Purified interleukin 2 (IL-2) was found to be sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer (LAK) cells. The LAK activation factor was directly and consistently associated with IL-2 activity using classic protein purification techniques, adsorption to IL-2-dependent cell lines, and inhibition with anti-Tac antibody. As yet, no other cytokines have been found that perform the same role.
A highly purified population of effector lymphokine-activated killer (LAK) cells was generated by culturing nylon-wool column nonadherent rat splenocytes in the presence of interleukin 2 (IL-2), and the cells which became adherent to the plastic flasks were separated and maintained in culture for a total of 5 days. More than 95% of these cells had the morphology of large granular lymphocytes (LGL), expressed surface phenotypes characteristic of rat natural killer (NK) cells, and were able to kill NK-sensitive and NK-resistant tumor target cells. 51Cr-labeled purified A-LAK cells injected intravenously into syngeneic F344 rats localized primarily in the lungs 2 hr after injection but then redistributed to the liver and the spleen by 24 hr after injection. The effects of various immunological manipulations on the distribution pattern of the isolated LAK cells were evaluated. Treatment of the host with 500 rad total body X-irradiation 24 hr before cell injection resulted in an early uptake of LAK cells into the liver and the spleen, whereas treatment with cyclophosphamide 1 day before cell injection, resulted in an early uptake of LAK cells into the liver but not into the spleen. Treatment of the recipient rats with up to 120,000 units recombinant interleukin-2 intraperitoneally did not result in the accumulation of LAK cells at the site of IL-2 injection, nor did it result in a modulation of the overall distribution pattern or total recovery of radiolabeled LAK cells. Rather, the administration of IL-2 was necessary to maintain the cytotoxic activity of the injected LAK cells isolated from the liver and spleen
The authors previously reported that the adoptive transfer of lymphokine-activated killer (LAK) cells plus repetitive injections of recombinant interleukin 2 (IL 2) produced a marked reduction in established pulmonary metastases from a variety of murine sarcomas. The requirement for the exogenous administration of IL 2 prompted a subsequent examination of the role of IL 2 in the in vivo function of transferred LAK cells. The in vivo proliferation and migration patterns of lymphoid cells in C57BL/6 mice were examined after i.v. transfer of LAK cells alone, i.p. injection of IL 2 alone, or the combination of LAK cells and IL 2. A model for in vivo labeling of the DNA of dividing cells was used in which mice were injected with 5-[125I]-iodo-2'-deoxyuridine (125IUdR) and, 20 hr later, their tissues were removed and were counted in a gamma analyzer. A proliferation index (PI) was calculated by dividing the mean cpm of organs of experimentally treated mice by the mean cpm of organs of control mice. In animals given LAK cells alone, the lungs and liver demonstrated little if any uptake of 125IUdR above saline-treated controls, whereas the same organs of mice receiving 6000 U of IL 2 alone displayed higher radiolabel incorporation. When mice were given LAK cells plus 6000 U of IL 2, their tissues showed an additional increase in 125IUdR uptake
Dannemann, B.R.; Morris, V.A.; Araujo, F.G.; Remington, J.S. (Palo Alto Medical Foundation, CA (USA))
Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in the absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant. In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively, as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites.
Interleukin 4 (IL-4) expresses multiple biologic activities, including B cell, mast cell, and T cell stimulation. We showed that the incubation of resting splenocytes from C57BL/6 mice solely in purified native or recombinant mouse IL-4 results in the generation of lymphokine-activated killer (LAK) activity directed against fresh, syngeneic sarcoma cells. The precursor activated by IL-4 expresses surface asialo-GM1. In addition, IL-4 is capable of amplifying the splenic LAK activity induced b...
Natural cell-mediated cytotoxicity against NK-resistant target tumor cells was found in the peripheral blood of tumor-bearing patients approximately 1 mo after combined chemotherapy. The recognition specificity of these effector cells was broad and had no restriction. From the experiments of negative selection with mAbs and complements, these newly developed killer cells after chemotherapy were thought to be LAK-like cells. Contribution of these LAK-like cells to the mechanism of action of an...
Anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells
Our previous studies demonstrated that the incubation of human peripheral blood lymphocytes or murine splenocytes in recombinant interleukin 2 (RIL 2) resulted in the generation of lymphokine-activated killer (LAK) cells capable of lysing a broad spectrum of fresh tumors in short-term chromium-release assays. Moreover, injections of LAK cells plus RIL 2 were highly effective in eliminating established 3 day metastases in the lung and liver. We have examined several parameters to define whether or not the cytolytic activity of LAK cells as measured in vitro correlated directly with the in vivo anti-tumor efficacy of adoptively transferred LAK cells. LAK cells plus RIL 2 could mediate marked reductions of established pulmonary metastases in mice rendered T cell deficient by adult thymectomy and lethal, total body irradiation followed by reconstitution with T cell-depleted bone marrow and spleen cells. Thus there was no requirement for additional T lymphocytes of host origin for successful therapy with adoptively transferred LAK cells plus RIL 2. Fresh splenocytes depleted of T cells by anti-Thy-1.2 monoclonal antibody plus complement generated LAK cells that were as highly lytic to fresh tumor in vitro and were as effective in reducing established pulmonary metastases as those generated from untreated or complement-treated splenocytes. Thus, the precursor to LAK cells with anti-tumor activity in vitro and in vivo did not express the Thy-1 antigenic marker. In contrast, treatment of LAK effector cells (those generated from a 3-day incubation of fresh, normal splenocytes in RIL 2) with anti-Thy-1.2 antibody plus complement reduced or abolished their in vitro cytolytic activity
A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC)
Precursor and effector cells of recombinant interleukin-2 (r-IL-2)-induced lymphokine-activated killer (LAK) activity were investigated for their expression of VGO1. Peripheral blood lymphocytes (PBL) from normal donors were purified and separated in a FACS 420 into VGO1+- and VGO1- cell fractions before and after culture for 96 hr with 100 U/ml of r-IL-2. Their lytic activity against K 562 and Daudi cells was measured in a 51Cr release assay. The majority, if not all, of the LAK effector and precursor cells was VGO1+ lymphocytes. The expression of VGO1 by LAK precursor cells remained stable under the culture conditions used in our experiments. VGO1- lymphocytes cultured with r-IL-2 demonstrated neither LAK-induced activity nor expression of VGO1 antigen
Mie, Keiichiro; Shimada, Terumasa; Akiyoshi, Hideo; Hayashi, Akiyoshi; Ohashi, Fumihito
We evaluated changes in peripheral blood lymphocyte (PBL) count in dogs following adoptive immunotherapy using lymphokine-activated T killer cells (T-LAK) in combination with surgery. Fifteen tumor-bearing dogs treated with T-LAK therapy combined with palliative resection of tumors were enrolled in the present study. T-LAK were generated from autologous peripheral blood mononuclear cells (PBMC) by culture with recombinant human interleukin -2 (rhIL-2) and solid phase anti-canine cluster of differentiation (CD)3 antibody. T-LAK were administrated intravenously at 2-4-week intervals. After the first administration of T-LAK, counts of PBL and T lymphocyte subsets (CD3(+), CD4(+) and CD8(+) cells) increased and the CD4/CD8 ratio decreased, with significant increases in CD8(+) cells (P<0.05). In 8 tumor-bearing dogs that were administered sequential T-LAK, available data on changes in PBL and T lymphocyte phenotypes until the fifth administration were also analyzed. In tumor-bearing dogs administered 5 rounds of T-LAK, CD8(+) cell counts were maintained high until the fifth administration of T-LAK. Moreover, the CD4/CD8 ratio remained low until the fifth administration of T-LAK. These results indicate that T-LAK therapy combined with surgery may increase peripheral blood T lymphocytes, particularly CD8(+) cells, in tumor-bearing dogs. PMID:27436446
Interleukin-2 (IL-2) at high doses or at low doses in concert with lymphokine-activated killer (LAK) cells can produce regression of established pulmonary and hepatic metastases from a variety of tumors in mice. IL-2 appears to mediate its antitumor effect through the generation of LAK cells in vivo from endogenous lymphocytes and by the stimulation of host and transferred LAK cell proliferation in tissues. In this paper we have investigated different strategies for IL-2 administration to determine which regimen produced maximal in vivo proliferation and optimal immunotherapeutic efficacy of LAK cells. Tissue expansion of lymphoid cells was assessed using an assay of in vivo labeling of dividing cells by the thymidine analogue, 5-[125I]iododeoxyuridine. The therapeutic effect of the different IL-2 administration protocols was determined by evaluating their efficacy in the treatment of established, 3-day pulmonary metastases from sarcomas in mice. The selection of IL-2 injection regimens for evaluation was based upon pharmacokinetic studies of IL-2 in mice. A single i.v. or i.p. dose yielded high peak IL-2 levels that could be measured for only a few hours after injection, while IL-2 given i.p. thrice daily produced titers that were detectable throughout the study periods (greater than or equal to 6 units/ml of serum after 100,000 units of IL-2 i.p. thrice daily). Using the proliferation and therapy models, we tested the same cumulative daily doses of IL-2 administered by i.v. or i.p. once daily, or i.p. thrice daily regimens. The i.p. thrice daily protocol stimulated greater lymphoid cell proliferation in the lungs, for example, than did the other regimens
Basse, P; Herberman, R B; Hokland, M;
by alternative direct visual methods for identification of the injected cells, such as fluorescent dyes (rhodamine and H33342) or immunohistochemical staining of asialo-GM1-positive cells. The number of i.v. injected A-LAK cells found in the liver by all visual methods ranged from 1% to 5% of the injected dose...
