the specific bond...

  1. Scale-Free Fluctuations in Behavioral Performance: Delineating Changes in Spontaneous Behavior of Humans with Induced Sleep Deficiency (United States)

    Beldzik, Ewa; Chialvo, Dante R.; Domagalik, Aleksandra; Fafrowicz, Magdalena; Gudowska-Nowak, Ewa; Marek, Tadeusz; Nowak, Maciej A.; Oginska, Halszka; Szwed, Jerzy


    The timing and dynamics of many diverse behaviors of mammals, e.g., patterns of animal foraging or human communication in social networks exhibit complex self-similar properties reproducible over multiple time scales. In this paper, we analyze spontaneous locomotor activity of healthy individuals recorded in two different conditions: during a week of regular sleep and a week of chronic partial sleep deprivation. After separating activity from rest with a pre-defined activity threshold, we have detected distinct statistical features of duration times of these two states. The cumulative distributions of activity periods follow a stretched exponential shape, and remain similar for both control and sleep deprived individuals. In contrast, rest periods, which follow power-law statistics over two orders of magnitude, have significantly distinct distributions for these two groups and the difference emerges already after the first night of shortened sleep. We have found steeper distributions for sleep deprived individuals, which indicates fewer long rest periods and more turbulent behavior. This separation of power-law exponents is the main result of our investigations, and might constitute an objective measure demonstrating the severity of sleep deprivation and the effects of sleep disorders. PMID:25222128

  2. Scale-free fluctuations in behavioral performance: delineating changes in spontaneous behavior of humans with induced sleep deficiency.

    Directory of Open Access Journals (Sweden)

    Jeremi K Ochab

    Full Text Available The timing and dynamics of many diverse behaviors of mammals, e.g., patterns of animal foraging or human communication in social networks exhibit complex self-similar properties reproducible over multiple time scales. In this paper, we analyze spontaneous locomotor activity of healthy individuals recorded in two different conditions: during a week of regular sleep and a week of chronic partial sleep deprivation. After separating activity from rest with a pre-defined activity threshold, we have detected distinct statistical features of duration times of these two states. The cumulative distributions of activity periods follow a stretched exponential shape, and remain similar for both control and sleep deprived individuals. In contrast, rest periods, which follow power-law statistics over two orders of magnitude, have significantly distinct distributions for these two groups and the difference emerges already after the first night of shortened sleep. We have found steeper distributions for sleep deprived individuals, which indicates fewer long rest periods and more turbulent behavior. This separation of power-law exponents is the main result of our investigations, and might constitute an objective measure demonstrating the severity of sleep deprivation and the effects of sleep disorders.

  3. Endogenous WNT Signals Mediate BMP-Induced and Spontaneous Differentiation of Epiblast Stem Cells and Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Dorota Kurek


    Full Text Available Therapeutic application of human embryonic stem cells (hESCs requires precise control over their differentiation. However, spontaneous differentiation is prevalent, and growth factors induce multiple cell types; e.g., the mesoderm inducer BMP4 generates both mesoderm and trophoblast. Here we identify endogenous WNT signals as BMP targets that are required and sufficient for mesoderm induction, while trophoblast induction is WNT independent, enabling the exclusive differentiation toward either lineage. Furthermore, endogenous WNT signals induce loss of pluripotency in hESCs and their murine counterparts, epiblast stem cells (EpiSCs. WNT inhibition obviates the need to manually remove differentiated cells to maintain cultures and improves the efficiency of directed differentiation. In EpiSCs, WNT inhibition stabilizes a pregastrula epiblast state with novel characteristics, including the ability to contribute to blastocyst chimeras. Our findings show that endogenous WNT signals function as hidden mediators of growth factor-induced differentiation and play critical roles in the self-renewal of hESCs and EpiSCs.


    African Journals Online (AJOL)


    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  5. Phosphotyrosine-Protein-Phosphatases and Human Reproduction: An Association between Low Molecular Weight Acid Phosphatase (ACPl and Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    F. Gloria-Bottini


    Full Text Available ACP1 (low molecular weight acid phosphatase genetic polymorphism has been studied in 173 women with a history of two or more consecutive spontaneous abortions and in 1508 control subjects, including 482 normal pregnant women. The proportion of carriers of ACP1 *C allele (* A/ *C, *B/*C in women with a history of repeated spontaneous abortion is lower than in normal pregnant women and other control groups, Women with repeated spontaneous abortion show a specific decrease of ACPI S isoform concentration as compared to normal pregnant women, The other component of ACP I activity, the F isoform, does not show a significant difference between the two groups. The data suggest that women with ACP1 genotypes showing a high concentration of S isoform are relatively 'protected' against spontaneous abortion, Preliminary analysis of a sample of 352 normal puerperae along with their newborn babies supports this hypothesis,

  6. Disruption of the p53-mediated G{sub 1}/S cell cycle checkpoint results in elevated rates of spontaneous genetic recombination in human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Strasfeld, L.; Brainerd, E.; Meyn, M.S. [Yale Univ. School of Medicine, New Haven, CT (United States)


    A key feature of the cancer-prone inherited disease ataxia-telangiectasia (A-T) is genetic instability. We recently demonstrated that one aspect of genetic instability in A-T is a marked elevation in the spontaneous rates of intrachromosomal mitotic recombination. We have proposed a model for A-T that attributes these high recombination rates to a lack of DNA damage-sensitive cell cycle checkpoints. One prediction of this model is that disrupting p53 function in normal cells should increase their spontaneous rates of recombination by interfering with their p53-dependent G{sub 1}/S cell cycle checkpoint. To test this prediction, we transfected control and A-T fibroblast lines that each harbor a single integrated copy of lacZ-based recombination vector (pLrec) with derivatives of a eukaryotic expression vector (pRep5) that contain either a dominant-negative p53 mutant (143{sup val{yields}ala}) or a human papilloma virus E6 gene (HPV18 E6). Expression of either of these genes results in loss of p53 function and abolition of the G{sub 1}/S cell cycle checkpoint. Four independent p53{sup 143ala} transformants of the control line showed 25-80 fold elevations in spontaneous recombination rates when compared to their parent cell line. Elevations in spontaneous recombination rates were also detected following transfection with the HPV18 E6 gene. In contrast, four independent p53{sup 143ala} transformants of the A-T cell line showed no significant changes in their already high spontaneous recombination rates. We are now extending these observations to additional normal human fibroblast lines and carrying out molecular analyses of the products of these recombinational events. Our results support our hypothesis that the lack of a p53-dependent G{sub 1}/S cell cycle checkpoint contributes to the hyperrecombination seen in A-T.

  7. Functional Architecture of Noise Correlations in Human Early Visual Cortex and its Relationship with Coherent Spontaneous Activity

    Directory of Open Access Journals (Sweden)

    Jungwon Ryu


    Full Text Available Responses of single sensory neurons to stimuli are ‘noisy’, varying substantially across repeated trials of identical stimulation. Intriguingly, these individual ‘noise responses’ (NR—deviations from their means—are not isolated; rather they are highly correlated, referred to as ‘noise correlation’ (NC. From a computational viewpoint, the presence and nature of NC exert great impacts on the information processing capacity of neurons as they encode sensory events as a population, decode those encoded neural responses, and contribute to perceptual choices for action. Regarding the origin of NR, on the other hand, there has been growing evidence pointing to its tight linkage with ‘spontaneous responses’ (SR—fluctuations of neural activity in the absence of external input or tasks. To investigate the functional structure of NC and its relationship with ‘correlations in SR’ (SC, we defined population receptive fields (pRFs of unit volumes of gray matter (UV in human early visual cortex and computed NRs and SRs using fMRI. NC increased with an increasing degree of similarity in pRF tuning properties such as orientation, spatial frequency, and visuotopic position, particularly between UV pairs close in cortical distance. This ‘like-to-like’ structure of NC remained unaltered across scan runs with different stimuli, even among between-area UV pairs. SC was higher than NC, and its functional and temporal structures were quite similar to those of NC. Furthermore, the partial correlation analysis revealed that NC between a given pair of UVs was best predicted by their SC than by any other factors examined in the current study.

  8. A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice.

    Directory of Open Access Journals (Sweden)

    Jing He

    Full Text Available The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX, but not male (XY human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/- mouse as a model for understanding BOLL function during human oogenesis.

  9. A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice. (United States)

    He, Jing; Stewart, Kayleigh; Kinnell, Hazel L; Anderson, Richard A; Childs, Andrew J


    The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL) that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX), but not male (XY) human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/-) mouse as a model for understanding BOLL function during human oogenesis.

  10. Non-Helicobacter pylori helicobacters detected in the stomach of humans comprise several naturally occurring Helicobacter species in animals. (United States)

    Baele, Margo; Pasmans, Frank; Flahou, Bram; Chiers, Koen; Ducatelle, Richard; Haesebrouck, Freddy


    Besides the well-known gastric pathogen Helicobacter pylori, other Helicobacter species with a spiral morphology have been detected in a minority of human patients who have undergone gastroscopy. The very fastidious nature of these non-Helicobacter pylori helicobacters (NHPH) makes their in vitro isolation difficult. These organisms have been designated 'Helicobacter heilmannii'. However, sequencing of several genes detected in NHPH-infected tissues has shown that the 'H. heilmannii' group comprises at least five different Helicobacter species, all of them known to colonize the stomach of animals. Recent investigations have indicated that Helicobacter suis is the most prevalent NHPH species in human. This species has only recently been isolated in vitro from porcine stomach mucosa. Other NHPH that colonize the human stomach are Helicobacter felis, Helicobacter bizzozeronii, Helicobacter salomonis and 'Candidatus Helicobacter heilmannii'. In numerous case reports of human gastric NHPH infections, no substantial information is available about the species status of the infecting strain, making it difficult to link the species with certain pathologies. This review aims to clarify the complex nomenclature of NHPH species associated with human gastric disease and their possible animal origin. It is proposed to use the term 'gastric NHPH' to designate gastric spirals that are morphologically different from H. pylori when no identification is available at the species level. Species designations should be reserved for those situations in which the species is defined.

  11. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  12. Aberrant DNA methylation of imprinted loci in human spontaneous abortions after assisted reproduction techniques and natural conception. (United States)

    Zheng, Hai-Yan; Tang, Yan; Niu, Jing; Li, Pu; Ye, De-Sheng; Chen, Xin; Shi, Xiao-Yun; Li, Li; Chen, Shi-Ling


    Do assisted reproduction techniques (ARTs) affect DNA methylation of imprinted genes and does aberrant methylation of imprinted genes account for the incidence of human spontaneous abortion (SA)? Our results show that imprinting errors of imprinted genes may contribute to human SA, and the occurrence of aberrant methylation of imprinted genes in ART pregnancies was comparable with that in natural pregnancies. Animal data and human studies demonstrated that in vitro culture of embryos can cause methylation defects in individual genes, which might affect subsequent embryonic development and contribute to SA. However, our previous studies showed an abnormal methylation pattern of PEG1 in human aborted chrionic villus samples (CVS) but an increased occurrence of aberrant methylation in CVS from ART-derived pregnancies was not observed. CVS were collected from women who underwent abortion procedures in the Department of Gynecology and Obstetrics in Nanfang Hospital from May 2008 to July 2011. Muscle samples (MS) were obtained from aborted fetuses and stillbirths. The samples were divided into four experimental groups: (A) SA/stillbirth after ART (n = 75), (B) multi-fetal reduction after ART (n = 73), (C) SA/stillbirth of natural pregnancies (n = 90) and (D) induced abortion (IA) of natural pregnancies (n = 82). The mean ± SD age of patients was 31.0 ± 4.1 (range: 18-45 years). The DNA methylation patterns of one paternally methylated (H19) and two maternally methylated (LIT1 and SNRPN) genes were analyzed in CVS and MS using pyrosequencing and bisulfite sequencing PCR. Clear hypo-methylation (90%) were not detected in LIT1 and SNRPN but two regions of hyper-methylation (91.7 and 91.4%) were observed in H19. The mean percentage of methylation in the SA samples (groups A and C) was higher than that in the IA samples (groups B and D; P<0.05). Box plot analyses showed that in the 165 SA samples, methylation values for 40/495 (8.1%) differentially methylated regions of the

  13. Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R; Henriksen, Zanne; Sørensen, Ole


    that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling...

  14. Detailed semantic analyses of human error incidents occurring at domestic nuclear power plants to fiscal year 2000

    International Nuclear Information System (INIS)

    Tsuge, Tadashi; Hirotsu, Yuko; Takano, Kenichi; Ebisu, Mitsuhiro; Tsumura, Joji


    Analysing and evaluating observed cases of human error incidents with the emphasis on human factors and behavior involved was essential for preventing recurrence of those. CRIEPI has been conducting detailed and structures analyses of all incidents reported during last 35 year based on J-HPES, from the beginning of the first Tokai nuclear power operation till fiscal year of 2000, in which total 212 human error cases are identified. Results obtained by the analyses have been stored into the J-HPES data-base. This summarized the semantic analyses on all case-studies stored in the above data-base to grasp the practical and concrete contents and trend of more frequently observed human errors (as are called trigger actions here), causal factors and preventive measures. These semantic analyses have been executed by classifying all those items into some categories that could be considered as having almost the same meaning using the KJ method. Followings are obtained typical results by above analyses: (1) Trigger action-Those could be classified into categories of operation or categories of maintenance. Operational timing errors' and 'operational quantitative errors' were major actions in trigger actions of operation, those occupied about 20% among all actions. At trigger actions of maintenance, 'maintenance quantitative error' were major actions, those occupied quarter among all actions; (2) Causal factor- 'Human internal status' were major factors, as in concrete factors, those occupied 'improper persistence' and 'lack of knowledge'; (3) Preventive measure-Most frequent measures got were job management changes in procedural software improvements, which was from 70% to 80%. As for preventive measures of operation, software improvements have been implemented on 'organization and work practices' and 'individual consciousness'. Concerning preventive measures of maintenance, improvements have been implemented on 'organization and work practices'. (author)

  15. Environmental and human health risk assessment of organic micro-pollutants occurring in a Spanish marine fish farm

    International Nuclear Information System (INIS)

    Munoz, Ivan; Martinez Bueno, Maria J.; Agueera, Ana; Fernandez-Alba, Amadeo R.


    In this work the risk posed to seawater organisms, predators and humans is assessed, as a consequence of exposure to 12 organic micro-pollutants, namely metronidazole, trimethoprim, erythromycin, simazine, flumequine, carbaryl, atrazine, diuron, terbutryn, irgarol, diphenyl sulphone (DPS) and 2-thiocyanomethylthiobenzothiazole (TCMTB). The risk assessment study is based on a 1-year monitoring study at a Spanish marine fish farm, involving passive sampling techniques. The results showed that the risk threshold for irgarol concerning seawater organisms is exceeded. On the other hand, the risk to predators and especially humans through consumption of fish is very low, due to the low bioconcentration potential of the substances assessed. - Exposure and effects of twelve organic micro-pollutants are evaluated at a Spanish fish farm.

  16. Environmental and human health risk assessment of organic micro-pollutants occurring in a Spanish marine fish farm

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Ivan, E-mail: ivanmuno@ual.e [Departamento de Hidrogeologia y Quimica Analitica, Universidad de Almeria, 04120 Almeria (Spain); Martinez Bueno, Maria J., E-mail: mjbueno@ual.e [Departamento de Hidrogeologia y Quimica Analitica, Universidad de Almeria, 04120 Almeria (Spain); Agueera, Ana, E-mail: aaguera@ual.e [Departamento de Hidrogeologia y Quimica Analitica, Universidad de Almeria, 04120 Almeria (Spain); Fernandez-Alba, Amadeo R., E-mail: amadeo@ual.e [Departamento de Hidrogeologia y Quimica Analitica, Universidad de Almeria, 04120 Almeria (Spain)


    In this work the risk posed to seawater organisms, predators and humans is assessed, as a consequence of exposure to 12 organic micro-pollutants, namely metronidazole, trimethoprim, erythromycin, simazine, flumequine, carbaryl, atrazine, diuron, terbutryn, irgarol, diphenyl sulphone (DPS) and 2-thiocyanomethylthiobenzothiazole (TCMTB). The risk assessment study is based on a 1-year monitoring study at a Spanish marine fish farm, involving passive sampling techniques. The results showed that the risk threshold for irgarol concerning seawater organisms is exceeded. On the other hand, the risk to predators and especially humans through consumption of fish is very low, due to the low bioconcentration potential of the substances assessed. - Exposure and effects of twelve organic micro-pollutants are evaluated at a Spanish fish farm.

  17. α-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. (United States)

    Mazzulli, Joseph R; Zunke, Friederike; Isacson, Ole; Studer, Lorenz; Krainc, Dimitri


    Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with α-syn remains unclear. Here, we find that α-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of α-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum-Golgi localization of rab1a, a key mediator of vesicular transport. Overexpression of rab1a restored Golgi structure, improved hydrolase trafficking and activity, and reduced pathological α-syn in patient neurons. Our work suggests that enhancement of lysosomal hydrolase trafficking may prove beneficial in synucleinopathies and indicates that human midbrain disease models may be useful for identifying critical therapeutic pathways in PD and related disorders.

  18. DNA methyltransferase 3A promoter polymorphism is associated with the risk of human spontaneous abortion after assisted reproduction techniques and natural conception. (United States)

    Liu, Yudong; Zheng, Haiyan; Guo, Pingping; Feng, Shuxian; Zhou, Xingyu; Ye, Desheng; Chen, Xin; Chen, Shiling


    The aim of this study was to explore the association of the DNA-methyltransferase (DNMT)-3A and DNMT3B promoter polymorphisms with the risk of human spontaneous abortion after assisted reproduction techniques (ARTs) and natural conception. We collected tissues from women who underwent abortion procedures: (a) chorionic villus samples (CVS) and muscle samples (MS) from spontaneous abortions conceived by ART and natural cycle (study group), n = 152; and (b) CVS and MS from normal early pregnancy and second trimester (control group), n = 155. The single-nucleotide polymorphism (SNP) -448A > G in the DNMT3A promoter region and -149C/T polymorphism of DNMT3B were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. The allele frequency of -448A among pregnancy loss group and control group was 34.2 % vs. 16.5 %, respectively. Compared with GG carriers, the DNMT3A -448AA homozygotes had an about 16-fold increased risk of spontaneous abortion [odds ratio (OR) = 16.130, 95 % confidence interval (CI), 3.665-70.984], and AG heterozygotes had an OR of 2.027 (95 % CI, 1.247-3.293). However, the distribution of -448A > G in individuals derived from ART pregnancies was not statistically significantly compared with those derived from spontaneous pregnancies (P = 0.661). For DNMT3B, we observed genotype frequencies of 100 % (TT) in the study group and the control group. The DNMT3A -448A > G polymorphism may be a novel functional SNP and contribute to its genetic susceptibility to spontaneous abortion in Chinese women, and ART may not affect the distribution of -448A > G in pregnancy loss and normal pregnancy. The observed TT genotype of DMNT3B suggests that this is the predominant genotype of this population. The findings provide new insights into the etiology of human spontaneous abortion.

  19. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

    Directory of Open Access Journals (Sweden)

    Girgis Hani Z


    Full Text Available Abstract Background Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF binding sites (TFBSs. Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. Results We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was

  20. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs. (United States)

    Girgis, Hani Z; Ovcharenko, Ivan


    Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs) and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF) binding sites (TFBSs). Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was 21-75% more precise than a related CRM

  1. Identification of GATA2 and AP-1 activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene (United States)

    Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study ...

  2. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.


    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  3. The naturally occurring α-tocopherol stereoisomer RRR-α-tocopherol is predominant in the human infant brain

    DEFF Research Database (Denmark)

    Kuchan, J M; Jensen, Søren Krogh; Johnson, E J


    α-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with synthetic α-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural stereois......α-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with synthetic α-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural...... stereoisomer RRR-α-tocopherol. α-Tocopherol stereoisomer profiles have not been previously reported in the human brain. In the present study, we analysed total α-tocopherol and α-tocopherol stereoisomers in the frontal cortex (FC), hippocampus (HPC) and visual cortex (VC) of infants (n 36) who died of sudden...

  4. High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt. (United States)

    Mosbah, Alaa; Barakat, Rafik; Nabiel, Yasmin; Barakat, Ghada


    This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

  5. Human exposure to anopheline mosquitoes occurs primarily indoors, even for users of insecticide-treated nets in Luangwa Valley, South-east Zambia

    Directory of Open Access Journals (Sweden)

    Seyoum Aklilu


    Full Text Available Abstract Background Current front line malaria vector control methods such as indoor residual spraying (IRS and long-lasting insecticidal nets (LLINs, rely upon the preference of many primary vectors to feed and/or rest inside human habitations where they can be targeted with domestically-applied insecticidal products. We studied the human biting behaviour of the malaria vector Anopheles funestus Giles and the potential malaria vector Anopheles quadriannulatus Theobald in Luangwa valley, south-east Zambia. Methods Mosquitoes were collected by human landing catch in blocks of houses with either combined use of deltamethrin-based IRS and LLINs or LLINs alone. Human behaviour data were collected to estimate how much exposure to mosquito bites indoors and outdoors occurred at various times of the night for LLIN users and non-users. Results Anopheles funestus and An. quadriannulatus did not show preference to bite either indoors or outdoors: the proportions [95% confidence interval] caught indoors were 0.586 [0.303, 0.821] and 0.624 [0.324, 0.852], respectively. However, the overwhelming majority of both species were caught at times when most people are indoors. The proportion of mosquitoes caught at a time when most people are indoors were 0.981 [0.881, 0.997] and 0.897 [0.731, 0.965], respectively, so the proportion of human exposure to both species occuring indoors was high for individuals lacking LLINs (An. funestus: 0.983 and An. quadriannulatus: 0.970, respectively. While LLIN users were better protected, more than half of their exposure was nevertheless estimated to occur indoors (An. funestus: 0.570 and An. quadriannulatus: 0.584. Conclusions The proportion of human exposure to both An. funestus and An. quadriannulatus occuring indoors was high in the area and hence both species might be responsive to further peri-domestic measures if these mosquitoes are susceptible to insecticidal products.

  6. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P


    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  7. Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine-like amino acid palythine. (United States)

    Lawrence, K P; Gacesa, R; Long, P F; Young, A R


    Solar ultraviolet radiation (UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage; however, most formulations contain organic and inorganic UVR filters that are nonbiodegradable and can damage fragile marine ecosystems. Mycosporine-like amino acids (MAAs) are natural UVR-absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow-water habitats. To determine if palythine, a photostable model MAA, could offer protection against a range of UVR-induced damage biomarkers that are important in skin cancer and photoageing. HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of end points including cell viability, DNA damage (nonspecific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The antioxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays. Palythine offered statistically significant protection (P photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to currently approved UVR filters. © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

  8. Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays. (United States)

    Amin, Hayder; Maccione, Alessandro; Marinaro, Federica; Zordan, Stefano; Nieus, Thierry; Berdondini, Luca


    The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs). These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after 3 months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e., poly-dl-ornithine (PDLO), poly-l-ornithine (PLO), and polyethylenimine (PEI), that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even 3-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings and emerging network

  9. Naturally occurring IgG antibody levels to the Staphylococcus aureus protein IsdB in humans. (United States)

    Zorman, Julie K; Esser, Mark; Raedler, Michael; Kreiswirth, Barry N; Ala'Aldeen, Dlawer A A; Kartsonis, Nicholas; Smugar, Steven S; Anderson, Annaliesa S; McNeely, Tessie; Arduino, Jean Marie


    Staphylococcus aureus is a well-recognized, clinically important cause of nosocomial infections, and as such, a vaccine to prevent S. aureus infections would be an important achievement. A Phase IIB/III study of V710, a vaccine containing iron-regulated surface determinant B (IsdB), demonstrated significant sero-conversion rates in cardiovascular surgery patients following a single pre-surgery immunization. However, the vaccine was not efficacious in preventing bacteremia or deep sternal wound infection post-surgery, thus raising the possibility that IsdB might not be available for immune recognition during infection. The purpose of the work described herein was to evaluate and quantify the naturally occurring anti-IsdB levels at baseline and over time during infection, to understand whether IsdB is expressed during a S. aureus infection in hospitalized non-vaccinated patients. We evaluated baseline and follow-up titers in 3 populations: (1) healthy subjects, (2) hospitalized patients with non-S. aureus infections, and (3) hospitalized patients with S. aureus infections. Baseline anti-IsdB levels generally overlapped between the 3 groups, but were highly variable within each group. In healthy subjects, baseline and follow-up levels were highly correlated (Spearman's rho = 0.93), and the geometric mean fold-rise (GMFR) in anti-IsdB levels between study entry and last value was 0.9-fold (95% confidence interval (CI): 0.8 to 1.0 ; p = 0.09), showing no trend over time. The convalescent GMFR in anti-IsdB levels from baseline was 1.7-fold (95% CI: 1.3 to 2.2, p = 0.0008) during S. aureus infection, significantly different from the 1.0-fold GMFR (95% CI: 0.9-1.2, p = 0.60) in non-S. aureus infection, p = 0.005. Additionally, S. aureus isolates (51) obtained from the hospitalized patient group expressed the IsdB protein in vitro. Collectively, these data suggest that IsdB expression levels rise substantially following infection with S. aureus, but not with other pathogens

  10. Destruction of the Capsid and Genome of GII.4 Human Norovirus Occurs during Exposure to Metal Alloys Containing Copper. (United States)

    Manuel, C S; Moore, M D; Jaykus, L A


    Human norovirus (HuNoV) represents a significant public health burden worldwide and can be environmentally transmitted. Copper surfaces have been shown to inactivate the cultivable surrogate murine norovirus, but no such data exist for HuNoV. The purpose of this study was to characterize the destruction of GII.4 HuNoV and virus-like particles (VLPs) during exposure to copper alloy surfaces. Fecal suspensions positive for a GII.4 HuNoV outbreak strain or GII.4 VLPs were exposed to copper alloys or stainless steel for 0 to 240 min and recovered by elution. HuNoV genome integrity was assessed by reverse transcription-quantitative PCR (RT-qPCR) (without RNase treatment), and capsid integrity was assessed by RT-qPCR (with RNase treatment), transmission electron microscopy (TEM), SDS-PAGE/Western blot analysis, and a histo-blood group antigen (HBGA) binding assay. Exposure of fecal suspensions to pure copper for 60 min reduced the GII.4 HuNoV RNA copy number by ∼3 log10 units when analyzed by RT-qPCR without RNase treatment and by 4 log10 units when a prior RNase treatment was used. The rate of reduction of the HuNoV RNA copy number was approximately proportional to the percentage of copper in each alloy. Exposure of GII.4 HuNoV VLPs to pure-copper surfaces resulted in noticeable aggregation and destruction within 240 min, an 80% reduction in the VP1 major capsid protein band intensity in 15 min, and a near-complete loss of HBGA receptor binding within 8 min. In all experiments, HuNoV remained stable on stainless steel. These results suggest that copper surfaces destroy HuNoV and may be useful in preventing environmental transmission of the virus in at-risk settings. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. [Spontaneous bacterial peritonitis]. (United States)

    Strauss, Edna; Caly, Wanda Regina


    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  12. Effects of human-induced alteration of groundwater flow on concentrations of naturally-occurring trace elements at water-supply wells (United States)

    Ayotte, J.D.; Szabo, Z.; Focazio, M.J.; Eberts, S.M.


    The effects of human-induced alteration of groundwater flow patterns on concentrations of naturally-occurring trace elements were examined in five hydrologically distinct aquifer systems in the USA. Although naturally occurring, these trace elements can exceed concentrations that are considered harmful to human health. The results show that pumping-induced hydraulic gradient changes and artificial connection of aquifers by well screens can mix chemically distinct groundwater. Chemical reactions between these mixed groundwaters and solid aquifer materials can result in the mobilization of trace elements such as U, As and Ra, with subsequent transport to water-supply wells. For example, in the High Plains aquifer near York, Nebraska, mixing of shallow, oxygenated, lower-pH water from an unconfined aquifer with deeper, confined, anoxic, higher-pH water is facilitated by wells screened across both aquifers. The resulting higher-O2, lower-pH mixed groundwater facilitated the mobilization of U from solid aquifer materials, and dissolved U concentrations were observed to increase significantly in nearby supply wells. Similar instances of trace element mobilization due to human-induced mixing of groundwaters were documented in: (1) the Floridan aquifer system near Tampa, Florida (As and U), (2) Paleozoic sedimentary aquifers in eastern Wisconsin (As), (3) the basin-fill aquifer underlying the California Central Valley near Modesto (U), and (4) Coastal Plain aquifers of New Jersey (Ra). Adverse water-quality impacts attributed to human activities are commonly assumed to be related solely to the release of the various anthropogenic contaminants to the environment. The results show that human activities including various land uses, well drilling, and pumping rates and volumes can adversely impact the quality of water in supply wells, when associated with naturally-occurring trace elements in aquifer materials. This occurs by causing subtle but significant changes in

  13. Rosuvastatin ameliorates inflammation, renal fat accumulation, and kidney injury in transgenic spontaneously hypertensive rats expressing human C-reactive protein

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Mancini, M.; Pravenec, Michal


    Roč. 64, č. 3 (2015), s. 295-301 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : rosuvastatin * kidney damage * CRP * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.643, year: 2015

  14. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Czech Academy of Sciences Publication Activity Database

    Malínská, H.; Oliyarnyk, O.; Škop, V.; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, L.; Pravenec, Michal


    Roč. 11, č. 3 (2016), e0150924 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * spontaneously hypertensive rat * transgenic * C-reactive protein * dicarbonyl stress * metformin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.806, year: 2016

  15. The Effects of Air Pressure on Spontaneous Otoacoustic Emissions of Lizards

    NARCIS (Netherlands)

    van Dijk, Pim; Manley, Geoffrey A.

    Small changes of air pressure outside the eardrum of five lizard species led to changes in frequency, level, and peak width of spontaneous otoacoustic emissions (SOAE). In contrast to humans, these changes generally occurred at very small pressures (<20 mbar). As in humans, SOAE amplitudes were

  16. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson


    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  17. CD25 shedding by human natural occurring CD4+CD25+ regulatory T cells does not inhibit the action of IL-2

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Lauritsen, Jens Peter Holst


    Tregs are known to inhibit CD4+ T cell in a contact-dependent manner, but at the same time, various suppressive factors are secreted. We, here, demonstrate that human naturally occurring CD4+CD25+ Tregs are able to shed large amounts of soluble CD25 upon activation. Secretion of sCD25 could add......Regulatory T (Treg) cells are important for the maintenance of peripheral tolerance and inhibition of pathogenic T-cell responses. Therefore, they are important for the limitation of chronic inflammation but can also be deleterious by e.g. limiting antitumour immune responses. Natural occurring...... to the inhibitory effect of Tregs as such secretion in other settings has been proposed to act as a sink for local IL-2. However, we here demonstrate that supernatant from human Tregs containing high concentration of sCD25 does not inhibit proliferation of CD4+CD25(-) T cells or inhibit the action of IL-2...

  18. Spontaneous micronucleus frequencies in human peripheral blood lymphocytes as a screening test for an individual variation in a different population and radiation-induced micronucleus induction

    International Nuclear Information System (INIS)

    Kang, Chang-Mo; Jeon, Hye-Jeong; Cho, Chul-Koo


    Our studies were to evaluate the role of epigenetic factors in the variation of radiosensitivity on human peripheral blood lymphocytes by measuring the frequencies of micronucleus (MN) from 293 healthy subjects of different population for assessing the radiation health risk in Korea. We analyzed the frequencies of both spontaneous and in vitro 60 Co γ-rays or 50MeV neutron-induced MNs. The frequencies of spontaneous NMs not only vary greatly between individuals, but also working or living areas. The increased levels of cells with spontaneous MNs were observed with an increasing age. The frequencies of spontaneous MNs were significantly higher in females than in males. For both sexes, MN frequency was significantly and positively correlated with age. Age and gender are the most important demographic variables impacting on the MN index. Donors who had ever smoked showed significantly increased frequencies of MNs compared to nonsmokers. The main lifestyle factors influencing the MN index in the subjects are correlated significantly and positively with smoke while measuring the spontaneous frequencies of micronuclei. Therefore, it is evident that with regard to the application of MN assay all future studies to evaluate the association between radiosensitivity and susceptibility for radiation health risks in different populations should take into account the effect of age, gender and lifestyle. For the dose-response study, the induced MNs were observed at all doses, and the numerical changes according to doses. The dose-response curves were fitted with a linear-quadratic forms of the dose, and the results were different for γ-rays and neutrons significantly. Neutrons were more effective than γ-rays in producing MN with a dose-dependent manner. The frequency of MN varies with dose. The RBE for a micronuclei was 2.37 ± 0.17. The results suggested that the MN assay have a high potential to ensure appropriate quality control and a standard documentation protocol, which

  19. Development of a new cause classification method considering plant ageing and human errors for adverse events which occurred in nuclear power plants and some results of its application

    International Nuclear Information System (INIS)

    Miyazaki, Takamasa


    The adverse events which occurred in nuclear power plants are analyzed to prevent similar events, and in the analysis of each event, the cause of the event is classified by a cause classification method. This paper shows a new cause classification method which is improved in several points as follows: (1) the whole causes are systematically classified into three major categories such as machine system, operation system and plant outside causes, (2) the causes of the operation system are classified into several management errors normally performed in a nuclear power plant, (3) the content of ageing is defined in detail for their further analysis, (4) human errors are divided and defined by the error stage, (5) human errors can be related to background factors, and so on. This new method is applied to the adverse events which occurred in domestic and overseas nuclear power plants in 2005. From these results, it is clarified that operation system errors account for about 60% of the whole causes, of which approximately 60% are maintenance errors, about 40% are worker's human errors, and that the prevention of maintenance errors, especially worker's human errors is crucial. (author)

  20. Fusarium musae infected banana fruits as potential source of human fusariosis: May occur more frequently than we might think and hypotheses about infection. (United States)

    Triest, David; Piérard, Denis; De Cremer, Koen; Hendrickx, Marijke


    The banana fruit infecting fungus Fusarium musae was originally known as a distinct population within Fusarium verticillioides. However, recently, Fusarium musae was installed as a separate species and the first cases of human infection associated with Fusarium musae were found. In this article, we report an additional survey indicating that human pathogenic Fusarium musae infections may occur more frequently than we might think. Moreover, we evaluate the hypotheses on how infection can be acquired. A first hypothesis is that banana fruits act as carriers of Fusarium musae spores and thereby be the source of human infection with Fusarium musae. Acquisition is likely to be caused through contact with Fusarium musae contaminated banana fruits, either being imported or after traveling of the patient to a banana-producing country. An alternative hypothesis is that Fusarium musae is not only present on banana fruits, but also on other plant hosts or environmental sources.