Human lymphokine-activated killer cell system. V. Purified recombinant interleukin 2 activates cytotoxic lymphocytes which lyse both natural killer-resistant autologous and allogeneic tumors and trinitrophenyl-modified autologous peripheral blood lymphocytes
Culture of human peripheral blood lymphocytes (PBL) in purified natural or recombinant interleukin 2 in the absence of exogenous antigen or mitogen causes the differentiation of nonlytic precursor cells into lymphokine-activated killers (LAK). A titration of purified Jurkat IL-2 (BRMP, FCRC, NIH) IL-2 showed that the relatively low concentration of 5 U/ml was optimal for LAK activation. When the responding PBL were pretreated with either mitomycin C or gamma irradiation, LAK activation did not occur, indicating that proliferation, in addition to differentiation, is required. The spectrum of target cells susceptible to LAK lysis in a 4-hr chromium-51-release assay includes fresh NK-resistant tumor cells and trinitrophenyl (TNP)-modified autologous PBL. Unmodified PBL are not lysed. Cold target inhibition studies indicated that LAK lysis of autologous TNP-PBL is totally inhibited by fresh tumors cells, and that tumor lysis is inhibited by TNP-PBL. Additionally, allogeneic tumors totally inhibit lysis of autologous tumor cells in other cold target studies. These results demonstrate that the lytic activity expressed by LAK is not HLA restricted, is not limited to tumor cells, and is polyspecific as indicated by the cross-reactive recognition of multiple target cell types in these cold target inhibition studies
Human lymphokine-activated killer (LAK) cells: III. Effect of L-phenylalanine methyl ester on LAK cell activation from human peripheral blood mononuclear cells: possible protease involvement of monocytes, natural killer cells and LAK cells.
Leung, K H
We have shown that depletion of monocytes from human peripheral blood mononuclear cells (PBMC) by L-phenylalanine methyl ester (PheOMe) enhanced lymphokine-activated killer cell (LAK) generation by recombinant interleukin-2 (rIL-2) at high cell density. In this study, we have investigated the mechanism of action of PheOMe on LAK activation by using trypsin, chymotrypsin, tosylphenylalaninechloromethanol (TPCK, a chymotrypsin inhibitor), tosyl-L-lysinechloromethane (TLCK, a trypsin inhibitor), phenylalaninol (PheOH), and benzamidine. PBMC were treated with 1-5 mM PheOMe for 40 min at room temperature in combination with the various agents, washed and assessed for their effects on natural killer (NK) activity against K562 cells and monocyte depletion. The treated cells were then cultured with or without rIL-2 for 3 days. LAK cytotoxicity was assayed against 51Cr-labeled K562 and Raji tumor target cells. TPCK at 10 micrograms/ml partially inhibited depletion of monocytes by PheOMe. TLCK did not prevent depletion of monocytes nor inhibition of NK activity induced by PheOMe. TPCK and TLCK inhibited NK activity by themselves. TPCK but not TLCK inhibited rIL-2 induction of LAK cells. On the other hand, PheOH and benzamidine (analogs of PheOMe) lacked any effect on monocyte depletion but abrogated the inhibitory effect of PheOMe on NK activity. They had no effect on rIL-2 activation of LAK activity enhanced by PheOMe. Trypsin potentiated the inhibitory effect of PheOMe on NK activity and monocyte depletion. Trypsin partially inhibited IL-2 activation of LAK activity enhanced by PheOMe. Chymotrypsin had little effect on NK activity but prevented the inhibitory effect of PheOMe on NK activity. It had little effect on monocyte depletion induced by PheOMe. PheOMe was hydrolysed by monocytes and chymotrypsin to Phe and methanol as determined by HPLC. TPCK inhibited hydrolysis of PheOMe by monocytes. Our data suggest that the effects of PheOMe on monocytes, NK cells and LAK
The authors showed previously that adoptive immunotherapy with the combination of LAK cells and recombinant IL 2 (RIL 2) can markedly reduce pulmonary micrometastases from multiple sarcomas established 3 days after the i.v. injection of syngeneic tumor cells in C57BL/6 mice. In this report, they analyzed the factors required for successful therapy. Titration analysis in vivo revealed an inverse relationship between the number of pulmonary metastases remaining after treatment and both the number of LAK cells and the amount of RIL 2 administered. Fresh or unstimulated splenocytes had no anti-tumor effect; a 2- to 3-day incubation of splenocytes in RIL 2 was required. LAK cells generated from allogeneic DBA (H-2d) splenocytes were as effective in vivo as syngeneic, C57BL/6 (H-2b) LAK cells. The anti-metastatic capacity of LAK cells was significantly reduced or eliminated when irradiated with 3000 rad before adoptive transfer. The combined therapy of LAK cells plus RIL 2 was shown to be highly effective in mice immunosuppressed by 500 rad total body irradiation and in treating macrometastases established in the lung 10 days after the i.v. injection of sarcoma cells. Further, reduction of both micrometastases and macrometastases could also be achieved by RIL 2 alone when administered at higher levels than were required with LAK cells. The value of LAK cell transfer and of IL 2 administration for the treatment of tumors established at other sites is currently under investigation
Yamaue, H; Tanimura, H; Tsunoda, T; Iwahashi, M; Tani, M; Tamai, M; Noguchi, K; Hotta, T; Arii, K
We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.
Full Text Available Natural Killer (NK cells are the main lymphocyte population expressing P75 B chain of the IL-2 receptor (IL-2R. Consequently, incubation of peripheral blood lymphocytes with IL-2 induce selective activation of NK cells and results in NK activity and generation of Lymphokine activated killer (LAK cells activity and proliferation. One of the early events during IL-2 activation of peripheral blood lymphocyte in both rodents and humans is adherence of some NK cells to plastic surface. The cells adherence to plastic after 24 hr of culture with IL-2 are almost exclusively CD56+, have the morphology large granular cells to yield a highly entiched population of activated NK cells that have been used for systemic adoptive immunotherapy. To test these hypothesis, we used highly purified population of human peripheral NK cells through the biological and nonimmunclogical phenotyping technique. Blood mononuclear cells were separated by centrifugation of ficol-hypaque gradient from normal blood donor (20-30 years age. We depleted after purification of nonadherent cells with nylonwool. We collected with rosette technique to remove cells with high affinity SRBC receptors. These cells separate in two parts A-NK and NA-NK by mononuclear celss activated supernatant media. The main objective results of this study show that the subpopulation of human NK cell which develope early adherent to plastic surface in the presence of supernatant mononuclear celss activation media was functionally more cytotoxic and killed K562 targets in single cell sytotoxicity manner and LDH activity assay than nonadherent NK cells and resting NK cells
郑宁; 叶胜龙; 孙瑞霞; 赵燕; 汤钊猷
Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods:\tA-LAK cells were obtained from peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) by using L-phenylalanine methyl ester (PME) to deplete immunosuppressive monocytes. The proliferation of SMMC7721 cell line treated with PA was studied. A-LAK cells were treated with the supernatant of SMMC7721 cells which had been pretreated with PA and the changes of the proliferation and anti-tumor activity of A-LAK cells were investigated. Results: The expansion of A-LAK cells was significantly higher than that of non-adherent LAK (NA-LAK) cells as well as regular LAK cells. The growth of SMMC7721 cells was significantly suppressed by PA. The supernatant of cultured tumor cells intensively suppressed the proliferation and cytotoxicity of A-LAK cells, but the suppressive effect of supernatant treated with PA previously was decreased. Conclusion: A-LAK cells could be simply prepared by using PME, and showed a synergistic anti-tumor effect with the combination of PA.
Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.
Qing Li; Tomoyuki Kawada
The main toxicity of organophosphorus pesticides (OPs) is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect immune responses including effects on antibody production, IL-2 production,T cell proliferation, decreasement of CD5 cells, and increasement of CD26 cells and autoantibodies. However, there have been few papers investigating the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews the new mechanism of OP-induced inhibition of activities of natural killer (NK),lymphokine-activated killer (LAK) and cytotoxic T lymphocytes (CTL). NK, LAK and CTL induce cell death in tumor or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain perforin, granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas !igand (Fas-L)/Fas pathway. To date, it has been reported that OPs inhibit NK, LAK and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting the activity of granzymes, and by decreasing the intracellular level of perforin, granzyme A and granulysin, which was mediated by inducing degranulation of NK cells and by inhibiting the transcript of mRNA of perforin, granzyme A and granulysin; 2)OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional; 3) OPs induce apoptosis of immune cells.
Caspersen, Michael Edelgaard; Alphonce, Carl; Decker, Adrienne
Giving students an appreciation of the benefits of using design patterns and an ability to use them effectively in developing code presents several interesting pedagogical challenges. This paper discusses pedagogical lessons learned at the "Killer Examples" for Design Patterns and Objects First...... series of workshops held at the Object Oriented Programming, Systems, Languages and Applications (OOPSLA) conference over the past four years. It also showcases three "killer examples" which can be used to support the teaching of design patterns....
Lester, David; White, John
In a sample of 248 killers of two victims in America from 1900 to 2005, obtained from an encyclopedia of serial killers by Newton (2006), those completing suicide did not differ in sex, race, or the motive for the killing from those who were arrested. PMID:20402450
Devassy, V.P.; Bhat, S.R.
Toxic red tide is a disastrous phenomenon causEd. by sudden blooming of certain killer microorganisms often encountered in the seas. Certain killer red tides have caused wide-spread losses to human life and to the fishing industry at several places...
Lester, David; White, John
In a sample of 248 killers of two victims in America from 1900 to 2005, obtained from an encyclopedia of serial killers by Newton (2006), those completing suicide did not differ in sex, race, or the motive for the killing from those who were arrested.
Promish, D I; Lester, D
We attempted to match the appearance and demeanor of 27 serial killers to the postmortem 'signatures' found on their victims' bodies. Our results suggest that a link may exist between postmortem signatures and two complementary appearance-demeanor types.
Leon is a 1994 French action film. This movie is about a tough girl named Mathilda who wants to become a professional killer when her entire families are killed by a vicious government agent. At the same time, she meets the man-Leon, a professionally paid killer, who she chooses as her teacher. Eventually, she becomes soul mate of Leon. At the end of the film, Leon even dies for saving Mathlida.
Steiner, John F
In 2012, the Centers for Medicare & Medicaid Services (CMS) will introduce measures of adherence to oral hypoglycemic, antihypertensive, and cholesterol-lowering drugs into its Medicare Advantage quality program. To meet these quality goals, delivery systems will need to develop and disseminate strategies to improve adherence. The design of adherence interventions has too often been guided by the mistaken assumptions that adherence is a single behavior that can be predicted from readily available patient characteristics and that individual clinicians alone can improve adherence at the population level.Effective interventions require recognition that adherence is a set of interacting behaviors influenced by individual, social, and environmental forces; adherence interventions must be broadly based, rather than targeted to specific population subgroups; and counseling with a trusted clinician needs to be complemented by outreach interventions and removal of structural and organizational barriers. To achieve the adherence goals set by CMS, front-line clinicians, interdisciplinary teams, organizational leaders, and policymakers will need to coordinate efforts in ways that exemplify the underlying principles of health care reform. PMID:23070491
At the close of Sherman Alexie's "Indian Killer," in a final chapter titled "Creation Story," a killer carries a backpack containing, among other things, "dozens of owl feathers, a scrapbook, and two bloody scalps in a plastic bag." Readers schooled in the psychopathologies of real and fictional serial killers will be familiar with the detail:…
"Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…
Inguito, G B; Sekula-Perlman, A; Lynch, M J; Callery, R T
The violent murder of Shirley Ellis on November 29, 1987, marked the beginning of the strange and terrible tale of Steven Bryan Pennell's reign as the state of Delaware's first convicted serial killer. Three more bodies followed the first victim, and all had been brutally beaten and sadistically tortured. The body of a fifth woman has never been found. State and county police collaborated with the FBI to identify and hunt down their suspect, forming a task force of over 100 officers and spending about one million dollars. Through their knowledge and experience with other serial killers, the FBI was able to make an amazingly accurate psychological profile of Delaware's serial killer. After months of around-the-clock surveillance, Steven Pennell was arrested on November 29, 1988, one year to the day after the first victim was found. Pennell was found guilty in the deaths of the first two victims on November 29, 1989, and plead no contest to the murder of two others on October 30, 1991. Still maintaining his innocence, he asked for the death penalty so that he could spare his family further agony. Steven Pennell was executed by lethal injection on March 15, 1992.
Inguito, G B; Sekula-Perlman, A; Lynch, M J; Callery, R T
The violent murder of Shirley Ellis on November 29, 1987, marked the beginning of the strange and terrible tale of Steven Bryan Pennell's reign as the state of Delaware's first convicted serial killer. Three more bodies followed the first victim, and all had been brutally beaten and sadistically tortured. The body of a fifth woman has never been found. State and county police collaborated with the FBI to identify and hunt down their suspect, forming a task force of over 100 officers and spending about one million dollars. Through their knowledge and experience with other serial killers, the FBI was able to make an amazingly accurate psychological profile of Delaware's serial killer. After months of around-the-clock surveillance, Steven Pennell was arrested on November 29, 1988, one year to the day after the first victim was found. Pennell was found guilty in the deaths of the first two victims on November 29, 1989, and plead no contest to the murder of two others on October 30, 1991. Still maintaining his innocence, he asked for the death penalty so that he could spare his family further agony. Steven Pennell was executed by lethal injection on March 15, 1992. PMID:11125664
HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...
Xiao-ling ZHU; Zhi-bin LIN
Aim: To study the effects (and the mechanisms thereof) of Ganoderma lucidum polysaccharides (Gl-PS) on the proliferation and the anti-tumor activity of cytokineinduced killer (CIK) cells, and to make use of CIK cells as a means to investigate the interactions between Gl-PS and cytokines. Methods: CIK cells were prepared by using the standard protocol as a positive control. Experimental groups also underwent the standard protocol, except that Gl-PS (400 mg/L or 100 mg/L) was added and the dose of anti-CD3 and interleukin-2 they received was reduced by 50% and 75%, respectively. For negative controls, Gl- PS in the experimental protocol was replaced with soluble starch or methylcellulose (400 mg/L or 100 mg/L).CIK cell proliferation, cytotoxicity, and phenotype weredetermined by using the Trypan blue exclusion method, MTT assay, and flow cytometry. Results: By synergizing cytokines, Gl-PS (400 mg/L or 100 mg/L) could decrease the amount of cytokine in lymphokine activated killer (LAK) cells and CIK cells culture, but had no significant effect on the proliferation, cytotoxicity, or phenotype of LAK cells, or CIK cells induced by cytokines at higher doses alone, in which CIK cells expanded about 80-fold and the main effectors, CD3+NK1.1+ cells, expanded by more than 15%. The cytotoxicity of CIK cells in experimental groups was 79.3%±4.7%, 76.9%±6.8% versus the positive control 80.7%±6.8% against P815 (P＞0.05)and 88.9%±5.5%, 84.7%±7.9% versus the positive control 89.8%±4.5% against YAC-1 (P＞0.05). The activity of Gl-PS could mostly be blocked by anti-CR3.Conclusion: Gl-PS was shown to be a promising biological response modifier and immune potentiator. The effect of Gl-PS on CIK cells is possibly mediated primarily through complement receptor type 3.