  1. Detailed semantic analyses of human error incidents occurring at nuclear power plants. Extraction of periodical transition of error occurrence patterns by applying multivariate analysis

    International Nuclear Information System (INIS)

    Hirotsu, Yuko; Suzuki, Kunihiko; Takano, Kenichi; Kojima, Mitsuhiro


    It is essential for preventing the recurrence of human error incidents to analyze and evaluate them with the emphasis on human factor. Detailed and structured analyses of all incidents at domestic nuclear power plants (NPPs) reported during last 31 years have been conducted based on J-HPES, in which total 193 human error cases are identified. Results obtained by the analyses have been stored into the J-HPES database. In the previous study, by applying multivariate analysis to above case studies, it was suggested that there were several occurrence patterns identified of how errors occur at NPPs. It was also clarified that the causes related to each human error are different depending on age of their occurrence. This paper described the obtained results in respects of periodical transition of human error occurrence patterns. By applying multivariate analysis to the above data, it was suggested there were two types of error occurrence patterns as to each human error type. First type is common occurrence patterns, not depending on the age, and second type is the one influenced by periodical characteristics. (author)

  2. Spontaneous synchronized tapping to an auditory rhythm in a chimpanzee. (United States)

    Hattori, Yuko; Tomonaga, Masaki; Matsuzawa, Tetsuro


    Humans actively use behavioral synchrony such as dancing and singing when they intend to make affiliative relationships. Such advanced synchronous movement occurs even unconsciously when we hear rhythmically complex music. A foundation for this tendency may be an evolutionary adaptation for group living but evolutionary origins of human synchronous activity is unclear. Here we show the first evidence that a member of our closest living relatives, a chimpanzee, spontaneously synchronizes her movement with an auditory rhythm: After a training to tap illuminated keys on an electric keyboard, one chimpanzee spontaneously aligned her tapping with the sound when she heard an isochronous distractor sound. This result indicates that sensitivity to, and tendency toward synchronous movement with an auditory rhythm exist in chimpanzees, although humans may have expanded it to unique forms of auditory and visual communication during the course of human evolution.

  3. Silk-Fibroin and Graphene Oxide Composites Promote Human Periodontal Ligament Stem Cell Spontaneous Differentiation into Osteo/Cementoblast-Like Cells. (United States)

    Vera-Sánchez, Mar; Aznar-Cervantes, Salvador; Jover, Eva; García-Bernal, David; Oñate-Sánchez, Ricardo E; Hernández-Romero, Diana; Moraleda, Jose M; Collado-González, Mar; Rodríguez-Lozano, Francisco Javier; Cenis, Jose Luis


    Graphene represents one of the most interesting additions to the tissue engineering toolbox. Novel graphene-based composites are required to improve the beneficial graphene properties in terms of tridimensional polymeric structure, conferring a higher mechanical strength and favoring the differentiation of human mesenchymal stem cells. Here, we have demonstrated in a wide range of composite combinations, the successful use of graphene and silk-fibroin constructs for future bioengineering applications in the field of clinical regenerative dentistry using human periodontal ligament stem cells. Our results provide exciting new data for the development of suitable scaffolds that allow good cell engrafting, preservation of cell viability and proliferation, promotion of spontaneous osteoblastic differentiation, and importantly, stimulation of a higher cementum physiological synthesis than using other different available biomaterials.

  4. Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses. (United States)

    Chen, Haifen; Zhou, Xinrui; Zheng, Jie; Kwoh, Chee-Keong


    The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. We obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the "observed" mutations in different years. The sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites. Our study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.

  5. Early modern human settlement of Europe north of the Alps occurred 43,500 years ago in a cold steppe-type environment. (United States)

    Nigst, Philip R; Haesaerts, Paul; Damblon, Freddy; Frank-Fellner, Christa; Mallol, Carolina; Viola, Bence; Götzinger, Michael; Niven, Laura; Trnka, Gerhard; Hublin, Jean-Jacques


    The first settlement of Europe by modern humans is thought to have occurred between 50,000 and 40,000 calendar years ago (cal B.P.). In Europe, modern human remains of this time period are scarce and often are not associated with archaeology or originate from old excavations with no contextual information. Hence, the behavior of the first modern humans in Europe is still unknown. Aurignacian assemblages--demonstrably made by modern humans--are commonly used as proxies for the presence of fully behaviorally and anatomically modern humans. The site of Willendorf II (Austria) is well known for its Early Upper Paleolithic horizons, which are among the oldest in Europe. However, their age and attribution to the Aurignacian remain an issue of debate. Here, we show that archaeological horizon 3 (AH 3) consists of faunal remains and Early Aurignacian lithic artifacts. By using stratigraphic, paleoenvironmental, and chronological data, AH 3 is ascribed to the onset of Greenland Interstadial 11, around 43,500 cal B.P., and thus is older than any other Aurignacian assemblage. Furthermore, the AH 3 assemblage overlaps with the latest directly radiocarbon-dated Neanderthal remains, suggesting that Neanderthal and modern human presence overlapped in Europe for some millennia, possibly at rather close geographical range. Most importantly, for the first time to our knowledge, we have a high-resolution environmental context for an Early Aurignacian site in Central Europe, demonstrating an early appearance of behaviorally modern humans in a medium-cold steppe-type environment with some boreal trees along valleys around 43,500 cal B.P.

  6. Effect of distance vision and refractive error on the spontaneous eye blink activity in human subjects in primary eye gaze. (United States)

    Doughty, Michael J


    To evaluate whether visual target character and visibility affects spontaneous eye blink rate (SEBR) in primary eye gaze and silence. Video recordings were made of young healthy adults who were either emmetropic (n=32) or who wore spectacles for refractive error (range -4.75D and +4.50D (n=31). Emmetropes had 5min recordings made whilst seated and looking towards a distant whiteboard. For spectacle wearers, recordings were made whilst looking towards the whiteboard with a 35mm sized cross, and repeated after spectacle removal. The average number of eye blinks over 5min was assessed, and its intra-subject variability as the coefficient of variation (COV). Over 5min without a distance target, an average SEBR of 10.4blinks/min was observed in emmetropes with a of COV=38.1%, and a significant increase in SEBR over the 5th minute to 13.6blinks/min. Hyperopes being asked to look towards a distant target showed the essentially same blinking rate of 11.1/min with or without spectacle wear with the intra-subject variability (COV) being 21.3%. Myopic subjects showed a slightly higher SEBR if looking towards a target without their spectacles (12.4 vs. 11.0blinks/min), with the COV being 18.8%. The studies indicate that some form of visual target could be useful to promote constancy of spontaneous eye blink activity over time, but that a distance visual target (when provided) does not need to be seen clearly. Crown Copyright © 2018. Published by Elsevier España, S.L.U. All rights reserved.

  7. Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks

    Directory of Open Access Journals (Sweden)

    Heikki Kiiski


    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC-derived neural cells could be cultured in human cerebrospinal fluid (CSF in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  8. Spontaneous Intracranial Hypotension without Orthostatic Headache

    Directory of Open Access Journals (Sweden)

    Tülay Kansu


    Full Text Available We report 2 cases of spontaneous intracranial hypotension that presented with unilateral abducens nerve palsy, without orthostatic headache. While sixth nerve palsies improved without any intervention, subdural hematoma was detected with magnetic resonance imaging. We conclude that headache may be absent in spontaneous intracranial hypotension and spontaneous improvement of sixth nerve palsy can occur, even after the development of a subdural hematoma

  9. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    International Nuclear Information System (INIS)

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.


    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function

  10. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    Energy Technology Data Exchange (ETDEWEB)

    Jumat, Muhammad Raihan [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Yan, Yan [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Ravi, Laxmi Iyer [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wong, Puisan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Huong, Tra Nguyen [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Li, Chunwei [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Tan, Boon Huan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Wang, De Yun [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Sugrue, Richard J., E-mail: [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)


    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  11. Pyrolysed 3D-Carbon Scaffolds Induce Spontaneous Differentiation of Human Neural Stem Cells and Facilitate Real-Time Dopamine Detection

    DEFF Research Database (Denmark)

    Amato, Letizia; Heiskanen, Arto; Caviglia, Claudia


    -dimensional (2D) and 3D environment. Due to conductive properties and 3D environment, the p3D-carbon serves as a neurotransmitter trap, enabling electrochemical detection of a signifi cantly larger dopamine fraction released by the hNSC derived neurons than on conventional 2D electrodes. This is the first study......Structurally patterned pyrolysed three-dimensional carbon scaffolds (p3Dcarbon) are fabricated and applied for differentiation of human neural stem cells (hNSCs) developed for cell replacement therapy and sensing of released dopamine. In the absence of differentiation factors (DF) the pyrolysed...... carbon material induces spontaneous hNSC differentiation into mature dopamine-producing neurons and the 3D-topography promotes neurite elongation. In the presence and absence of DF, ≈73–82% of the hNSCs obtain dopaminergic properties on pyrolysed carbon, a to-date unseen efficiency in both two...

  12. Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition (United States)

    HASSAN, Sonia S.; ROMERO, Roberto; TARCA, Adi L.; DRAGHICI, Sorin; PINELES, Beth; BUGRIM, Andrej; KHALEK, Nahla; CAMACHO, Natalia; MITTAL, Pooja; YOON, Bo Hyun; ESPINOZA, Jimmy; KIM, Chong Jai; SOROKIN, Yoram; MALONE, John


    Objective This study aimed to discover ‘signature pathways’ characterizing biological processes based on genes differentially expressed in the uterine cervix before and after spontaneous labor. Study Design The cervical transcriptome was previously characterized from biopsies taken before and after term labor. Pathway analysis was used to study the differentially expressed genes based on two gene-to-pathway annotation databases (KEGG and Metacore™). Over-represented and highly impacted pathways and connectivity nodes were identified. Results Fifty-two pathways in the Metacore™ database were significantly enriched in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling.Two novel pathways were: plasmin signaling and plasminogen activator urokinase (PLAU) signaling. The same analysis in the KEGG database identified 4 significant pathways, of which impact analysis confirmed. Multiple nodes providing connectivity within the plasmin and PLAU signaling pathways were identified.. Conclusions Three strategies for pathway analysis were consistent in their identification of novel, unexpected as well as expected networks, suggesting that this approach is both valid and effective for the elucidation of biological mechanisms involved in cervical dilation and remodeling. PMID:17826407

  13. The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In Silico Biomarker for Detecting Changes Occurring in the Human Microbiome. (United States)

    Ma, Zhanshan Sam


    Relatively little progress in the methodology for differentiating between the healthy and diseased microbiomes, beyond comparing microbial community diversities with traditional species richness or Shannon index, has been made. Network analysis has increasingly been called for the task, but most currently available microbiome datasets only allows for the construction of simple species correlation networks (SCNs). The main results from SCN analysis are a series of network properties such as network degree and modularity, but the metrics for these network properties often produce inconsistent evidence. We propose a simple new network property, the P/N ratio, defined as the ratio of positive links to the number of negative links in the microbial SCN. We postulate that the P/N ratio should reflect the balance between facilitative and inhibitive interactions among microbial species, possibly one of the most important changes occurring in diseased microbiome. We tested our hypothesis with five datasets representing five major human microbiome sites and discovered that the P/N ratio exhibits contrasting differences between healthy and diseased microbiomes and may be harnessed as an in silico biomarker for detecting disease-associated changes in the human microbiome, and may play an important role in personalized diagnosis of the human microbiome-associated diseases.

  14. Spontaneity and Equilibrium II: Multireaction Systems (United States)

    Raff, Lionel M.


    The thermodynamic criteria for spontaneity and equilibrium in multireaction systems are developed and discussed. When N reactions are occurring simultaneously, it is shown that G and A will depend upon N independent reaction coordinates, ?a (a = 1,2, ..., N), in addition to T and p for G or T and V for A. The general criteria for spontaneity and…

  15. Spontaneous cryptococcal peritonitis in cirrhotic patients.

    Directory of Open Access Journals (Sweden)

    Sungkanuparph S


    Full Text Available Spontaneous bacterial peritonitis is a common complication in patients with cirrhosis and ascites. However, spontaneous peritonitis caused by Cryptococcus neoformans is uncommon. Delayed diagnosis of cryptococcal peritonitis often results in death. We describe three cases of spontaneous cryptococcal peritonitis in patients with decompensated cirrhosis. One case had associated symptomatic human immunodeficiency virus infection. Clinical awareness of this entity may lead to the early diagnosis and proper treatment.

  16. Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells. (United States)

    Ninomiya, Masayuki; Nishida, Kyohei; Tanaka, Kaori; Watanabe, Kunitomo; Koketsu, Mamoru


    Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure-activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

  17. Endoplasmic reticulum stress is increased after spontaneous labor in human fetal membranes and myometrium where it regulates the expression of prolabor mediators. (United States)

    Liong, Stella; Lappas, Martha


    Increasing evidence indicates that endoplasmic reticulum (ER) stress is involved in various diseases. In nongestational tissues, several markers of the unfolded protein response (UPR) have been shown to regulate the inflammatory response. Thus, the aim of this study was to determine the effect of human labor on markers of ER stress in fetal membranes and myometrium. In addition, the effect of ER stress inhibition on the expression and secretion of proinflammatory and prolabor mediators was also assessed. The markers of ER stress, GRP78, IRE1, and spliced XBP1 (XBP1s), were significantly increased in fetal membranes and myometrium after term and preterm labor compared to nonlaboring samples. Given that inflammation is considered to be one of the leading causes of spontaneous preterm birth, here we used bacterial endotoxin lipopolysaccharide (LPS) as a model for infection-induced preterm birth. In term nonlabored fetal membranes and myometrium, LPS induced UPR activation as evidenced by a significant increase in the expression of GRP78, IRE1, and XBP1s in fetal membranes and myometrium. The use of the chemical chaperones 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA) alleviated ER stress induced by LPS. 4-PBA and TUDCA also ameliorated the increase in LPS-induced prolabor mediators. Our data suggest that the UPR may regulate the inflammatory responses associated with labor or infection in fetal membranes and myometrium of pregnant term and preterm women. Thus, the use of ER stress inhibitors, in particular 4-PBA or TUDCA, may be a potential therapeutic strategy for the prevention of infection-mediated spontaneous preterm birth. © 2014 by the Society for the Study of Reproduction, Inc.

  18. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk


    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.


    Effects of the Antimutagens Vanillin and Cinnamaldehyde on Spontaneous Mutation in E. coli lacI Strains and on Global Gene Epression in Salmonella TAlO4 and Human HepG2 Cells In previous work we have shown that vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutag...

  20. Spontaneous silencing of humanized green fluorescent protein (hGFP) gene expression from a retroviral vector by DNA methylation

    DEFF Research Database (Denmark)

    Gram, G J; Nielsen, S D; Hansen, J E


    We have constructed a functional murine leukemia virus (MLV)-derived retroviral vector transducing two genes encoding the autofluorescent humanized green fluorescent protein (hGFP) and neomycin phosphotransferase (Neo). This was done to determine whether hGFP could function as a marker gene...

  1. Omega-3 fatty acids from fish oil lower anxiety, improve cognitive functions and reduce spontaneous locomotor activity in a non-human primate.

    Directory of Open Access Journals (Sweden)

    Nina Vinot

    Full Text Available Omega-3 (ω3 polyunsaturated fatty acids (PUFA are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus, a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group. Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05, while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001, a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty

  2. Spontaneous Trait Inferences on Social Media. (United States)

    Levordashka, Ana; Utz, Sonja


    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  3. Spontaneous bilateral avulsion fracture of the tuberositas tibiae in a New Zealand White rabbit - a counterpart to Osgood-Schlatter disease in humans? (United States)

    Nehrbass, D; Arens, D; Zeiter, S


    The first reported case describing a spontaneous bilateral avulsion fracture of the tuberositas tibiae in a New Zealand White rabbit is presented. So far in animals, this condition has been only described in dogs and horses. In humans, this condition is also called Osgood-Schlatter disease (OSD) or syndrome, traction apophysitis of the tibial tubercle (ATT) or patellar tendon enthesopathy of the tibial tuberosity respectively. It is mainly seen in young adolescents coinciding with periods of growth spurts. In humans, its pathogenesis is believed to be caused by repetitive tendon/muscle strain at the insertion of the patellar tendon to the immature tibial tuberosity, which has its own secondary ossification center. Morphologically this case is characterized by bilateral chronic avulsion with incomplete separation of the tuberositas tibae, and proximal dislocation of the patella (patella alta). Despite these marked pathological changes, the animal was clinically without findings. Nevertheless, this case emphasizes the need for thorough clinical and radiological examination of rabbits intended for preclinical research studies prior to study begin, especially in orthopedic research. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice. (United States)

    Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin


    Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

  5. Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions

    International Nuclear Information System (INIS)

    Burrai, Giovanni P; Mohammed, Sulma I; Miller, Margaret A; Marras, Vincenzo; Pirino, Salvatore; Addis, Maria F; Uzzau, Sergio; Antuofermo, Elisabetta


    Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues. Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs. The remarkable similarity of feline mammary IELs to those of humans, with the tendency to lose hormone

  6. Does leaching of naturally occurring radionuclides from roadway pavements stabilised with coal fly ash have negative impacts on groundwater quality and human health? (United States)

    Almahayni, T; Vanhoudt, N


    We assessed the potential impact of using coal fly ash to stabilise roadway pavements on groundwater quality and human health. The leaching potential of naturally occurring radionuclides (NORs) typically present in the fly ash was assessed with the HYDRUS-1D code and data representative of a segment of the Wisconsin State Trunk Highway 60 as a case study. Our assessment suggests that the impact would be mainly from the chemical toxicity of uranium (U). In our particular case study, U concentration in the leachate exceeded the maximum contaminant level for this element (MCL = 30 μg L -1 ) in almost all the scenarios. In the groundwater, the MCL was only exceeded under conditions of high leaching and low dilution in the aquifer. The radiological toxicity from the consumption of the contaminated groundwater by a hypothetical adult, however, was at maximum 43% of the individual dose criterion (IDC = 0.1 mSv y -1 ). The results also highlight the need to consider site-specific conditions such as climate and hydrogeology when assessing the environmental impacts of utilising fly ash in roadway construction applications since they could have profound effects on the assessment findings. There is also a pressing need for reliable and representative data to support realistic assessments. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

  8. Spontaneous silencing of humanized green fluorescent protein (hGFP) gene expression from a retroviral vector by DNA methylation

    DEFF Research Database (Denmark)

    Gram, G J; Nielsen, S D; Hansen, J E


    packaging cells returned to untreated control levels within 2 weeks. Using flow cytometric analysis, hGFP expression was detected in up to 15% of transduced MT4 cells (a CD4+ lymphocytic cell line) after coculturing with packaging cells for 4 days. A 3-day postcoculture treatment with 5-azacytidine......We have constructed a functional murine leukemia virus (MLV)-derived retroviral vector transducing two genes encoding the autofluorescent humanized green fluorescent protein (hGFP) and neomycin phosphotransferase (Neo). This was done to determine whether hGFP could function as a marker gene...... in a retroviral vector and to investigate the expression of genes in a retroviral vector. Surprisingly, clonal vector packaging cell lines showed variable levels of hGFP expression, and expression was detected in as few as 49% of the cells in a clonally derived culture. This indicated that hGFP expression...

  9. A third measure-metastable state in the dynamics of spontaneous shape change in healthy human's white cells.

    Directory of Open Access Journals (Sweden)

    Karen A Selz


    Full Text Available Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 µm diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, "random" state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t, served as a computable order parameter. Comparison of R(t series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the "random" appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence, sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R

  10. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    Directory of Open Access Journals (Sweden)

    Abadie Jerome


    Full Text Available Abstract Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model

  11. [Analysis of the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion among ethnic Han Chinese from Wenzhou region]. (United States)

    Zheng, Jiayong; Zhang, Hongping; Xu, Xiaomin; Ma, Weide; Li, Jianxin; Xia, Shuqi; Wang, Hai; Shen, Xiaolu


    To assess the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese from Wenzhou region. Fifty couples with URSA (URSA group) and 66 couples with normal pregnancy history (control group) were recruited. The alleles of HLA-DQA1 and HLA-DQB1 were analyzed by polymerase chain reaction with specific sequence primers (PCR-SSP) in all subjects. The frequency distribution of HLA-DQ alleles, odds ratios (OR) between each group and sharing of HLA-DQ alleles were calculated. The frequency distribution of HLA-DQB1*03:03 allele in the females with URSA was significantly higher than that healthy females (21.00% vs. 9.85%, OR=2.433, 95%CI: 1.232-4.894, χ(2)=5.657, PHLA-DQA1 alleles in couples with URSA was increased compared with the control group (70.27% vs. 44.64%, OR=2.931, 95%CI: 1.216-7.067, PHLA-DQA1 alleles may contribute to the susceptibility of URSA among ethnic Han Chinese from Wenzhou region. The allele of HLA-DQB1*03:03 in the females may be predisposing factor for URSA. However, the HLA-DQB1*05:02 allele in both gender and HLA-DQB1*05:03 allele in females may confer a protective effect.

  12. Spontaneous pneumothorax in weightlifters. (United States)

    Marnejon, T; Sarac, S; Cropp, A J


    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  13. Clinical Holistic Medicine: Induction of Spontaneous Remission of Cancer by Recovery of the Human Character and the Purpose of Life (the Life Mission

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt


    Full Text Available The recovery of the human character and purpose of life with consciousness-based medicine seems to be able to induce spontaneous remissions in several diseases. On two different occasions, we observed breast tumors reduced to less than half their original diameters (clinically judged during a holistic session, when working with the patients in accordance with the holistic process theory of healing, the life mission theory, and the theory of human character. One tumor was histologically diagnosed as malign breast cancer prior to the session, while the other was under examination. As both patients had the affected regions of the breast surgically removed immediately after the session, we are unable to determine if they were actually healed by the holistic treatment. We find it extremely interesting that the size of a tumor can be reduced dramatically within a few hours of holistic treatment, when the patient is highly motivated for personal development. The reduction of tumor size is in accordance with the holistic view that many types of cancer are caused by emotional and existential disturbances. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called “a blockage”, where the function of the cells is changed from their original function in the tissue to a function of holding emotions. The reduction of the tumor in the two cases happened when old painful emotions were identified in the tissues, in and around the tumor, and processed into understanding; when the patients finally did let go of negative beliefs and attitudes that had kept the feeling(s repressed to that part of the body, the tumor first softened and then disappeared, presumably by apoptosis. We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients, and we will therefore strongly encourage the

  14. The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives. (United States)

    Garland, Theodore; Schutz, Heidi; Chappell, Mark A; Keeney, Brooke K; Meek, Thomas H; Copes, Lynn E; Acosta, Wendy; Drenowatz, Clemens; Maciel, Robert C; van Dijk, Gertjan; Kotz, Catherine M; Eisenmann, Joey C


    Mammals expend energy in many ways, including basic cellular maintenance and repair, digestion, thermoregulation, locomotion, growth and reproduction. These processes can vary tremendously among species and individuals, potentially leading to large variation in daily energy expenditure (DEE). Locomotor energy costs can be substantial for large-bodied species and those with high-activity lifestyles. For humans in industrialized societies, locomotion necessary for daily activities is often relatively low, so it has been presumed that activity energy expenditure and DEE are lower than in our ancestors. Whether this is true and has contributed to a rise in obesity is controversial. In humans, much attention has centered on spontaneous physical activity (SPA) or non-exercise activity thermogenesis (NEAT), the latter sometimes defined so broadly as to include all energy expended due to activity, exclusive of volitional exercise. Given that most people in Western societies engage in little voluntary exercise, increasing NEAT may be an effective way to maintain DEE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviours (e.g. watching television). The effects of voluntary exercise on other components of physical activity are highly variable in humans, partly as a function of age, and have rarely been studied in rodents. However, most rodent studies indicate that food consumption increases in the presence of wheels; therefore, other aspects of physical activity are not reduced enough to compensate for the energetic cost of wheel running. Most rodent studies also show negative effects of wheel access on body fat, especially in males. Sedentary behaviours per se have not been studied in rodents in relation to obesity. Several lines of evidence demonstrate the important role of dopamine, in addition to other neural signaling networks (e.g. the endocannabinoid system), in the control of voluntary exercise. A

  15. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination? (United States)

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte


    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  16. Spontaneous pepsin C-catalyzed activation of human pepsinogen C in transgenic rice cell suspension culture: Production and characterization of human pepsin C. (United States)

    Islam, Md Reyazul; Kim, Nan-Sun; Jung, Jae-Wan; Kim, Hyo-Boon; Han, So-Chon; Yang, Moon-Sik


    A human pepsinogen C (hPGC) gene was synthesized with rice-optimized codon usage and cloned into a rice expression vector containing the promoter, signal peptide, and terminator derived from the rice α-amylase 3D (Ramy3D) gene. In addition, a 6-His tag was added to the 3' end of the synthetic hPGC gene for easy purification. The plant expression vector was introduced into rice calli (Oryza sativa L. cv. Dongjin) mediated by Agrobacterium tumefaciens. The integration of the hPGC gene into the chromosome of the transgenic rice callus and hPGC expression in transgenic rice cell suspensions was verified via genomic DNA polymerase chain reaction amplification and Northern blot analysis. Western blot analysis indicated both hPGC and its mature form, human pepsin C, with masses of 42- and 36-kDa in the culture medium under sugar starvation conditions. Human pepsin C was purified from the culture medium using a Ni-NTA agarose column and the NH 2 -terminal 5-residue sequences were verified by amino acid sequencing. The hydrolyzing activity of human pepsin C was confirmed using bovine hemoglobin as a substrate. The optimum pH and temperature for pepsin activity were 2.0 and 40°C, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Postmenopausal spontaneous uterine perforation: Case report (United States)

    İşlek Seçen, Elçin; Ağış, Hilal; Altunkaya, Canan; Avşar, Ayşe Filiz


    Spontaneous uterine rupture and generalized peritonitis caused by pyometra occurs rarely with high morbidity and mortality. A correct and definite diagnosis can be made with laparotomy or laparoscopy. The clinical findings of perforated pyometra are similar to perforation of the gastrointestinal tract and gynecologic symptoms are less frequent, which makes preoperative diagnosis difficult. We report a case of a patient aged 82 years who underwent surgery for spontaneous uterine rupture and generalized peritonitis as a result of pyometra. PMID:28913055

  18. Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro

    International Nuclear Information System (INIS)

    Del Prete, G.F.; Vercelli, D.; Tiri, A.; Maggi, E.; Rossi, O.; Romagnani, S.; Ricci, M.


    The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone

  19. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  20. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L


    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  1. Spontaneous lateral temporal encephalocele. (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat


    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  2. Successful vaccines for naturally occurring protozoal diseases of animals should guide human vaccine research. A review of protozoal vaccines and their designs. (United States)

    McAllister, Milton M


    Effective vaccines are available for many protozoal diseases of animals, including vaccines for zoonotic pathogens and for several species of vector-transmitted apicomplexan haemoparasites. In comparison with human diseases, vaccine development for animals has practical advantages such as the ability to perform experiments in the natural host, the option to manufacture some vaccines in vivo, and lower safety requirements. Although it is proper for human vaccines to be held to higher standards, the enduring lack of vaccines for human protozoal diseases is difficult to reconcile with the comparatively immense amount of research funding. Common tactical problems of human protozoal vaccine research include reliance upon adapted rather than natural animal disease models, and an overwhelming emphasis on novel approaches that are usually attempted in replacement of rather than for improvement upon the types of designs used in effective veterinary vaccines. Currently, all effective protozoal vaccines for animals are predicated upon the ability to grow protozoal organisms. Because human protozoal vaccines need to be as effective as animal vaccines, researchers should benefit from a comparison of existing veterinary products and leading experimental vaccine designs. With this in mind, protozoal vaccines are here reviewed.

  3. ATPase N-ethylmaleimide-sensitive Fusion Protein: A Novel Key Player for Causing Spontaneous Network Excitation in Human Temporal Lobe Epilepsy. (United States)

    Herold, Christina; Bidmon, Hans-Jürgen; Pannek, Heinz W; Hans, Volkmar; Gorji, Ali; Speckmann, Erwin-Josef; Zilles, Karl


    The molecular basis for onset, maintenance and propagation of excitation along neuronal networks in epilepsy is still poorly understood. Besides different neurotransmitter receptors that control signal transfer at the synapse, one key regulator involved in all of these processes is the ATPase N-ethylmaleimide-sensitive fusion protein (NSF). Therefore, we analyzed receptor subunits and NSF levels in tissues from the medial temporal gyrus (MTG) of patients with pharmaco-resistant focal temporal lobe epilepsy resected during epilepsy surgery and autopsy controls. The resected tissues were further characterized by field potential recordings into tissues with and without spontaneous sharp wave activity. We detected increased levels of NSF, NMDA 1.1, 2A and GABA A γ 2 receptor subunits associated with spontaneous sharp wave spiking activity. We further identified correlations between NSF, AMPA receptor subunit, metabotropic glutamate receptor and adenosine 1 receptor levels in the spontaneous sharp wave spiking tissues. Our findings suggest that NSF plays a key role in controlling spontaneous network excitation in epilepsy by two mechanisms of action: (1) directly via controlling transmitter release at the presynaptic side, and (2) indirectly via altering the function of possible receptor crosstalk and directing/integrating specific receptor compounds through/into the postsynaptic membrane. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Spontaneous osteonecrosis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kattapuram, Taj M. [Department of Radiology, Massachusetts General Hospital (United States); Kattapuram, Susan V. [Department of Radiology, Massachusetts General Hospital (United States)], E-mail:


    Spontaneous osteonecrosis of the knee presents with acute onset of severe, pain in elderly patients, usually female and usually without a history of trauma. Originally described as idiopathic osteonecrosis, the exact etiology is still debated. Evidence suggests that an acute fracture occurs as a result of chronic stress or minor trauma to a weakened subchondral bone plate. The imaging characteristics on MR reflect the age of the lesion and the symptoms. More appropriate terminology may be ' subchondral insufficiency fracture of the knee' or 'focal subchondral osteonecrosis'.

  5. Cursed lamp: the problem of spontaneous abortion. (United States)

    Simkulet, William


    Many people believe human fetuses have the same moral status as adult human persons, that it is wrong to allow harm to befall things with this moral status, and thus voluntary, induced abortion is seriously morally wrong. Recently, many prochoice theorists have argued that this antiabortion stance is inconsistent; approximately 60% of human fetuses die from spontaneous abortion, far more than die from induced abortion, so if antiabortion theorists really believe that human fetuses have significant moral status, they have strong moral obligations to oppose spontaneous abortion. Yet, few antiabortion theorists devote any effort to doing so. Many prochoice theorists argue that to resolve this inconsistency, antiabortion theorists should abandon their opposition to induced abortion. Here, I argue that those who do not abandon their opposition to induced abortion but continue to neglect spontaneous abortion act immorally. Aristotle argues that moral responsibility requires both control and awareness; I argue that once an antiabortion theorist becomes aware of the frequency of spontaneous abortion, they have a strong moral obligation to redirect their efforts towards combating spontaneous abortion; failure to do so is morally monstrous. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. pol gene diversity of five human immunodeficiency virus type 1 subtypes: evidence for naturally occurring mutations that contribute to drug resistance, limited recombination patterns, and common ancestry for subtypes B and D

    NARCIS (Netherlands)

    Cornelissen, M.; van den Burg, R.; Zorgdrager, F.; Lukashov, V.; Goudsmit, J.


    Naturally occurring mutations in the polymerase gene of human immunodeficiency virus type 1 (HIV-1) have important implications for therapy and the outcome of clinical studies. Using 42 virus isolates obtained from the UNAIDS sample collection, we analyzed the protease (99 amino acids [aa]) and the

  7. Elevated maternal serum-free β-human chorionic gonadotropin (β-hCG) and reduced risk of spontaneous preterm delivery. (United States)

    Soni, Shelly; Krantz, David A; Blitz, Matthew J; Vohra, Nidhi; Rochelson, Burton


    To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

  8. Fumaric Acid Esters Can Block Pro-Inflammatory Actions of Human CRP and Ameliorate Metabolic Disturbances in Transgenic Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Mlejnek, Petr; Landa, Vladimír; Šimáková, Miroslava; Strnad, Hynek; Oliyarnyk, O.; Škop, V.; Kazdová, L.; Kurtz, T.; Pravenec, Michal


    Roč. 9, č. 7 (2014), e101906 E-ISSN 1932-6203 R&D Projects: GA MZd(CZ) NT14325; GA MŠk(CZ) LH12061; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fumaric acid esters * C-reactive protein * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  9. Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner. (United States)

    Haspot, Fabienne; Lavault, Amélie; Sinzger, Christian; Laib Sampaio, Kerstin; Stierhof, York-Dieter; Pilet, Paul; Bressolette-Bodin, Céline; Halary, Franck


    Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs) fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs). The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection), and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain) are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a "Trojan horse" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.

  10. Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner.

    Directory of Open Access Journals (Sweden)

    Fabienne Haspot

    Full Text Available Human cytomegalovirus (HCMV is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs. The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection, and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a "Trojan horse" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.

  11. Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region

    Directory of Open Access Journals (Sweden)

    García-Aguirre Laura


    Full Text Available Abstract Background Hepatitis C virus (HCV has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Previous and recent studies have suggested a diversification of type 1 HCV in the South American region. The degree of genetic variation among HCV strains circulating in Bolivia and Colombia is currently unknown. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' non-coding region (5'NCR sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America. Methods Phylogenetic tree analysis was performed using the neighbor-joining method under a matrix of genetic distances established under the Kimura-two parameter model. Signature pattern analysis, which identifies particular sites in nucleic acid alignments of variable sequences that are distinctly representative relative to a background set, was performed using the method of Korber & Myers, as implemented in the VESPA program. Prediction of RNA secondary structures was done by the method of Zuker & Turner, as implemented in the mfold program. Results Phylogenetic tree analysis of HCV strains isolated in the South American region revealed the presence of a distinct genetic lineage inside genotype 1. Signature pattern analysis revealed that the presence of this lineage is consistent with the presence of a sequence signature in the 5'NCR of HCV strains isolated in South America. Comparisons of these results with the ones found for Europe or North America revealed that this sequence signature is characteristic of the South American region. Conclusion Phylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct

  12. Large allele frequency differences between human continental groups are more likely to have occurred by drift during range expansions than by selection. (United States)

    Hofer, T; Ray, N; Wegmann, D; Excoffier, L


    Several studies have found strikingly different allele frequencies between continents. This has been mainly interpreted as being due to local adaptation. However, demographic factors can generate similar patterns. Namely, allelic surfing during a population range expansion may increase the frequency of alleles in newly colonised areas. In this study, we examined 772 STRs, 210 diallelic indels, and 2834 SNPs typed in 53 human populations worldwide under the HGDP-CEPH Diversity Panel to determine to which extent allele frequency differs among four regions (Africa, Eurasia, East Asia, and America). We find that large allele frequency differences between continents are surprisingly common, and that Africa and America show the largest number of loci with extreme frequency differences. Moreover, more STR alleles have increased rather than decreased in frequency outside Africa, as expected under allelic surfing. Finally, there is no relationship between the extent of allele frequency differences and proximity to genes, as would be expected under selection. We therefore conclude that most of the observed large allele frequency differences between continents result from demography rather than from positive selection.

  13. Human platelets activation by convulxin is accompanied by tyrosyl-phosphorylation of PLCgamma2 and occurs independently of integrin alphaIIbbeta3. (United States)

    Francischetti, I M; Carlini, C R; Guimàraes, J A


    In the present report we show that convulxin (Cvx), a C-type lectin from Crotalus durissus terrificus venom, induces platelet agregation and phospholipase C (PLC) activation by a protein tyrosine kinase (PTK)-dependent pathway. In addition, Cvx stimulates a rapid increase in tyrosine phosphorylation of human platelet proteins with molecular masses of 40, 72/74, 78/80 and 120 kDa, followed by dephosphorylation of some proteins. However, platelet aggregation was accompanied by the phosphorylation of a 105-kDa molecular mass protein. Furthermore, Cvx stimulates a rapid-tyrosyl phosphorylation of a 145-kDa protein that was identified as PLC gamma 2. Protein tyrose phosphatase (PTP) induced by Cvx was not blocked when platelets were stimulated in the presence of indomethacin, apyrase, EDTA or RGDS peptide, but inhibited by staurosporine and genistein. These results indicate that PTP is chronologically proximal to Cvx binding to platelets, and it is independent of platelet aggregation or fibrinogen binding to integrin alphaIIbbeta3. On the other hand, the phosphorylation step, and the phosphorylation of the 105-kDa protein, were both inhibited by RGDS and EDTA, which suggests that the integrin alphaIIbbeta3 beta is involved in these steps. Our results, taken together, show that Cvx induces platelet IIb 3 aggregation in a similar manner as collagen and collagen-related peptides that also trigger platelet aggregation by a PTK-dependent pathway, and stimulate tyrosyl-phosphorylation of PLC gamma 2. However, Cvx is unique among platelet receptor agonists, because under test-tube stirring conditions it induces a PTP profile independently of integrin alphaIIbbeta3.