Campbell, Kerry S
Natural killer (NK) cells are innate lymphoid cells that have adopted activating and inhibitory signaling mechanisms enabling them to be tolerant of normal cells but to distinguish and eliminate tumor cells and virus-infected cells. In this issue of Science Signaling, Matalon et al show how inhibitory receptors disrupt NK cell activation by stimulating dephosphorylation of the adaptor protein LAT (linker of activated T cells) and phospholipase C-γ by the phosphatase SHP-1 [Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1], as well as ubiquitylation of LAT by Cbl family E3 ubiquitin ligases. PMID:27221707
Full Text Available Photodynamic therapy (PDT is a cancer treatment modality in which a photosensitizing dye is administered and exposed to light to kill tumor cells via the production of reactive oxygen species (ROS. A fundamental obstacle for PDT is the low specificity for staining solid tumors with dyes. Recently, a tumor targeting system guided by anaerobic bacteria was proposed for tumor imaging and treatment. Here, we explore the feasibility of the genetically encoded photosensitizer KillerRed, which is expressed in Escherichia coli, to treat tumors. Using nitroblue tetrazolium (NBT, we detected a lengthy ROS diffusion from the bodies of KillerRed-expressing bacteria in vitro, which demonstrated the feasibility of using bacteria to eradicate cells in their surroundings. In nude mice, Escherichia coli (E. coli expressing KillerRed (KR-E. coli were subcutaneously injected into xenografts comprising CNE2 cells, a human nasopharyngeal carcinoma cell line, and HeLa cells, a human cervical carcinoma cell line. KR-E. coli seemed to proliferate rapidly in the tumors as observed under an imaging system. When the intensity of fluorescence increased and the fluorescent area became as large as the tumor one day after KR-E. coli injection, the KR-E. coli-bearing tumor was irradiated with an orange light (λ = 540-580 nm. In all cases, the tumors became necrotic the next day and were completely eliminated in a few days. No necrosis was observed after the irradiation of tumors injected with a vehicle solution or a vehicle carrying the E. coli without KillerRed. In successfully treated mice, no tumor recurrence was observed for more than two months. E. coli genetically engineered for KillerRed expression are highly promising for the diagnosis and treatment of tumors when the use of bacteria in patients is cleared for infection safety.
Tobin, A M
Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-alpha, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known to be involved in psoriatic lesions, natural killer and natural killer T cells appear to have a unique role. We review the evidence supporting a role for natural killer cells in psoriasis.
National Oceanic and Atmospheric Administration, Department of Commerce — In this project, we are using genetic variation to infer mating patterns in the southern killer whale community. In Canada, this population was listed as threatened...
Fu-Sheng Wang; Ming-Xu Liu; Bing Zhang; Ming Shi; Zhou-Yun Lei; Wen-Bing Sun; Qing-You Du; Ju-Mei Chen
AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptiveimmunotherapy for the patients with primary hepatocellularcarcinoma (HCC), we evaluated the proliferation rate,phenotype and the antitumor activity of human CIK cellsfrom healthy donors and HCC patients in vitro and in vivo.METHODS: Peripheral blood mononuclear cells (PBMC) fronhealthy donors and patients with primary HCC were incubatedin vitro and induced into ClK cells in the presence of variouscytokines such as interferon-gamma (IFN-γ), interleukin-1(IL-1), IL-2, and monoclonal antibody (mAb) against CD3.The phenotype and characterization of CIK cells wereidentified by flow cytometric analysis. The cytotoxicity of CIKcells was determined by 51 Cr release assay.RESULTS: The CIK cells were shown to be a heterogeneouspopulation with different cellular phenotypes. Thepercentage of CD3+/CD56+ positive cells, the dominanteffector cells, in total CIK cells from healthy donors andHCC patients, significantly increased from 0.1-0.13 % at day0 to 19.0-20.5 % at day 21 incubation, which suggested thatthe CD3+ CD56+ positive cells proliferated faster than othercell populations of CIK cells in the protocol used in thisstudy. After 28 day in vitro incubation, the ClK cells frompatients with HCC and healthy donors increased by morethan 300-fold and 500-fold in proliferation cell number,respectively. CIK cells originated from HCC patientspossessed a higher in vitro antitumor cytotoxic activity onautologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivoanimal experiment, CIK cells had stronger effects on theinhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate,84.7 % vs 52.8 %, P ＜ 0.05) or PBMC (mean inhibitoryrate, 84.7% vs37.1%, P＜0.01).CONCLUSION: Autologous CIK cells are of highly efficientcytotoxic effector cells against primary hepatocellularcarcinoma
Discovery Communications, Inc., Bethesda, MD.
This lesson plan presents activities designed to help students understand that Keiko, the killer whale, lived for a long time in an aquarium and had to be taught to live independently; and that computer users can get updates on how Keiko is doing. The main activity of the lesson involves middle school students working in small groups to produce a…
National Oceanic and Atmospheric Administration, Department of Commerce — Prey selectivity by southern resident killer whales is being determined by analyses of fish scales and tissue from predation events and feces. Information on killer...
van Mechelen, Dook
Terahertz technology is mature enough for large-volume sensing applications. However, Dook van Mechelen says there are a few hurdles preventing its industrial debut. THz spectroscopy has a number of advantages that point to abundant industrial applications, in areas such quality control, security and biomedical imaging. Yet despite those advantages, the search for a THz "killer application"--a novel, innovative use with a business case strong enough to bring the technology into the industrial mainstream--has remained fruitless, and even the hope of finding such an application has begun to falter. Why has a killer app for THz radiation been so elusive? And how can the road to industrial application of this versatile technology be cleared?
Full Text Available While major depression is considered a frequent mental illness there are ongoing reports of high non-adherence to antidepressant medications which places suffers at high risk for relapse, recurrence, or greater impairment,. The World Health Organization (WHO defines adherence as the extent to which a person′s behavior (e.g. taking medications can align with the agreed recommendations of a health care provider. Unfortunately while patient may recognize the importance of adherence to antidepressant medications the majority of patients do not adhere to their prescribed antidepressants. Some of the factors that may contribute to or lead to non-adherence include knowingly or unknowingly missing doses, taking extra doses, delaying administration times, or taking drug holidays. Pharmacists have the unique ability to deter non-adherence through the performance of continuous assessment and monitoring of adherence in this population given these accessibility. Additionally, pharmacists are able to develop therapeutic alliances with patients that can help to increase the likelihood of achieving positive patient outcomes. Antidepressant non-adherence can be viewed as a significant public health concern so it is important for patients to be educated about the importance of adherence, and health care professionals should be aware of factors or patient characteristics that can serve as barriers to non-adherence.
Serebrovskaya, Ekaterina O.; Ryumina, Alina P.; Boulina, Maria E.; Shirmanova, Marina V.; Zagaynova, Elena V.; Bogdanova, Ekaterina A.; Lukyanov, Sergey A.; Lukyanov, Konstantin A.
KillerRed is a unique phototoxic red fluorescent protein that can be used to induce local oxidative stress by green-orange light illumination. Here we studied phototoxicity of KillerRed targeted to cytoplasmic surface of lysosomes via fusion with Rab7, a small GTPase that is known to be attached to membranes of late endosomes and lysosomes. It was found that lysosome-associated KillerRed ensures efficient light-induced cell death similar to previously reported mitochondria- and plasma membrane-localized KillerRed. Inhibitory analysis demonstrated that lysosomal cathepsins play an important role in the manifestation of KillerRed-Rab7 phototoxicity. Time-lapse monitoring of cell morphology, membrane integrity, and nuclei shape allowed us to conclude that KillerRed-Rab7-mediated cell death occurs via necrosis at high light intensity or via apoptosis at lower light intensity. Potentially, KillerRed-Rab7 can be used as an optogenetic tool to direct target cell populations to either apoptosis or necrosis.
Wilson, W; Hilton, T
The modus operandi of female serial killers was examined from a chronology of 58 cases in America and 47 cases in 17 other countries, compiled over 25-year intervals. Female serial killers in other countries accounted for a disproportionately greater number of victims, but those in America managed a longer killing career when associated with a low profile modus operandi. PMID:9621726
Wilson, W; Hilton, T
The modus operandi of female serial killers was examined from a chronology of 58 cases in America and 47 cases in 17 other countries, compiled over 25-year intervals. Female serial killers in other countries accounted for a disproportionately greater number of victims, but those in America managed a longer killing career when associated with a low profile modus operandi.
Seidel, H.J.; Stolz, W.; Sutter, H.; Kreja, L.
In order to relate a reduced natural killer (NK) cell function to leukemogenesis, NK cells in the spleen and peritoneal exudate cells, with and without stimulation by Corynebacterium parvum, were tested in mice of various strains after split dose irradiation and after leukemogenic treatment with butyl- and methylnitrosourea. The investigations included also mice submitted to non-leukemogenic irradiation (1 x 1.5 and 1 x 4.5 Gy) and mice submitted to an additional treatment with hydrocortisone, which delays leukemia development after methylnitrosourea. There was, indeed, a NK-cell depression, but no major differences were seen between mice prone to leukemia development and those after cytotoxic, but nonleukemogenic, treatment.
The reconstruction of a death scene provides an overall picture of the crime and will indicate the murder as an event or one of a series of events and also the criminal. But when the criminal is declared a serial killer, many questions are raised up. How could a person kill some else without a reason or why people react in such a disorganized way and become so brutal or what made them act like that and so many questions with also so many answers. This project explains the psycholo...
Full Text Available The reconstruction of a death scene provides an overall picture of the crime and will indicate the murder as an event or one of a series of events and also the criminal. But when the criminal is declared a serial killer, many questions are raised up. How could a person kill some else without a reason or why people react in such a disorganized way and become so brutal or what made them act like that and so many questions with also so many answers. This project explains the psychology of a murderer, his own way of thinking and acting by presuming that we may accurately discover what is in their minds when they kill. It is about a very complex issue regarding murder investigations, biological factors and psychological profile of a serial killer. Dealing with this problem we will at last reach to the question that could solve finally the puzzle: ―Are serial murderers distorted reflections of society's own values?
Sinclair, Robert M
Killing is perhaps the most definite form of communication possible. Microbes such as yeasts and gut bacteria have been shown to exhibit killer phenotypes. The killer strains are able to kill other microbes occupying the same ecological niche, and do so with impunity. It would therefore be expected that, wherever a killer phenotype has arisen, all members of the population would soon be killers or dead. Surprisingly, (1) one can find both killer and sensitive strains in coexistence, both in the wild and in in vitro experiments, and (2) the absolute fitness cost of the killer phenotype often seems to be very small. We present an explicit model of such coexistence in a fragmented or discrete environment. A killer strain may kill all sensitive cells in one patch (one piece of rotting fruit, one cave or one human gut, for example), allowing sensitives to exist only in the absence of killer strains on the same patch. In our model, populations spread easily between patches, but in a stochastic manner: one can imagine spores borne by the wind over a field of untended apple trees, or enteric disease transmission in a region in which travel is effectively unrestricted. What we show is that coexistence is not only possible, but that it is possible even if the absolute fitness advantage of the sensitive strain over the killer strain is arbitrarily small. We do this by performing a specifically targeted mathematical analysis on our model, rather than via simulations. Our model does not assume large population densities, and may thus be useful in the context of understanding the ecology of extreme environments. PMID:25071753
Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour 51Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder
Alanen, A.; Lassila, O.
Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.
Seki, Tetsuji; Choi, Eon-Ho; Ryu, Dewey
A double-stranded RNA plasmid which confers the superkiller phenotype was transferred into a wine yeast (Montrachet strain 522) and its leucine-requiring derivative (strain 694) by cytoduction, using the protoplast fusion technique. The killer wine yeast constructed completely suppressed the growth of killer-sensitive strains of Saccharomyces cerevisiae in yeast extract-peptone-glucose medium at pH 4.5, whereas the killer effect was somewhat decreased at pH 3.5. The wine yeast harboring the k...
Full Text Available The complex and multisided study of serial killers is partly made difficult by the current level of progress that has led these deviant people to evolve in relation to the aspects of shrewdness (concerning the staging and mobility. Despite the important work of some scholars who proposed important theories, all this shows that, concerning serial murders, it is still particularly frequent not to pay attention to links among homicides committed by the same person but in different parts of the world. It is therefore crucial to develop a worldwide database that allows all police forces to access information collected on crime scenes of murders which are particularly absurd and committed without any apparent reason. It will then be up to the profiler, through ad hoc and technologically advanced tools, to collect this information on the crime scene that would be made available to all police forces thanks to the worldwide database.
Robert Michael Sinclair
Full Text Available Killing is perhaps the most definite form of communication possible. Microbes such as yeasts and gutbacteria have been shown to exhibit killer phenotypes. The killer strains are able to kill othermicrobes occupying the same ecological niche, and do so with impunity. It would therefore beexpected that, wherever a killer phenotype has arisen, all members of the population would soon bekillers or dead. Surprisingly, (i one can find both killer and sensitive strains in coexistence, both inthe wild and in in-vitro experiments, and (ii the absolute fitness cost of the killer phenotype oftenseems to be very small. We present an explicit model of such coexistence in a fragmented or discreteenvironment. A killer strain may kill all sensitive cells in one patch (one piece of rotting fruit, onecave or one human gut, for example, allowing sensitives to exist only in the absence of killer strainson the same patch. In our model, populations spread easily between patches, but in a stochasticmanner: One can imagine spores borne by the wind over a field of untended apple trees, or entericdisease transmission in a region in which travel is effectively unrestricted. What we show is thatcoexistence is not only possible, but that it is possible even if the absolute fitness advantage of thesensitive strain over the killer strain is arbitrarily small. We do this by performing a specificallytargeted mathematical analysis on our model, rather than via simulations. Our model does not assumelarge population densities, and may thus be useful in the context of understanding the ecology ofextreme environments.
Whitehead, Hal; Reeves, Randall
Killer whales (Orcinus orca) frequently scavenged from the carcasses produced by whalers. This practice became especially prominent with large-scale mechanical whaling in the twentieth century, which provided temporally and spatially clustered floating carcasses associated with loud acoustic signals. The carcasses were often of species of large whale preferred by killer whales but that normally sink beyond their diving range. In the middle years of the twentieth century floating whaled carcas...
Incorvaia, Cristoforo; Mauro, Marina; Leo, Gualtiero; Ridolo, Erminia
Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. PMID:26758865
Sandi ORLIC; POGAČIĆ, Martina; Ana JEROMEL; Marko KAROGLAN; Kozina, Bernard; IACUMIN, Lucilla; Redžepović, Sulejman
Wild wine yeasts with killer phenotype are widespread in many wine regions of the world. The presence of killer yeasts may become particularly important in wine fermentations conducted by inoculation with selected strains of Saccharomyces cerevisiae. Wild killer yeasts may suppress selected sensitive yeasts inoculated into the must during the fermentation. The goal of this investigation was to identify killer yeast in Istra region using physiological and molecular methods. In total 50 S.cerev...
Simkin, M V; Roychowdhury, V P
We analyze the time pattern of the activity of a serial killer, who during 12 years had murdered 53 people. The plot of the cumulative number of murders as a function of time is of "Devil's staircase" type. The distribution of the intervals between murders (step length) follows a power law with the exponent of 1.4. We propose a model according to which the serial killer commits murders when neuronal excitation in his brain exceeds certain threshold. We model this neural activity as a branching process, which in turn is approximated by a random walk. As the distribution of the random walk return times is a power law with the exponent 1.5, the distribution of the inter-murder intervals is thus explained. We illustrate analytical results by numerical simulation. Time pattern activity data from two other serial killers further substantiate our analysis.
Angela Frances Yap, BSc (Pharm) (Hons); Thiru Thirumoorthy, MBBS, FRCP (London), FAMS; Yu Heng Kwan, BSc (Pharm) (Hons)
Medication adherence is a crucial component in the treatment of chronic diseases. In the elderly, clinicians are faced with a unique set of problems associated with adherence that they may not have been adequately trained for. In this paper, we demonstrate the importance of medication adherence in the elderly through a case study. The different factors affecting medication adherence in the elderly are highlighted: patient, medication, health care providers, health care system, and socioeconom...
Bajaj, Bijender Kumar; Raina, Sandeepu; Singh, Satbir
The killer phenomenon of yeast may have technological implications in many areas like beverage fermentation, food technology, biological control in agriculture, and in medicine. In the present study the killer phenomenon in Pichia kudriavzevii (P. kudriavzevii RY55) is being reported for the first time. The P. kudriavzevii RY55 toxin exhibited excellent antibacterial activity against several pathogens of human health significance such as Escherichia coli, Enterococcus faecalis, Klebsiella sp., Staphylococcus aureus, Pseudomonas aeruginosa and Pseudomonas alcaligenes. Killer toxin was purified to homogeneity by using ammonium sulphate precipitation and ion exchange chromatography and characterized for few properties. P. kudriavzevii RY55 killer toxin may be of vast significance in the development of novel antimicrobial chemotherapeutic agents, new bio-based safer candidates for food preservation and biocontrol, and starter cultures for fermentation industries. PMID:22961241
Objective To examine the effect of human cytomegalovirus(CMV)on the expressions of natural-killer group2-members(NKG2),including natural-killer group 2-member A(NKG2A),natural-killer group 2-member C(NKG2C)and natural-killer group 2-member D(NKG2D)receptors on the natural killer(NK)cells.Methods NK cells were isolated from the peripheral blood mononuclear cells of 20 healthy individuals using
Johnson, B R; Becker, J V
Today's society seems enthralled with serial killers in the news and the media. Forensic psychiatrists often interview serial killers after they have been caught. There are retrospective studies and case reports of individuals who have committed sexually sadistic serial murders. However, there exists a dearth of case reports on adolescents who have expressed serious fantasies about becoming serial killer prior to actualizing their fantasy. This article presents nine clinical cases of 14- to 18-year-olds who have clinically significant fantasies of becoming a serial killer. Similarities exist in these adolescent cases when compared with retrospective studies and case reports of serial killers on the role of sexually sadistic fantasies and actual killings. Since it has been established that sexual paraphilias may develop at a young age, one can surmise that sadistic paraphilias may also develop in some adolescents. The question is posed, can we predict which of these adolescents may go on to actually become serial killers? This article focuses on how the sexually sadistic fantasy can eventually be acted out and possible motives for the act to be repeated multiple times. Finally, recommendations are made about assessing and treating a youngster who expresses violent sexually sadistic killing fantasies so that attempts can be made to interrupt the progression to actual killing.