  14. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin


    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; thi...

  15. Spontaneous magnetization in high-density quark matter

    DEFF Research Database (Denmark)

    Tsue, Yasuhiko; da Providência, João; Providência, Constanca


    It is shown that spontaneous magnetization occurs due to the anomalous magnetic moments of quarks in high-density quark matter under the tensor-type four-point interaction. The spin polarized condensate for each flavor of quark appears at high baryon density, which leads to the spontaneous...

  16. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

    NARCIS (Netherlands)

    Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, C.


    Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in

  17. Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence different aspects of motor sequence learning in humans. (United States)

    Baetu, Irina; Burns, Nicholas R; Urry, Kristi; Barbante, Girolamo Giovanni; Pitcher, Julia B


    Performing sequences of movements is a ubiquitous skill that involves dopamine transmission. However, it is unclear which components of the dopamine system contribute to which aspects of motor sequence learning. Here we used a genetic approach to investigate the relationship between different components of the dopamine system and specific aspects of sequence learning in humans. In particular, we investigated variations in genes that code for the catechol-O-methyltransferase (COMT) enzyme, the dopamine transporter (DAT) and dopamine D1 and D2 receptors (DRD1 and DRD2). COMT and the DAT regulate dopamine availability in the prefrontal cortex and the striatum, respectively, two key regions recruited during learning, whereas dopamine D1 and D2 receptors are thought to be involved in long-term potentiation and depression, respectively. We show that polymorphisms in the COMT, DRD1 and DRD2 genes differentially affect behavioral performance on a sequence learning task in 161 Caucasian participants. The DRD1 polymorphism predicted the ability to learn new sequences, the DRD2 polymorphism predicted the ability to perform a previously learnt sequence after performing interfering random movements, whereas the COMT polymorphism predicted the ability to switch flexibly between two sequences. We used computer simulations to explore potential mechanisms underlying these effects, which revealed that the DRD1 and DRD2 effects are possibly related to neuroplasticity. Our prediction-error algorithm estimated faster rates of connection strengthening in genotype groups with presumably higher D1 receptor densities, and faster rates of connection weakening in genotype groups with presumably higher D2 receptor densities. Consistent with current dopamine theories, these simulations suggest that D1-mediated neuroplasticity contributes to learning to select appropriate actions, whereas D2-mediated neuroplasticity is involved in learning to inhibit incorrect action plans. However, the

  18. Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation.

    Directory of Open Access Journals (Sweden)

    Zhilong Li

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.

  19. Spontaneous mechanical and electrical activities of human calf musculature at rest assessed by repetitive single-shot diffusion-weighted MRI and simultaneous surface electromyography. (United States)

    Schwartz, Martin; Steidle, Günter; Martirosian, Petros; Ramos-Murguialday, Ander; Preißl, Hubert; Stemmer, Alto; Yang, Bin; Schick, Fritz


    Assessment of temporal and spatial relations between spontaneous mechanical activities in musculature (SMAM) at rest as revealed by diffusion-weighted imaging (DWI) and electrical muscular activities in surface EMG (sEMG). Potential influences of static and radiofrequency magnetic fields on muscular activity on sEMG measurements at rest were examined systematically. Series of diffusion-weighted stimulated echo planar imaging were recorded with concurrent sEMG measurements. Electrical activities in sEMG were analyzed by non-parametric Friedman and two-sample Kolmogorov-Smirnov test. Direct correlation of both modalities was investigated by temporal mapping of electrical activity in sEMG to DWI repetition interval. Electrical activities in sEMG and number of visible SMAMs in DWI showed a strong correlation (ρ = 0.9718). High accordance between sEMG activities and visible SMAMs in DWI in a near-surface region around sEMG electrodes was achieved. Characteristics of sEMG activities were almost similar under varying magnetic field conditions. Visible SMAMs in DWI have shown a close and direct relation to concurrent signals recorded by sEMG. MR-related magnetic fields had no significant effects on findings in sEMG. Hence, appearance of SMAMs in DWI should not be considered as imaging artifact or as effects originating from the special conditions of MR examinations. Spatial and temporal distributions of SMAMs indicate characteristics of spontaneous (microscopic) mechanical muscular action at rest. Therefore, DWI techniques should be considered as non-invasive tools for studying physiology and pathophysiology of spontaneous activities in resting muscle. Magn Reson Med 79:2784-2794, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  20. Spontaneous regression of a lumbar disc herniation: case report

    Directory of Open Access Journals (Sweden)

    Mostarchid Brahim El


    Full Text Available Lumbar disc herniation is a common disease that induces back pain and radicular pain. Some cases require conservative treatment or at times relived spontaneously. Spontaneous regression of disc herniation is an atypical clinical presentation, and it has been recognized with the advancement of recent advances in imaging techniques. We present a 35-year-old woman presented a spontaneous regression of a lumbar disc herniation with good outcome after intensive physical therapy program. Spontaneous regression of disc herniation is thought to occur via an inflammatory reaction with molecular mechanisms of phagocytic processes.

  1. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin


    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...

  2. Spontaneous splenic rupture and Anisakis appendicitis presenting as abdominal pain: a case report

    Directory of Open Access Journals (Sweden)

    Valle Joaquín


    Full Text Available Abstract Introduction Anisakidosis, human infection with nematodes of the family Anisakidae, is caused most commonly by Anisakis simplex. Acquired by the consumption of raw or undercooked marine fish or squid, anisakidosis occurs where such dietary customs are practiced, including Japan, the coastal regions of Europe and the United States. Rupture of the spleen is a relatively common complication of trauma and many systemic disorders affecting the reticuloendothelial system, including infections and neoplasias. A rare subtype of rupture occurring spontaneously and arising from a normal spleen has been recognized as a distinct clinicopathologic entity. Herein we discuss the case of a woman who presented to our institution with appendicitis secondary to Anisakis and spontaneous spleen rupture. Case presentation We report the case of a 53-year-old Caucasian woman who presented with hemorrhagic shock and abdominal pain and was subsequently found to have spontaneous spleen rupture and appendicitis secondary to Anisakis simplex. She underwent open surgical resection of the splenic rupture and the appendicitis without any significant postoperative complications. Histopathologic examination revealed appendicitis secondary to Anisakis simplex and splenic rupture of undetermined etiology. Conclusions To the best of our knowledge, this report is the first of a woman with the diagnosis of spontaneous spleen rupture and appendicitis secondary to Anisakis simplex. Digestive anisakiasis may present as an acute abdomen. Emergency physicians should know and consider this diagnosis in patients with ileitis or colitis, especially if an antecedent of raw or undercooked fish ingestion is present. Spontaneous rupture of the spleen is an extremely rare event. Increased awareness of this condition will enhance early diagnosis and effective treatment. Further research is required to identify the possible risk factors associated with spontaneous rupture of the spleen.

  3. [The effect of polymorphism of genes of xenobiotics detoxication on the frequencies of spontaneous and induced chromosome aberrations in human lymphocytes]. (United States)

    Sal'nikova, L E; Akaeva, E A; Elisova, T V; Kuznetsova, G I; Kuz'mina, N S; Vesnina, I N; Lapteva, N Sh; Chumachenko, A G; Romanchuk, V A; Rubanovich, A V


    Here presented the data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 97 volunteers depending on genotypes by genes of xenobiotics detoxication before and after gamma-irradiation with dose of 1 Gy in vitro. The frequencies of aberrations were estimated by analyzing not less than 500-1000 metaphases per person. The data of cytogenetic analysis were compared with the results of PCR-genotyping of loci GSTM1, GSTT1, GSTP1, CYP1A1, CYP2D6, NAT2, and MTHFR. The significant differences by the frequencies of aberrations between "single-locus" genotypes were not found except for GSTM1 locus, for which the enhanced frequency of spontaneous aberrations of chromosome type in "positive" genotypes compared to "zero" ones, i.e., homozygotes by deletion (p = 0.04) was observed. The minimum frequency of spontaneous aberrations of chromosome type was recorded for carriers of double homozygotes by deletion of GSTM1-GSTT1: 0.0006 +/- 0.0003 against 0.0027 +/- 0.0003 for the rest of genotypes (p = 0.016 by the Mann-Witney test). The frequency of gamma-induced chromosome aberrations was correlated with the total amount of minor alleles in loci GSTP1, NAT2, and MTHFR (r = 0.25 at p = 0.0065).

  4. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd


    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

  5. Spontaneous hemothorax: primary pleural epithelioid angiosarcoma

    Directory of Open Access Journals (Sweden)

    Amit Panjwani


    Full Text Available Spontaneous hemothorax is a rare condition seen in coagulation and vascular disorders. Uncommonly, malignant neoplasms may cause spontaneous hemothorax. Primary pleural epithelioid angiosarcomas (excluding the cases with pleuropulmonary or chest wall involvement are extremely rare pleural tumors, which may be mistaken for mesothelioma or adenocarcinoma, and only 19 cases (one of them from India have been reported in the English literature, to date. It commonly occurs in older men, has a nonspecific clinicoradiological presentation, and carries a poor prognosis with no survivors beyond a year of establishing the diagnosis. We report a case of primary pleural epithelioid angiosarcoma presenting as a life-threatening spontaneous hemothorax. We also present a brief literature review on pleural angiosarcoma.

  6. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  7. Spontaneous Grammar Explanations. (United States)

    Tjoo, Hong Sing; Lewis, Marilyn


    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  8. Spontaneous dimensional reduction? (United States)

    Carlip, Steven


    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  9. Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion. (United States)

    Yuan, Jing; Li, Jian; Huang, Shi-Yun; Sun, Xin


    The objective was to investigate the subsets of natural killer T (NKT)-like cells and the expression of Th1/Th2 cytokines in the peripheral blood (PB) and/or decidual tissue of patients with unexplained recurrent spontaneous abortion (URSA). The percentages of NKT-like cells in the PB and deciduas of URSA patients in early pregnancy and in the PB of nonpregnant women were analyzed by flow cytometry. The expression of interferon (IFN)-γ (Th1 cytokine) and Th2 cytokines, interleukin (IL)-4 and IL-10, in the PB and decidual tissue was measured by quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA). Most percentages of subsets of NKT-like cells (CD3(+)CD56(+), CD3(+)CD56(+)CD16(+)) in the PB and deciduas were significantly greater in URSA patients than in normal pregnant and nonpregnant women. A cut-off value of 3.75% for the increased percentage of CD3(+)CD56(+)CD16(+) NKT-like cells in the PB appeared to be predictive of pregnancy failure. Moreover, we found that in the decidua, IFN-γ expression was significantly higher, while IL-4 and IL-10 expression was significantly lower in URSA patients compared with those with a normal pregnancy. The ratio of decidual Th1/Th2 cytokines in URSA patients was significantly increased compared with that in normal pregnant women. Decidual IL-4 expression correlated negatively with the percentages of blood CD3(+)CD56(+)CD16(+) NKT-like cells and the decidual CD3(+)CD56(+) and CD3(+)CD56(+)CD16(+) NKT-like cells. NKT-like cells may play an important role in maintaining normal pregnancy. Measurement of CD3(+)CD56(+)CD16(+) NKT-like cells in the PB may provide a potential tool for assessing patients' risk of spontaneous abortion. Copyright © 2015. Published by Elsevier Ireland Ltd.

  10. Bilateral spontaneous rupture of 'hale' kidneys

    International Nuclear Information System (INIS)

    Naumov, N.; Zozikov, B.; Otzetov, A.; Kamenova, M.; Martinova, F.; Kalyonski, R.


    A rare case of spontaneous bilateral rupture of the kidneys, occurring consecutively over a one-year period in a young male patient with 'hale' kidneys until then, is described. The patient's past history and thorough examination performed do not justify to assign the case under the heading of some of the etiological factors as the underlying cause of spontaneous kidney rupture. The literature survey on spontaneous bilateral non-tumor ruptures of kidneys shows that over a 20-year period, only 3 cases of bilateral spontaneous ruptures have been reported. It is pointed out that panarteritis nodosa followed by hemorrhagic fever with renal syndrome is the commonest underlying cause of such ruptures. Clinically spontaneous ruptures become manifest with emergency condition presenting severe renal colic, impaired to serious general condition, often with acute abdomen and hemodynamic breakdown, and no past history evidence of renal disease or injury. In the initial phase diagnosing is not always easy; it is usually made on the ground of physical examination and the full range of imaging studies used in urological practice and during operative treatment. Emphasis is laid on the fact that the imaging methods are not invariably sufficient to identify the exact etiological factor giving rise to such a severe condition, but nevertheless these methods have an essential practical bearing on diagnosing a rupture. (authors)

  11. Naturally occurring Vpr inhibitors from medicinal plants of Myanmar. (United States)

    Win, Nwet Nwet; Ngwe, Hla; Abe, Ikuro; Morita, Hiroyuki


    Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN). Drug resistance likely emerges because of spontaneous mutations that occur during viral replication. Therefore, new drugs that effectively block other viral components must be developed to reduce the rate of resistance and suppress viral replication with little or no long-term toxicity. The accessory proteins may expand treatment options. Viral protein R (Vpr) is one of the promising drug targets among the HIV accessory proteins. However, the search for inhibitors continues in anti-HIV drug discovery. In this review, we summarize the naturally occurring compounds discovered from two Myanmar medicinal plants as well as their structure-activity relationships. A total of 49 secondary metabolites were isolated from Kaempferia pulchra rhizomes and Picrasama javanica bark, and the types of compounds were identified as isopimarane diterpenoids and picrasane quassinoids, respectively. Among the isolates, 7 diterpenoids and 15 quassinoids were found to be Vpr inhibitors lacking detectable toxicity, and their potencies varied according to their respective functionalities.

  12. Dorsomedial prefontal cortex supports spontaneous thinking per se. (United States)

    Raij, T T; Riekki, T J J


    Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Spontaneous healing of spontaneous coronary artery dissection. (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den


    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  14. Characterization of a single peptide derived from cytochrome P4501B1 that elicits spontaneous human leukocyte antigen (HLA)-A1 as well as HLA-B35 restricted CD8 T-cell responses in cancer patients

    DEFF Research Database (Denmark)

    Kvistborg, P.; Hadrup, S.R.; Andersen, M.H.


    Cytochrome P450 1B1 (CYP1B1) is widely expressed in human malignancies, but silent in most normal tissues. Importantly, the protein is believed to play an important role in the survival and growth of cancer cells in a stressed environment, e.g., as a result of hypoxia or chemotherapy. Thus......, targeting of CYP1B1 represents a potentially successful strategy in the treatment of metastatic cancer, e.g., by therapeutic vaccination. Herein, we describe the characterization of a novel peptide from the CYP1B1 protein (CYP240), which is spontaneously recognized by CD8 T cells in cancer patients....... Rare but strong responses were detected in HLA-A1-positive patients, and more frequent responses were detected in HLA-B35-positive patients. No reactivity against the peptide could be detected in healthy donors. Furthermore, we demonstrated that peptide-specific T cells were able to lyze target cells...

  15. Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU). (United States)

    Dreyfus, D H


    Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU. © 2015 British Society for Immunology.

  16. Crows spontaneously exhibit analogical reasoning. (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward


    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The effects of age and divided attention on spontaneous recognition. (United States)

    Anderson, Benjamin A; Jacoby, Larry L; Thomas, Ruthann C; Balota, David A


    Studies of recognition typically involve tests in which the participant's memory for a stimulus is directly questioned. There are occasions however, in which memory occurs more spontaneously (e.g., an acquaintance seeming familiar out of context). Spontaneous recognition was investigated in a novel paradigm involving study of pictures and words followed by recognition judgments on stimuli with an old or new word superimposed over an old or new picture. Participants were instructed to make their recognition decision on either the picture or word and to ignore the distracting stimulus. Spontaneous recognition was measured as the influence of old vs. new distracters on target recognition. Across two experiments, older adults and younger adults placed under divided-attention showed a greater tendency to spontaneously recognize old distracters as compared to full-attention younger adults. The occurrence of spontaneous recognition is discussed in relation to ability to constrain retrieval to goal-relevant information.

  18. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin


    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...... of therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional...

  19. The probability of spontaneous regression of lumbar herniated disc: a systematic review. (United States)

    Chiu, Chun-Chieh; Chuang, Tai-Yuan; Chang, Kwang-Hwa; Wu, Chien-Hua; Lin, Po-Wei; Hsu, Wen-Yen


    To determine the probability of spontaneous disc regression among each type of lumbar herniated disc, using a systematic review. Medline, Cochrane Library, CINAHL, and Web of Science were searched using key words for relevant original articles published before March 2014. Articles were limited to those published in English and human studies. Articles had to: (1) include patients with lumbar disc herniation treated conservatively; (2) have at least two imaging evaluations of the lumbar spine; and (3) exclude patients with prior lumbar surgery, spinal infections, tumors, spondylolisthesis, or spinal stenosis. Two reviewers independently extracted study details and findings. Thirty-one studies met the inclusion criteria. Furthermore, if the classification of herniation matched the recommended classification of the combined Task Forces, the data were used for combined analysis of the probability of disc regression of each type. Nine studies were applicable for probability calculation. The rate of spontaneous regression was found to be 96% for disc sequestration, 70% for disc extrusion, 41% for disc protrusion, and 13% for disc bulging. The rate of complete resolution of disc herniation was 43% for sequestrated discs and 15% for extruded discs. Spontaneous regression of herniated disc tissue can occur, and can completely resolve after conservative treatment. Patients with disc extrusion and sequestration had a significantly higher possibility of having spontaneous regression than did those with bulging or protruding discs. Disc sequestration had a significantly higher rate of complete regression than did disc extrusion. © The Author(s) 2014.

  20. Comparison of maintenance worker's human error events occurred at United States and domestic nuclear power plants. The proposal of the classification method with insufficient knowledge and experience and the classification result of its application

    International Nuclear Information System (INIS)

    Takagawa, Kenichi


    Human errors by maintenance workers in U.S. nuclear power plants were compared with those in Japanese nuclear power plants for the same period in order to identify the characteristics of such errors. As for U.S. events, cases which occurred during 2006 were selected from the Nuclear Information Database of the Institute to Nuclear Safety System while Japanese cases that occurred during the same period, were extracted from the Nuclear Information Archives (NUCIA) owned by JANTI. The most common cause of human errors was insufficient knowledge or experience' accounting for about 40% for U.S. cases and 50% or more of cases in Japan. To break down 'insufficient knowledge', we classified the contents of knowledge into five categories; method', 'nature', 'reason', 'scope' and 'goal', and classified the level of knowledge into four categories: 'known', 'comprehended', 'applied' and analytic'. By using this classification, the patterns of combination of each item of the content and the level of knowledge were compared. In the U.S. cases, errors due to 'insufficient knowledge of nature and insufficient knowledge of method' were prevalent while three other items', 'reason', scope' and 'goal' which involve work conditions among the contents of knowledge rarely occurred. In Japan, errors arising from 'nature not being comprehended' were rather prevalent while other cases were distributed evenly for all categories including the work conditions. For addressing insufficient knowledge or experience', we consider that the following approaches are valid: according to the knowledge level which is required for the work, the reflection of knowledge on the procedure or education materials, training and confirmation of understanding level, virtual practice and instruction of experience should be implemented. As for the knowledge on the work conditions, it is necessary to enter the work conditions in the procedure and education materials while conducting training or education. (author)

  1. Stock market speculation: Spontaneous symmetry breaking of economic valuation (United States)

    Sornette, Didier


    Firm foundation theory estimates a security's firm fundamental value based on four determinants: expected growth rate, expected dividend payout, the market interest rate and the degree of risk. In contrast, other views of decision-making in the stock market, using alternatives such as human psychology and behavior, bounded rationality, agent-based modeling and evolutionary game theory, expound that speculative and crowd behavior of investors may play a major role in shaping market prices. Here, we propose that the two views refer to two classes of companies connected through a "phase transition". Our theory is based on (1) the identification of the fundamental parity symmetry of prices (p→-p), which results from the relative direction of payment flux compared to commodity flux and (2) the observation that a company's risk-adjusted growth rate discounted by the market interest rate behaves as a control parameter for the observable price. We find a critical value of this control parameter at which a spontaneous symmetry-breaking of prices occurs, leading to a spontaneous valuation in absence of earnings, similarly to the emergence of a spontaneous magnetization in Ising models in absence of a magnetic field. The low growth rate phase is described by the firm foundation theory while the large growth rate phase is the regime of speculation and crowd behavior. In practice, while large "finite-time horizon" effects round off the predicted singularities, our symmetry-breaking speculation theory accounts for the apparent over-pricing and the high volatility of fast growing companies on the stock markets.

  2. Recurrent spontaneous attacks of dizziness. (United States)

    Lempert, Thomas


    This article describes the common causes of recurrent vertigo and dizziness that can be diagnosed largely on the basis of history. Ninety percent of spontaneous recurrent vertigo and dizziness can be explained by six disorders: (1) Ménière disease is characterized by vertigo attacks, lasting 20 minutes to several hours, with concomitant hearing loss, tinnitus, and aural fullness. Aural symptoms become permanent during the course of the disease. (2) Attacks of vestibular migraine may last anywhere from minutes to days. Most patients have a previous history of migraine headaches, and many experience migraine symptoms during the attack. (3) Vertebrobasilar TIAs affect older adults with vascular risk factors. Most attacks last less than 1 hour and are accompanied by other symptoms from the posterior circulation territory. (4) Vestibular paroxysmia is caused by vascular compression of the eighth cranial nerve. It manifests itself with brief attacks of vertigo that recur many times per day, sometimes with concomitant cochlear symptoms. (5) Orthostatic hypotension causes brief episodes of dizziness lasting seconds to a few minutes after standing up and is relieved by sitting or lying down. In older adults, it may be accompanied by supine hypertension. (6) Panic attacks usually last minutes, occur in specific situations, and are accompanied by choking, palpitations, tremor, heat, and anxiety. Less common causes of spontaneous recurrent vertigo and dizziness include perilymph fistula, superior canal dehiscence, autoimmune inner ear disease, otosclerosis, cardiac arrhythmia, and medication side effects. Neurologists need to venture into otolaryngology, internal medicine, and psychiatry to master the differential diagnosis of recurrent dizziness.

  3. Mesenchymal Stem Cells Derived from Human Exocrine Pancreas Spontaneously Express Pancreas Progenitor-Cell Markers in a Cell-Passage-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Song Lee


    Full Text Available Mesenchymal stem cells (MSCs derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies. Pancreatic tissue was digested by collagenase and an enriched exocrine-cell fraction was obtained by density-gradient separation. Crude exocrine cells were methodically cultured in suspension and then in adherent culture. We expanded the human pancreatic exocrine-derived MSCs (hpMSCs by cell passaging in culture and confirmed by flow cytometry that >90% expressed human classic surface markers of MSCs. Interestingly, these cells expressed pancreatic transcription factors, such as Pdx1, Ngn3, and MafA, similar to pancreatic progenitor cells. These results indicated that hpMSCs can be used for the differentiation of pancreatic endocrine cells and may be used in type 1 diabetes treatment.

  4. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K


    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  5. Surgical management of spontaneous ruptured hepatocellular adenoma

    Directory of Open Access Journals (Sweden)

    Marcelo Augusto Fontenelle Ribeiro Junior


    Full Text Available AIMS: Spontaneous ruptured hepatocellular adenoma (SRHA is a rare life-threatening condition that may require surgical treatment to control hemorrhaging and also stabilize the patient. We report a series of emergency surgeries performed at our institution for this condition. METHODS: We reviewed medical records and radiology files of 28 patients (from 1989 to 2006 with a proven diagnosis of hepatocellular adenoma (HA. Three (10.7% of 28 patients had spontaneous ruptured hepatocellular adenoma, two of which were associated with intrahepatic hemorrhage while one had intraperitoneal bleeding. Two patients were female and one was male. Both female patients had a background history of oral contraceptive use. Sudden abdominal pain associated with hemodynamic instability occurred in all patients who suffered from spontaneous ruptured hepatocellular adenoma. The mean age was 41.6 years old. The preoperative assessment included liver function tests, ultrasonography and computed tomography. RESULTS: The surgical approaches were as follows: right hemihepatectomy for controlling intraperitoneal bleeding, and right extended hepatectomy and non-anatomic resection of the liver for intrahepatic hemorrhage. There were no deaths, and the postoperative complications were bile leakage and wound infection (re-operation, as well as intraperitoneal abscess (re-operation and pleural effusion. CONCLUSION: Spontaneous ruptured hepatocellular adenoma may be treated by surgery for controlling hemorrhages and stabilizing the patient, and the decision to operate depends upon both the patient's condition and the expertise of the surgical team.

  6. Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

    Directory of Open Access Journals (Sweden)

    Pak Cheung Ng

    Full Text Available Necrotizing enterocolitis (NEC and spontaneous intestinal perforation (SIP are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology.We performed differential miRNA arrays on tissues of NEC (n = 4, SIP (n = 4 and surgical-control (Surg-CTL; n = 4, and validated target miRNAs by qPCR (n = 10 each group. The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples.We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p, mediated via key transcription factors NFKB2 (miR-203, AP-1/FOSL1 (miR-194-3p, FOXA1 (miR-21-3p, miR-431 and miR-1290 and HIF1A (miR-31, and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction.The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology.

  7. Spontaneous Tumour Lysis Syndrome in a Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Can Huzmeli


    Full Text Available The tumor lysis syndrome (TLS is a collection of metabolic abnormalities that occur in consequence of the release of intracellular contents following lysis of tumor cells. TLS occurs spontaneously or after chemotherapy. Spontaneous TLS is uncommon occurrence in multiple myeloma (MM. We define a case of a 70-year-old woman patient who was found to have MM with spontaneous TLS, following a compression fracture of the T-12 vertebrae. While serum uric acid and phosphorous levels were high, low calcium levels were identified. There were also acute kidney injury and metabolic acidosis. Upon the diagnosis of TLS, she was treated with hydration, allopurinol, sodium bicarbonate, and calcium gluconate. The improvement of her laboratory data was observed. We submitted this case in order to draw attention to the presentation of MM with spontaneous TLS.

  8. Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice.

    Directory of Open Access Journals (Sweden)

    Scott J Goldman


    Full Text Available In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for

  9. Pyrolysed 3D-Carbon Scaffolds Induce Spontaneous Differentiation of Human Neural Stem Cells and Facilitate Real-Time Dopamine Detection

    NARCIS (Netherlands)

    Amato, Letizia; Heiskanen, Arto; Caviglia, Claudia; Shah, Fozia; Zor, Kinga; Skolimowski, Maciej; Madou, Marc; Gammelgaard, Lauge; Hansen, Rasmus; Seiz, Emma G.; Ramos, Milagros; Ramos Moreno, Tania; Martinez-Serrano, Alberto; Keller, Stephan S.; Emneus, Jenny


    Structurally patterned pyrolysed three-dimensional carbon scaffolds (p3D-carbon) are fabricated and applied for differentiation of human neural stem cells (hNSCs) developed for cell replacement therapy and sensing of released dopamine. In the absence of differentiation factors (DF) the pyrolysed

  10. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD


    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

  11. Spontaneous Tricuspid Valve Chordal Rupture in Idiopathic Pulmonary Hypertension. (United States)

    Rodrigues, Ana Clara Tude; Afonso, José E; Cordovil, Adriana; Monaco, Claudia; Piveta, Rafael; Cordovil, Rodrigo; Fischer, Claudio H; Vieira, Marcelo; Lira-Filho, Edgar; Morhy, Samira S


    Rupture of tricuspid valve is unusual, occurring mainly in the setting of blunt trauma or endomyocardial biopsy. Spontaneous tricuspid valve chordal rupture is particularly rare. We report herein a case of a patient with severe pulmonary hypertension, on the lung transplantation waiting list, who presented with spontaneous chordal rupture, exacerbation of tricuspid insufficiency and worsening of clinical status. Diagnosis and treatment, along with possible mechanisms for this complication, are discussed. © 2015, Wiley Periodicals, Inc.

  12. Spontaneous Regression of Intervertebral Disc Herniation – Case Reports


    Rapan, Saša; Gulan, Gordan; Lovrić, Ivan; Jovanović, Savo


    Lumbar disc hernia (LDH) is a common cause of low back pain and radicular leg pain. It is well known that the majority of LDH patients recover spontaneously. Since the advent of MRI, a spontaneous regression of fragment size of disc hernia occurs, as well as mitigation of subjective difficulties and neurological disorders. Therefore, surgical treatment is not always method of choice in this disease. Two cases of conservatively treated large disc extrusion which result in significant ...

  13. A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies.

    Directory of Open Access Journals (Sweden)

    Jocelyn Plassais


    Full Text Available Human Hereditary Sensory Autonomic Neuropathies (HSANs are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact. Through a Genome Wide Association Study (GWAS with 24 affected and 30 unaffected sporting dogs using the Canine HD 170K SNP array (Illumina, we identified a 1.8 Mb homozygous locus on canine chromosome 4 (adj. p-val = 2.5x10-6. Targeted high-throughput sequencing of this locus in 4 affected and 4 unaffected dogs identified 478 variants. Only one variant perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in a long intergenic non-coding RNAs (lincRNA, GDNF-AS. Using human comparative genomic analysis, we observed that the canine variant maps onto an enhancer element. Quantitative RT-PCR of dorsal root ganglia RNAs of affected dogs showed a significant decrease of both GDNF mRNA and GDNF-AS expression levels (respectively 60% and 80%, as compared to unaffected dogs. We thus performed gel shift assays (EMSA that reveal that the canine variant significantly alters the binding of regulatory elements. Altogether, these results allowed the identification in dogs of GDNF as a relevant candidate for human HSAN and insensitivity to pain, but also shed light on the regulation of GDNF transcription. Finally, such results allow proposing these sporting dog breeds as natural models for clinical trials with a double benefit for human and veterinary medicine.

  14. Spontaneous blood pressure oscillations in mechanically ventilated patients with sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Greve, Anders M


    ') oscillations were absent in 9% and 22% of the patients, respectively. In patients in whom spontaneous blood pressure oscillations were preserved, the MF' oscillations occurred at 0.021 Hz (median, interquartile range 0.013-0.030), whereas the LF' oscillations occurred at 0.009 Hz (median, interquartile range 0...

  15. Spontaneous Metacognition in Rhesus Monkeys. (United States)

    Rosati, Alexandra G; Santos, Laurie R


    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  16. Comparative oncology: Integrating human and veterinary medicine ...

    African Journals Online (AJOL)

    Cancer constitutes the major health problem both in human and veterinary medicine. Comparative oncology as an integrative approach offers to learn more about naturally occurring cancers across different species. Canine models have many advantages as they experience spontaneous disease, have many genes similar ...

  17. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.


    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  18. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.


    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  19. Factors affecting the spontaneous mutational spectra in somatic mammalian cells

    Directory of Open Access Journals (Sweden)

    О.А. Ковальова


    Full Text Available  In our survey of references we are discussed the influence of factors biological origin on the spontaneous mutation specters in mammalian. Seasonal and age components influence on the frequence of cytogenetic anomalies. The immune and endocrinous systems are take part in control of the alteration of the spontaneous mutation specters. Genetical difference of sensibility in animal and human at the alteration of factors enviroment as and  genetical differences of repair systems activity are may influence on individual variation of spontaneous destabilization characters of chromosomal apparatus.

  20. Thermal influences on spontaneous rock dome exfoliation (United States)

    Collins, Brian D.; Stock, Greg M.; Eppes, Martha C.; Lewis, Scott W.; Corbett, Skye C.; Smith, Joel B.


    Rock domes, with their onion-skin layers of exfoliation sheets, are among the most captivating landforms on Earth. Long recognized as integral in shaping domes, the exact mechanism(s) by which exfoliation occurs remains enigmatic, mainly due to the lack of direct observations of natural events. In August 2014, during the hottest days of summer, a granitic dome in California, USA, spontaneously exfoliated; witnesses observed extensive cracking, including a ~8000 kg sheet popping into the air. Subsequent exfoliation episodes during the following two summers were recorded by instrumentation that captured—for the first time—exfoliation deformation and stress conditions. Here we show that thermal cycling and cumulative dome surface heating can induce subcritical cracking that culminates in seemingly spontaneous exfoliation. Our results indicate that thermal stresses—largely discounted in dome formation literature—can play a key role in triggering exfoliation and therefore may be an important control for shaping domes worldwide.

  1. Spontaneous Enterocutaneous Fistula Resulting from Richter's Hernia. (United States)

    Hajong, Ranendra; Khongwar, Donkupar; Komut, Ojing; Naku, Narang; Baru, Kappa


    Richter's hernia is due to the entrapment of a part of circumference of the bowel wall. As the bowel continuity is maintained, the patients usually do not have intestinal obstruction. Some patients with Richter's hernia may present with enterocutaneous fistula either spontaneous or due to surgical intervention mistaking the obstructed hernia to be inguinal abscess. This is more so in developing countries due to lack of awareness among the masses or due to the delay in seeking medical attention. Presenting here is a case of a 53-year-old male patient with enterocutaneous fistula which occurred spontaneously and sought medical attention only after about three years of repeated discharge of yellowish fluid from the left inguinal region. Magnetic resonance fistulogram confirmed the diagnosis of enterocutaneous fistula. Laparotomy with resection and primary anastomosis of the fistulous bowel was done. Patient recovered uneventfully without any complications or recurrence.

  2. In Situ Detection of Regulatory T Cells in Human Genital Herpes Simplex Virus Type 2 (HSV-2) Reactivation and Their Influence on Spontaneous HSV-2 Reactivation. (United States)

    Milman, Neta; Zhu, Jia; Johnston, Christine; Cheng, Anqi; Magaret, Amalia; Koelle, David M; Huang, Meei-Li; Jin, Lei; Klock, Alexis; Layton, Erik D; Corey, Lawrence


    Herpes simplex virus type 2 (HSV-2) reactivation is accompanied by a sustained influx of CD4(+) and CD8(+) T cells that persist in genital tissue for extended periods. While CD4(+) T cells have long been recognized as being present in herpetic ulcerations, their role in subclinical reactivation and persistence is less well known, especially the role of CD4(+) regulatory T cells (Tregs). We characterized the Treg (CD4(+)Foxp3(+)) population during human HSV-2 reactivation in situ in sequential genital skin biopsy specimens obtained from HSV-2-seropositive subjects at the time of lesion onset up to 8 weeks after healing. High numbers of Tregs infiltrated to the site of viral reactivation and persisted in proximity to conventional CD4(+) T cells (Tconvs) and CD8(+) T cells. Treg density peaked during the lesion stage of the reactivation. The number of Tregs from all time points (lesion, healed, 2 weeks after healing, 4 weeks after healing, and 8 weeks after healing) was significantly higher than in control biopsy specimens from unaffected skin. There was a direct correlation between HSV-2 titer and Treg density. The association of a high Treg to Tconv ratio with high viral shedding suggests that the balance between regulatory and effector T cells influences human HSV-2 disease. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail

  3. Spontaneous revisitation during visual exploration as a link among strategic behavior, learning, and the hippocampus. (United States)

    Voss, Joel L; Warren, David E; Gonsalves, Brian D; Federmeier, Kara D; Tranel, Dan; Cohen, Neal J


    Effective exploratory behaviors involve continuous updating of sensory sampling to optimize the efficacy of information gathering. Despite some work on this issue in animals, little information exists regarding the cognitive or neural mechanisms for this sort of behavioral optimization in humans. Here we examined a visual exploration phenomenon that occurred when human subjects studying an array of objects spontaneously looked "backward" in their scanning paths to view recently seen objects again. This "spontaneous revisitation" of recently viewed objects was associated with enhanced hippocampal activity and superior subsequent memory performance in healthy participants, but occurred only rarely in amnesic patients with severe damage to the hippocampus. These findings demonstrate the necessity of the hippocampus not just in the aspects of long-term memory with which it has been associated previously, but also in the short-term adaptive control of behavior. Functional neuroimaging showed hippocampal engagement occurring in conjunction with frontocerebellar circuits, thereby revealing some of the larger brain circuitry essential for the strategic deployment of information-seeking behaviors that optimize learning.

  4. Human cathelicidin antimicrobial protein 18 (hCAP18/LL-37) is increased in foetal membranes and myometrium after spontaneous labour and delivery. (United States)

    Lim, Ratana; Barker, Gillian; Lappas, Martha


    Infection and/or inflammation are most commonly associated with preterm birth. Studies have shown that antimicrobial peptides can modulate the inflammatory response in non-gestational tissues; the human cathelicidin hCAP18 (and its active component LL-37) has such anti-microbial and immunomodulatory properties. The aim of this study was to determine the effect of human labour on hCAP18 expression in foetal membranes and myometrium, and to determine the effect of the synthetic LL-37 peptide on pro-inflammatory and pro-labour mediators in foetal membranes and myometrium. The localisation and expression of hCAP18 in non-labouring and labouring tissues was determined by immunohistochemistry and Western blot, respectively. Tissue explants were used to determine the effect of LL-37 on pro-labour mediators. hCAP18 was localised to the amnion epithelium, cytotrophoblasts and decidua in the foetal membranes, and in the longitudinal and transverse muscle fibres of the myometrium. Additional hCAP18 staining was present in leukocytes. In foetal membranes and myometrium, human labour was associated with significantly higher hCAP18 protein expression. Treatment of foetal membranes and myometrium with LL-37 significantly induced the expression and secretion of the pro-inflammatory cytokines IL-6 and TNF-α, and the chemokines IL-8 and MCP-1. LL-37 also induced expression of MMP-9 mRNA and pro MMP-9 expression in foetal membranes. Co-treatment with BAY 11-7082 was associated with a decrease in LL-37-induced pro-inflammatory cytokine expression. Moreover, inhibition of MyD88 in myometrial cells decreased LL-37-induced pro-inflammatory cytokine expression and release. LL-37 also significantly increased NF-κB transcriptional activity. In conclusion, hCAP18/LL-37 induces pro-inflammatory and pro-labour mediators, via the MyD88/NF-κB pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.


    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  6. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.


    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  7. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS


    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  8. Hypovolemic shock following induced abortion and spontaneous heterotopic pregnancy. (United States)

    Pakniyat, Abdolghader; Yazdanbakhsh, Arash; Moshar-Mowahed, Ghasem; Talebi, Fatimah


    Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extrauterine pregnancies occur at the same time. It is rare, estimated to occur in 1 in 30,000 pregnancies. The case was a 38-year-old woman with spontaneously conceived heterotopic pregnancy. She was admitted to our center with hypovolemic shock. Focused assessment sonography for trauma examination in emergency department showed large amount of free fluid in peritoneal cavity. She was managed surgical laparotomy. Considering spontaneous pregnancies, physician should be aware of the possibility of heterotopic pregnancy in all reproductive age women, especially those with history of recent abortion. It can occur without any predisposing risk factors. Patients should be informed about possible side effects of nonprescription medicines, and also the health care centers must be safe peaceful environment for them without severe legal consequences.

  9. Spontaneous Coronary Artery Dissection Associated With Pregnancy. (United States)

    Tweet, Marysia S; Hayes, Sharonne N; Codsi, Elisabeth; Gulati, Rajiv; Rose, Carl H; Best, Patricia J M


    Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated myocardial infarction and remains poorly characterized. This study sought to assess presentation, clinical factors, and outcomes of pregnancy-associated spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissection not associated with pregnancy (NP-SCAD). A Mayo Clinic registry was established in 2010 to include comprehensive retrospective and prospective SCAD data. Records were reviewed to identify women who were pregnant or ≤12 weeks postpartum at time of SCAD. Complete records were available for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 269 women with NP-SCAD. Most events occurred within the first month postpartum (35 of 50). Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment elevation myocardial infarction (57% vs. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p vs. 14%; p = 0.0027, respectively), and left ventricular function ≤35% (26% vs. 10%; p = 0.0071). Among women with imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular dysplasia and extracoronary vascular abnormalities (42% vs. 64%; p = 0.047; and 46% vs. 77%; p = 0.0032, respectively). Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a history of infertility therapies (p = 0.0004), and had pre-eclampsia (p = 0.001). On long-term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the Kaplan Meier 5-year recurrence rates (10% vs. 23%; p = 0.18). P-SCAD patients had more acute presentations and high-risk features than women with NP-SCAD did. The highest frequency of P-SCAD occurred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abnormalities. Hormonal, hemodynamic variations, and yet

  10. Skeletal Muscle Estrogen Receptor Activation in Response to Eccentric Exercise Up-Regulates Myogenic-Related Gene Expression Independent of Differing Serum Estradiol Levels Occurring during the Human Menstrual Cycle

    Directory of Open Access Journals (Sweden)

    Mackenzie Haines, Sarah K. McKinley-Barnard, Thomas L. Andre, Josh J. Gann, Paul S. Hwang, Darryn S. Willoughby


    Full Text Available This study sought to determine if the differences in serum estradiol we have previously observed to occur during the mid-follicular (MF and mid-luteal (ML phases of the female menstrual cycle could be attributed to estrogen-induced receptor activation and subsequent effects on myogenic-related genes which may otherwise impact muscle regeneration in response to eccentric exercise. Twenty-two physically-active females (20.9 ± 1.4 years, 63.5 ± 9.0 kg, 1.65 ± 0.08 m underwent an eccentric exercise bout of the knee extensors during the MF and ML phases of their 28-day menstrual cycle. Prior to (PRE, at 6 (6HRPOST, and 24 (24HRPOST hours post-exercise for each session, participants had muscle biopsies obtained. Skeletal muscle estradiol and estrogen receptor-α (ER-α content and ER-DNA binding were determined with ELISA. Real-time PCR was used to assess ER-α, Myo-D, and cyclin D1 mRNA expression. Data were analyzed utilizing a 2 x 3 repeated measures univariate analyses of variance (ANOVA for each criterion variable (p ≤ .05. Skeletal muscle estradiol levels were not significantly impacted by either menstrual phase (p > 0.05; however, both ER-α mRNA and protein were significantly increased during MF (p < 0.05. ER-DNA binding and Myo-D mRNA expression increased significantly in both menstrual phases in response to exercise but were not different from one another; however, cyclin D1 mRNA expression was significantly greater during MF. This study demonstrates that skeletal muscle ER-α activation in response to eccentric exercise up-regulates myogenic-related gene expression independent of serum estradiol levels occurring during the human menstrual cycle.

  11. Skeletal Muscle Estrogen Receptor Activation in Response to Eccentric Exercise Up-Regulates Myogenic-Related Gene Expression Independent of Differing Serum Estradiol Levels Occurring during the Human Menstrual Cycle. (United States)

    Haines, Mackenzie; McKinley-Barnard, Sarah K; Andre, Thomas L; Gann, Josh J; Hwang, Paul S; Willoughby, Darryn S


    This study sought to determine if the differences in serum estradiol we have previously observed to occur during the mid-follicular (MF) and mid-luteal (ML) phases of the female menstrual cycle could be attributed to estrogen-induced receptor activation and subsequent effects on myogenic-related genes which may otherwise impact muscle regeneration in response to eccentric exercise. Twenty-two physically-active females (20.9 ± 1.4 years, 63.5 ± 9.0 kg, 1.65 ± 0.08 m) underwent an eccentric exercise bout of the knee extensors during the MF and ML phases of their 28-day menstrual cycle. Prior to (PRE), at 6 (6HRPOST), and 24 (24HRPOST) hours post-exercise for each session, participants had muscle biopsies obtained. Skeletal muscle estradiol and estrogen receptor-α (ER-α) content and ER-DNA binding were determined with ELISA. Real-time PCR was used to assess ER-α, Myo-D, and cyclin D1 mRNA expression. Data were analyzed utilizing a 2 x 3 repeated measures univariate analyses of variance (ANOVA) for each criterion variable (p ≤ .05). Skeletal muscle estradiol levels were not significantly impacted by either menstrual phase (p > 0.05); however, both ER-α mRNA and protein were significantly increased during MF (p < 0.05). ER-DNA binding and Myo-D mRNA expression increased significantly in both menstrual phases in response to exercise but were not different from one another; however, cyclin D1 mRNA expression was significantly greater during MF. This study demonstrates that skeletal muscle ER-α activation in response to eccentric exercise up-regulates myogenic-related gene expression independent of serum estradiol levels occurring during the human menstrual cycle.

  12. Use of spontaneously mutated human DNA as competitive internal standard for nucleic acid quantification by reverse transcription-polymerase chain reaction (RT-PCR)

    International Nuclear Information System (INIS)

    Rudnicka, L.; Diaz, A.; Varga, J.; Jimenez, S.A.; Christiano, A.; Uitto, J.


    Quantification of gene expression is of increasing interest in many medical sciences. Methods based on reverse transcription-polymerase chain reactions (RT-PCRs) are timesaving and require only very small amounts of RNA. A limiting factor, however, is the significant fluctuation in the efficacy of reverse transcription as well in the polymerase chain reactions. Various external and internal standards have been suggested for correcting these fluctuations. We describe a novel way of creating an internal standard for assessing the expression of type VII collagen in human cells. The total RNA of a patient with hereditary 'epidermilysis bulosa dystrophica' associated with a homozygous T to A point mutation in type VII collagen gene was reverse transcribed and a 382bp fragment of type VII collagen cDNA containing the mutation was amplified. The mutated cDNA, unlike normal type VII collagen cDNA could be cleaved by 'Ear I' endonuclease into 244bp and 138bp fragments. Semiquantitative PCR was performed with the mutated cDNA as internal standard and the studied cDNA sample in the same tube in the presence of α 32 P-labelled dCTP. The reaction was followed by 'Ear I' digestion, electrophoresis on a polyacrylamide gel and exposure to a X-ray film. In conclusion, we describe a timesaving method for creating internal standards for semiquantitative RT-PCR. (author). 12 refs, 3 figs

  13. Multifaceted processes controlling the distribution of hazardous compounds in the spontaneous combustion of coal and the effect of these compounds on human health. (United States)

    Oliveira, Marcos L S; da Boit, Kátia; Pacheco, Fernanda; Teixeira, Elba C; Schneider, Ismael L; Crissien, Tito J; Pinto, Diana C; Oyaga, Rafael M; Silva, Luis F O


    Pollution generated by hazardous elements and persistent organic compounds that affect coal fire is a major environmental concern because of its toxic nature, persistence, and potential risk to human health. The coal mining activities are growing in the state of Santa Catarina in Brazil, thus the collateral impacts on the health and economy are yet to be analyzed. In addition, the environment is also enduring the collateral damage as the waste materials directly influence the coal by-products applied in civil constructions. This study was aimed to establish the relationships between the composition, morphology, and structural characteristics of ultrafine particles emitted by coal mine fires. In Brazil, the self-combustions produced by Al-Ca-Fe-Mg-Si coal spheres are rich in chalcophile elements (As, Cd, Cu, Hg, Pb, Sb, Se, Sn, and Zn), lithophile elements (Ce, Hf, In, La, Th, and U), and siderophile elements (Co, Cr, Mo, Fe, Ni, and V). The relationship between nanomineralogy and the production of hazardous elements as analyzed by advanced methods for the geochemical analysis of different materials were also delineated. The information obtained by the mineral substance analysis may provide a better idea for the understanding of coal-fire development and assessing the response of particular coal in different combustion processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Spontaneous decoherence of coupled harmonic oscillators confined in a ring (United States)

    Gong, ZhiRui; Zhang, ZhenWei; Xu, DaZhi; Zhao, Nan; Sun, ChangPu


    We study the spontaneous decoherence of coupled harmonic oscillators confined in a ring container, where the nearest-neighbor harmonic potentials are taken into consideration. Without any external symmetry-breaking field or surrounding environment, the quantum superposition state prepared in the relative degrees of freedom gradually loses its quantum coherence spontaneously. This spontaneous decoherence is interpreted by the gauge couplings between the center-of-mass and the relative degrees of freedoms, which actually originate from the symmetries of the ring geometry and the corresponding nontrivial boundary conditions. In particular, such spontaneous decoherence does not occur at all at the thermodynamic limit because the nontrivial boundary conditions become the trivial Born-von Karman boundary conditions when the perimeter of the ring container tends to infinity. Our investigation shows that a thermal macroscopic object with certain symmetries has a chance for its quantum properties to degrade even without applying an external symmetry-breaking field or surrounding environment.

  15. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.


    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  16. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.


    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  17. Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease in a nonhuman primate (United States)

    Axthelm, Michael K.; Bourdette, Dennis N.; Marracci, Gail H.; Su, Weiping; Mullaney, Elizabeth T.; Manoharan, Minsha; Kohama, Steven G.; Pollaro, Jim; Witkowski, Ellen; Wang, Paul; Rooney, William D.; Sherman, Lawrence S.; Wong, Scott W.


    Objective To describe Japanese macaque encephalomyelitis (JME), a spontaneous inflammatory demyelinating disease occurring in the Oregon National Primate Research Center’s (ONPRC) colony of Japanese macaques (JM, Macaca fuscata). Methods JM with neurologic impairment were removed from the colony, evaluated and treated with supportive care. Animals were humanely euthanized and their central nervous system (CNS) examined. Results ONPRC’s JM colony was established in 1965 and no cases of JME occurred until 1986. Since 1986, 56 JM spontaneously developed a disease characterized clinically by paresis of one or more limbs, ataxia or ocular motor paresis. Most animals were humanely euthanized during their initial episode. Three recovered, later relapsed and were then euthanized. There was no gender predilection and the median age for disease was 4 years. Magnetic resonance imaging of eight cases of JME revealed multiple gadolinium enhancing T1-weighted hyperintensities in the white matter of the cerebral hemispheres, brainstem, cerebellum and cervical spinal cord. The CNS of monkeys with JME contained multifocal plaque-like demyelinated lesions of varying ages, including acute and chronic, active demyelinating lesions with macrophages and lymphocytic periventricular infiltrates, and chronic, inactive demyelinated lesions. A previously undescribed gamma-herpesvirus was cultured from acute JME white matter lesions. Cases of JME continue to affect 1–3% of the ONPRC colony per year. Interpretation JME is a unique spontaneous disease in a nonhuman primate that has similarities with multiple sclerosis (MS) and is associated with a novel simian herpesvirus. Elucidating the pathogenesis of JME may shed new light on MS and other human demyelinating diseases. PMID:21674589

  18. Exploratory Data Analysis of Synthetic Aperture Radar (SAR Measurements to Distinguish the Sea Surface Expressions of Naturally-Occurring Oil Seeps from Human-Related Oil Spills in Campeche Bay (Gulf of Mexico

    Directory of Open Access Journals (Sweden)

    Gustavo de Araújo Carvalho


    Full Text Available An Exploratory Data Analysis (EDA aims to use Synthetic Aperture Radar (SAR measurements for discriminating between two oil slick types observed on the sea surface: naturally-occurring oil seeps versus human-related oil spills—the use of satellite sensors for this task is poorly documented in scientific literature. A long-term RADARSAT dataset (2008–2012 is exploited to investigate oil slicks in Campeche Bay (Gulf of Mexico. Simple Classification Algorithms to distinguish the oil slick type are designed based on standard multivariate data analysis techniques. Various attributes of geometry, shape, and dimension that describe the oil slick Size Information are combined with SAR-derived backscatter coefficients—sigma-(σo, beta-(βo, and gamma-(γo naught. The combination of several of these characteristics is capable of distinguishing the oil slick type with ~70% of overall accuracy, however, the sole and simple use of two specific oil slick’s Size Information (i.e., area and perimeter is equally capable of distinguishing seeps from spills. The data mining exercise of our EDA promotes a novel idea bridging petroleum pollution and remote sensing research, thus paving the way to further investigate the satellite synoptic view to express geophysical differences between seeped and spilled oil observed on the sea surface for systematic use.

  19. Do positive spontaneous thoughts function as incentive salience? (United States)

    Rice, Elise L; Fredrickson, Barbara L


    The present work explores the theoretical relationship between positive spontaneous thoughts and incentive salience-a psychological property thought to energize wanting and approach motivation by rendering cues that are associated with enjoyment more likely to stand out to the individual when subsequently encountered in the environment (Berridge, 2007). We reasoned that positive spontaneous thoughts may at least be concomitants of incentive salience, and as such, they might likewise mediate the effect of liking on wanting. In Study 1, 103 adults recruited via Amazon's Mechanical Turk reported on key aspects of 10 everyday activities. As predicted, positive spontaneous thoughts mediated the relationship between liking an activity in the past and wanting to engage in it in the future. In Study 2, 99 undergraduate students viewed amusing and humorless cartoons and completed a thought-listing task, providing experimental evidence for the causal effect of liking on positive spontaneous thoughts. In Study 3, we tested whether positive spontaneous thoughts play an active role in energizing wanting rather than merely co-occurring with (inferred) incentive salience. In that experiment involving 80 undergraduates, participants who were led to believe that their spontaneous thoughts about a target activity were especially positive planned to devote more time to that activity over the coming week than participants who received no such information about their spontaneous thoughts. Collectively, these findings suggest that positive spontaneous thoughts may play an important role in shaping approach motivation. Broader implications and future directions in the study of positive spontaneous thoughts are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Spontaneous bacterial empyema in cirrhotic patients: analysis of eleven cases. (United States)

    Xiol, X; Castellote, J; Baliellas, C; Ariza, J; Gimenez Roca, A; Guardiola, J; Casais, L


    Eleven episodes of spontaneous bacterial empyema were identified in eight cirrhotic patients with ascites. Criteria for spontaneous bacterial empyema included positive pleural fluid culture or polymorphonuclear cell concentration greater than 500 cells/mm3, evidence of pleural effusion before an infectious episode and transudate characteristics during infection. In five cases, spontaneous bacterial empyema was culture-negative and was associated with spontaneous bacterial peritonitis. Ascitic fluid was culture-negative in two of these cases and culture-positive in three. Blood cultures were negative in all five of these cases. In six cases spontaneous bacterial empyema was culture-positive (Escherichia coli in four, Klebsiella pneumoniae in one and Clostridium perfringens in one). Four of these patients had the same organism in ascites; one had culture-negative spontaneous bacterial peritonitis and one had no infection of ascites. Blood cultures were positive in four of these patients; three died. Death was more frequent in patients with positive cultures than in those with negative ones (p less than 0.05). Patients with hydrothorax are prone to spontaneous bacterial empyema. This infection probably occurs through hematogenous seeding, but transfer of infected ascites from the abdominal cavity through the diaphragm cannot be excluded. Patients with spontaneous bacterial empyema may be asymptomatic or may be seen with fever, chills and dyspnea. Spontaneous bacterial empyema must be differentiated from parapneumonic empyemas. The presence of pleural effusion before the infectious episode, fluid characteristics and the organisms isolated are the clues for differential diagnosis. Treatment includes antibiotics; chest tube insertion probably is not necessary.

  1. [Bacterial vaginosis and spontaneous preterm birth]. (United States)

    Brabant, G


    To determine if bacterial vaginosis is a marker for risk of spontaneous preterm delivery and if its detection and treatment can reduce this risk. Consultation of the database Pubmed/Medline, Science Direct, and international guidelines of medical societies. Bacterial vaginosis (BV) is a dysbiosis resulting in an imbalance in the vaginal flora through the multiplication of anaerobic bacteria and jointly of a disappearance of well-known protective Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain with establishment of the Nugent score. The prevalence of the BV extraordinarily varies according to ethnic and/or geographical origin (4-58 %), in France, it is close to 7 % in the first trimester of pregnancy (EL2). The link between BV and spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV (EL3). It is recommended to prescribe one of these antibiotics in the case of symptomatic BV (Professional Consensus). The testing associated with the treatment of BV in the global population showed no benefit in the prevention of the risk of spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population (defined by the absence of antecedent of premature delivery), it has been failed profit to track and treat the BV in the prevention of the risk of spontaneous preterm delivery (EL1). Concerning the high-risk population (defined by a history of preterm delivery), it has been failed profit to track and treat the VB in the prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub population of patients with a history of preterm delivery occurred in a context of materno-fetal bacterial infection, there may be a benefit to detect and treat early and systematically genital infection, and in particular the BV (Professional Consensus). The screening and treatment of BV during pregnancy in asymptomatic low

  2. Bilateral spontaneous carotid artery dissection. (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis


    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  3. Bone changes occurring spontaneously and caused by estrogen in early postmenopausal women: a local generalized phenomenon?

    International Nuclear Information System (INIS)

    Christiansen, C.; Gotfredsen, A.; Riis, B.J.; Hassager, C.


    Regional values of bone mineral content and bone mineral density were calculated from total body dual photon absorptiometry scans of 52 early postmenopausal women treated with estrogen for one year and of 52 similar women treated with placebo. The six regions were head, arms, chest, spine, pelvis, and legs. In addition, bone mineral density of the spine was calculated by dual photon absorptiometry and bone mineral content of the forearm by single photon absorptiometry, using separate special purpose scanners. All regions were unchanged after one year of treatment with estrogen, excluding the lumbar spine, for which values rose. Values for all regions except the lumbar spine fell significantly in the placebo group. The rates of loss ranged from 2 to 8%, with no significant differences between the regions. It is concluded that loss of bone in the early menopause is a generalized phenomenon, affecting all parts of the skeleton. Furthermore, estrogen prophylaxis for loss of bone is effective in all parts of the skeleton. Finally, it is suggested that the measurement of bone mineral content in the forearm be used for clinical follow up of bone changes, as this method is superior to others in the ratio of change to precision

  4. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan


    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  5. Spontaneous prediction error generation in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Yuichi Yamashita

    Full Text Available Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.

  6. Spontaneity and international marketing performance


    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.


    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  7. Prediction of spontaneous preterm delivery from maternal factors, obstetric history and placental perfusion and function at 11-13 weeks. (United States)

    Beta, Jarek; Akolekar, Ranjit; Ventura, Walter; Syngelaki, Argyro; Nicolaides, Kypros H


    To develop a model for prediction of spontaneous delivery before 34 weeks based on maternal factors, placental perfusion and function at 11-13 weeks' gestation. Two groups of studies: first, screening study of maternal characteristics, serum pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG) and uterine artery pulsatility index (PI). Second, case-control studies of maternal serum or plasma concentration of placental growth factor (PlGF), placental protein 13 (PP13), a disintegrin and metalloprotease 12 (ADAM12), inhibin-A and activin-A. Regression analysis was used to develop a model for the prediction of spontaneous early delivery. Spontaneous early delivery occurred in 365 (1.1%) of the 34 025 pregnancies. A model based on maternal factors could detect 38.2% of the preterm deliveries in women with previous pregnancies at or beyond 16 weeks and 18.4% in those without, at a false positive rate (FPR) of 10%. In the preterm delivery group, compared with unaffected pregnancies there were no significant differences in the markers of placental perfusion or function, except for PAPP-A which was reduced. Patient-specific risk of preterm delivery is provided by maternal factors and obstetric history. Placental perfusion and function at 11-13 weeks are not altered in pregnancies resulting in spontaneous early delivery. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Spontaneous indices are inconsistent with arterial baroreflex gain. (United States)

    Lipman, Ruth D; Salisbury, Julie K; Taylor, J Andrew


    Spontaneously occurring, parallel fluctuations in arterial pressure and heart period are frequently used as indices of baroreflex function. Despite the convenience of spontaneous indices, their relation to the arterial baroreflex remains unclear. Therefore, in 97 volunteers, we derived 5 proposed indices (sequence method, alpha-index, transfer function, low-frequency transfer function, and impulse response function), compared them with arterial baroreflex gain (by the modified Oxford pharmacologic technique), and examined their relation to carotid distensibility and respiratory sinus arrhythmia. The subjects comprised men and women (n=41) aged 25 to 86 years, 30% of whom had established coronary artery disease. Generally, the indices were correlated with each other (except alpha-index and low-frequency transfer function) and with baroreflex gain. However, the Bland-Altman method demonstrated that the spontaneous indices had limits of agreement as large as the baroreflex gain itself. Even in individuals within the lowest tertile of baroreflex gain for whom baroreflex gain appears to be the most clinically relevant, spontaneous indices failed to relate to baroreflex gain. In fact, for these individuals, there was no correlation between any index and baroreflex gain. Forward stepwise linear regression showed that all spontaneous indices and baroreflex gain were related to respiratory sinus arrhythmia, but only baroreflex gain was related to carotid distensibility. Therefore, these data suggest that spontaneous indices are inadequate estimates of gain and are inconsistent with arterial baroreflex function.

  9. Angiodysplasia Occurring in Jejunal Diverticulosis



    The first case of angiodysplasia occurring in acquired jejunal diverticulosis is reported. The patient presented with occult gastrointestinal bleeding and chronic anemia, and was created successfully by resection of a 25 cm long segment of jejunum. Possible pathogenetic mechanisms for both angiodysplasia and jejunal diverticulosis are discussed.

  10. Chromosomal rearrangements occurred repeatedly and ...

    African Journals Online (AJOL)

    Furthermore, molecular and/or chromosomal data indicate that Paroedura is a monophyletic genus, in which chromosome rearrangements occurred repeatedly and independently during the specific diversification. Moreover both P. bastardi and P. gracilis in current definitions are paraphyletic assemblages of several ...

  11. Spontaneous carotid artery dissection causing a juvenile cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Trattnig, S.; Huebsch, P.; Schindler, E.


    The case of a 19-year-old patient is presented who was admitted with aphasia and hemiparesis due to basal ganglia infarction as a result of spontaneous dissection of the internal carotid artery. The difficulties in diagnosing this disease with CT and MRI in the acute stage are demonstrated. Angiography is still imperative in order to ascertain that a carotid dissection has occurred.

  12. Spontaneous rupture of incisional hernia- a case report | Nwashilli ...

    African Journals Online (AJOL)

    Spontaneous rupture of an abdominal hernia is rare and usually occurs in incisional or recurrent groin hernias. The rupture requires an emergency surgery to prevent obstruction, strangulation and to cover the herniated contents. The herniated contents can be covered primarily by mesh repair if the general condition of the ...

  13. Paediatric infant presenting with an atypical spontaneous biliary ...

    African Journals Online (AJOL)

    Spontaneous biliary perforation (SBP) is a life-threatening condition. Although rare, it is the second most common surgical cause of jaundice in infancy after biliary atresia. SBP is theorized to occur due to a localized injury to the embryological developing biliary tree, predominantly at the junction of the cystic and the ...

  14. Spontaneous Uterine Rupture at Twenty Weeks of Pregnancy ...

    African Journals Online (AJOL)

    Uterine rupture is one of the most feared obstetric complications affecting the pregnant woman and fetus. It is an obstetric dilemma. Most of the cases have various risk factors and mainly occur during the third trimester. However, spontaneous uterine rupture during the first and second trimester are extremely rare.

  15. Spontaneous rapture of an incisional hernia: A case report ...

    African Journals Online (AJOL)

    An incisional hernia develops in the scar of a surgical incision. Rarely, a particularly thin-walled large incisional hernia may actually ulcerate at its fundus so that omentum protrudes or there is even the development of an intestinal fistula. Spontaneous rupture of an abdominal hernia is very rare and usually occurs in ...

  16. Modulating spontaneous brain activity using repetitive transcranial magnetic stimulation

    NARCIS (Netherlands)

    van der Werf, Y.D.; Sanz-Arigita, E.J.; Menning, S.; van den Heuvel, O.A.


    Background: When no specific stimulus or task is presented, spontaneous fluctuations in brain activity occur. Brain regions showing such coherent fluctuations are thought to form organized networks known as 'resting-state' networks, a main representation of which is the default mode network.

  17. Spontaneous radiation emission during penetration of ions in solids

    International Nuclear Information System (INIS)

    Miraglia, J.E.; Pacher, M.C.


    In this work, the principal continuum radiative emission processes, which occur during the penetration of ions in solids or gases, are resumed. The characteristics of the following processes are discussed: secondary electron bremsstrahlung (SEB), atomic bremsstrahlung (AB), and internuclear bremsstrahlung (INB). Recent advances of the ion channeling effects in crystal solids on the spontaneous radiative spectra are exposed. (A.C.A.S.) [pt

  18. Spontaneous rupture of the spleen – a rare and potentially fatal ...

    African Journals Online (AJOL)

    Spontaneous (non-traumatic) rupture of the normal spleen in pregnancy is a rare clinical event that can endanger the lives of both mother and baby. The aetiology of the condition is unknown, but it occurs most commonly in multiple pregnancies and in the third trimester. We present a case of a spontaneous splenic rupture ...

  19. Spontaneous Heterotopic Triplet Pregnancy With Tubal Rupture

    Directory of Open Access Journals (Sweden)

    Lima Arsala MBBS, BBMedSci


    Full Text Available The recent increase in heterotopic pregnancies has been largely attributed to the increased use of assisted reproduction technologies. We report the rare case of a multiparous woman with a spontaneous conception resulting in a triplet heterotopic pregnancy: a twin intrauterine pregnancy and a single right tubal ectopic pregnancy. Heterotopic pregnancy is a rare and potentially life-threatening condition in which simultaneous gestations occur at 2 or more implantation sites. It is infrequent in natural conception cycles, occurring in 1:30 000 pregnancies. However, the prevalence is rising with the increased use of assisted reproduction techniques to that of 1:100 to 1:500 in these patient subgroups, highlighting the need to incorporate it into a clinician’s diagnostic algorithm.

  20. Corticomuscular Coherence Is Tuned to the Spontaneous Rhythmicity of Speech at 2-3 Hz


    Ruspantini, I.; Saarinen, T.; Belardinelli, P.; Jalava, A.; Parviainen, T.; Kujala, J.; Salmelin, Riitta


    Human speech features rhythmicity that frames distinctive, fine-grained speech patterns. Speech can thus be counted among rhythmic motor behaviors that generally manifest characteristic spontaneous rates. However, the critical neural evidence for tuning of articulatory control to a spontaneous rate of speech has not been uncovered. The present study examined the spontaneous rhythmicity in speech production and its relationship to cortex–muscle neurocommunication, which is essential for speech...

  1. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.


    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  2. Optical antenna enhanced spontaneous emission. (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C


    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  3. Alcohol consumption at the time of conception and spontaneous abortion

    DEFF Research Database (Denmark)

    Henriksen, T.B.; Hjollund, N.H.; Jensen, Tina Kold


    The authors studied the association between female and male alcohol intakes at the time of conception and the risk of spontaneous abortion, including early pregnancy loss detected by urinary human chorionic gonadotropin. After a nationwide mailing to about 50,000 members of four trade unions....... Women collected morning urine for 10 days from the first day of vaginal bleeding in each cycle. The authors detected 186 pregnancies: 131 resulted in childbirth, and 55 resulted in spontaneous abortion (34 detected by urinary human chorionic gonadotropin). Depending on the intake in the cycle...... of conception and the adjustment factors, female alcohol intake was associated with 2-3 times the adjusted risk of spontaneous abortion compared with no intake, and male alcohol intake was associated with 2-5 times the adjusted risk. Only the adjusted relative risks for 10 or more drinks/week compared...

  4. Bilateral spontaneous subluxation of scleral-fixated intraocular lenses. (United States)

    Assia, Ehud I; Nemet, Arie; Sachs, Dani


    Two young men with primary ectopic lenses had intracapsular cataract extraction and scleral fixation of posterior chamber intraocular lenses (PC IOLs) using 10-0 polypropylene sutures tied to the IOL eyelets. Three to 9 years after implantation, spontaneous IOL vertical subluxation occurred in all 4 eyes (5 IOL loops), probably because of suture breakage. Late subluxation of a sutured IOL may occur several years after implantation. Double fixation and thicker sutures should be considered, especially in young patients.

  5. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.


    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)


    Kobayashi, Ryosuke; Chambers, James K; Yoshida, Keiko; Nakamura, Takashi; Yasuno, Kyohei; Uchida, Kazuyuki; Kamiie, Junichi; Shirota, Kinji


    Lipoprotein glomerulopathy (LPG) is a rare human glomerular disease caused by abnormal lipid metabolism. Naturally occurring LPG has not been reported in animals. We describe the histopathological characterization of spontaneous LPG-like nephropathy in a captive squirrel ( Sciurus vulgaris ). Macroscopically, swollen glomeruli were distinctively identified as fine white granules in the renal cortex. Histologically, most glomeruli were markedly enlarged with distended capillaries containing faintly eosinophilic and amorphous materials. The amorphous material was negative using the periodic acid-Schiff reaction, periodic acid-methenamine silver stain, or Masson's trichrome stain. Sudan III staining revealed lipid in the materials, and immunohistochemistry demonstrated that the material additionally contained apolipoprotein E. Electron microscopy showed numerous lipid granules and vacuoles of various sizes in the capillary lumina associated with foot process effacement of podocytes. These pathological characteristics bear some resemblance to those of human LPG.

  7. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)


    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  8. Early occurring and continuing effects

    International Nuclear Information System (INIS)

    Scott, B.R.; Hahn, F.F.


    This chapter deals with health-risk estimates for early and continuing effects of exposure to ionizing radiations that could be associated with light water nuclear power plants accidents. Early and continuing effects considered are nonneoplastic diseases and symptoms that normally occur soon after radiation exposure, but may also occur after years have passed. They are generally associated with relatively high (greater than 1 Gy) doses. For most of the effects considered, there is a practical dose threshold. Organs of primary interest, because of their high sensitivity or the likelihood of receiving a large radiation dose, are bone marrow, gastrointestinal tract, thyroid glands, lungs, skin, gonads, and eyes. In utero exposure of the fetus is also considered. New data and modeling techniques available since publication of the Reactor Safety Study (WASH 1400, 1975) were used along with data cited in the Study to develop improved health-risk models for morbidity and mortality. The new models are applicable to a broader range of accident scenarios, provide a more detailed treatment of dose protraction effects, and include morbidity effects not considered in the Reactor Safety Study. 115 references, 20 figures, 19 tables

  9. Multiple genetic switches spontaneously modulating bacterial mutability

    Directory of Open Access Journals (Sweden)

    Johnston Randal N


    Full Text Available Abstract Background All life forms need both high genetic stability to survive as species and a degree of mutability to evolve for adaptation, but little is known about how the organisms balance the two seemingly conflicting aspects of life: genetic stability and mutability. The DNA mismatch repair (MMR system is essential for maintaining genetic stability and defects in MMR lead to high mutability. Evolution is driven by genetic novelty, such as point mutation and lateral gene transfer, both of which require genetic mutability. However, normally a functional MMR system would strongly inhibit such genomic changes. Our previous work indicated that MMR gene allele conversion between functional and non-functional states through copy number changes of small tandem repeats could occur spontaneously via slipped-strand mis-pairing during DNA replication and therefore may play a role of genetic switches to modulate the bacterial mutability at the population level. The open question was: when the conversion from functional to defective MMR is prohibited, will bacteria still be able to evolve by accepting laterally transferred DNA or accumulating mutations? Results To prohibit allele conversion, we "locked" the MMR genes through nucleotide replacements. We then scored changes in bacterial mutability and found that Salmonella strains with MMR locked at the functional state had significantly decreased mutability. To determine the generalizability of this kind of mutability 'switching' among a wider range of bacteria, we examined the distribution of tandem repeats within MMR genes in over 100 bacterial species and found that multiple genetic switches might exist in these bacteria and may spontaneously modulate bacterial mutability during evolution. Conclusions MMR allele conversion through repeats-mediated slipped-strand mis-pairing may function as a spontaneous mechanism to switch between high genetic stability and mutability during bacterial evolution.