Uhlig, R; Highfield, R
A chance fluctuation of the 'vacuum universe' could disintegrate all atoms, according to CERN associate, Dr Allanach. Alternatively, so-called killer strangelets could "eat up the universe from the inside out". Should either of these scenarios occur, the most likely starting point is the Relativistic Heavy Ion Collider in Long Island, New York state (1 page).
Foote, Andrew David; Morin, Phillip A; Durban, John W;
Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches...
Killer protein 4 (KP4) is a well studied toxin secreted by the maize smut fungus Ustilago maydis that kills sensitive Ustilago strains as well as inhibits Fusarium and plant root growth. This small, cysteine rich protein is encoded by a virus that depends on host survival for replication. KP4 functi...
Ceccato-Antonini Sandra Regina
Full Text Available The number of killer, neutral and sensitive yeasts was determined from strains isolated from substrates related to alcoholic fermentations. From 113 isolates, 24 showed killer activity against NCYC 1006 (standard sensitive strain, while 30 were sensitive to NCYC 738 (standard killer strain, and 59 had no reaction in assays at 25-27°C. Two wild yeast strains of Saccharomyces cerevisiae and one of Candida colliculosa were tested against 10 standard killer strains and one standard sensitive strain in a cell x cell and well-test assays at four different pHs. None of the isolates displayed strong killer activity or were sensitive to the standard strains. All belonged to the neutral type. It was concluded that although the number of killer strains was high, this character cannot be used to protect ethanol fermentation processes against yeast contaminants like those which form cell clusters.
Simkin, M V
We analyze the time pattern of the activity of a serial killer, who during twelve years had murdered 53 people. The plot of the cumulative number of murders as a function of time is of "Devil's staircase" type. The distribution of the intervals between murders (step length) follows a power law with the exponent of 1.4. We propose a model according to which the serial killer commits murders when neuronal excitation in his brain exceeds certain threshold. We model this neural activity as a branching process, which in turn is approximated by a random walk. As the distribution of the random walk return times is a power law with the exponent 1.5, the distribution of the inter-murder intervals is thus explained. We confirm analytical results by numerical simulation.
Villano, P; Bastianoni, P; Melotti, G
The representation of serial killers was examined from the analysis of 317 Web pages in the Italian language to study how the psychological profiles of serial killers are described on the Italian Internet. The correspondence analysis of the content of these Web pages shows that in Italy the serial killer is associated with words such as "monster" and "horror," which suggest and imply psychological perversion and aberrant acts. These traits are peculiar for the Italian scenario.
Villano, P; Bastianoni, P; Melotti, G
The representation of serial killers was examined from the analysis of 317 Web pages in the Italian language to study how the psychological profiles of serial killers are described on the Italian Internet. The correspondence analysis of the content of these Web pages shows that in Italy the serial killer is associated with words such as "monster" and "horror," which suggest and imply psychological perversion and aberrant acts. These traits are peculiar for the Italian scenario. PMID:11783573
Full Text Available Hypertension is an overwhelming global challenge. Despite the development of many effective anti hypertensive drugs, target to reduce morbidity and mortality due to high blood pressures are reached in only a minor of patients in clinical practice. Poor adherence is one of the biggest obstacles in therapeutic control of blood pressures. There are complaints from patients and physicians that the poor result of actual antihypertensive drug therapies. Many people with age indifference are attacked by this silent killer or which results in target organ damage as a complication. The aim of this study was to assess the magnitude of adherence and the factors associated with non-adherence to anti-hypertensive medication. Cross sectional exclusively convenient study was conducted by using structured questionnaires consisting of open and closed-ended questions on patients diagnosed for hypertension and have already been on anti hypertensive medications at least for three months at Dessie Referral hospital from 20/01/2012 to 29/01/2012. A total of hundred hypertensive patients were screened from hundred six cases by the exclusive criteria and the overall incidence of anti-hypertensive medication non adherence was 26%. The study identifies reasons why patients dont adherent with the drug regiments. Among Factors associated with non adherence were health system and health care provider poor interaction with patient and therapy factors like frustration and unwanted effect of the medication in the long run. There was indication of non adherence from the study area. Great emphasis should be placed on intervention strategies such as patient counseling and increasing awareness of the physicians, all other prescribers and health care providers at large about the non adherence of anti hypertensive drugs as well as the complication what comes due to this medication non adherence. [Int J Res Med Sci 2013; 1(3.000: 191-197
Filatova, Olga A; Burdin, Alexandr M; Hoyt, Erich
The killer whale is among the few species in which cultural change accumulates over many generations, leading to cumulative cultural evolution. Killer whales have group-specific vocal repertoires which are thought to be learned rather than being genetically coded. It is supposed that divergence between vocal repertoires of sister groups increases gradually over time due to random learning mistakes and innovations. In this case, the similarity of calls across groups must be correlated with pod relatedness and, consequently, with each other. In this study we tested this prediction by comparing the patterns of call similarity between matrilines of resident killer whales from Eastern Kamchatka. We calculated the similarity of seven components from three call types across 14 matrilines. In contrast to the theoretical predictions, matrilines formed different clusters on the dendrograms made by different calls and even by different components of the same call. We suggest three possible explanations for this phenomenon. First, the lack of agreement between similarity patterns of different components may be the result of constraints in the call structure. Second, it is possible that call components change in time with different speed and/or in different directions. Third, horizontal cultural transmission of call features may occur between matrilines.
Objective To study the clinicopathologic features,diagnosis and differential diagnosis of intestinal natural killer(NK)/T-cell lymphoma.Methods The clinical features,histopathology,immunohistochemical
Dogra, T D; Leenaars, Antoon A; Chadha, R K; Manju, Mehta; Lalwani, Sanjeev; Sood, Mamta; Lester, David; Raina, Anupuma; Behera, C
Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer.
Dogra, T D; Leenaars, Antoon A; Chadha, R K; Manju, Mehta; Lalwani, Sanjeev; Sood, Mamta; Lester, David; Raina, Anupuma; Behera, C
Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer. PMID:23115894
Lencer, R; Korn, D
Effective psychopharmacological medication with good tolerability represents the cornerstone of treatment for severe mental illness; however, the 1-year adherence rates are only approximately 50%. The term adherence emphasizes the collaborative responsibility of the clinician and the patient for a positive treatment outcome. Reasons for non-adherence are manifold and include patient-specific factors, such as self-stigmatization, lack of social and familial support, cognitive impairment and substance use besides insufficient effectiveness and the occurrence of side effects of the psychotropic drugs. To enhance adherence, both clinician and patient have to fully understand all the reasons for and against adherence to medication before a collaborative decision is made on future long-term treatment. A positive attitude towards medication critically depends on whether patients feel that the medication supports the attainment of the individual goals. PMID:25903501
Sha, Shuang; Qin, Lingsong; Wang, Anle; Liu, Zheng; Yang, Fei; Jin, Honglin; Zhang, Zhihong
KillerRed is a unique red fluorescent protein exhibiting excellent phototoxic properties. It has the ability to produce reactive oxygen species (ROS), for killing tumor cells in vitro upon laser irradiation and has the potential to act as a photosensitizer in the application of tumor therapy. Here, we investigated the effects of KillerRed-based photodynamic therapy (PDT) on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of pyridine nucleotide (PN) and flavoprotein (Fp), two important metabolic coenzymes of tumor cells. Results showed that the tumor was scabbed in response to 561 nm laser irradiation at 80 mV for 3 min, and the tumor growth had been significantly inhibited by KillerRed-based PDT treatment compared to control groups. More importantly, a home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The flavoprotein was remarkable elevated and the PN was seldom increased with concomitant photobleaching of KillerRed fluorescence after irradiation, suggesting that flavoprotein and PN were oxidized in the course of KillerRed-based PDT.