  10. Novel spontaneous deletion of artemis exons 10 and 11 in mice leads to T- and B-cell deficiency.

    Directory of Open Access Journals (Sweden)

    Christian Barthels

    Full Text Available Here we describe a novel, spontaneous, 4035 basepairs long deletion in the DNA cross-link repair 1C (Dclre1c-locus in C57BL/6-mice, which leads to loss of exons 10 and 11 of the gene encoding for Artemis, a protein involved into V(D J-recombination of antigen receptors of T and B cells. While several spontaneous mutations of Artemis have been described to cause SCID in humans, in mice, only targeted deletions by knockout technology are known to cause the same phenotype so far. The deletion we observed causes a loss of Artemis function in the C57BL/6 strain and, consequently, the absence of T and B cells, in presence of normal numbers of NK cells and cells of the myeloid lineage. Thus, for the first time we present T(-B(-NK(+ severe combined immunodeficiency (SCID phenotype after spontaneously occurring modification of Artemis gene in mice. Our mouse model may serve as a valuable tool to study mechanisms as well as potential therapies of SCID in humans.

  11. Heterogeneity in arterial remodeling among sublines of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Bakker, Erik N. T. P.; Groma, Gergely; Spijkers, Léon J. A.; de Vos, Judith; van Weert, Angela; van Veen, Henk; Everts, Vincent; Arribas, Silvia M.; VanBavel, Ed


    Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that the pathophysiology of vascular

  12. Male-mediated spontaneous abortion among spouses of stainless steel welders

    DEFF Research Database (Denmark)

    Hjollund, N H; Bonde, J P; Jensen, T K


    Male-mediated spontaneous abortion has never been documented for humans. The welding of stainless steel is associated with the pulmonary absorption of hexavalent chromium, which has genotoxic effects on germ cells in rodents. Clinical and early subclinical spontaneous abortions were examined among...

  13. Spontaneous emission by moving atoms

    International Nuclear Information System (INIS)

    Meystre, P.; Wilkens, M.


    It is well known that spontaneous emission is not an intrinsic atomic property, but rather results from the coupling of the atom to the vacuum modes of the electromagnetic field. As such, it can be modified by tailoring the electromagnetic environment into which the atom can radiate. This was already realized by Purcell, who noted that the spontaneous emission rate can be enhanced if the atom placed inside a cavity is resonant with one of the cavity is resonant with one of the cavity modes, and by Kleppner, who discussed the opposite case of inhibited spontaneous emission. It has also been recognized that spontaneous emission need not be an irreversible process. Indeed, a system consisting of a single atom coupled to a single mode of the electromagnetic field undergoes a periodic exchange of excitation between the atom and the field. This periodic exchange remains dominant as long as the strength of the coupling between the atom and a cavity mode is itself dominant. 23 refs., 6 figs

  14. Spontaneous Development of Moral Concepts (United States)

    Siegal, M.


    Moral competence is more difficult to attain than scientific competence. Since language comprehension plays a central role in conceptual development, and moral language is difficult to learn, there is a common deficiency in moral conceptual development. This suggests a theory of non-spontaneous solutions to moral problems. (Author/MS)

  15. Shell theorem for spontaneous emission

    DEFF Research Database (Denmark)

    Kristensen, Philip Trøst; Mortensen, Jakob Egeberg; Lodahl, Peter


    and therefore is given exactly by the dipole approximation theory. This surprising result is a spontaneous emission counterpart to the shell theorems of classical mechanics and electrostatics and provides insights into the physics of mesoscopic emitters as well as great simplifications in practical calculations....

  16. Prediction of Spontaneous Preterm Birth

    NARCIS (Netherlands)

    Dijkstra, Karolien


    Preterm birth is a leading cause of neonatal morbidity and mortality. It is a major goal in obstetrics to lower the incidence of spontaneous preterm birth (SPB) and related neonatal morbidity and mortality. One of the principal objectives is to discover early markers that would allow us to identify

  17. EAMJ Dec. Spontaneous.indd

    African Journals Online (AJOL)


    Dec 12, 2008 ... surgical abortion at one month gestation without any complication. The second pregnancy which was a year prior resulted in a spontaneous miscarriage at two months followed by evacuation of retained products of conception with no post abortion complications. Antibiotics were taken following both.

  18. Spontaneous fission of superheavy nuclei

    Indian Academy of Sciences (India)

    the Yukawa-plus-exponential potential. The microscopic shell and pairing corrections are obtained using the Strutinsky and BCS approaches and the cranking formulae yield the inertia tensor. Finally, the WKB method is used to calculate penetrabilities and spontaneous fission half-lives. Calculations are performed for the ...

  19. Timing of spontaneous sleep-paralysis episodes. (United States)

    Girard, Todd A; Cheyne, J Allan


    The objective of this prospective naturalistic field study was to determine the distribution of naturally occurring sleep-paralysis (SP) episodes over the course of nocturnal sleep and their relation to bedtimes. Regular SP experiencers (N = 348) who had previously filled out a screening assessment for SP as well as a general sleep survey were recruited. Participants reported, online over the World Wide Web, using a standard reporting form, bedtimes and subsequent latencies of spontaneous episodes of SP occurring in their homes shortly after their occurrence. The distribution of SP episodes over nights was skewed to the first 2 h following bedtime. Just over one quarter of SP episodes occurred within 1 h of bedtime, although episodes were reported throughout the night with a minor mode around the time of normal waking. SP latencies following bedtimes were moderately consistent across episodes and independent of bedtimes. Additionally, profiles of SP latencies validated self-reported hypnagogic, hypnomesic, and hypnopompic SP categories, as occurring near the beginning, middle, and end of the night/sleep period respectively. Results are consistent with the hypothesis that SP timing is controlled by mechanisms initiated at or following sleep onset. These results also suggest that SP, rather than uniquely reflecting anomalous sleep-onset rapid eye movement (REM) periods, may result from failure to maintain sleep during REM periods at any point during the sleep period. On this view, SP may sometimes reflect the maintenance of REM consciousness when waking and SP hallucinations the continuation of dream experiences into waking life.

  20. Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model. (United States)

    Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M; Longatto-Filho, Adhemar; Castro, António G; Pedrosa, Jorge; Fraga, Alexandra G


    Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies.

  1. Gene Expression Signature for Spontaneous Cancer Regression in Melanoma Pigs

    Directory of Open Access Journals (Sweden)

    Florian Rambow


    Full Text Available Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms leading to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aiming to enhance the patient's natural immunity against melanoma have yet to meet their expectations. Reasons for failure include various immune escape mechanisms, induced by the tumor, that subsequently lead to tolerance. Here, we performed time-dependent gene expression profiling to unravel molecular changes involved in the transition of progressive melanoma to complete tumor regression using a porcine model. The melanoblastomabearing Libechov minipigs are highly suitable for this study because these animals exhibit naturally occurring and regressing melanomas. We were able to identify a molecular signature of the melanoma regression process. Genes regulated in this signature were associated with 1 cell cycle, 2 immune response, and 3 melanocyte differentiation. These genes may shed light on molecular mechanisms involved in complete melanoma regression and indicate what improvements are needed for successful antimelanoma therapy.

  2. Shared risk aversion in spontaneous and induced abortion. (United States)

    Catalano, Ralph; Bruckner, Tim A; Karasek, Deborah; Adler, Nancy E; Mortensen, Laust H


    will not capture all spontaneous abortions and that results may not generalize beyond Denmark. Our findings imply that abortion, intentional or 'spontaneous,' follows from a woman's estimate, made consciously or otherwise, of the costs and benefits of extending gestation given characteristics of the prospective offspring, likely environmental circumstances at birth, and maternal resources. The Robert Wood Johnson Health and Society Scholars Program funded the research described in this manuscript. None of the authors has any conflict of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:

  3. Does overtraining occur in triathletes?

    Directory of Open Access Journals (Sweden)

    I Margaritis


    Full Text Available 1. Objective: Long distance triathlon training is characterized by considerably high volume training loads. This volume can provoke an overtraining state. The aim of the study was to determine whether overtraining occurs in well-trained male triathletes in relation with their volume training loads. 2. Experimental design: A questionnaire investigation was completed two days before the Nice long-distance triathlon (October 1995: 4-km swim, 120-km bike ride and 30-km run. 3. Participants: Ninety-three well-trained male triathletes who took part in the triathlon race. 4. Measures: A questionnaire to relate clinical symptoms, which are known to appear in case of overtraining, was collected. 5. Results: 39.8% of the questioned triathletes reported a decrease in triathlon performances within the last month preceding the race. Moreover, these triathletes exhibited significantly more overtraining-relied symptoms than the others (5.9±3.8 vs 3.4±2.6, P<0.05. Surprisingly, the occurrence of overtraining in triathletes appears not to depend on the volume training loads. 6. Conclusions: These results suggest that overtraining has to be considered in the case of triathletes. This preliminary study evidences the need for further investigation in order to monitor triathletes training respond and prevent overtraining.

  4. Earl occurring and continuing effects

    International Nuclear Information System (INIS)

    Scott, B.R.; Hahn, F.F.


    This chapter develops health-risk models for early and continuing effects of exposure to beta or gamma radiation that could be associated with light water nuclear power plant accidents. The main purpose of the chapter is to provide details on each health-risk model and on the data used. Early and continuing effects considered are prodromal symptoms and nonneoplastic diseases that usually occur soon after a brief radiation exposure. These effects are generally associated with relatively high (greater than 1 Gy) absorbed organ doses. For most of the effects considered, there is an absorbed organ dose threshold below which no effects are seen. Some information is provided on health effects observed in victims of the Chernobyl power plant accident. Organs of primary interest, because of their high sensitivity or their potential for receiving large doses, are bone marrow, gastrointestinal tract, thyroid glands, lungs, skin, gonads, and eyes. Exposure of the fetus is also considered. Additional data and modeling techniques available since publication of the Reactor Safety Study were used to obtain models for morbidity and mortality

  5. Spontaneous Retropharyngeal Emphysema: A Case Report | Chi ...

    African Journals Online (AJOL)

    ... is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema. Keywords: Iatrogenic injury, retropharyngeal emphysema, spontaneous retropharyngeal emphysem, trauma ...

  6. Spontaneous galactosylation of agalactoglycoproteins in colostrum. (United States)

    Oubihi, M; Kitajima, K; Aoki, N; Matsuda, T


    We have found that spontaneous galactosylation of GlcNAc residues occurs in bovine colostrum, but not in dialyzed colostrum, without adding UDP-Gal as a donor substrate. UDP-Gal was shown to be present in bovine colostrum at a level ranging from 200 to 600 microM. When a tracer UDP-[(14)C]Gal was added to the dialyzed colostrum together with a Gal beta1,4-specific beta-galactosidase, remarkable incorporation of radioactivity into 24-28 kDa and 33 kDa RCA1-positive glycoproteins was demonstrated by SDS-PAGE/autoradiography. Some 100-140 kDa agalactoglycoproteins of a CHO mutant cell line were also galactosylated on a blotted membrane by the incubation in the colostrum.

  7. Spontaneous jamming in one-dimensional systems (United States)

    O'Loan, O. J.; Evans, M. R.; Cates, M. E.


    We study the phenomenon of jamming in driven diffusive systems. We introduce a simple microscopic model in which jamming of a conserved driven species is mediated by the presence of a non-conserved quantity, causing an effective long-range interaction of the driven species. We study the model analytically and numerically, providing strong evidence that jamming occurs; however, this proceeds via a strict phase transition (with spontaneous symmetry breaking) only in a prescribed limit. Outside this limit, the nearby transition (characterised by an essential singularity) induces sharp crossovers and transient coarsening phenomena. We discuss the relevance of the model to two physical situations: the clustering of buses, and the clogging of a suspension forced along a pipe.

  8. Spontaneous closure of midline diastema following frenectomy

    Directory of Open Access Journals (Sweden)

    Koora Kiran


    Full Text Available Maxillary midline diastema is a common aesthetic problem in mixed and early permanent dentitions. The space can occur either as a transient malocclusion or created by developmental, pathological or iatrogenical factors. Many innovative therapies varying from restorative procedures such as composite build-up to surgery (frenectomies and orthodontics are available. Although literature says every frenectomy procedure should be preceded by orthodontic treatment, we opted for frenectomy technique without any orthodontic intervention. Presented herewith is a case report of a 9-year-old girl with a high frenal attachment that had caused spacing of the maxillary central incisors. A spontaneous closure of the midline diastema was noted within 2 months following frenectomy. The patient was followed up for 4 months after which the space remained closed and there was no necessity for an orthodontic treatment at a later stage.

  9. Systematics of spontaneous positron lines

    International Nuclear Information System (INIS)

    Mueller, U.; Reus, T. de; Reinhardt, J.; Mueller, B.; Greiner, W.


    Dynamical and spontaneous positron emission are investigated for heavy-ion collisions with long time delay using a semiclassical description. Numerical results and analytical expressions for the characteristic quantities of the resulting spontaneous positron line, i.e., its position, width, and cross section, are compared. The expected behaviour of the line position and cross section and its visibility against the spectrum of dynamically created positrons is discussed in dependence of the united charge Zsub(u) of projectile and target nucleus in a range of systems from Zsub(u)=180 up to Zsub(u)=188. The results are confronted with presently available experimental data, and possible implications on further experiments are worked out. (orig.)

  10. Spontaneous Rotational Inversion in Phycomyces

    KAUST Repository

    Goriely, Alain


    The filamentary fungus Phycomyces blakesleeanus undergoes a series of remarkable transitions during aerial growth. During what is known as the stagea IV growth phase, the fungus extends while rotating in a counterclockwise manner when viewed from above (stagea IVa) and then, while continuing to grow, spontaneously reverses to a clockwise rotation (stagea IVb). This phase lasts for 24-48Ah and is sometimes followed by yet another reversal (stageAIVc) before the overall growth ends. Here, we propose a continuum mechanical model of this entire process using nonlinear, anisotropic, elasticity and show how helical anisotropy associated with the cell wall structure can induce spontaneous rotation and, under appropriate circumstances, the observed reversal of rotational handedness. © 2011 American Physical Society.

  11. Spontaneous regression of colon cancer. (United States)

    Kihara, Kyoichi; Fujita, Shin; Ohshiro, Taihei; Yamamoto, Seiichiro; Sekine, Shigeki


    A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  12. Management of intractable spontaneous epistaxis (United States)

    Rudmik, Luke


    Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario. PMID:22391084

  13. Spontaneous baryogenesis in warm inflation


    Brandenberger, Robert H.; Yamaguchi, Masahide


    We discuss spontaneous baryogenesis in the warm inflation scenario. In contrast with standard inflation models, radiation always exists in the warm inflation scenario, and the inflaton must be directly coupled to it. Also, the transition to the post-inflationary radiation dominated phase is smooth and the entropy is not significantly increased at the end of the period of inflation. In addition, after the period of warm inflation ends, the inflaton does not oscillate coherently but slowly roll...

  14. Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection--the InC3 Study

    NARCIS (Netherlands)

    Sacks-Davis, Rachel; Grebely, Jason; Dore, Gregory J.; Osburn, William; Cox, Andrea L.; Rice, Thomas M.; Spelman, Timothy; Bruneau, Julie; Prins, Maria; Kim, Arthur Y.; McGovern, Barbara H.; Shoukry, Naglaa H.; Schinkel, Janke; Allen, Todd M.; Morris, Meghan; Hajarizadeh, Behzad; Maher, Lisa; Lloyd, Andrew R.; Page, Kimberly; Hellard, Margaret; Lauer, Georg; Hahn, Judy; Alavi, Maryam; Bouchard, Rachel; Evans, Jennifer; Grady, Bart; Aneja, Jasneet; Teutsch, Suzy; White, Bethany; Wells, Brittany; Zang, Geng; Applegate, Tanya; Matthews, Gail; Yeung, Barbara; van de Laar, Thijs; Erin Prince, Leslie; Roy, Elise; Bates, Anna; Enriquez, Jarliene; Chow, Sammy; Park, Ju; McCredie, Luke; Aitken, Campbell; Bowden, Scott; Higgs, Peter; Tracy, Lilly; Briceno, Alya


    We aimed to characterize the natural history of hepatitis C virus (HCV) reinfection and spontaneous clearance following reinfection (reclearance), including predictors of HCV reclearance. Data were synthesized from the 9 prospective cohorts of the International Collaboration of Incident Human

  15. Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer's Disease

    DEFF Research Database (Denmark)

    Schütt, Trine; Helboe, Lone; Pedersen, Lars Østergaard


    Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study...

  16. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian


    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  17. Spontaneous aortic dissecting hematoma in two dogs. (United States)

    Boulineau, Theresa Marie; Andrews-Jones, Lydia; Van Alstine, William


    This report describes 2 cases of spontaneous aortic dissecting hematoma in young Border Collie and Border Collie crossbred dogs. Histology was performed in one of the cases involving an unusual splitting of the elastin present within the wall of the aorta, consistent with elastin dysplasia as described in Marfan syndrome in humans. The first case involved a young purebred Border Collie that died suddenly and the second case involved a Border Collie crossbred dog that died after a 1-month history of seizures. Gross lesions included pericardial tamponade with dissection of the ascending aorta in the former case and thoracic cavity hemorrhage, mediastinal hematoma, and aortic dissection in the latter. Histologic lesions in the case of the Border Collie crossbred dog included a dissecting hematoma of the ascending aorta with elastin dysplasia and right axillary arterial intimal proliferation.

  18. Technologically enhanced naturally occurring radioactive materials. (United States)

    Vearrier, David; Curtis, John A; Greenberg, Michael I


    Naturally occurring radioactive materials (NORM) are ubiquitous throughout the earth's crust. Human manipulation of NORM for economic ends, such as mining, ore processing, fossil fuel extraction, and commercial aviation, may lead to what is known as "technologically enhanced naturally occurring radioactive materials," often called TENORM. The existence of TENORM results in an increased risk for human exposure to radioactivity. Workers in TENORM-producing industries may be occupationally exposed to ionizing radiation. TENORM industries may release significant amounts of radioactive material into the environment resulting in the potential for widespread exposure to ionizing radiation. These industries include mining, phosphate processing, metal ore processing, heavy mineral sand processing, titanium pigment production, fossil fuel extraction and combustion, manufacture of building materials, thorium compounds, aviation, and scrap metal processing. A search of the PubMed database ( ) and Ovid Medline database ( ) was performed using a variety of search terms including NORM, TENORM, and occupational radiation exposure. A total of 133 articles were identified, retrieved, and reviewed. Seventy-three peer-reviewed articles were chosen to be cited in this review. A number of studies have evaluated the extent of ionizing radiation exposure both among workers and the general public due to TENORM. Quantification of radiation exposure is limited because of modeling constraints. In some occupational settings, an increased risk of cancer has been reported and postulated to be secondary to exposure to TENORM, though these reports have not been validated using toxicological principles. NORM and TENORM have the potential to cause important human health effects. It is important that these adverse health effects are evaluated using the basic principles of toxicology, including the magnitude and type of exposure, as well as threshold and dose response.

  19. Naturally occurring tumours in the basal metazoan Hydra. (United States)

    Domazet-Lošo, Tomislav; Klimovich, Alexander; Anokhin, Boris; Anton-Erxleben, Friederike; Hamm, Mailin J; Lange, Christina; Bosch, Thomas C G


    The molecular nature of tumours is well studied in vertebrates, although their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring tumours in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that most metazoans might be prone to develop tumours. Here we provide first evidence for naturally occurring tumours in two species of Hydra. Histological, cellular and molecular data reveal that these tumours are transplantable and might originate by differentiation arrest of female gametes. Growth of tumour cells is independent from the cellular environment. Tumour-bearing polyps have significantly reduced fitness. In addition, Hydra tumours show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows that spontaneous tumours have deep evolutionary roots and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis.

  20. Clinical Characteristics of Stroke Occurring while Bathing. (United States)

    Inamasu, Joji; Nakatsukasa, Masashi; Oshima, Takeo; Tomiyasu, Kazuhiro; Mayanagi, Keita; Imai, Akira


    Stroke can occur during any human activity. Although cardiac arrests or drowning accidents while bathing have been studied extensively, there are few studies focusing on stroke occurring while bathing. The objectives of this study were to evaluate the clinical characteristics of stroke occurring while bathing and the association between stroke and drowning accidents. Clinical data prospectively acquired between January 2011 and December 2015 on 1939 patients with stroke (1224 cerebral infarctions [CIs], 505 intracerebral hemorrhages [ICHs], and 210 subarachnoid hemorrhages [SAHs]) were reviewed to identify patients who sustained a stroke while bathing. The ratio of bathing-related strokes to strokes occurring during other activities was evaluated. Moreover, the demographics of these 2 groups were compared in each stroke type. Among the 1939 patients, 78 (CI, 32; ICH, 28; and SAH, 18) sustained a stroke while bathing. The ratio of bathing to other activities in the SAH group was the highest (8.6%), followed by the ICH group (5.5%), whereas that in the CI group was the lowest (2.6%). Regardless of stroke type, only a minority of patients were found to have collapsed inside the bathtub. The higher ratio of bathing in hemorrhagic strokes may indicate that there is a small risk of hemorrhagic stroke while bathing in vulnerable subjects. This retrospective study did not establish a causal relationship between bathing and stroke nor identify risk factors, which means that future prospective studies are warranted. The finding that the great majority of bathing-related stroke patients were found to have collapsed outside the bathtub suggests that the involvement of stroke in drowning accidents in the bathtub may be small. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Experiments on Detection of Voiced Hesitations in Russian Spontaneous Speech

    Directory of Open Access Journals (Sweden)

    Vasilisa Verkhodanova


    Full Text Available The development and popularity of voice-user interfaces made spontaneous speech processing an important research field. One of the main focus areas in this field is automatic speech recognition (ASR that enables the recognition and translation of spoken language into text by computers. However, ASR systems often work less efficiently for spontaneous than for read speech, since the former differs from any other type of speech in many ways. And the presence of speech disfluencies is its prominent characteristic. These phenomena are an important feature in human-human communication and at the same time they are a challenging obstacle for the speech processing tasks. In this paper we address an issue of voiced hesitations (filled pauses and sound lengthenings detection in Russian spontaneous speech by utilizing different machine learning techniques, from grid search and gradient descent in rule-based approaches to such data-driven ones as ELM and SVM based on the automatically extracted acoustic features. Experimental results on the mixed and quality diverse corpus of spontaneous Russian speech indicate the efficiency of the techniques for the task in question, with SVM outperforming other methods.

  2. Ensemble spontaneous activity alterations detected by CISA approach. (United States)

    Boudaoud, Sofiane; Rix, Hervé; Meste, Olivier; Cazals, Yves


    In this paper, we propose a method for detecting alterations in the Ensemble Spontaneous Activity (ESA), a random signal representing the composite spontaneous contribution of the auditory nerve recorded on the round window. The proposed method is based on shape analysis of the ESA amplitude histogram. For this task, we use a recent approach, the Corrected Integral Shape Averaging (CISA). Using this approach, a shape clustering algorithm is proposed to classify healthy and pathological ESA signals generated by a recent ESA model. This model allows a precise simulation of neural mechanisms occurring in the auditory nerve. The obtained results demonstrate that this shape analysis is very sensitive for detecting a small number of fibers with correlated firing, supposed to occur during a particular type of tinnitus. In comparison, the classical spectral index fails in this detection.

  3. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H


    PAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically...... conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling....

  4. The Effect of Pore Volume of Hard Coals on Their Susceptibility to Spontaneous Combustion

    Directory of Open Access Journals (Sweden)

    Agnieszka Dudzińska


    Full Text Available In this paper the results of the experimental studies on a relationship between pore volume of hard coals and their tendency to spontaneous combustion are presented. Pore volumes were determined by the gas adsorption method and spontaneous combustion tendencies of coals were evaluated by determination of the spontaneous combustion indexes Sza and Sza′ on the basis of the current Polish standards. An increase in the spontaneous combustion susceptibility of coal occurs in the case of the rise both in micropore volumes and in macropore surfaces. Porosity of coal strongly affects the possibility of oxygen diffusion into the micropores of coal located inside its porous structure. The volume of coal micropores determined on the basis of the carbon dioxide adsorption isotherms can serve as an indicator of a susceptibility of coal to spontaneous combustion.

  5. Spontaneous carotid artery dissection causing a juvenile cerebral infarction

    International Nuclear Information System (INIS)

    Trattnig, S.; Huebsch, P.; Schindler, E.


    The case of a 19-year-old patient is presented who was admitted with aphasia and hemiparesis due to basal ganglia infarction as a result of spontaneous dissection of the internal carotid artery. The difficulties in diagnosing this disease with CT and MRI in the acute stage are demonstrated. Angiography is still imperative in order to ascertain that a carotid dissection has occurred. (orig.) [de

  6. Spontaneous Spinal Epidural Hematoma as a Potentially Important Stroke Mimic

    Directory of Open Access Journals (Sweden)

    Tetsu Akimoto


    Full Text Available Hemiparesis develops in response to a wide range of neurological disorders, such as stroke, neoplasms and several inflammatory processes. Occasionally, it may also occur due to a lesion located in the high cervical spinal cord. In this concise review, we describe the features of spontaneous spinal epidural hematoma, which should be included in the large list of stroke mimics. Various concerns regarding the diagnostic and therapeutic conundrums relating to the condition are also discussed.

  7. Spontaneous fission of neutron-rich superheavy nuclei

    International Nuclear Information System (INIS)

    Gherghiescu, R.A.


    Neutron-rich isotopes of the superheavy elements 112, 114, and 116 have been studied for neutron numbers 184, 186, and 188. The spontaneous fission life-time calculations have been performed within the WKB method. Large values have been obtained due to the proton-shell closure 114. The maximum of the fission lifetime occurs for the double-magic superheavy nucleus (114,184). (author)

  8. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H


    -associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We......PAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically...... lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor...

  9. Age-related spontaneous lumbar intervertebral disc degeneration in a mouse model. (United States)

    Ohnishi, Takashi; Sudo, Hideki; Tsujimoto, Takeru; Iwasaki, Norimasa


    The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224-232, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  10. Spontaneous oscillations in microfluidic networks (United States)

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson


    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  11. General features of spontaneous baryogenesis (United States)

    Arbuzova, Elena


    The classical version of spontaneous baryogenesis is studied in details. It is shown that the relation between the time derivative of the (pseudo)goldstone field and the baryonic chemical potential essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). The kinetic equation, used for the calculations of the cosmological baryon asymmetry, is generalized to the case of non-stationary background. The effects of the finite interval of the integration over time are also included into consideration.

  12. Spontaneous Cervical Artery Dissection: The Borgess Classification

    Directory of Open Access Journals (Sweden)

    Firas eAl-Ali


    Full Text Available ABSTRACTBackground and Purpose: The pathogenesis of spontaneous cervical artery dissections (sCAD and its best medical treatment are debated. This may be due to a lack of clear classification of sCAD. We propose the new Borgess classification of sCAD, based on the presence or absence of intimal tear as depicted on imaging studies and effect on blood flow. Materials and Methods: This is a single-center investigator-initiated registry on consecutive patients treated for sCAD. In the Borgess classification, type I dissections have intact intima and type II dissections have an intimal tear. Results: Forty-four patients and 52 dissected arteries were found. Forty-nine of 52 dissections (93% were treated with dual anti-platelet therapy. Twenty-one of 52 dissections were type I; 31 were type II. Type I dissections were more likely to present with ischemic symptoms (stroke, TIA (p=0.001. More type I dissections occurred in the vertebral artery, while more type II dissections occurred in the internal carotid artery (p

  13. Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

    Directory of Open Access Journals (Sweden)

    Fei Kong


    Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

  14. A reliable spatially normalized template of the human spinal cord--Applications to automated white matter/gray matter segmentation and tensor-based morphometry (TBM) mapping of gray matter alterations occurring with age. (United States)

    Taso, Manuel; Le Troter, Arnaud; Sdika, Michaël; Cohen-Adad, Julien; Arnoux, Pierre-Jean; Guye, Maxime; Ranjeva, Jean-Philippe; Callot, Virginie


    Recently, a T2*-weighted template and probabilistic atlas of the white and gray matter (WM, GM) of the spinal cord (SC) have been reported. Such template can be used as tissue-priors for automated WM/GM segmentation but can also provide a common reference and normalized space for group studies. Here, a new template has been created (AMU40), and accuracy of automatic template-based WM/GM segmentation was quantified. The feasibility of tensor-based morphometry (TBM) for studying voxel-wise morphological differences of SC between young and elderly healthy volunteers was also investigated. Sixty-five healthy subjects were divided into young (n=40, age50years old, mean age 57±5years old) groups and scanned at 3T using an axial high-resolution T2*-weighted sequence. Inhomogeneity correction and affine intensity normalization of the SC and cerebrospinal fluid (CSF) signal intensities across slices were performed prior to both construction of the AMU40 template and WM/GM template-based segmentation. The segmentation was achieved using non-linear spatial normalization of T2*-w MR images to the AMU40 template. Validation of WM/GM segmentations was performed with a leave-one-out procedure by calculating DICE similarity coefficients between manual and automated WM/GM masks. SC morphological differences between young and elderly healthy volunteers were assessed using the same non-linear spatial normalization of the subjects' MRI to a common template, derivation of the Jacobian determinant maps from the warping fields, and a TBM analysis. Results demonstrated robust WM/GM automated segmentation, with mean DICE values greater than 0.8. Concerning the TBM analysis, an anterior GM atrophy was highlighted in elderly volunteers, demonstrating thereby, for the first time, the feasibility of studying local structural alterations in the SC using tensor-based morphometry. This holds great promise for studies of morphological impairment occurring in several central nervous system

  15. Spontaneous non-thermal leptogenesis in high-scale inflation models

    International Nuclear Information System (INIS)

    Endo, M.; Takahashi, F.; Yanagida, T.T.; Tokyo Univ.


    We argue that a non-thermal leptogenesis occurs spontaneously, without direct couplings of the inflation with right-handed neutrinos, in a wide class of high-scale inflation models such as the chaotic and hybrid inflation. It is only a finite vacuum expectation value of the inflaton, of more precisely, a linear term in the Kaehler potential, that is a prerequisite for the spontaneous non-thermal leptogenesis. To exemplify how it works, we show that a chaotic inflation model in supergravity naturally produces a right amount of baryon asymmetry via the spontaneous non-thermal leptogenesis. We also discuss the gravitino production from the inflation. (orig.)

  16. Developmental trends in different types of spontaneous false memories: Implications for the legal field


    Otgaar, H.; Howe, M. L.; Peters, M.; Sauerland, M.; Raymaekers, L.


    An emerging area of memory research is showing that a certain type of false memory called spontaneous false memories follows a developmental trajectory that is the opposite of what is commonly assumed in false memory research. That is, spontaneous false memories are more likely to occur in adults than in children. The present study focused on developmental trends of different types of spontaneous false memories. Specifically, in the current study, 6-8-year-olds, 10-12-year-olds, and adults we...

  17. Spontaneous intracranial extradural haematoma associated with frontal sinusitis and orbital involvement. (United States)

    Spennato, Pietro; De Paulis, Danilo; Bocchetti, Antonio; Michele Pipola, A; Sica, Giuseppe; Galzio, Renato J


    Intracranial extradural hematoma is usually traumatic. Rarely, it can occur spontaneously associated with coagulative disorders (spontaneous or iatrogenic), dural vascular malformation, cranio-facial tumors and infections. In these cases, spontaneous extradural hematoma (SEH) is a serious event that needs to be recognized and managed in time to avoid fatal outcome. The authors report a case of a 12-year-old young girl with a 3-year history of right frontal sinusitis treated urgently for a right frontal extradural hematoma involving the orbit. Diagnosis and management of this case is discussed reviewing the pertinent literature.

  18. Radiological evaluation of spontaneous pneumoperitoneum

    International Nuclear Information System (INIS)

    Kim, H. S.; Kim, J. D.; Rhee, H. S.


    112 cases of spontaneous penumoperitoneum, the causes of which were confirmed by clinical and surgical procedure at Presbyterian Medical Center from January, 1977 to July, 1981 were reviewed radiologically. The results were as follows: 1. Perforation of duodenal ulcer (46/112: 41.1%), stomach ulcer (22/112: 19.6%), and stomach cancer (11/112: 9.8%) were the three most common causes of spontaneous penumoperitoneum. These were 70.5% of all causes. 2. The most common site of free gas was both subdiaphragmatic areas (46: 41.1%). Others were Rt. subdiaphragmatic only (31: 27.7%), both subdiaphragmatic with subhepatic (16: 14.3%), Rt. subdiaphragmatic with subhepatic (7: 6.2%), Rt. subdiaphragmatic only (5: 4.4%), diffuse in abdomen (4: 3.6%), and subhepatic only (3: 2.7%). So 92.0% (103/112) were located in RUQ. 3. The radiological shape of free gas was classified: crescent (52: 46.4%) of small amount; half-moon (21: 18.8%) of moderate amount; large or diffuse (39: 34.8%) of large amount.4. The age between 31 and 60 occupied 69.1% (77/112), and male was predominant (5.2 times). 5. The patient's position showing free air most frequently was erect

  19. A Case of Multiple Spontaneous Keloid Scars

    Directory of Open Access Journals (Sweden)

    Abdulhadi Jfri


    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  20. Spontaneity of communication in individuals with autism. (United States)

    Chiang, Hsu-Min; Carter, Mark


    This article provides an examination of issues related to spontaneity of communication in children with autism. Deficits relating to spontaneity or initiation are frequently reported in individuals with autism, particularly in relation to communication and social behavior. Nevertheless, spontaneity is not necessarily clearly conceptualized or measured. Several approaches to conceptualization of communicative spontaneity are examined with a particular focus on the continuum model and how it might be practically applied. A range of possible explanations for deficits in spontaneity of communication in children with autism is subsequently explored, including external factors (highly structured teaching programs, failure to systematically instruct for spontaneity) and intrinsic characteristics (intellectual disability, stimulus overselectivity, weak central coherence). Possible implications for future research are presented.

  1. A Case of Hemophilia A Associated with Spontaneous Hemorrhagic Pleural Effusion and Intracranial Hem

    Directory of Open Access Journals (Sweden)

    Nuri Tutar


    Full Text Available Hemophilia A is a sex-linked recessive coagulation disorder almost exclusively occurring in male subjects and caused by a deficiency of factor VIII. It  is a rare disorder characterized by spontaneous hemorrhages. Spontaneous bleeding in the pleural space is very rare in hemophilia both in children and adults. Here in, we present the case of a 56-year-old hemophilia A patient with hemorrhagic pleural effusion and intracranial hematoma.

  2. Dietary cation-anion difference may explain why ammonium urate nephrolithiasis occurs more frequently in common bottlenose dolphins () under human care than in free-ranging common bottlenose dolphins. (United States)

    Ardente, A J; Wells, R S; Smith, C R; Walsh, M T; Jensen, E D; Schmitt, T L; Colee, J; Vagt, B J; Hill, R C


    Ammonium urate nephrolithiasis frequently develops in common bottlenose dolphins () managed under human care but is rare in free-ranging common bottlenose dolphins. In other species, the dietary cation-anion difference (DCAD) can affect ammonium urate urolith formation by increasing proton excretion as ammonium ions. Therefore, differences in diet between the 2 dolphin populations could affect urolith formation, but the DCAD of most species consumed by free-ranging and managed dolphins is unknown. To compare the nutrient composition of diets consumed by free-ranging and managed bottlenose dolphins, samples ( = 5) of the 8 species of fish commonly consumed by free-ranging bottlenose dolphins in Sarasota Bay, FL, and the 7 species of fish and squid commonly fed to managed bottlenose dolphins were analyzed for nutrient content. Metabolizable energy was calculated using Atwater factors; the DCAD was calculated using 4 equations commonly used in people and animals that use different absorption coefficients. The nutrient composition of individual species was used to predict the DCAD of 2 model diets typically fed to managed common bottlenose dolphins and a model diet typically consumed by common bottlenose dolphins in Sarasota Bay. To mimic differences in postmortem handling of fish for the 2 populations of bottlenose dolphins, "free-ranging" samples were immediately frozen at -80°C and minimally thawed before analysis, whereas "managed" samples were frozen for 6 to 9 mo at -18°C and completely thawed. "Free-ranging" species contained more Ca and P and less Na and Cl than "managed" fish and squid species. As a consequence, the DCAD of both model managed dolphin diets obtained using 3 of the 4 equations was much more negative than the DCAD of the model free-ranging bottlenose dolphin diet ( dolphins must excrete more protons in urine than free-ranging bottlenose dolphins, which will promote nephrolith formation. The nutrient composition of the free-ranging bottlenose

  3. Spontaneous renal hematoma - a case report

    International Nuclear Information System (INIS)

    Obrzut, M.; Obrzut, M.; Homa, J.; Obrzut, B.


    Spontaneous pararenal hematoma is a rare pathology most frequently coexisting with renal tumours, vascular anomalies and inflammatory processes. In some cases one cannot establish its etiology. The paper describes a case of a 58-year-old man with a spontaneous pararenal hematoma and presents a diagnostic algorithm. Ultrasonography and CT play an important role in diagnostics of spontaneous pararenal haemorrhages. These methods enable a precise evaluation of size and location of hematoma and its evolution. (author)

  4. Control technique of spontaneous combustion in fully mechan ized stope during period of end caving under complex mining influence (United States)

    Yuan, Benqing


    In view of the phenomenon of spontaneous combustion of coal seam occurring during the period of end caving under complex mining conditions, taking the 1116 (3) stope of Guqiao mine as the object of study, the causes of spontaneous combustion during the period of end caving are analyzed, according to the specific geological conditions of the stope to develop corresponding fire prevention measures, including the reduction of air supply and air leakage in goaf, reduce the amount of coal left, reasonable drainage, nitrogen injection for spontaneous combustion prevention, grouting for spontaneous combustion prevention and permanent closure, fundamentally eliminates the potential for spontaneous combustion during the period of 1116(3) stope end caving. The engineering practice shows that this kind of measure has reference value for the prevention and control of spontaneous combustion during the period of stope end caving.

  5. [Comparative mutagenesis of human cells in vivo and in vitro]. Progress report, January 1-December 30, 1985

    International Nuclear Information System (INIS)


    Annual progress report is made on project focusing on the comparative mutagenesis of human cells in vivo and in vitro. The study employs the HGPRT gene to explore the changes in nucleotide sequence which has occurred in spontaneous mutations or mutations induced by MNNG or ICR191. Reports on the individual projects have been abstracted and indexed for the Energy Data Base. (DT)

  6. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian


    predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal......Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable......) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. By this systematic review, we conclude that multiplex assays...

  7. Spontaneous Strategies in Innovation Networks

    DEFF Research Database (Denmark)

    Plesner, Ursula; Husted, Emil Krastrup

    and a site ontology, we show how physical sites and objects become constitutive of the inside of virtual worlds through innovation processes. This argument is in line with ANT’s perspective on strategy, where sites and objects are considered a strategically relevant resource in the innovation process...... of materiality in relation to the organization and structuring of virtual worlds. We examine various innovation processes in five Danish entrepreneurial companies where actors continuously struggle to stabilize virtual worlds as platforms for professional communication. With inspiration from actor-network theory....... Empirically, the analysis is founded on descriptive accounts from the five entrepreneurs. By highlighting the spontaneous strategies described by actors, we show how sites and objects are actively used as an element in their strategy, and also how the sites and objects end up facilitating new ways of thinking...

  8. Introduction to naturally occurring radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Egidi, P.


    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

  9. Introduction to naturally occurring radioactive material

    International Nuclear Information System (INIS)

    Egidi, P.


    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. Some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose-based standards. So when is TENORM a problem? Where is it a problem? That depends on when, where, and whom you talk to exclamation point We will start by reviewing background radioactivity, then we will proceed to the geology, mobility, and variability of these

  10. Spontaneous symmetry breaking in the $S_3$-symmetric scalar sector

    CERN Document Server

    Emmanuel-Costa, D.; Osland, P.; Rebelo, M.N.


    We present a detailed study of the vacua of the $S_3$-symmetric three-Higgs-doublet potential, specifying the region of parameters where these minimisation solutions occur. We work with a CP conserving scalar potential and analyse the possible real and complex vacua with emphasis on the cases in which the CP symmetry can be spontaneously broken. Results are presented both in the reducible-representation framework of Derman, and in the irreducible-representation framework. Mappings between these are given. Some of these implementations can in principle accommodate dark matter and for that purpose it is important to identify the residual symmetries of the potential after spontaneous symmetry breakdown. We are also concerned with constraints from vacuum stability.

  11. Cytopathologic diagnosis of spontaneous infarction of fibroadenoma of the breast. (United States)

    Wadhwa, Neelam; Joshi, Richa; Mangal, Nidhi; Khan, Nirupma Panikar; Joshi, Mohit


    Infarction is an uncommon event in a fibroadenoma, which is the commonest benign tumor of the breast. Most often it occurs in pregnancy, lactation or is secondary to fine needle aspiration. Spontaneous infarction of a fibroadenoma in the absence of a predisposing condition is very rare. The cytopathologic features of infarction are necrosis and worrisome nuclear features, which are often misinterpreted as either inflammation or malignancy. We detail a report of accurate cytopathologic diagnosis of spontaneous infarction of fibroadenoma in a 17-year-old adolescent non pregnant girl. Careful attention to the cytopathologic clues like uniform thickness of the necrotic epithelial fragments, branching pattern reminiscent of the staghorn pattern despite atypical nuclear features and clinical details like young age of the patient and recent onset pain in a pre-existing lump helped arrive at the correct diagnosis and spared the patient of a radical excision. To the best of our knowledge, there are no earlier reports of correct cytopathologic diagnosis.

  12. Spontaneous Infarction in a Fibroadenoma of the Breast (United States)

    Toy, Hatice; Esen, Haci H.; Sonmez, Fatma C.; Kucukkartallar, Tevfik


    Summary Background Fibroadenomas are common neoplasms in young women but occur in a wide age range from adolescent females to octogenians. Case Report A 21-year-old female patient presented with a 10-week history of a mass in her breast. Ultrasound examination demonstrated a 3.5 × 3 cm, well-circumscribed, semisolid mass. An excisional biopsy but no fine needle aspiration was performed. The patient had no history of pregnancy or lactation, or trauma or infection to the area of the lesion. The histopathological examination showed a spontaneously infarcted fibroadenoma. Conclusions Spontaneous infarction is an uncommon complication in fibroadenoma of the breast, and there are very few reported cases in the literature. PMID:21547027

  13. Spontaneous coronary artery dissection associated with apical hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Tuncer, M.; Gumrukcuoglu, H.A.; Ekim, H.; Gunes, Y.; Simsek, H.


    Apical hypertrophic cardiomyopathy (HCM) is a relatively uncommon inherited disease. Spontaneous coronary artery dissection (SCAD) is also uncommonly observed, which often occurs in pregnant or post partum women but is rare in men. This report describes a 38 years old man with apical hypertrophic cardiomyopathy who developed SCAD leading to acute inferior myocardial infarction. After emergent appendectomy operation at another hospital, he was immediately transferred to the Cardiology Department of our hospital due to acute myocardial infarction. He emergently underwent coronary angiography which showed a long dissection involving the right coronary. He underwent an emergent CABG with cardiopulmonary bypass. Postoperative recovery was uneventful and he was discharged. According to our knowledge, no case of spontaneous coronary artery dissection associated with apical hypertrophic cardiomyopathy unrelated to postpartum period or oral contraceptive use has been reported so far. (author)

  14. Spontaneous Enterocutaneous Fistula Resulting from Richter’s Hernia (United States)

    Khongwar, Donkupar; Komut, Ojing; Naku, Narang; Baru, Kappa


    Richter’s hernia is due to the entrapment of a part of circumference of the bowel wall. As the bowel continuity is maintained, the patients usually do not have intestinal obstruction. Some patients with Richter’s hernia may present with enterocutaneous fistula either spontaneous or due to surgical intervention mistaking the obstructed hernia to be inguinal abscess. This is more so in developing countries due to lack of awareness among the masses or due to the delay in seeking medical attention. Presenting here is a case of a 53-year-old male patient with enterocutaneous fistula which occurred spontaneously and sought medical attention only after about three years of repeated discharge of yellowish fluid from the left inguinal region. Magnetic resonance fistulogram confirmed the diagnosis of enterocutaneous fistula. Laparotomy with resection and primary anastomosis of the fistulous bowel was done. Patient recovered uneventfully without any complications or recurrence. PMID:28969198

  15. Spontaneous Hemothorax in Neurofibromatosis Treated with Percutaneous Embolization

    International Nuclear Information System (INIS)

    Arai, Kazunori; Sanada, Junichiro; Kurozumi, Akiko; Watanabe, Toshio; Matsui, Osamu


    We evaluated the effectiveness of transcatheter arterial coil embolization therapy for the treatment of spontaneous hemothorax followed by aneurysm rupture in neurofibromatosis patients. Three patients were treated for massive hemothorax caused by arterial lesions associated with neurofibromatosis. Bleeding episodes were secondary to ascending cervical artery aneurysm and dissection of vertebral artery in 1 patient, and intercostal artery aneurysm with or without arteriovenous fistula in 2 patients. Patients were treated by transarterial coil embolization combined with chest drainage. In 1 patient, the ruptured ascending cervical artery aneurysm was well embolized but, shortly after the embolization, fatal hemorrhage induced by dissection of the vertebral artery occurred and the patient died. In the other 2 patients, the ruptured intercostal artery aneurysm was well embolized and they were successfully treated and discharged. Transcatheter arterial coil embolization therapy is an effective method for the treatment of spontaneous hemothorax followed by aneurysm rupture in neurofibromatosis patients

  16. Endo- and exocytic rate constants for spontaneous and protein kinase C-activated T cell receptor cycling

    DEFF Research Database (Denmark)

    Menné, Charlotte; Møller Sørensen, Tine; Siersma, Volkert


    To determine the rate constants of spontaneous and activated TCR cycling, we examined TCR endo- and exocytosis in the human T cell line Jurkat by three different methods. Using a simple kinetic model for TCR cycling and non-linear regression analyses, we found that the spontaneous endocytic rate...

  17. Spontaneous neutrophil activation in HTLV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Jaqueline B. Guerreiro

    Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

  18. Stabiliteit spontane taal bij chronische milde afasie

    NARCIS (Netherlands)

    Wolthuis, Nienke; Mendez Orellana, Carolina; Nouwens, Femke; Jonkers, Roel; Visch-Brink, Evy; Bastiaanse, Roelien


    In aphasia, an analysis of spontaneous speech provides opportunities to establish the linguistic and communicative abilities, to create suitable therapy plans and to measure language progress. The current study investigated the stability of spontaneous speech within an interview of ten mild aphasic

  19. Spontaneously broken abelian gauge invariant supersymmetric model

    International Nuclear Information System (INIS)

    Mainland, G.B.; Tanaka, K.

    A model is presented that is invariant under an Abelian gauge transformation and a modified supersymmetry transformation. This model is broken spontaneously, and the interplay between symmetry breaking, Goldstone particles, and mass breaking is studied. In the present model, spontaneously breaking the Abelian symmetry of the vacuum restores the invariance of the vacuum under a modified supersymmetry transformation. (U.S.)

  20. Spontaneous Achilles tendon rupture in alkaptonuria | Mohammed ...

    African Journals Online (AJOL)

    Spontaneous Achilles tendon ruptures are uncommon. We present a 46-year-old man with spontaneous Achilles tendon rupture due to ochronosis. To our knowledge, this has not been previously reported in Sudan literature. The tendon of the reported patient healed well after debridement and primary repairs.

  1. Spontaneous rupture of choledochal cyst: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ho Seob; Nam, Kyung Jin; Lee, Jin Hwa; Kim, Chan Sung; Choi, Jong Cheol; Oh, Jong Young [Dong-a University College of Medicine, Pusan (Korea, Republic of)


    Spontaneous rupture of a choledochal cyst leading to biliary peritonitis is a rare complication which can be fatal if not promptly diagnosed. The authors report the ultrasound and CT findings of two cases of spontaneous choledochal cystic rupture and the biliary peritonitis which ensued.

  2. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth


    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  3. Carcinogenic Substances Naturrally Occuring in the Human Diet

    Directory of Open Access Journals (Sweden)

    Mogos Viorel T.


    Full Text Available Oncogenesis is a result of the combined action of numerous factors peculiar to the body and the environment (the latter are more effective. Among dietary factors directly implied in the occurrence of malignant tumors we can mention: food additives, contaminated food, polycyclic aromatic hydrocarbons, nitrosamines and some components which are naturally present in food. Moreover, food-related malignancies are a consequence of the increased consumption of fats, proteins, alcohol in parallel with decreases in the consumption of dietary fibers and some micronutrients. Carcinogenic substances naturally present in food are of a particular interest for both nutritionist’s and patient’s, usually not being perceived as being harmful.

  4. Developmental trends in different types of spontaneous false memories: implications for the legal field. (United States)

    Otgaar, Henry; Howe, Mark L; Peters, Maarten; Sauerland, Melanie; Raymaekers, Linsey


    In an emerging area of memory research, it is becoming apparent that one particular type of false memory, called spontaneous false memory, follows a developmental trajectory that is the opposite of what is commonly assumed in false memory research - that is, spontaneous false memories are more likely to occur in adults than in children. The present study focused on developmental trends of different types of spontaneous false memories. Specifically, in the current study, 6-8 year-olds, 10-12 year-olds, and adults were presented with two methods to induce spontaneous false memories: (i) semantically related word lists that are commonly used to evoke spontaneous false memories [i.e, Deese-Roediger-McDermott (DRM) paradigm]; and (ii) a video in which related details were not shown but were presented during a recognition task. The results showed that children were more likely to form false memories than adults in the video false memory paradigm, whereas DRM false memories were more evident in adults than in children. Furthermore, we found that on a general level, DRM false memories were positively related to video spontaneous false memories. We explain that stimuli that contain obvious themes attenuate or even reverse developmental trends in spontaneous false memories. Copyright © 2013 John Wiley & Sons, Ltd.

  5. The (perceived) meaning of spontaneous thoughts. (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I


    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  6. Spontaneous Bacterial Peritonitis due to Lactobacillus paracasei in Cirrhosis

    Directory of Open Access Journals (Sweden)

    Emily Harding-Theobald


    Full Text Available Lactobacillus species colonize the human gastrointestinal tract and are rarely pathogenic. We present a case involving a cirrhotic patient who presented with sepsis and was found to have peritoneal cultures demonstrating Lactobacillus as the sole pathogen concerning for spontaneous bacterial peritonitis. Treatment was achieved with high-dose penicillin and clindamycin but the patient developed hepatorenal syndrome and died from acute renal failure. Intra-abdominal Lactobacillus infections are typically seen in patients undergoing peritoneal dialysis or who have recently had bowel perforation. There are few case reports of spontaneous Lactobacillus peritonitis in patients with cirrhosis. Our case report addresses the challenges of Lactobacillus treatment and suggests antibiotic coverage of commensal organisms in patients who do not improve with standard management.

  7. TENORM (Technologically Enhanced Naturally Occurring Radioactive Materials) (United States)

    ... the beginning of time, naturally occurring. radionuclides or radioactive elements as they occur in nature, such as radium , uranium , thorium , potassium, and their radioactive decay products decay products The atoms formed and ...

  8. Spontaneous appearance of Tay-Sachs disease in an animal model. (United States)

    Zeng, B J; Torres, P A; Viner, T C; Wang, Z H; Raghavan, S S; Alroy, J; Pastores, G M; Kolodny, E H


    Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of beta-hexosaminidase A (Hex A). Deficiency of Hex A in TSD is caused by a defect of the alpha-subunit resulting from mutations of the HEXA gene. To date, there is no effective treatment for TSD. Animal models of genetic diseases, similar to those known to exist in humans, are valuable and essential research tools for the study of potentially effective therapies. However, there is no ideal animal model of TSD available for use in therapeutic trials. In the present study, we report an animal model (American flamingo; Phoenicopterus ruber) of TSD with Hex A deficiency occurring spontaneously in nature, with accumulation of G(M2)-ganglioside, deficiency of Hex A enzymatic activity, and a homozygous P469L mutation in exon 12 of the hexa gene. In addition, we have isolated the full-length cDNA sequence of the flamingo, which consists of 1581 nucleotides encoding a protein of 527 amino acids. Its coding sequence indicates approximately 71% identity at the nucleotide level and about 72.5% identity at the amino acid level with the encoding region of the human HEXA gene. This animal model, with many of the same features as TSD in humans, could represent a valuable resource for investigating therapy of TSD.

  9. Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes.

    Directory of Open Access Journals (Sweden)

    Jong-Hyuk Kim

    Full Text Available Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15 and without (N = 15 diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.

  10. Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes. (United States)

    Kim, Jong-Hyuk; Furrow, Eva; Ritt, Michelle G; Utz, Paul J; Robinson, William H; Yu, Liping; Eckert, Andrea; Stuebner, Kathleen; O'Brien, Timothy D; Steinman, Lawrence; Modiano, Jaime F


    Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15) and without (N = 15) diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter) using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.

  11. SWAP-70 contributes to spontaneous transformation of mouse embryo fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yu-Tzu; Shu, Chung-Li; Lai, Jing-Yang; Lin, Ching-Yu; Chuu, Chih-Pin [Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC (China); Morishita, Kazuhiro; Ichikawa, Tomonaga [Division of Tumor and Cellular Biochemistry Department of Medical Sciences Faculty of Medicine University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-shi, Miyazaki 889-1692 Japan (Japan); Jessberger, Rolf [Faculty of Medicine Carl Gustav Carus, Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany); Fukui, Yasuhisa, E-mail: [Institute of Cellular and System Medicine National Health Research Institute, Zhunan Town 35053, Miaoli County, Taiwan, ROC (China)


    Mouse embryo fibroblasts (MEFs) grow slowly after cultivation from animals, however, after an extended period of cultivation, their growth accelerates. We found that SWAP-70 deficient MEFs failed to increase growth rates. They maintain normal growth rates and proliferation cycles for at least 5 years. Complementing SWAP-70 deficiency in one of these MEF clones, MEF1F2, by expressing human SWAP-70 resulted in fast growth of the cells after further cultivation for a long period. The resulting cells show a transformation phenotype, since they grow on top of each other and do not show contact inhibition. This phenotype was reverted when sanguinarine, a putative SWAP-70 inhibitor, was added. Two SWAP-70 expressing clones were examined in detail. Even after cell density became very high their cdc2 and NFκB were still activated suggesting that they do not stop growing. One of the clones formed colonies in soft agar and formed tumors in nude mice. Lately, one more clone became transformed being able to make colonies in soft agar. We maintain 4 human SWAP-70 expressing MEF1F2 cell lines. Three out of 4 clones exhibited transforming phenotypes. The mouse SWAP-70 gene also promoted transformation of MEFs. Taken together our data suggest that SWAP-70 is not a typical oncogene, but is required for spontaneous transformation of MEFs. - Highlights: • Mouse embryo fibroblasts (MEFs) lacking SWAP-70 do not cause spontaneous transform. • Adding back of SWAP-70 to SWAP-70-deficient MEFs induces spontaneous transformation. • SWAP-70 is required for spontaneous transformation of MEFs.

  12. Spontaneous epileptic rats show changes in sleep architecture and hypothalamic pathology. (United States)

    Bastlund, Jesper F; Jennum, Poul; Mohapel, Paul; Penschuck, Silke; Watson, William P


    The goal of the present study was to investigate the relationship between sleep, hypothalamic pathology, and seizures in spontaneous epileptic rats. Rats were implanted with radiotelemetry transmitters for measuring electrocorticogram (ECoG) and stimulation electrodes in the hippocampus. Epileptogenesis was triggered by 2 h of electical stimulation-induced self-sustained status epilepticus (SSSE). After SSSE, ECoGs were monitored over a 15-week period for the occurrence of interictal high-amplitude low-frequency (HALF) acitvity and spontaneous reoccurring seizures (SRSs). Spontaneous epileptic rats showed clinical features of temporal lobe epilepsy (TLE), such as spontaneous seizures, interictal activity and neuronal cell loss in the dorsomedial hypothalamus, a region important for normal sleep regulation. Interestingly, epileptic rats showed disturbances in sleep architecture, with a high percentage of the seizures occurring during sleep. Therefore we conclude that a close association exists between epileptiform activity and alterations in sleep architecture that may be related to hypothalamic pathology.

  13. Spontaneous mutation rate in Chinese hamster cell clones differing in UV-sensitivity

    International Nuclear Information System (INIS)

    Manuilova, E.S.; Bagrova, A.M.; Moskovskij Gosudarstvennyj Univ.


    The spontaneous rate of appearance of mutations to 6-mercaptopurine (6 MP) resistence in the cells of CHR2 and CHs2 clones dofferent in sensitivity to lethal and matagenous effect of UV-rays, is investigated. Increased UV-sensitivity of CHs2 clone is caused by the violation of postreplicative DNA reparation. It is established that the purity of spontaneously occuring mutations in both clones turns out to be similar, i.e. (1.5-1.8)x10 -5 for the cell pergeneration. It is shown that the effect of postreplicative DNA reparation in the cells of chinese hamster is not connected with the increase of spontaneous mutation ability. The problem on the possible role of reparation in the mechanism of appearance of spontaneous and induced mutations in the cells of Chinese hamster with increased UV-sensitivity is discussed

  14. Simultaneous bilateral primary spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Arife Zeybek


    Full Text Available Simultaneous bilateral primary pneumothorax is a very rare (1.6 / 100,000 and life-threatening condition. Clinical presentation may vary from mild dyspnea to tension pneumothorax. It may be milder particularly in younger patients, but more severe in patients with advanced age, and tube thoracostomy is a life preserver in the latter group. Since mortality and recurrence rates following tube thoracostomy are high, endoscopic approaches to bilateral hemithorax have been reported in literature. Apical wedge resection and pleural procedures are recommended in video thoracoscopy or mini thoracotomy even if no bulla and/or bleb are detected. Bilateral surgical interventions and additional pleural procedures are associated with increased rate of post-operative complications and longer postoperative hospital-stays. As a first-line approach, the surgical method toward any side of lung with air leakage following a previous tube thoracostomy is considered less invasive, especially in younger patients. Here, we present a case of simultaneous bilateral primary spontaneous pneumothorax (SBPSP in a 21-year old male with no history of smoking and chronic pulmonary disease. A unilateral surgical intervention was performed, and no recurrence was observed during 5-year follow up.

  15. Bilateral spontaneous hemotympanum: Case report

    Directory of Open Access Journals (Sweden)

    Economou Nicolas C


    Full Text Available Abstract Background The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. Case presentation A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. Conclusion Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder.

  16. Is there a predilection for breech infants to demonstrate spontaneous stabilization of DDH instability? (United States)

    Sarkissian, Eric J; Sankar, Wudbhav N; Baldwin, Keith; Flynn, John M


    Breech position subjects the fetal hip to abnormal mechanical forces. However, unlike genetic or tissue factors linked to developmental dysplasia of the hip (DDH), the causative effect of the breech position ends when the infant is born. The purpose of this study was to evaluate the rate of spontaneous stabilization in mildly unstable hips of breech-presenting infants compared with similarly lax hips in infants with a genetic or tissue-related cause of DDH. We studied a consecutive series of infants presenting to our institution at 8 weeks of age or younger with DDH from January 2008 to January 2012. Infants with increased hip laxity on dynamic ultrasound examination but without frank instability on clinical provocation maneuvers and no history of prior treatment were evaluated. The endpoint was spontaneous stabilization of ultrasound-detected instability, or intervention due to persistent instability on follow-up dynamic ultrasound. A logistic regression model using backward likelihood ratio method was used to analyze predictors of spontaneous stabilization. We identified 122 hips in 79 infants with instability on dynamic ultrasound evaluation but with stable clinical examinations. Spontaneous stabilization of sonographic instability occurred in 90 hips (74%) at a mean age of 9 weeks (range, 4 to 18 wk). Breech hips more frequently spontaneously stabilized compared with nonbreech hips (80% vs. 66%). Regression analysis determined that breech presentation was a strong independent predictor for spontaneous hip stabilization (odds ratio, 3.72; 95% confidence interval, 1.45-9.60; P=0.006). Sex, family history, intrauterine positioning syndromes, side involved, bilateralism, and grade of sonographic hip instability were not independently predictive of spontaneous hip stabilization. DDH infants with a history of breech presentation are 3.72 times more likely to experience spontaneous resolution of mild hip instability compared with nonbreech infants. Awareness that

  17. Evidence for spontaneous serial refreshing in verbal working memory? (United States)

    Vergauwe, Evie; Langerock, Naomi; Cowan, Nelson


    Working memory (WM) keeps information temporarily accessible for ongoing cognition. One proposed mechanism to keep information active in WM is refreshing. This mechanism is assumed to operate by bringing memory items into the focus of attention, thereby serially refreshing the content of WM. We report two experiments in which we examine evidence for the spontaneous occurrence of serial refreshing in verbal WM. Participants had to remember series of red letters, while black probe letters were presented between these memory items, with each probe to be judged present in or absent from the list presented so far, as quickly as possible (i.e., the probe-span task). Response times to the probes were used to infer the status of the representations in WM and, in particular, to examine whether the content of the focus of attention changed over time, as would be expected if serial refreshing occurs spontaneously during inter-item pauses. In sharp contrast with this hypothesis, our results indicate that the last-presented memory item remained in the focus of attention during the inter-item pauses of the probe-span task. We discuss how these findings help to define the boundary conditions of spontaneous refreshing of verbal material in WM, and discuss implications for verbal WM maintenance and forgetting.

  18. Spontaneous emission effects in optically pumped x-ray FEL

    Energy Technology Data Exchange (ETDEWEB)

    Smetanin, I.V.; Grigor`ev, S.V. [P.N. Lebedev Physics Institute, Moscow (Russian Federation)


    An effect of spontaneous emission in both quantum and classical regimes of the optically pumped X-ray free electron laser (FEL) in investigated. The quantum properties of an FEL are determined by the ratio of the separation {h_bar} between the absorption and emission lines (i.e. the quanta emitted) and their effective width {Delta}{epsilon} {eta}={h_bar}/{Delta}{epsilon}. In the conventional classical regime {eta} {much_lt} 1 an electron emits and absorbes a great number of shortwavelength photons over the interaction region, the gain in FEL being the result of these competitive processes. In the quantum limit {eta} {much_gt} 1 the emission and absorption lines are completely separated and thus the FEL becomes a two-level quantum oscillator with a completely inverted active medium. Spontaneous emission causes the electron to leave the range of energies where resonant interaction with the laser field occurs, thus effectively reducing the number of particles that take part in generating the induced X-ray signal. This effect is found to be crucial for lasing in optically pumped X-ray FEL. The characteristic relaxation times are calculated for both classical and quantum FEL regimes. It is shown that spontaneous emission results in FEL electron beam threshold current, which is of rather high value. An optimal range of pumping laser intensities is determined.

  19. [Relation Between Stress During Pregnancy and Spontaneous Preterm Birth]. (United States)

    Ortiz Martínez, Roberth Alirio; Castillo, Alejandro


    Preterm birth occurs before 37 completed weeks, its causes are multifactorial and vary according to the gestational age, ethnicity and geographical context. Although several medical/social factors have been clearly identified, over 50% of cases are unknown or unclear; however, psychopathological components emerge as potentially important risk factors. To determine the relationship between the presence of stress during pregnancy and spontaneous preterm birth. Through a study of cases and controls in a level III hospital, with a sample of 360 patients during the period from March to November of 2013, where sociodemographic characteristics were collected. In addition, they were applied scales social adjustment, coping strategies and social support. Logistic regression models were developed; psychological, biological and social. Based on the significant variables in each of these generated a final one. The final model was found that stress during pregnancy increases the odds of spontaneous preterm birth 1.91 times (adjusted OR=2.91; 95%CI, 1.67-5.08; P<.05). Other significant variables were: history of preterm delivery, unplanned pregnancy, no emotional support, rural residence, inadequate prenatal care and non-stable partner. The findings support the hypothesis that stress during pregnancy is associated with spontaneous preterm delivery. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  20. Clock frequency estimation under spontaneous emission (United States)

    Qin, Xi-Zhou; Huang, Jia-Hao; Zhong, Hong-Hua; Lee, Chaohong


    We investigate the quantum dynamics of a driven two-level system under spontaneous emission and its application in clock frequency estimation. By using the Lindblad equation to describe the system, we analytically obtain its exact solutions, which show three different regimes: Rabi oscillation, damped oscillation, and overdamped decay. From the analytical solutions, we explore how the spontaneous emission affects the clock frequency estimation. We find that under a moderate spontaneous emission rate, the transition frequency can still be inferred from the Rabi oscillation. Our results enable potential practical applications in frequency measurement and quantum control under decoherence.

  1. Spontaneous Bacterial Peritonitis in Subclinical Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Dalip Gupta


    Full Text Available Hypothyroidism is an uncommon cause of ascites. Here we describe a case of a 75 year-old female patient with spontaneous bacterial peritonitis and subclinical hypothyroidism that resolved with thyroid replacement and antibiotic therapy respectively. Ascitic fluid analysis revealed a gram-positive bacterium on gram staining. A review of the literature revealed just one other reported case of myxoedema ascites with concomitant spontaneous bacterial peritonitis and no case has till been reported of spontaneous bacterial peritonitis in subclinical hypothyroidism.

  2. Spontaneous regression of an invasive thymoma. (United States)

    Yutaka, Yojiro; Omasa, Mitsugu; Shikuma, Kei; Okuda, Masato; Taki, Toshihiko


    Although there are many reports of spontaneous regression of noninvasive thymoma, there are no reports of spontaneous regression of an invasive thymoma. Moreover, the mechanism of the spontaneous regression is still unknown. The present case concerns a 47-year-old man who presented with chest pain. Computed tomography (CT) showed a large anterior mediastinal mass with left pleural effusion that occluded the innominate vein. The tissue obtained by video-assisted thoracic surgery suggested a diagnosis of invasive thymic carcinoma. One month later CT showed prominent regression of the tumor, and the tumor was completely resected. On pathology, the diagnosis was thymoma type B3.

  3. Spontaneous Dissection of the Superior Mesenteric Artery

    International Nuclear Information System (INIS)

    Sheldon, Patrick J.; Esther, James B.; Sheldon, Elana L.; Sparks, Steven R.; Brophy, David P.; Oglevie, Steven B.


    Spontaneous dissection of the superior mesenteric artery (SMA) is a rare occurrence, especially when not associated with aortic dissection. Currently, only 28 cases appear to have been reported. Due to the scarcity of cases in the literature, the natural history of isolated, spontaneous SMA dissection is unclear. CT has been reported to be useful for the initial diagnosis of SMA dissection [2-5]. We present two recent cases of spontaneous SMA dissection in which enhanced spiral CT was instrumental in following the disease process and guiding clinical decision making

  4. Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.

    Directory of Open Access Journals (Sweden)

    Yuval Tabach

    Full Text Available Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification.

  5. Cysteines introduced into extracellular loops 1 and 4 of human P-glycoprotein that are close only in the open conformation spontaneously form a disulfide bond that inhibits drug efflux and ATPase activity. (United States)

    Loo, Tip W; Clarke, David M


    P-glycoprotein (P-gp) is an ATP-binding cassette drug pump that protects us from toxic compounds and confers multidrug resistance. The protein is organized into two halves. The halves contain a transmembrane domain (TMD) with six transmembrane segments and a nucleotide-binding domain (NBD). The drug- and ATP-binding sites reside at the TMD1/TMD2 and NBD1/NBD2 interfaces, respectively. ATP-dependent drug efflux involves changes between the open inward-facing (NBDs apart, extracellular loops (ECLs) close together) and the closed outward-facing (NBDs close together, ECLs apart) conformations. It is controversial, however, whether the open conformation only exists transiently in intact cells because of the presence of high levels of ATP. To test for the presence of an open conformation in intact cells, reporter cysteines were placed in extracellular loops 1 (A80C, N half) and 4 (R741C, C half). The rationale was that cysteines A80C/R741C would only come close enough to form a disulfide bond in an open conformation (6.9 Å apart) because they are separated widely (30.4 Å apart) in the closed conformation. It was observed that the mutant A80C/R741C cross-linked spontaneously (>90%) when expressed in cells. In contrast to previous reports showing that trapping P-gp in a closed conformation highly activated ATPase activity, here we show that A80C/R741C cross-linking inhibited ATPase activity and drug efflux. Both activities were restored when the cross-linked mutant was treated with a thiol-reducing agent. The results show that an open conformation can be readily detected in cells and that cross-linking of cysteines placed in ECLs 1 and 4 inhibits activity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Altered insulin receptor messenger ribonucleic acid splicing in liver is associated with deterioration of glucose tolerance in the spontaneously obese and diabetic rhesus monkey: Analysis of controversy between monkey and human studies

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ze; Shuldiner, A.R.; Zenilman, M.E. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others


    There are two insulin receptor (IR) isoforms (designated type A and type B), derived from alternative splicing of exon 11 of the IR gene. Recently, we reported that an increase in the exon 11- (i.e. lacking exon 11) (type A) IR messenger RNA (mRNA) variant in muscle is associated with hyperinsulinemia, an early risk factor for noninsulin-dependent diabetes mellitus (NIDDM), in the spontaneously obese, diabetic rhesus monkey. To explore further the role of IR mRNA splicing in insulin resistance of NIDDM, we studied liver, another target organ that is resistant to insulin action in NIDDM. The relative amounts of the two IR mRNA-splicing variants in liver were quantitated by RT-PCR in normal, prediabetic, and diabetic (NIDDM) monkeys. The percentage of the exon 11- mRNA variant in liver (n = 24) was significantly correlated with fasting plasma glucose (r = 0.55, P < 0.01) and intravenous glucose disappearance rate (r = -0.45, P < 0.05). The exon 11- mRNA variant was increased significantly from 29.8 {+-} 1.6% in monkeys with normal fasting glucose to 39.2 {+-} 2.9% in monkeys with elevated fasting glucose (P < 0.01). These studies provide the first direct evidence in vivo that the relative expression of the two IR mRNA-splicing variants is altered in liver and suggest that increased expression of the exon 11- IR isoform may contribute to hepatic insulin resistance and NIDDM or may compensate for some yet unidentified defect. 33 refs., 3 figs., 1 tab.