Full Text Available The influence of surgical stress on the natural killer (NK activity of peripheral blood lymphocytes in patients with carcinoma of the lung or gastrointestinal system was studied. The peripheral blood lymphocytes of the patients showed a marked decrease in NK activity against K-562 cells as target cells 1-2 days after surgery. The activity remained lowered for 2 weeks after thoractomy and for 1 week after laparotomy. No appreciable suppression of NK activity was observed with normal human peripheral blood lymphocytes preincubated with postoperative patient sera. Peripheral blood mononuclear cells obtained postoperatively from patients lost NK activity after ultraviolet irradiation, without any detectable loss of viability. Such irradiated mononuclear cells showed inhibition of NK activity after a 24-hour preincubation with peripheral blood lymphocytes from normal subjects. Similar suppressive activity was demonstrable in a fraction of mononuclear cells with adhesiveness to plastic petri dishes, while non-adherent cells had no such activity. When added immediately to the cytotoxicity assay system without the 24-hour preincubation, patient mononuclear cells caused no inhibition of NK activity, whereas adherent cells from normal subjects enhanced NK activity. The findings seems to indicate that, following surgical stress, plastic dish-adherent peripheral blood mononuclear cells become deprived of NK helper activity and exert suppression, thus causing postoperative depression of NK activity.
... under the ESA is warranted (75 FR 316, January 5, 2010). Based on the overlap between the Insular and... National Oceanic and Atmospheric Administration RIN 0648-XT76 False Killer Whale Take Reduction Team... (NOAA), Department of Commerce. ACTION: Notice of establishment of a False Killer Whale Take...
Several strains of Ustilago maydis, a causal agent of corn smut disease, exhibit a 'killer' phenotype that is due to persistent infection by double-stranded RNA Totiviruses. These viruses produce potent killer proteins that are secreted by the host. This is a rare example of virus/host symbiosis in ...
Paluszynski, John P.; Klassen, Roland; Meinhardt, Friedhelm
The gene responsible for self-protection in the Pichia acaciae killer plasmid system was identified by heterologous expression in Saccharomyces cerevisiae. Resistance profiling and conditional toxin/immunity coexpression analysis revealed dose-independent protection by pPac1-2 ORF4 and intracellular interference with toxin function, suggesting toxin reinternalization in immune killer cells.
van Beekhuizen, H J; Joosten, I; Lotgering, F K; Bulten, J; van Kempen, L C
Retained placenta is caused by abnormal adherence of the placenta to the uterine wall, leading to delayed expulsion of the placenta and causing postpartum haemorrhage. The mildest form of retained placenta is the placenta adhesiva (PA), of which the cause is unknown. The aim of our study was to explore possible differences in immune response in the basal decidua between PA and control placentas (CP). We performed a descriptive analysis of immunohistochemical differences in 17 PA and 10 CP. Our results show that in PA the amount of uterine natural killer (uNK) cells is significantly reduced (0.2 uNK cell/standardised area) as compared to CP (9.8 uNK cell/standardised area, p placenta.
Antiretroviral therapy places extraordinarily high demands on adherence, since non-adherence affects both individuals and society due to the spread of resistant viral strains. The aims of the thesis were to investigate the prevalence of adherence in Swedish HIV-infected patients, changes in adherence over time, and factors associated with adherence, including patients’ readiness to adhere. Further, to investigate the collaboration between nurses, doctors and pharmacists after the introduction...
Golic, Michaela; Haase, Nadine; Herse, Florian; Wehner, Anika; Vercruysse, Lisbeth; Pijnenborg, Robert; Balogh, Andras; Saether, Per Christian; Dissen, Erik; Luft, Friedrich C; Przybyl, Lukasz; Park, Joon-Keun; Alnaes-Katjavivi, Patji; Staff, Anne Cathrine; Verlohren, Stefan; Henrich, Wolfgang; Muller, Dominik N; Dechend, Ralf
Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth. PMID:27550919
HEALTH and politics don’t always mix.In January,as increasing numbers of returnees from North Sudan entered Southern Sudan to vote on a referendum for independence, the World Health Organization(WHO) reported that a major visceral leishmaniasis epidemic was in danger of breaking out.Incidences of the disease - the world’s second deadliest parasitic killer after malaria - had nearly doubled within the span of a month,according to case records from last November. WHO officials speculated that the surge was due to that fact that returnees typically did not have immunity against the disease.
Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.
Gulbiniene, Gintare; Kondratiene, Laima; Jokantaite, Tautvile; Serviene, Elena; Melvydas, Vytautas; Petkuniene, Giedre
Apple, cranberry, chokeberry and Lithuanian red grape wine yeast populations were used for the determination of killer yeast occurrence. According to the tests of the killer characteristics and immunity the isolated strains were divided into seven groups. In this work the activity of killer toxins purified from some typical strains was evaluated. The analysed strains produced different amounts of active killer toxin and some of them possessed new industrially significant killer properties. To...
Urszula Błaszczyk; Pawel Satora; Pawel Sroka
Killer yeasts are able to produce toxins that antagonize the growth of susceptible yeasts cells of the same species or the ones that are related to them. Killer strains are resistant to their own toxins but can be sensitive to killer proteins of other yeasts. The killer proteins of Pichia spp. are known for its broad spectrum of antifungal activity including pathogens such as Candida albicans. The aim of the study was to investigate the potential of the partly purified killer toxi...
Matkin, Craig O.; Barrett-Lennard, Lance G.; Yurk, Harald; Ellifrit, David; Andrew W Trites
From 2001 to 2004 in the eastern Aleutian Islands, Alaska, killer whales (Orcinus orca) were encountered 250 times during 421 days of surveys that covered a total of 22,491 miles. Three killer whale groups (resident, transient, and offshore) were identified acoustically and genetically. Resident killer whales were found 12 times more frequently than transient killer whales, and offshore killer whales were encountered only once. A minimum of 901 photographically identified resident wh...
Polonelli, Luciano; Magliani, Walter; Ciociola, Tecla; Giovati, Laura; Conti, Stefania
"Antibiobodies", antibodies (Abs) with antibiotic activity, internal image of a Pichia anomala killer toxin (PaKT) characterized by microbicidal activity against microorganisms expressing β-glucans cell-wall receptors (PaKTRs), were produced by idiotypic vaccination with a PaKT-neutralizing monoclonal Ab (PaKT-like Abs) or induced by a protein-conjugated β-glucan. Human natural PaKT-like Abs (PaKTAbs) were found in the vaginal fluid of women infected with KT-sensitive microorganisms. Monoclonal and recombinant PaKT-like Abs, and PaKTAbs proved to be protective against experimental candidiasis, cryptococcosis and aspergillosis. A killer decapeptide (KP), synthesized from the sequence of a recombinant PaKT-like Ab or produced in transgenic plants, showed a microbicidal activity in vitro, neutralized by β-glucans, a therapeutic effect in vivo, against experimental mucosal and systemic mycoses, and a prophylactic role in planta, against phytopathogenic microorganisms, respectively. KP showed fungicidal properties against all the defective mutants of a Saccharomyces cerevisiae library, inclusive of strains recognized to be resistant to conventional antifungal drugs. KP inhibited in vitro, ex vivo and/or in vivo HIV-1 and Influenza A virus replication, owing to down-regulation of CCR5 co-receptors, physical block of the gp120-receptor interaction and reduction in the synthesis of glycoproteins, HA and M1 in particular. KP modulated the expression of costimulatory and MHC molecules on murine dendritic cells, improving their capacity to induce lymphocyte proliferation. KP, proven to be devoid of cytotoxicity on human cells, showed self-assembly-releasing hydrogel-like properties, catalyzed by β 1,3 glucan. PaKT's biotechnological derivatives may represent the prototypes of novel antifungal vaccines and anti-infective drugs characterized by different mechanisms of action. PMID:20714805
Martin, Leslie R; Williams, Summer L; Haskard, Kelly B; Dimatteo, M Robin
Quality healthcare outcomes depend upon patients' adherence to recommended treatment regimens. Patient nonadherence can be a pervasive threat to health and wellbeing and carry an appreciable economic burden as well. In some disease conditions, more than 40% of patients sustain significant risks by misunderstanding, forgetting, or ignoring healthcare advice. While no single intervention strategy can improve the adherence of all patients, decades of research studies agree that successful attempts to improve patient adherence depend upon a set of key factors. These include realistic assessment of patients' knowledge and understanding of the regimen, clear and effective communication between health professionals and their patients, and the nurturance of trust in the therapeutic relationship. Patients must be given the opportunity to tell the story of their unique illness experiences. Knowing the patient as a person allows the health professional to understand elements that are crucial to the patient's adherence: beliefs, attitudes, subjective norms, cultural context, social supports, and emotional health challenges, particularly depression. Physician-patient partnerships are essential when choosing amongst various therapeutic options to maximize adherence. Mutual collaboration fosters greater patient satisfaction, reduces the risks of nonadherence, and improves patients' healthcare outcomes. PMID:18360559
Mandal, Arundhati; Viswanathan, Chandra
Natural killer (NK) cells constitute our bodies' frontline defense system, guarding against tumors and launching attacks against infections. The activities of NK cells are regulated by the interaction of various receptors expressed on their surfaces with cell surface ligands. While the role of NK cells in controlling tumor activity is relatively clear, the fact that they are also linked to various other disease conditions is now being highlighted. Here, we present an overview of the role of NK cells during normal body state as well as under diseased state. We discuss the possible utilization of these powerful cells as immunotherapeutic agents in combating diseases such as asthma, autoimmune diseases, and HIV-AIDS. This review also outlines current challenges in NK cell therapy.