  7. Hematoma tegmento-mesencefálico espontâneo: aspectos neurocomportamentais do terço rostral do tronco encefálico humano Spontaneous tegmento-mesencephalic hematoma: neurobehavioral insights concerning the rostral human brainstem

    Directory of Open Access Journals (Sweden)

    Ricardo de Oliveira-Souza


    Full Text Available O tegmento do mesencéfalo é área complexa, dada a quantidade de fibras que o atravessam, provenientes de circuitos locais, de sistemas ativadores ascendentes e de feixes descendentes dos hemisférios cerebrais. No presente artigo, relatamos o caso de um senhor de 67 anos, que sofreu hemorragia mesencefálica de localização tegmental, vindo a falecer 1 mês depois. Inicialmente, foi julgado em coma, por apresentar ptose bilateral, ausência de fala e de movimentos espontâneos. Por volta da segunda semana, descobriu-se que podia cumprir comandos verbais, sentar, sustentar-se de pé e andar. O caso demonstra o quanto o diagnóstico do coma em bases clínicas pode ser enganoso em pacientes como esse, no qual a aparente irresponsividade de olhos fechados se deve à combinação inesperada de abulia e oftalmoplegia.The tegmentum of the midbrain is a complex area traversed by a number of anatomical and functional systems, including local circuits, ascending activating systems and descending fibers from the cerebral hemispheres. In the present paper we report on the case of a 67-year-old man who suffered a spontaneous central tegmental hemorrhage and was initially supposed to be in coma due to bilateral ptosis and lack of speech and initiative. By the second hospital week, however, he was shown to be able to respond to verbal commands, sit, stand and walk. He died in sepsis one month later. This case shows that the clinical diagnosis of coma may be misleading in certain patients in whom wakefulness is preserved, though concealed from a casual bedside examination due to abulia and ophthalmoplegia.

  8. Spontaneous Multiseptated Cystic Pneumomediastinum in a Term Newborn

    Directory of Open Access Journals (Sweden)

    Cheng-Ting Lee


    Full Text Available Pneumomediastinum usually occurs after assisted ventilation. Spontaneous pneumomediastinum without preceding assisted ventilation, and presenting as a huge cystic mass in a term newborn infant has rarely been reported. We report a term baby who developed respiratory distress at 2 days of age. A huge cystic tumor of the thymus or a congenital mediastinal cystic tumor was initially suggested by chest radiography and computed tomography. Follow-up chest film revealed a “spinnaker sail sign” which is a typical radiographic presentation of pneumomediastinum.

  9. Fatal Disseminated Tuberculous Peritonitis following Spontaneous Abortion: A Case Report

    Directory of Open Access Journals (Sweden)

    Munire Erman Akar


    Full Text Available We describe a rare case of fatal disseminated tuberculous peritonitis in a young woman with rapid progressive clinical course following spontaneous abortion of 20-week gestation. Clinical and laboratory findings were initially unremarkable. She underwent diagnostic laparoscopy which revealed numerous tiny implants on the peritoneum and viscera. Histopathology showed chronic caseating granulomas, and the tissue culture grew Mycobacterium tuberculosis. At fifth day of the antituberculous treatment multiorgan failure occurred in terms of pulmonary, hepatic, and renal insufficiency. She developed refractory metabolic acidosis with coagulopathy and pancytopenia, and she died of acute respiratory distress syndrome and septic shock on her twelfth day of hospitalization.

  10. Laparoscopic splenectomy for spontaneous rupture of the spleen

    Directory of Open Access Journals (Sweden)

    Pinky M Thapar


    Full Text Available Laparoscopic splenectomy is a gold standard for management of planned benign splenic pathologies. Spontaneous rupture of the spleen (SRS leading to acute abdomen occurs in only 1% of all splenic ruptures. Laparoscopic splenectomy in traumatic and atraumatic rupture due to intra-splenic pathology is reported. We present the first reported case of laparoscopic splenectomy in a 23-year-old male who presented with hemoperitoneum due to idiopathic or SRS. The procedure was safely accomplished with slight modified technique and minimum usage of advanced gadgets.

  11. Spontaneous Splenic Rupture in Vascular Ehlers-Danlos Syndrome. (United States)

    Batagini, Nayara Cioffi; Gornik, Heather; Kirksey, Lee


    Vascular Ehlers-Danlos Syndrome (VEDS) is a rare autosomal dominant collagen vascular disorder. Different from other Ehler-Danlos Syndrome subtypes, VEDS has poor prognosis due to severe fragility of connective tissues and association with life-threatening vascular and gastrointestinal complications. Spontaneous splenic rupture is a rare but hazardous complication related to this syndrome. To date, only 2 cases have been reported in the literature. Here we present another case of this uncommon complication, occurring in a 54-year-old woman in clinical follow-up for VEDS who presented with sudden onset of abdominal pain and hypotension. © The Author(s) 2015.

  12. The MHV Lagrangian for a spontaneously broken gauge theory (United States)

    Buchta, Sebastian; Weinzierl, Stefan


    Starting from the standard Lagrangian for a SU(2) × U(1) gauge theory plus a Higgs field we derive the corresponding "maximal helicity violating" (MHV) Lagrangian. From this MHV Lagrangian one deduces simple diagrammatic rules for the calculation of multi-particle scattering amplitudes. We arrive at the MHV Lagrangian by a canonical change of the field variables in the light-cone gauge. We comment on the modifications which occur in a spontaneously broken gauge theory as compared to a pure (unbroken) Yang-Mills theory.

  13. Vital tooth with periapical lesion: spontaneous healing after conservative treatment

    Directory of Open Access Journals (Sweden)

    Hyun-Joo Kim


    Full Text Available It is often presumed that apical periodontitis follows total pulp necrosis, and consequently root canal treatment is commonly performed. Periapical lesion development is usually caused by bacteria and its byproduct which irritate pulp, develop pulpitis, and result in necrosis through an irreversible process. Afterwards, apical periodontitis occurs. This phenomenon is observed as an apical radiolucency in radiographic view. However, this unusual case presents a spontaneous healing of periapical lesion, which has developed without pulp necrosis in a vital tooth, through conservative treatment.

  14. Spontaneous intracranial hypotension syndrome: magnetic resonance findings in two patients

    International Nuclear Information System (INIS)

    Ortega, R.; Pastor, J.; Escamilla, F.; Romero, M. I.


    The postural headache syndrome associated with a decrease in the cerebrospinal fluid (CSF) pressure is generally secondary to the CSF leakage that usually occurs after diagnostic lumbar puncture. Spontaneous intracranial hypotension can not be attributed to any known cause or previous diagnostic or therapeutic intervention. The syndrome is characterized by severe headache that is relieved by lying supine. During lumbar puncture, the CSF pressure is normally low. We present two patients in whom gadolinium-enhanced magnetic resonance imaging showed widespread thickening and enhancement of the dura mater and subdural fluid collections. (Author) 13 refs

  15. Epstein-Barr virus latency type and spontaneous reactivation predict lytic induction levels. (United States)

    Phan, An T; Fernandez, Samantha G; Somberg, Jessica J; Keck, Kristin M; Miranda, Jj L


    The human Epstein-Barr virus (EBV) evades the immune system by entering a transcriptionally latent phase in B cells. EBV in tumor cells expresses distinct patterns of genes referred to as latency types. Viruses in tumor cells also display varying levels of lytic transcription resulting from spontaneous reactivation out of latency. We measured this dynamic range of lytic transcription with RNA deep sequencing and observed no correlation with EBV latency types among genetically different viruses, but type I cell lines reveal more spontaneous reactivation than isogenic type III cultures. We further determined that latency type and spontaneous reactivation levels predict the relative amount of induced reactivation generated by cytotoxic chemotherapy drugs. Our work has potential implications for personalizing medicine against EBV-transformed malignancies. Identifying latency type or measuring spontaneous reactivation may provide predictive power in treatment contexts where viral production should be either avoided or coerced. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Right Diaphragm Spontaneous Rupture: A Surgical Approach

    Directory of Open Access Journals (Sweden)

    Duilio Divisi


    Full Text Available We present a case of spontaneous rupture of the diaphragm, characterized by nonspecific symptoms. The rapid diagnosis and appropriate surgical approach led to a positive resolution of the pathology.

  17. Spontaneous cecal perforation secondary to acute fulminant ...

    African Journals Online (AJOL)

    Spontaneous cecal perforation secondary to acute fulminant gastroenteritis: report of a rare case. Duvuru Ram, Vilvapathy S. Karthikeyan, Sarath C. Sistla, Sheik M. Ali, Parnandi Sridhar, Nagarajan Rajkumar ...

  18. Spontane abdominale arteriovenøse fistler

    DEFF Research Database (Denmark)

    Flarup, S; Lindholt, Jes Sanddal


    Spontaneous arteriovenous fistulas between major abdominal vessels (AAVF) complicates about 1% of abdominal aortic aneurysms. AAVF produces severe circulatory disturbances with high operative mortality. Preoperative diagnosis is important but difficult due to the varied nature of presentation. Fo...

  19. An Evolutionary Game Theory Model of Spontaneous Brain Functioning. (United States)

    Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano


    Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

  20. Spontaneous pain attacks: neuralgic pain

    NARCIS (Netherlands)

    de Bont, L.G.


    Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either

  1. Depressive disorder and grief following spontaneous abortion. (United States)

    Kulathilaka, Susil; Hanwella, Raveen; de Silva, Varuni A


    Abortion is associated with moderate to high risk of psychological problems such as depression, use of alcohol or marijuana, anxiety, depression and suicidal behaviours. The increased risk of depression after spontaneous abortion in Asian populations has not been clearly established. Only a few studies have explored the relationship between grief and depression after abortion. A study was conducted to assess the prevalence and risk factors of depressive disorder and complicated grief among women 6-10 weeks after spontaneous abortion and compare the risk of depression with pregnant women attending an antenatal clinic. Spontaneous abortion group consisted of women diagnosed with spontaneous abortion by a Consultant Obstetrician. Women with confirmed or suspected induced abortion were excluded. The comparison group consisted of randomly selected pregnant, females attending the antenatal clinics of the two hospitals. Diagnosis of depressive disorder was made according to ICD-10 clinical criteria based on a structured clinical interview. This assessment was conducted in both groups. The severity of depressive symptoms were assessed using the Patients Health Questionnaire (PHQ-9). Grief was assessed using the Perinatal Grief Scale which was administered to the women who had experienced spontaneous abortion. The sample consisted of 137 women in each group. The spontaneous abortion group (mean age 30.39 years (SD = 6.38) were significantly older than the comparison group (mean age 28.79 years (SD = 6.26)). There were more females with ≥10 years of education in the spontaneous abortion group (n = 54; SD = 39.4) compared to the comparison group (n = 37; SD = 27.0). The prevalence of depression in the spontaneous abortion group was 18.6 % (95 CI, 11.51-25.77). The prevalence of depression in the comparison group was 9.5 % (95 CI, 4.52-14.46). Of the 64 women fulfilling criteria for grief, 17 (26.6 %) also fulfilled criteria for a depressive episode. The relative risk of

  2. Endometriosis-related spontaneous diaphragmatic rupture. (United States)

    Triponez, Frédéric; Alifano, Marco; Bobbio, Antonio; Regnard, Jean-François


    Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.

  3. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J


    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  4. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)


    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  5. Spontaneous intracranial epidural hematoma during rivaroxaban treatment. (United States)

    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jerônimo Buzetti; Jung, Gustavo Simiano; Silva, Luis Fernando; Ramina, Ricardo


    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xareltor. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban.

  6. FEL gain optimisation and spontaneous radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others


    Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

  7. Toxin profiles of Bacillus cereus occurring in high numbers in spontaneously fermented African locust beans (Parkia biglobosa)

    DEFF Research Database (Denmark)

    Thorsen, Line; Azokpota, Paulin; Hansen, Bjarne Munk

    to be potentially pathogenic by harboring and expressing enterotoxin and emetic genes. Isolates from afiitin were the most cytotoxic as detected by a Vero-cell assay, while an isolate from sonru was a potent cereulide producer. Interestingly B. cereus food poisoning frm the consumption of the fermented condiments...

  8. Effect of pH on the spontaneous synthesis of palladium nanoparticles on reduced graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiaorui [Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Ooki, Wataru; Kosaka, Yoshinori R.; Okonogi, Akinori [Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Marzun, Galina; Wagener, Philipp; Barcikowski, Stephan [Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Universitaetsstrasse 7, D-45141 Essen (Germany); NanoEnergieTechnikZentrum (NETZ), University of Duisburg-Essen, Carl-Benz-Strasse 199, D-47057 Duisburg (Germany); Kondo, Takahiro [Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Tsukuba Research Center for Interdisciplinary Materials Science (TIMS) & Center for Integrated Research in Fundamental Science and Engineering (CiRfSE), University of Tsukuba, 1-1-1 Tennodai, 305-8573 (Japan); Nakamura, Junji, E-mail: [Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Tsukuba Research Center for Interdisciplinary Materials Science (TIMS) & Center for Integrated Research in Fundamental Science and Engineering (CiRfSE), University of Tsukuba, 1-1-1 Tennodai, 305-8573 (Japan)


    Highlights: • Palladium metal nanoparticles were spontaneously formed on reduced graphene oxide (rGO) via a redox reaction in H{sub 2}O. • The amount of Pd deposited on rGO was affected by pH. • The amount of oxygen-containing functional groups in rGO was increased with the deposition of palladium. • The importance of redox potential in spontaneous deposition was demonstrated by an experiment with Zn, Ni, Pt, Pd, etc.. • The spontaneous redox deposition method is facile, environmentally friendly, and needs no external reducing agents. - Abstract: Palladium (Pd) nanoparticles were spontaneously deposited on reduced graphene oxide (rGO) without any external reducing agents. The prepared Pd/rGO composites were then characterized by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Spontaneous deposition occurred because of a redox reaction between the Pd precursor and rGO, which involved reduction of bivalent Pd to metallic Pd{sup 0} and oxidation of the sp{sup 2} carbon of rGO to oxygen-containing functional groups. The amount of Pd deposited on rGO varied with pH, and this was attributed to electrostatic interactions between the Pd precursor and rGO based on the results of zeta potential measurements. The importance of the redox reaction in the spontaneous deposition was demonstrated in the experiment with Zn, Ni, Cu, Ag, Pt, Pd, and Au.

  9. Sympathovagal effects of spinal anesthesia assessed by the spontaneous cardiac baroreflex. (United States)

    Gratadour, P; Viale, J P; Parlow, J; Sagnard, P; Counioux, H; Bagou, G; Annat, G; Hughson, R; Quintin, L


    The changes in sympathovagal balance induced by spinal anesthesia remain controversial. The spontaneous baroreflex method allows the continuous assessment of the spontaneous engagement of the cardiac baroreflex, giving an index of sympathovagal balance. The purpose of this study was to follow the effects of spinal anesthesia on spontaneous baroreflex sensitivity. Continuous electrocardiogram and noninvasive blood pressure were recorded in 24 patients scheduled for elective inguinal hernia repair and randomly assigned to three groups: (1) no volume loading, (2) volume loading of 15 ml/kg lactated Ringer's solution, and (3) continuous infusion of etilefrine (an ephedrine-like drug). Each patient was studied before, during, and after bupivacaine-induced spinal anesthesia (mean sensory block: T4). Spontaneous baroreflex sensitivity and parameters of time-domain analysis of heart rate variability were calculated from 30 min of recording of each period. No significant change in spontaneous baroreflex slope or parameters of time-domain analysis were observed after regional anesthesia in any group. However, three patients experienced episodes of bradycardia and hypotension in the absence of a high block; these three patients showed an increase in spontaneous baroreflex sensitivity and time-domain parameters. Using a noninvasive, continuous technique to estimate cardiac sympathovagal balance, no significant variation in autonomic balance induced by spinal anesthesia was observed. However, untoward episodes of bradycardia and hypotension occurred in three patients, who could not be prospectively identified by the parameters studied.

  10. Occur of death in Edgar Moren's work

    Directory of Open Access Journals (Sweden)

    Nedeljković Zoran


    Full Text Available In this work author presented Edgar Moren's antrolology of death. This thinker understands and explains event of the universe, humans and the end of the life. Myth is one of the ways for human to become the master of the death, but science becomes new weapon in mans war against it. Morens worns us that death and life can not be separated, and every human desire for physical immortality is absolutely absurd.

  11. Synthetic and naturally occurring hydrazines as possible cancer causative agents. (United States)

    Toth, B


    The various synthetic substituted hydrazines, which cause tumors in animals, are briefly enumerated. To date, 19 of them have proved to be tumorigenic in animals. A number of these chemicals are found today in the environment, in industry, in agriculture, and in medicine, and the human population is exposed to a certain degree to some of them. Hydrazine also occurs in nature in tobacco and tobacco smoke. The three other naturally occurring hydrazine compounds are N-methyl-N-formylhydrazine, which occurs in the wild edible mushroom, Gyromitra esculenta, and beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine and 4-hydroxymethylphenylhydrazine, which are found in the commonly eaten cultivated mushroom, Agaricus bisporus. Tumorigenesis studies with the naturally occurring hydrazines are in progress.

  12. Words from spontaneous conversational speech can be recognized with human-like accuracy by an error-driven learning algorithm that discriminates between meanings straight from smart acoustic features, bypassing the phoneme as recognition unit.

    Directory of Open Access Journals (Sweden)

    Denis Arnold

    Full Text Available Sound units play a pivotal role in cognitive models of auditory comprehension. The general consensus is that during perception listeners break down speech into auditory words and subsequently phones. Indeed, cognitive speech recognition is typically taken to be computationally intractable without phones. Here we present a computational model trained on 20 hours of conversational speech that recognizes word meanings within the range of human performance (model 25%, native speakers 20-44%, without making use of phone or word form representations. Our model also generates successfully predictions about the speed and accuracy of human auditory comprehension. At the heart of the model is a 'wide' yet sparse two-layer artificial neural network with some hundred thousand input units representing summaries of changes in acoustic frequency bands, and proxies for lexical meanings as output units. We believe that our model holds promise for resolving longstanding theoretical problems surrounding the notion of the phone in linguistic theory.

  13. Spontaneous malignant transformation of conventional giant cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Grote, H.J.; Pomjanski, N.; Boecking, A. [Institute of Cytopathology, Heinrich Heine University, Moorenstrasse 5, 40225, Duesseldorf (Germany); Braun, M. [Orthopedic Hospital Volmarstein, University of Witten/Herdecke, Hartmannstrasse 24, 58300, Wetter (Ruhr) (Germany); Kalinski, T.; Roessner, A. [Department of Pathology, Otto von Guericke University, Leipziger Strasse 44, 39120, Magdeburg (Germany); Back, W.; Bleyl, U. [Department of Pathology, Ruprecht Karls University Heidelberg, University Hospital Mannheim, Theodor-Kutzer-Ufer, 68167, Mannheim (Germany)


    Spontaneous malignant transformation of conventional giant cell tumor (GCT) of bone is exceedingly rare. We report on a case of GCT of the iliac crest in a 35-year-old woman with malignant change into a high-grade osteosarcoma 10 years after the first appearance of GCT on a radiograph. Since the patient refused therapy for personal reasons the tumor remained untreated until sarcomatous transformation occurred. Image cytometry showed DNA aneuploidy and a suspiciously high 2c deviation index (2cDI) in the primary bone lesion. A thorough review of the world literature revealed only seven fully documented cases of secondary malignant GCT which matched the definition of a ''sarcomatous growth that occurs at the site of a previously documented benign giant cell tumor'' and not treated by radiotherapy. These cases as well as the current one suggest that a spontaneous secondary malignant GCT presents as a frankly sarcomatous tumor in the form of an osteosarcoma or malignant fibrous histiocytoma. It usually appears at sites of typical GCTs - often without any recurrent intermediate state - and is diagnosed 3 or more years after the primary bone lesion. The prognosis is poor. (orig.)

  14. Spontaneous splenic rupture during the recovery phase of dengue fever. (United States)

    de Silva, W T T; Gunasekera, M


    Spontaneous splenic rupture is a rare but known complication of dengue fever. Previously reported cases have occurred early during the course of the disease and most cases have led to a fatal outcome. Here we report a case of spontaneous splenic rupture in a patient with dengue fever, which occurred during the recovery phase of the illness. A 28-year-old Sinhalese, Sri Lankan man presented with a history of fever, myalgia and vomiting of 4 days duration. Investigations revealed a diagnosis of dengue fever with no signs of plasma leakage. He was managed in the ward as per local protocol. During the recovery phase the patient developed severe abdominal distention with circulatory failure. Radiology revealed splenic rupture with massive amounts of abdominal free fluid. The patient was resuscitated and Emergency laparotomy with splenectomy was performed. The outcome was excellent with the patient making a complete recovery. Although splenic rupture is a known complication of dengue fever it may be manifested late in the disease process. A high degree of suspicion should be maintained and patients must be monitored even during the recovery phase of dengue fever. Early diagnosis and intervention can prevent mortality.

  15. Cultivation of Staphylococcus epidermidis in the Human Spaceflight Environment Leads to Alterations in the Frequency and Spectrum of Spontaneous Rifampicin-Resistance Mutations in the rpoB Gene. (United States)

    Fajardo-Cavazos, Patricia; Nicholson, Wayne L


    Bacteria of the genus Staphylococcus are persistent inhabitants of human spaceflight habitats and represent potential opportunistic pathogens. The effect of the human spaceflight environment on the growth and the frequency of mutations to antibiotic resistance in the model organism Staphylococcus epidermidis strain ATCC12228 was investigated. Six cultures of the test organism were cultivated in biological research in canisters-Petri dish fixation units for 122 h on orbit in the International Space Station (ISS) as part of the SpaceX-3 resupply mission. Asynchronous ground controls (GCs) consisted of identical sets of cultures cultivated for 122 h in the ISS Environmental Simulator at Kennedy Space Center. S. epidermidis exhibited significantly lower viable counts but significantly higher frequencies of mutation to rifampicin (Rif) resistance in space vs. GC cultures. The spectrum of mutations in the rpoB gene leading to Rif(R) was altered in S. epidermidis isolates cultivated in the ISS compared to GCs. The results suggest that the human spaceflight environment induces unique physiologic stresses on growing bacterial cells leading to changes in mutagenic potential.

  16. Spontaneous Rupture of the Bicornuate Uterus During 12th Week of Pregnancy

    Directory of Open Access Journals (Sweden)

    Tayfun Özçakır


    uterus bicornis was diagnosed. The fetus and placenta were found in the abdominal cavity. Spontaneous rupture of the pregnant uterus generally occurs in congenitally malformed uteri like unicornuate or bicornuate uterus with or without rudimentary communicating-noncommunicating horn. It can be life threatening and should be diagnosed and treated immediately.

  17. Histopathology of a spontaneously developing mast cell sarcoma in a Wistar rat

    NARCIS (Netherlands)

    Baselmans, A.H.C.; Kuijpers, M.H.M.; Dijk, J.E. van


    A case report is given of a very rare spontaneous mast cell tumor in the eyelid of the left eye of a female Wistar rat used in a long-term oral toxicity study. Metastasis of the tumor had occurred in the mandibular lymph nodes and in the liver. Clinically, the animal showed blepharospasm,

  18. Spontaneous resolution of a case of anti-retroviral treatmentnaïve ...

    African Journals Online (AJOL)

    The outcomes of some ARDs may be better in individuals with HIV when compared with individuals without HIV. Here we report the first case of spontaneous resolution of HIV-Associated Polymyositis (HAM) presenting with profound proximal muscle weakness occurring in a treatment-naïve patient with HIV and discuss the ...

  19. Are the Concepts of Dynamic Equilibrium and the Thermodynamic Criteria for Spontaneity, Nonspontaneity, and Equilibrium Compatible? (United States)

    Silverberg, Lee J.; Raff, Lionel M.


    Thermodynamic spontaneity-equilibrium criteria require that in a single-reaction system, reactions in either the forward or reverse direction at equilibrium be nonspontaneous. Conversely, the concept of dynamic equilibrium holds that forward and reverse reactions both occur at equal rates at equilibrium to the extent allowed by kinetic…

  20. Mode of delivery following successful external cephalic version : Comparison with spontaneous cephalic presentations at delivery

    NARCIS (Netherlands)

    Kuppens, S.M.; Hutton, E.K.; Hasaart, T.H.; Aichi, N.; Wijnen, H.; Pop, V.J.M.


    Objective To compare the obstetric outcomes of pregnant women after successful external cephalic version (ECV) (cases) with a large group of pregnant women with a spontaneously occurring cephalic fetal position at delivery (controls). Methods We conducted a retrospective matched cohort study in a

  1. Dynamic spatial structure of spontaneous beams in photorefractive bismuth sillicon oxide

    DEFF Research Database (Denmark)

    Buchhave, Preben; Lyuksyutov, S.; Vasnetsov, M.


    We report the domain structure of spontaneously occurring beams (subharmonics) in photorefractive bismuth silicon oxide with an applied electric field from 1 to 6 kV/cm and a running grating. The subharmonic beams are generated in a pattern of domains that evolve dynamically as they move through...

  2. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice

    NARCIS (Netherlands)

    HogenEsch, H.; Gijbels, M. J.; Offerman, E.; van Hooft, J.; van Bekkum, D. W.; Zurcher, C.


    Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and

  3. Trichotillomania and co-occurring anxiety. (United States)

    Grant, Jon E; Redden, Sarah A; Leppink, Eric W; Chamberlain, Samuel R


    Trichotillomania appears to be a fairly common disorder, with high rates of co-occurring anxiety disorders. Many individuals with trichotillomania also report that pulling worsens during periods of increased anxiety. Even with these clinical links to anxiety, little research has explored whether trichotillomania with co-occurring anxiety is a meaningful subtype. One hundred sixty-five adults with trichotillomania were examined on a variety of clinical measures including symptom severity, functioning, and comorbidity. Participants also underwent cognitive testing assessing motor inhibition and cognitive flexibility. Clinical features and cognitive functioning were compared between those with current co-occurring anxiety disorders (i.e. social anxiety, generalized anxiety disorder, panic disorder, and anxiety disorder NOS) (n=38) and those with no anxiety disorder (n=127). Participants with trichotillomania and co-occurring anxiety reported significantly worse hair pulling symptoms, were more likely to have co-occurring depression, and were more likely to have a first-degree relative with obsessive compulsive disorder. Those with anxiety disorders also exhibited significantly worse motor inhibitory performance on a task of motor inhibition (stop-signal task). This study suggests that anxiety disorders affect the clinical presentation of hair pulling behavior. Further research is needed to validate our findings and to consider whether treatments should be specially tailored differently for adults with trichotillomania who have co-occurring anxiety disorders, or more pronounced cognitive impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells. (United States)

    Khan, Arif A; Srivastava, Ruchi; Chentoufi, Aziz A; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir


    Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8(+) T cells from "naturally" protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T-cell epitopes (gD(53-61), gD(70-78), and gD(278-286)) were linked with a promiscuous CD4(+) T-cell epitope (gD(287-317)) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells. The results underscore the potential of an ASYMP CD8(+) T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most blinding

  5. The rad52-Y66A allele alters the choice of donor template during spontaneous chromosomal recombination

    DEFF Research Database (Denmark)

    de Mayolo, A.A.; Sunjevaric, I.; Reid, R.


    Spontaneous mitotic recombination is a potential source of genetic changes Such as loss of heterozygosity and chromosome translocations, which may lead to genetic disease. In this study we have used a rad52 hyper-recombination mutant, rad52-Y66A, to investigate the process of spontaneous...... heteroallelic recombination in the yeast Soccharomyces cerevisiae. We find that spontaneous recombination has different genetic requirements, depending on whether the recombination event occurs between chromosomes or between chromosome and plasmid sequences. The hyper-recombination phenotype of the rad52-Y66A...... that spontaneous DNA lesions that require recombinational repair occur at the same frequency in wild-type and rad52-Y66A cells, but that the recombination process is slow in rad52-Y66A cells. Taken together, we propose that the slow recombinational DNA repair in the rad52-Y66A mutant leads to a by...

  6. [Correlation of genomic DNA methylation level with unexplained early spontaneous abortion]. (United States)

    Chao, Yuan; Weng, Lidong; Zeng, Rong


    To investigate the correlation of genomic DNA methylation level with unexplained early spontaneous abortion and analyze the role of DNMT1, DNMT3A and DNMT3B. Forty-five villus samples from spontaneous abortion cases (with 33 maternal peripheral blood samples) and 44 villus samples from induced abortion (with 34 maternal peripheral blood samples) were examined with high-pressure liquid chromatography (HPLC) to measure the overall methylation level of the genomic DNA. The expressions of DNMT mRNAs were detected using fluorescence quantitative-PCR in the villus samples from 33 induced abortion cases and 30 spontaneous abortion cases. Genomic DNA methylation level was significantly lower in the villus in spontaneous abortion group than in induced abortion group (P0.05). The mean mRNA expression levels of DNMT1 and DNMT3A in the villus were significantly lower in spontaneous abortion group than in induced abortion group (P0.05). Insufficient genomic DNA methylation in the villus does exist in human early spontaneous abortion, and this insufficiency is probably associated with down-regulated expressions of DNMT1 and DNMT3A.

  7. Imaging findings of spontaneous detachment of the deltoid muscle as a complication of massive rotator cuff tear

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Stefano [Institut de Radiologie, Clinique et Fondation des Grangettes, Geneva (Switzerland); Martinoli, Carlo [Istituto di Radiologia, Universita di Genova, Genoa (Italy); Abdelwahab, Ibrahim Fikry [Coney Island Hospital and Downstate School of Medicine, Department of Radiology, New York, New York (United States)


    A tear at the origin of the deltoid muscle is uncommon and usually occurs as a complication of shoulder surgery. We report a case of spontaneous deltoid detachment as a complication of massive rotator cuff tear in a 70-year-old woman evaluated by standard radiographs, ultrasound, arthrography and MR-arthrography. We present the multimodality imaging findings with review of the literature. We found that ultrasound is an accurate modality in detecting and assessing spontaneous detachment of the deltoid muscle. As ultrasound is a noninvasive, low-cost, and universally available imaging modality we suggest using ultrasound as the first modality for evaluation of spontaneous detachment of the deltoid muscle. (orig.)

  8. Age differences in the spontaneous termination of sleep. (United States)

    Murphy, P J; Rogers, N L; Campbell, S S


    The stage from which the spontaneous ending of sleep occurred was investigated in 138 sleep episodes obtained from 14 younger (19-28 years) and 11 older (60-82 years) individuals. The possible influences of circadian phase and quality of the preceding sleep period, as well as the impact of aging on characteristics of sleep termination were examined. Under experimental conditions in which subjects were isolated from time cues, and behavioral options to sleep were limited, no age-associated differences in the duration of sleep periods, or in the number or duration of REM episodes were observed. Despite similar percentages of NREM (stages 2-4) and REM sleep across age groups, younger subjects awakened preferentially from REM while older subjects did not. Of the sleep episodes obtained from older subjects, those with sleep efficiencies higher than the median were more likely to terminate from REM than those with lower sleep efficiencies. For all subjects, the REM episodes from which sleep termination occurred were truncated relative to those that did not end the sleep period. In addition, nonterminating REM episodes that were interrupted by a stage shift were most often interrupted by brief arousals to stage 0. Such arousals within nonterminating REM episodes occurred, on average, after a similar duration as the terminating point of sleep-ending REM episodes. The results from this study demonstrate that there are age-related differences in the sleep stage from which spontaneous awakenings occur, and that these differences may be due in part to the quality of the sleep period preceding termination. Findings regarding the characteristics of both terminating and nonterminating REM episodes are consistent with the notion that the neural and biochemical context of REM sleep may facilitate a smooth transition to wakefulness. It is speculated that age-associated changes in sleep continuity may render unnecessary the putative role of REM sleep in providing a 'gate' to

  9. Spontaneous body movements in spatial cognition

    Directory of Open Access Journals (Sweden)

    Sergiu eTcaci Popescu


    Full Text Available People often perform spontaneous body movements during spatial tasks such as giving complex directions or orienting themselves on maps. How are these spontaneous gestures related to spatial problem-solving? We measured spontaneous movements during a perspective-taking task inspired by map reading. Analyzing the motion data to isolate rotation and translation components of motion in specific geometric relation to the task, we found out that most participants executed spontaneous miniature rotations of the head that were significantly related to the main task parameter. These head rotations were as if participants were trying to align themselves with the orientation on the map either in the image plane or on the ground plane, but with tiny amplitudes, typically below 1% of the actual movements. Our results are consistent with a model of sensorimotor prediction driving spatial reasoning. The efference copy of planned movements triggers this prediction mechanism. The movements themselves may then be mostly inhibited; the small spontaneous gestures that we measure are the visible traces of these planned but inhibited actions.

  10. Surgical management of spontaneous hypertensive brainstem hemorrhage

    Directory of Open Access Journals (Sweden)

    Bal Krishna Shrestha


    Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.

  11. Clinical pitfalls in misoprostol-based medical management of first-trimester induced and presumed spontaneous abortion. (United States)

    Wax, Joseph R; Conroy, Kelley; Pinette, Michael G; Litton, Christian; Cartin, Angelina


    When administered inappropriately, first-trimester misoprostol management of induced or spontaneous abortion can result in loss or damage of a continuing pregnancy. Despite these serious consequences, such misoprostol exposures continue to occur. Unfortunately, contributing factors and preventive measures receive little attention. We describe the cases of 4 women in whom misoprostol was inappropriately administered during management of induced and presumed spontaneous abortion. In each case, careful adherence to published clinical guidance could have avoided the exposures. © 2017 Wiley Periodicals, Inc.


    Directory of Open Access Journals (Sweden)

    A. T. Gubin


    Full Text Available A mathematical model for radiogenic increasing of mortality was proposed, taking into account spontaneous background damages of the genetic material, that always occur in cells due to the influence of non-radiation internal and environmental factors. The model is based on the representation of indistinguishability between radiogenic andspontaneous cancers and on the postulates of the Kellerer-Rossi dual action theory. It was proposed that duringformation of premalignant damages dual interactions occur both between primary radiation damages, and betweenradiation and spontaneous primary damages (hybrid interactions. The role of the latter is particularly important at low levels exposure that corresponds to a linear dependence of cancer incidence on dose. Their significance is indicated by the following factor: at the adopted value of the nominal (radiation risk factor (0,05 Sv-1 and cancer mortality share among the population (0,15–0,2, the contribution of non-radiative carcinogenic factors for the total life is equivalent to radiation dose of 3–4 Sv or radiation at a constant dose rate of 40–50 mSv / year.The model assumes formation in DNA of both spaced apart (single damages with high probability of recovery, and nearby (double damages, which are more likely to interact, entering into the permanent state. Permanent damages being formed in certain portions of DNA can be inherited to daughter cells as premalignant defects. The relative role of spontaneous primary damages is greater the more single damages are formed as compared to double ones within the area of potential interaction.It was shown within this model that the presence of background cancer mortality for initial and finite population in the used by ICRP expression for interpopulation risk transfer has logical and biophysical justifications. Accounting of spontaneous primary damages and hybrid interactions enhances the capabilities for development of radiation risk models.

  13. Forecasting seizures in dogs with naturally occurring epilepsy.

    Directory of Open Access Journals (Sweden)

    J Jeffry Howbert

    Full Text Available Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG. The iEEG spectral power in six frequency bands: delta (0.1-4 Hz, theta (4-8 Hz, alpha (8-12 Hz, beta (12-30 Hz, low-gamma (30-70 Hz, and high-gamma (70-180 Hz, were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring.

  14. Spontaneous Regression of Lumbar Herniated Disc

    Directory of Open Access Journals (Sweden)

    Chun-Wei Chang


    Full Text Available Intervertebral disc herniation of the lumbar spine is a common disease presenting with low back pain and involving nerve root radiculopathy. Some neurological symptoms in the majority of patients frequently improve after a period of conservative treatment. This has been regarded as the result of a decrease of pressure exerted from the herniated disc on neighboring neurostructures and a gradual regression of inflammation. Recently, with advances in magnetic resonance imaging, many reports have demonstrated that the herniated disc has the potential for spontaneous regression. Regression coincided with the improvement of associated symptoms. However, the exact regression mechanism remains unclear. Here, we present 2 cases of lumbar intervertebral disc herniation with spontaneous regression. We review the literature and discuss the possible mechanisms, the precipitating factors of spontaneous disc regression and the proper timing of surgical intervention.

  15. Computed tomographic findings of spontaneous intracranial hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Seung Sook; Kim, Young Sook; Kim, Young Chul [College of Medicine, Chosun University, Kwangju (Korea, Republic of)


    Computed tomography (CT) was a reliable technique to evaluate the exact size and location of spontaneous intracranial hemorrhage and to predict it's prognosis. Fifty-nine cases of spontaneous intracranial hemorrhage were evaluated and reviewed by CT scan. The following results were obtained. 1. The sex ratio of male to female was 1 to 1.4, The highest incidence was in 6th and 7th decades. 2. The most common cause of spontaneous intracranial hemorrhage was hypertension (74.6%), followed by the aneurysm (13.5%), arteriovenous malformation (5.1%), occlusive vascular disease (3.4%), and blood dyscrasia (3.4%). 3. The most common location was basal ganglia and thalamic hemorrhage (37.3%), followed by lobar hemorrhage (27.1%), cerebellar hemorrhage (13.5%), and subarachnoid hemorrhage (11.9%). 4. Primary intraventricular hemorrhage carried the highest mortality. 5. The larger volume of hematoma, the higher the mortality rate.

  16. Spontaneous Perforation of Pyometra: A Case Report

    Directory of Open Access Journals (Sweden)


    Full Text Available Pyometra is the accumulation of purulent material in the uterine cavity. Its reported incidence is 0.01–0.5% in gynecologic patients; however, as far as elderly patients are concerned, its incidence is 13.6% [3]. The most common cause of pyometra is malignant diseases of genital tract and the consequences of their treatment (radiotherapy. Other causes are benign tumors like leiomyoma, endometrial polyps, senile cervicitis, cervical occlusion after surgery, puerperal infections, and congenital cervical anomalies. Spontaneous rupture of the uterus is an extremely rare complication of pyometra. To our knowledge, only 21 cases of spontaneous perforation of pyometra have been reported in English literature since 1980. This paper reports an additional case of spontaneous uterine rupture.

  17. Endogone lactiflua (Zygomycota, Endogonales occurs in Poland

    Directory of Open Access Journals (Sweden)

    Janusz Błaszkowski


    Full Text Available Morphological properties of sporocarps and spores of Endogone lactiflua (Zygomycota, Endogonales, a fungus for the first time found in Poland, are described and illustrated. Endogone lactiflua was wet sieved and decanted from a sample taken from the zone extending from the upper soil layer to rhizosphere of Pinus sylvestris growing in a forest dune in northern Poland. The recovered spores mainly occurred in large and compact sporocarps, although both small aggregates with a few spores and single zygosporangia of this fungus were also isolated. Endogone lactiflua is the fourth species of the genus Endogone found to occur in Poland. The distribution of the fungus in the world is also presented.

  18. Yeast dynamics during spontaneous fermentation of mawe and tchoukoutou, two traditional products from Benin

    DEFF Research Database (Denmark)

    Greppi, Anna; Rantisou, Kalliopi; Padonou, Wilfrid


    Mawe and tchoukoutou are two traditional fermented foods largely consumed in Benin, West Africa. Their preparations remain as a house art and they are the result of spontaneous fermentation processes. In this study, dynamics of the yeast populations occurring during spontaneous fermentations...... of mawe and tchoukoutou were investigated using both culture-dependent and -independent approaches. For each product, two productions were followed. Samples were taken at different fermentation times and yeasts were isolated, resulting in the collection of 177 isolates. They were identified by the PCR...

  19. The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents. (United States)

    Tucker, J C; File, S E


    With the exception of amineptin, buproprion and nomifensine all tricyclic and 'atypical' antidepressants have been reported to reduce spontaneous motor activity in rodents, after both acute and chronic administration. However, with the diversity of chemical actions of these drugs it is unlikely that a single neurochemical mechanism is underlying this one behavioral effect. These widespread sedative effects have implications for interpreting behavioral changes in other test situations, since sedation generally occurs at doses that fall within the dose-range effective in other tests. We also review the effects on spontaneous motor activity of withdrawal from chronic antidepressant treatment.

  20. Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient

    Directory of Open Access Journals (Sweden)

    Nicholas R. Forsyth


    Full Text Available Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancersuppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni or viral oncogene expression (SV40 large T, HPV16/18, E6/E7 can lead to escape from senescence, additional doublings, entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP patient. The preimmortal (C26C and the spontaneously immortalized derivative (C26Ci cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.

  1. On spontaneous breakdown in Σ-models

    International Nuclear Information System (INIS)

    Ivanov, E.A.


    The group theory aspects of spontaneous breakdown in linear Σ-models are discussed. General conditions are formulated under which multiplet of group G (compact or noncompact) is suitable for constructing the Σ-model with a given subgroup of stability of vacuum. It is shown that the Σ-models of spontaneously broken space-time symmetries can be constructed in general only if some extra coordinates are introduced in addition to an ordinary 4-coordinate xsub(μ). The connection between Σ-models of internal symmetries and appropriate nonlinear realizations has also been investigated

  2. Two cases of spontaneous temporal encephalocele. (United States)

    Kamiya, Kouhei; Mori, Harushi; Kunimatsu, Akira; Kawai, Kensuke; Usami, Kenichi; Ohtomo, Kuni


    This is a report of two cases of spontaneous temporal encephalocele: one was anteroinferior and presented with epilepsy; the other was posteroinferior and presented with facial neuritis and labyrinthitis. Spontaneous temporal encephalocele is relatively rare and apparently not familiar to a majority of primary physicians. It may present with a variety of symptoms according to its anatomical location, including cerebrospinal fluid fistulas, recurrent meningitis, chronic otitis media, hearing loss, facial nerve palsy and medically intractable epilepsy. Attention should be paid to this disease entity, as it is easily overlooked in imaging studies and can leave serious neurological deficits. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. Spontaneous abortion and physical strain around implantation

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter


    Existing studies of physical strain and spontaneous abortion are mainly retrospective or based only on pregnancies that have survived the first trimester. Furthermore, almost all studies have relied on averaged measures of physical strain, which tend to blur an effect if peak values during short...... pregnancy the women recorded physical strain prospectively in a structured diary. Physical strain around the time of implantation was associated with later spontaneous abortion. The adjusted risk ratio for women who reported physical strain higher than average at day 6 to 9 after the estimated date...

  4. Need for spontaneous breakdown of chiral symmetry

    International Nuclear Information System (INIS)

    Salomone, A.; Schechter, J.; Tudron, T.


    The question of whether the chiral symmetry of the theory of strong interactions (with massless quarks) is required to be spontaneously broken is examined in the framework of a previously discussed effective Lagrangian for quantum chromodynamics. The assumption that physical masses of the theory be finite leads in a very direct way to the necessity of spontaneous breakdown. This result holds for all N/sub F/> or =2, where N/sub F/ is the number of different flavors of light quarks. The atypical cases N/sub F/ = 1,2 are discussed separately

  5. Spontaneous subdural hematoma associated to Duret hemorrhage

    Directory of Open Access Journals (Sweden)

    William Alves Martins, MD


    Full Text Available Subdural hematoma (SH is a neurosurgical emergency, usually caused by head trauma. Non-traumatic causes include aneurysm or arterial–venous malformation rupture, coagulopathy and others. We report the case of a 66 year-old man who developed apparently unprovoked signs of increased intracranial pressure. Brain computed tomography scan showed an acute spontaneous SH, surgically treated. Throughout surgery, a ruptured cortical artery with intensive bleeding appeared and was cauterized. After surgery, patient remained comatose and a new CT demonstrated Duret hemorrhage at the brainstem. Acute spontaneous SH of arterial origin is rare and highly lethal, in which a good prognosis relies on early diagnosis and treatment.

  6. Primer on spontaneous heating and pyrophoricity

    Energy Technology Data Exchange (ETDEWEB)


    This primer was prepared as an information resource for personnel responsible for operation of DOE nuclear facilities. It has sections on combustion principles, spontaneous heating/ignition of hydrocarbons and organics, pyrophoric gases and liquids, pyrophoric nonmetallic solids, pyrophoric metals (including Pu and U), and accident case studies. Although the information in this primer is not all-encompassing, it should provide the reader with a fundamental knowledge level sufficient to recognize most spontaneous combustion hazards and how to prevent ignition and widespread fires. This primer is provided as an information resource only, and is not intended to replace any fire protection or hazardous material training.

  7. Cavity enhanced rephased amplified spontaneous emission

    International Nuclear Information System (INIS)

    A Williamson, Lewis; J Longdell, Jevon


    Amplified spontaneous emission is usually treated as an incoherent noise process. Recent theoretical and experimental work using rephasing optical pulses has shown that rephased amplified spontaneous emission (RASE) is a potential source of wide bandwidth time-delayed entanglement. Due to poor echo efficiency the plain RASE protocol does not in theory achieve perfect entanglement. Experiments done to date show a very small amount of entanglement at best. Here we show that RASE can, in principle, produce perfect multimode time-delayed two mode squeezing when the active medium is placed inside a Q-switched cavity. (paper)

  8. Spontaneous supersymmetry breaking on the lattice

    Energy Technology Data Exchange (ETDEWEB)

    Wenger, Urs [Albert Einstein Center for Fundamental Physics, Institute for Theoretical Physics, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland)


    We discuss various strategies for regularising supersymmetric quantum field theories on a space-time lattice. In general, simulations of lattice models with spontaneously broken supersymmetry suffer from a fermion sign problem related to the vanishing of the Witten index. We discuss a novel approach which evades this problem in low dimensions by formulating the path integral on the lattice in terms of fermion loops. Then we present exact results on the spectrum and the Witten index for N=2 supersymmetric quantum mechanics and results from simulations of the spontaneously broken N=1 Wess-Zumino model.

  9. Co-occurring mycotoxins in animal feeds

    African Journals Online (AJOL)



    Jul 4, 2008 ... Co-occurring mycotoxins in animal feeds. Phakamile T. Mngadi1, Roshini Govinden2, and Bharti Odhav1*. 1Department of Biotechnology, M.L. Sultan Campus, Durban University of Technology, P.O. Box 1334, Durban 4000,. South Africa. 2Medical Research Council, PO Box 70380, Over port 4091, ...

  10. Percieved functions of naturally occurring autobiographical memories

    DEFF Research Database (Denmark)

    Treebak, L. S.; Henriksen, J. R.; Lundhus, S.


    The main empirical reference on functions of autobiographical memories is still Hyman & Faries (1992) who used the cue-word-method and retrospective judgements. We used diaries to sample naturally occurring autobiographical memories and participants? perceived use of these. Results partly replicate...

  11. Chemical and Biological Significance of Naturally Occurring ...

    African Journals Online (AJOL)


    Chemical and Biological Significance of Naturally Occurring Additives on. African Black Soap and its Performance. IKOTUN, A. ... attribute of the soap includes gentleness on the skin, rich lather, protection against skin disorders ... soap, the effects of its modifications with some commonly used natural products, as well as the ...

  12. A naturally occurring trap for antiprotons

    International Nuclear Information System (INIS)

    Eades, J.; Morita, N.; Ito, T.M.


    The phenomenon of delayed annihilation of antiprotons in helium is the first instance of a naturally occurring trap for antimatter in ordinary matter. Recent studies of this effect at CERN are summarized, and plans are described for laser excitation experiments to test its interpretation in terms of metastable exotic helium atom formation. (author)

  13. Formal synthesis of naturally occurring norephedrine

    Indian Academy of Sciences (India)

    A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives has been achieved following classical organic transformations using commercially available chiral pools. The said derivatives were explored for the synthesis of naturally occurring bio-active small molecules. Formal synthesis of norephedrine, virolin ...

  14. Spontaneous biliary peritonitis: Is bed side diagnosis possible?

    Directory of Open Access Journals (Sweden)

    Vijai Datta Upadhyaya


    Full Text Available Background: Spontaneous biliary peritonitis is a rare cause of acute abdomen. In spontaneous biliary peritonitis there is perforation in the wall of the extra-hepatic or intra-hepatic duct occurs without any traumatic or iatrogenic injury and have been described more often in neonates. The symptoms may be acute or insidious delaying the diagnosis. Present manuscript deals with diagnosis and management of these cases. Materials and Methods: This is a prospective study and all patients of suspected biliary peritonitis presented during Dec 2010 to Feb 2012 were included in the study. After preliminary investigations in all patients abdominal paracentesis was done and in cases where intra-abdominal fluid bilirubin level was several fold higher than serum bilirubin level were subjected to exploratory laparotomy. Further investigation like T-tube cholangiogram and magnetic resonance cholangiopancreatography (MRCP was done to rule out choledochal cyst before leveling these cases as SPBD. Results: A total of 6 patients were included in present series commonest presenting symptom was progressive abdominal distension without signs of overt peritonitis followed by progressive jaundice, fever and abdominal pain. On exploration site of perforation was observed in 50% of cases and in 50% of cases bile duct was not dilated. Second surgery was not required in 34% of cases. There was no mortality or significant morbidity in our series. Conclusion: Spontaneous perforation of bile duct is rare disease and high index of suspicion is required for diagnosis. Simple bed side test can help in diagnosis but T tube cholangiogram or MRCP are must to rule out choledochal cyst.

  15. Evaluation of the implantation site morphology in spontaneous abortion. (United States)

    Manolea, Maria Magdalena; Dijmărescu, Anda Lorena; Popescu, Florina Carmen; Novac, Marius Bogdan; DiŢescu, Damian


    The aim of this study was the characterization of the implantation site through histological and immunohistochemical exams and the evaluation of the changes that appear in the pregnancies ended by spontaneous abortion compared to normal pregnancies ended by requested abortion. One hundred eight patients were divided in two groups: the study group that included 58 patients with spontaneous abortion and the control group that included 50 patients with requested abortion. There has been made uterine curettage in all the cases after a complete preoperative evaluation and the obtained product was sent for histopathological evaluation and immunohistochemical study using a VEGF antibody. Studying the histological sections, we noticed the vasculogenesis stages chronology and then according to the histological aspects of normal pregnancy we noticed the histological changes that occurred at the site of implantation in the cases with pathological pregnancies ended by miscarriage. Our results from this study seem to indicate a correlation between decidual vascular changes and the appearance of miscarriage. In pregnancies ended by miscarriage, we found delays in the trophoblast development according to the gestational age at which the event abortifacient happened. The study emphases the temporal differentiation of utero-placental angiogenesis comparing to villous vasculogenesis and angiogenesis in the first trimester miscarriage and normal pregnancy. At the control group, VEGF expression was positive in 88% of cases, while in the study group, pregnancies ended by spontaneous abortion, positive expression of VEGF was present in only 31% of cases. Our data suggest vascular disorders and are in concordance with other histological and ultrasound studies postulating the idea of a link between miscarriage and placental vascular bed pattern changes.

  16. Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

    Energy Technology Data Exchange (ETDEWEB)

    Radi, Zaher, E-mail: [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States); Bartholomew, Phillip, E-mail: [Pfizer Worldwide Research and Development, Drug Safety R and D, Eastern Point Road, Groton, CT 06340 (United States); Elwell, Michael, E-mail: [Covance Laboratories, Chantilly, VA 20151 (United States); Vogel, W. Mark, E-mail: [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States)


    In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas

  17. Spontaneous dewetting of a perfluoropolyether (United States)

    Shogrin, Bradley; Jones, William R., Jr.; Herrera-Fierro, Pilar


    Eight different production lots of a commercial perfluoropolyether (PFPE) based on hexafluoropropene oxide (HFPO) were applied to polished metal surfaces by spinning. One of the lots repeatedly dewetted from a clean 440C steel surface, forming droplets on the surface, whereas the other seven did not dewet. This dewetting phenomenon also repeatedly occurred on 2024 aluminum and 1018 steel, but not on copper or gold. Fourier transform infrared microspectroscopy (mu-FTIR) was used to determine thickness and uniformity of the PFPE films. The dewetting lot was found to dewet from 440C steel at a film thickness greater than 520 A. A portion of the dewetting lot was heated at 316 C for 12 days in the presence of oxygen and M-50 steel. This fluid did not dewet. Sequentially, samples of the dewetting lot were filtered either with an alumina or a silica cartridge which can remove polar impurities. Neither of the filtered samples dewetted from 440C steel. It was concluded that an unknown impurity, both thermally labile and polar, present at very low concentration and undetected by our analytical techniques (FTIR, proton NMR, or F-19 NMR), was responsible for the dewetting phenomenon.

  18. Naturally occurring mutations in the canine CFTR gene


    Spadafora, Domenico; Hawkins, Eleanor C.; Murphy, Keith E.; Clark, Leigh Anne; Ballard, Stephen T.


    Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression rate of CFTR mutations than the at-large population. Temporal temperature-gradient gel electrophoresis (TTGE) was used to screen canine CFTR in 40...

  19. Probiotic properties of yeasts occurring in fermented food and beverages

    DEFF Research Database (Denmark)

    Jespersen, Lene

    Besides being able to improve the quality and safety of many fermented food and beverages some yeasts offer a number of probiotic traits. Especially a group of yeast referred to as "Saccharomyces boulardii", though taxonomically belonging to Saccharomyces cerevisiae, has been claimed to have...... probiotic properties. Besides, yeasts naturally occurring globally in food and beverages will have traits that might have a positive impact on human health....

  20. A deletion mutation in GDF9 in sisters with spontaneous DZ twins.

    NARCIS (Netherlands)

    Montgomery, GW; Zhao, Z.Z.; Marsh, A.J.; Mayne, R.; Treloar, S.A.; James, M.; Martin, N.G.; Boomsma, D.I.; Duffy, DL


    A loss of function mutation in growth differentiation factor 9 (GDF9) in sheep causes increased ovulation rate and infertility in a dosage-sensitive manner. Spontaneous dizygotic (DZ) twinning in the human is under genetic control and women with a history of DZ twinning have an increased incidence

  1. Expert opinion : Defining response to omalizumab in patients with chronic spontaneous urticaria

    NARCIS (Netherlands)

    Ferrer, Marta; Boccon-Gibod, Isabelle; Gonçalo, Margarida; İnalöz, Hüseyin Serhat; Knulst, André; Lapeere, Hilde; Parthasaradhi, Anchala; Stingl, Georg; Tagka, Anna; Valenzuela, Fernando; Yeung, Jensen; Thomsen, Simon Francis


    Omalizumab (a recombinant, humanized anti-immunoglobulin-E antibody) has been shown in three pivotal Phase III trials (ASTERIA I, II and GLACIAL) and real-world studies to be effective and well-tolerated for the treatment of chronic spontaneous urticaria (CSU), and is the only licensed third-line

  2. The Associations of HLA-A*02:01 and DRB1*11:01 with Hepatitis C Virus Spontaneous Clearance Are Independent of IL28B in the Chinese Population. (United States)

    Huang, Jieting; Huang, Ke; Xu, Ru; Wang, Min; Liao, Qiao; Xiong, Huaping; Li, Chengyao; Tang, Xi; Shan, Zhengang; Zhang, Ming; Rong, Xia; Nelson, Kenrad; Fu, Yongshui


    Spontaneous clearance of hepatitis C virus (HCV) occurs in 10-40% of the infections. Specific human leukocyte antigen (HLA) alleles have been identified in associating with HCV clearance. However, data on the association of HLA with the spontaneous clearance of HCV are scarce in the Chinese population. In the current study we studied the HLA class I and class II genes in 231 Chinese voluntary blood donors who had cleared HCV infection spontaneously compared to 429 subjects with chronic HCV infections. We also studied their IL28B SNP (rs8099917) genotype, since a number of investigators have found a strong association of IL28B with spontaneous or treatment induced HCV clearance. We found that HLA-A*02:01 and DQB1*05:02 distributed differently between the two groups after Bonferroni correction (odds ratio [OR] = 1.839, Pc = 0.024 and OR = 0.547, Pc = 0.016, respectively). Multivariate logistic regression analysis suggested that A*02:01 and DRB1*11:01 (OR = 1.798, P = 0.008 and OR = 1.921, P = 0.005, respectively) were associated with HCV spontaneous clearance, independent of age, gender and IL28B polymorphism. We concluded that in the Chinese population, HLA-A*02:01 and DRB1*11:01 might be associated with the host capacity to clear HCV independent of IL28B, which suggesting that the innate and adaptive immune responses both play an important role in the control of HCV.

  3. Acute Abdomen Due to Uncontrolled Use of Warfarin: Spontaneous Intra-abdominal

    Directory of Open Access Journals (Sweden)

    Fatih Dal


    Full Text Available Warfarin is an oral anticoagulant, which is commonly used in the treatment and prophylaxis of thromboembolic conditions. Bleeding is the primary adverse effect associated with warfarin. The majority of warfarin-related bleedings are spontaneous minor hemorrhages occurring in the subcutaneous or intramuscular tissues and can be treated by decreasing the dose of oral anticoagulants. However, although rare, it is possible to encounter spontaneous major bleedings with increased risk of mortality. Conservative approach is the preferred initial therapy for hemodynamically stable patients with major intra-abdominal hemorrhages that we define as the intermediate group patients. Nevertheless, surgery is required for hemodynamically unstable patients with acute abdominal pain in cases of ongoing active hemorrhage, generalized peritonitis, obstruction, acute abdomen, intestinal ischemia, and perforation. In this article, we present a rare case of acute abdomen and spontaneous intra-abdominal hemorrhage resulting from uncontrolled use of warfarin and a new classification requirement.

  4. A rare case of postauricular spontaneous keloid in an elderly patient. (United States)

    Monarca, Cristiano; Maruccia, Michele; Palumbo, Francesca; Parisi, Paola; Scuderi, Nicolò


    Keloid represents an exuberant wound healing response, usually secondary to trauma, inflammation, surgery, or burns. Spontaneous keloid formation is rare and it is controversial whether it is really spontaneous. It usually occurs in young people, and it is rare in elderly. Its main features are the infiltration of surrounding normal tissue, the rare regression and the evolution over time. We report the case of an 81 -year -old man with unexpected spontaneous keloid lesion in the right postauricular region. The diagnosis was hard to be performed because of the patient's age, the anatomical site of the lesion and the absence of skin trauma or injury history. Only the histological examination allowed us to perform the right diagnosis.

  5. An adolescent with prolapsed omentum per rectum: Spontaneous rectal perforation managed laparoscopically

    Directory of Open Access Journals (Sweden)

    Ameet Kumar


    Full Text Available Spontaneous rupture of the rectum is a rare occurrence. A total laparoscopic approach to rectal perforation has only occasionally been reported. We report an unusual case of a young boy who developed a spontaneous rupture of the rectum following a trivial fall. A magnetic resonance imaging revealed a tear in the rectum at the peritoneal reflection with the omentum plugging it. He denied any history of rectal instrumentation or abnormal sexual activity. He had no history of constipation or rectal prolapse. The tear was repaired laparoscopically and a covering loop sigmoid colostomy was added. He made an uneventful post-operative recovery. Spontaneous rupture of the rectum can occur in younger age groups and even in the absence of significant trauma. One needs to diligently bring out a history of rectal trauma. Equally important is to rule out any underlying pathological condition. A laparoscopic approach is feasible, especially in early cases.

  6. Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

    Directory of Open Access Journals (Sweden)

    Kamalidehghan Behnam


    Full Text Available Abstract Background Breast cancer is one of the most common cancers among women throughout the world. Therefore, established cell lines are widely used as in vitro experimental models in cancer research. Methods Two continuous human breast cell lines, designated MBC1 and MBC2, were successfully established and characterized from invasive ductal breast carcinoma tissues of Malaysian patients. MBC1 and MBC2 have been characterized in terms of morphology analysis, population doubling time, clonogenic formation, wound healing assay, invasion assay, cell cycle, DNA profiling, fluorescence immunocytochemistry, Western blotting and karyotyping. Results MBC1 and MBC2 exhibited adherent monolayer epithelial morphology at a passage number of 150. Receptor status of MBC1 and MBC2 show (ER+, PR+, HER2+ and (ER+, PR-, HER2+, respectively. These results are in discordance with histopathological studies of the tumoral tissues, which were triple negative and (ER-, PR-, HER2+ for MBC1 and MBC2, respectively. Both cell lines were capable of growing in soft agar culture, which suggests their metastatic potential. The MBC1 and MBC2 metaphase spreads showed an abnormal karyotype, including hyperdiploidy and complex rearrangements with modes of 52–58 chromosomes per cell. Conclusions Loss or gain in secondary properties, deregulation and specific genetic changes possibly conferred receptor changes during the culturing of tumoral cells. Thus, we hypothesize that, among heterogenous tumoral cells, only a small minority of ER+/PR+/HER2+ and ER+/PR-/HER2+ cells with lower energy metabolism might survive and adjust easily to in vitro conditions. These cell lines will pave the way for new perspectives in genetic and biological investigations, drug resistance and chemotherapy studies, and would serve as prototype models in Malaysian breast carcinogenesis investigations.

  7. Spontaneous Extensor Tendon Rupture in the Rheumatoid Wrist: Risk Factors and Preventive Role of Extended Tenosynovectomy. (United States)

    Hsueh, Jung-Hua; Liu, Wen-Chung; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Chen, Lee-Wei


    Spontaneous extensor tendon rupture is often seen in rheumatoid arthritis (RA) patients, but the risk factors are not clearly defined. We therefore collected the data of RA patients with previous extensor tendon rupture and those with tenosynovitis and analyzed the relationship between extended tenosynovectomy and spontaneous extensor tendon rupture. We retrospectively reviewed 17 spontaneous extensor tendon rupture episodes in 15 RA patients and 14 tenosynovitis episodes that required tenosynovectomy in 12 RA patients from 1997 to 2013. Correlations between the incidence of tendon rupture, X-ray findings, and clinical findings in the affected wrists before tendon rupture were analyzed statistically using the test for proportion. The following parameters were significantly correlated with spontaneous extensor tendon rupture: disease duration longer than 8 years, persistent tenosynovitis longer than 1 year duration, and Larsen grade greater than 4 (P = 0.02, 0.03, and 0.01, respectively). Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray contributed to a higher spontaneous extensor tendon rupture rate among RA patients (P = 0.01, 0.05, and 0.03, respectively). Extended tenosynovectomy was performed on 14 wrists in 12 RA patients with persistent tenosynovitis longer than 6 months, and Larsen grade did not deteriorate in this group compared with those who did not undergo the surgery. No spontaneous extensor tendon rupture occurred following the surgery. Risk factors of spontaneous extensor tendon rupture included disease duration longer than 8 years, persistent tenosynovitis longer than 1 year, and wrist Larsen grade greater than 4. Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray indicated a higher probability of extensor tendon rupture. Rheumatologists should consult with hand surgeons promptly to preserve hand function before tendon rupture. Prophylactic extended tenosynovectomy

  8. Natural occurring radioactive substances. Vol. 1

    International Nuclear Information System (INIS)

    Emara, A.E.


    Naturally occurring radioactive substances produced by cosmic rays of those of terrestrial origin are surveyed. The different radioactive decay series are discussed. Special emphasis is given to the element radium as regards its properties and distribution in different environmental samples. The properties of naturally occurring k-40 and its distribution in different natural media are also outlined. Induced radionuclides which are formed as a result of the interaction of cosmic rays with the constituents of the atmosphere are mentioned. In this respect the intensity of natural background radiation and the dose at different locations and levels is surveyed. Some regions of exceptionally high radioactivity which result in high exposure rates are mentioned. Monazite deposits and water springs are mentioned in some detail. The Oklo phenomenon as a natural reactor is also discussed. 8 tabs

  9. Naturally Occuring Fish Poisons from Plants (United States)

    Cannon, Jonathan G.; Burton, Robert A.; Wood, Steven G.; Owen, Noel L.


    Since prehistoric times, cultures throughout the world have used piscicidal (fish poisoning) plants for fishing. In recent times, scientists have identified many of the plant compounds responsible for killing the fish and have found that these compounds possess other important biological properties, such as insecticidal and anti-cancer activities. This article reviews some of the chemical research that has been performed on naturally occurring fish poisons, including plant sources, methods of use, toxicity, and mechanisms of action of piscicides.

  10. Diverticulitis occurs early after lung transplantation. (United States)

    Larson, Eric S; Khalil, Hassan A; Lin, Anne Y; Russell, Marcia; Ardehali, Abbas; Ross, David; Yoo, James


    Lung transplantation recipients are at an increased risk for developing diverticulitis. However, the incidence and natural history of diverticulitis have not been well characterized. Our objective was to identify patient and transplant-related factors that may be associated with an increased risk of developing diverticulitis in this patient population. This is a retrospective single institution study. All patients who received a lung transplant between May 2008 and July 2013 were evaluated using an existing lung transplantation database. Patient-related factors, the incidence and timing of diverticulitis, and outcomes of medical and surgical management were measured. Of the 314 patients who received a lung transplant, 14 patients (4.5%) developed diverticulitis. All episodes (100%) of diverticulitis occurred within the first 2 y after transplantation. Eight patients (57%) required surgery with a mortality rate of 12.5%. Six patients (43%) were managed medically and did not require surgery with a mean follow-up period of 442 d. Diverticulitis is common after lung transplantation and occurs with a higher incidence compared with the general population. Diverticulitis occurs early in the posttransplant period, and the majority of patients require surgery. Patients who respond promptly to medical treatment may not require elective resection. A greater awareness of the risk of diverticulitis in the early posttransplant period may allow for earlier diagnosis and treatment. Copyright © 2014 Elsevier Inc. All rights reserved.


    Directory of Open Access Journals (Sweden)



    Full Text Available Maize was traditionally the second most common staple food in Indonesia. Conversion to maize flour has been accomplished to improve its convenience. Traditionally, maize flour is produced by soaking the kernels in water followed by grinding. It was reported that final physicochemical characteristics of the maize flour were influenced by spontaneous fermentation which occurred during soaking. This research aimed to isolate and identify important microorganisms that grew during fermentation thus a standardized starter culture can be developed for a more controlled fermentation process. Soaking of maize grits was conducted in sterile water (grits:water=1:2, w/v in a closed container at room temperature (±28ºC for 72 hours. After 0, 4, 12, 24, 36, 48, 72 hours, water and maize grits were sampled and tested for the presence of mold, yeast, and lactic acid bacteria (LAB. Isolates obtained from the spontaneous fermentation were reinoculated into the appropriate media containing starch to observe their amylolytic activity. Individual isolate was then identified; mold by slide culture method, while yeast and LAB by biochemical rapid kits, i.e. API 20C AUX and API CH50, respectively. The number of each microorganism was plotted against time to obtain the growth curve of the microorganisms during spontaneous fermentation. The microorganisms were identified as Penicillium chrysogenum, P. citrinum, A. flavus, A. niger, Rhizopus stolonifer, R.oryzae, Fusarium oxysporum, Acremonium strictum, Candida famata, Kodamaea ohmeri, Candida krusei/incospicua, Lactobacillus plantarum 1a, Pediococcus pentosaceus, L. brevis 1, L. plantarum 1b, and L. paracasei ssp paracasei 3. Four molds and one yeast were amylolytic while none of the LAB was capable of starch hydrolysis. The growth curve suggested that the amylolitic mold and yeast grew to hydrolyze starch during the course of fermentation, while the LABs benefited from the hydrolyzed products and dominated the later

  12. Wheaten ferments spontaneous fermantation in biotechnological methods




    In article are shown results of research of biotechnological properties of wheaten leavens of spontaneous fermentation (in the example of pea-anisetree leaven) and their analysis. Also is established influence of the given type of leavens on the basic biopolymers of the flour, on the property of the pastry and quality of bread from wheaten flour.

  13. Original article Spontaneous Pregnancy Outcome after Surgical ...

    African Journals Online (AJOL)


    Sep 28, 2011 ... Table 2: Spontaneous pregnancy in relation to postoperative semen parameters. (no statistically significant difference), comparable to the mean ages of 22, 28.4 and. 34.9 years, respectively, reported by Bach et al9, Abdel- Meguid et al10 and Baazeem et al11. The mean age of the wives who did or did.

  14. Spontaneous symmetry breakdown in gauge theories

    International Nuclear Information System (INIS)

    Scadron, M.D.


    The dynamical theory of spontaneous breakdown correctly predicts the bound states and relates the order parameters of electron-photon superconductivity and quark-gluon chiral symmetry. A similar statement cannot be made for the standard electro-weak gauge symmetry. (author)

  15. Identical Twin Primigravid Sisters -Spontaneous Labour and ...

    African Journals Online (AJOL)

    We report 2 cases of identical twin sisters, the older sibling getting married 14 months earlier but both got pregnant for their first child at about the same time and were managed by the same Obstetrician and fell into spontaneous labour within a few hours of each other. Both were delivered by emergency caesarean section ...


    Energy Technology Data Exchange (ETDEWEB)



    I explore the regions of quark masses where CP will be spontaneously broken in the strong interactions. The boundaries of these regions are controlled by the chiral anomaly, which manifests itself in ambiguities in the definition of non-degenerate quark masses. In particular, the concept of a single massless quark is ill defined.


    African Journals Online (AJOL)


    Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico-chemical and sensory qualities of maize based foods thereby improving the qualities as ...

  18. Association between Nutritional Status with Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Rahimeh Ahmadi


    Full Text Available Background: Spontaneous abortion is the most common adverse pregnancy outcome. We aimed to investigate a possible link between nutrient deficiencies and the risk of spontaneous abortion. Materials and Methods: This case-control study included the case group (n=331 experiencing a spontaneous abortion before 14 weeks of pregnancy and the control group (n=331 who were healthy pregnant women over 14 weeks of pregnancy. The participants filled out Food Frequency Questionnaire (FFQ, in which they reported their frequency of consumption for a given serving of each food item during the past three months, on a daily, weekly or monthly basis. The reported frequency for each food item was converted to a daily intake. Then, consumption of nutrients was compared between the two groups. Results: There are significant differences between the two groups regarding consumed servings/day of vegetables, bread and cereal, meat, poultry, fish, eggs, beans, fats, oils and dairy products (P=0.012, P<0.001, P=0.004, P<0.001, P=0.019, respectively. There are significant differences between the two groups in all micronutrient including folic acid, iron, vitamin C, vitamin B6, vitamin B12 and zinc (P<0.001. Conclusion: Poor nutrientions may be correlated with increased risk of spontaneous abortion

  19. Spontaneous regression of an intraspinal disc cyst

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, P.; Eerens, I.; Wilms, G. [University Hospital, Leuven (Belgium). Dept. of Radiology; Goffin, J. [Dept. of Neurosurgery, University Hospitals, Leuven (Belgium)


    We present a patient with a so-called disc cyst. Its location in the ventrolateral epidural space and its communication with the herniated disc are clearly shown. The disc cyst developed rapidly and regressed spontaneously. This observation, which has not been reported until now, appears to support focal degeneration with cyst formation as the pathogenesis. (orig.)

  20. Spontaneous rupture of an infected renal cyst

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, W.; Toelly, E.; Ebner, F.; Kullnig, P.


    Spontaneous or traumatic rupture of renal cysts is a rare occurrence. The contents of the cyst can perforate into the renal calyx system or into the perirenal space. Perforation into the peritoneal cavity has also been described (1, 2, 4, 5).