Lotzova, E.; Herberman, R.B.
This book provides a review of natural killer (NK) cell-mediated immunity in humans and experimental animal system. Topics for the volume include: In vivo activities of NK cells against primary and metastatic tumors in experimental animals; involvement of NK cells in human malignant disease; impaired NK cell profile in leukemia patients; in vivo modulation of NK activity in cancer patients; implications of aberrant NK cell activity in nonmalignant, chronic diseases; NK cell role in regulation of the growth and functions of hemopoietic and lymphoid cells; NK cells active against viral, bacterial, protozoan, and fungal infections; cytokine secretion and noncytotoxic functions of human large granular lymphocytes; augmentation of NK activity; regulation of NK cell activity by suppressor cells; NK cell cloning technology and characteristics of NK cell clones; comparison of antibody-dependent cellular cytotoxicity (ADCC) and NK activity, and index.
Shirmanova, Marina; Yuzhakova, Diana; Snopova, Ludmila; Perelman, Gregory; Serebrovskaya, Ekaterina; Lukyanov, Konstantin; Turchin, Ilya; Subochev, Pavel; Lukyanov, Sergey; Kamensky, Vladislav; Zagaynova, Elena
The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation. PMID:26657001
Full Text Available The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm and pulsed laser (584 nm, 10 Hz, 18 ns modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.
"European Organization for Nuclear Research is reporting that results from a three year study of antiprotons for neoplasm irrdiation showed a better cellular killer with a smaller lethal dose." (1,5 page)
Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A
Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides.
Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A
Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides. PMID:25682709
... medlineplus.gov/news/fullstory_160436.html Cancer Now Leading Killer in 12 European Nations Gains against heart ... has overtaken heart disease and stroke as the leading cause of death in 12 European countries, a ...
US Fish and Wildlife Service, Department of the Interior — A geospatial data set depicting the boundaries of marine areas designated as critical habitat under the Endangered Species Act (ESA) for Southern Resident killer...
National Oceanic and Atmospheric Administration, Department of Commerce — Photo-identification data on killer whales occupying the northern Gulf of Mexico have been collected in association with large vessel surveys since 1991....
Polonelli, L; Morace, G
Monoclonal antibodies were obtained after fusion of mouse myeloma cells with spleen cells isolated from mice primed with a crude extract of yeast killer toxin produced by a strain of Hansenula anomala. Hybridomas were selected by specific immunoassay reaction of their fluid with crude yeast killer toxin extract. Among the monoclonal antibodies, which were characterized by the Western blot technique, one (designated KT4) proved to have precipitating properties, thus permitting the neutralizati...
Full Text Available Suboptimal adherence with preventive medication is common and often unrecognised as a cause of poor asthma control. A number of risk factors for nonadherence have emerged from well-conducted studies. Unfortunately, patient report a physician's estimation of adherence and knowledge of these risk factors may not assist in determining whether non-adherence is a significant factor. Electronic monitoring devices are likely to be more frequently used to remind patients to take medication, as a strategy to motivate patients to maintain adherence, and a tool to evaluate adherence in subjects with poor disease control. The aim of this paper is to review non-adherence with preventive medication in childhood asthma, its impact on asthma control, methods of evaluating non-adherence, risk factors for suboptimal adherence, and strategies to enhance adherence.
Emily A Hornett
Full Text Available Male-killing bacteria are widespread in arthropods, and can profoundly alter the reproductive biology of their host species. Here we detail the first case of complete suppression of a male killer. The nymphalid butterfly Hypolimnas bolina is infected with a strain of the bacterium Wolbachia, wBol1, which kills male host embryos in Polynesian populations, but does not do so in many areas of Southeast Asia, where both males and female adults are naturally infected, and wBol1-infected females produce a 1:1 sex ratio. We demonstrate that absence of male killing by wBol1 is associated with dominant zygotic suppression of the action of the male killer. Simulations demonstrate host suppressors of male-killer action can spread very rapidly, and historical data indicating the presence of male killing in Southeast Asia in the very recent past suggests suppressor spread has been a very recent occurrence. Thus, male killer/host interactions are much more dynamic than previously recognised, with rapid and dramatic loss of the phenotype. Our results also indicate that suppression can render male killers completely quiescent, leading to the conclusion that some species that do not currently express a male killer may have done so in the past, and thus that more species have had their biology affected by these parasites than previously believed.
National Oceanic and Atmospheric Administration, Department of Commerce — Transient killers whales inhabit the West Coast of the United States. Their range and movement patterns are difficult to ascertain, but are vital to understanding...
W. van de Vrie (Wim); S.A.M. van der Heyden (Sylke); E.E.O. Gheuens (Eric); H.H. Bijma (Hilmar); E.A. de Bruijn (Ernst); R.L. Marquet (Richard); A.T. van Oosterom (Allan); A.M.M. Eggermont (Alexander)
textabstractThe development of resistance to anticancer drugs urges the search for different treatment modalities. Several investigators have reported the concomitant development of drug resistance and resistance to natural killer (NK), lymphokine-activated killer (LAK) or monocyte/macrophage cell l
Waldeck, Waldemar; Mueller, Gabriele; Wiessler, Manfred; Tóth, Katalin; Braun, Klaus
Fluorescent proteins (FPs) are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED), used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS) resulting in photokilling processes. It is a given that the extent of...
Maria Cristina Meneghin
Full Text Available The aim of this work was to study the in vitro antibacterial activity possessed by killer yeast strains against bacteria contaminating alcoholic fermentation (Bacillus subtilis, Lactobacillus plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides, in cell X cell and cell X crude toxin preparations. The bacteria were not inhibited by any S. cerevisiae killer strains (5 out of 11. The inhibition caused by two crude toxin preparations (Trichosporon figueirae and Candida sp against L. plantarum was surprisingly high but not in the same extent for B. subtilis, especially with three killer strains (Candida glabrata, Pichia anomala and Candida sp. L. mesenteroides and L. fermentum strains were neither inhibited in cell X cell nor crude toxin X cell tests. The results suggested that killer activity of yeasts might operate over bacteria and it could be used for the biocontrol of contaminating bacteria from alcoholic fermentation if additional tests on toxin application in fermentation shown to be successful. A wider panel of S. cerevisiae killer strains should be used to confirm that they were really unable to control the growth of these Gram-positive bacteria.Este estudo mostrou a atividade antibacteriana in vitro de linhagens de leveduras killer contra bactérias contaminantes da fermentação alcoólica (Bacillus subtilis, Lactobacillus plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides, em testes célula X célula e célula X toxina bruta. As bactérias não foram inibidas por linhagens killer de Saccharomyces cerevisiae (5 dentre 11. Os preparados brutos de toxina de duas leveduras (Trichosporon figueirae e Candida sp causaram uma alta inibição no crescimento de L. plantarum, mas não na mesma extensão para B. subtilis, especialmente para três leveduras killer (Candida glabrata, Pichia anomala e Candida sp. Linhagens de L. mesenteroides e L. fermentum não foram inibidas em nenhum dos testes. Os resultados obtidos neste
Shirmanova, Marina V.; Serebrovskaya, Ekaterina O.; Snopova, Ludmila B.; Kuznetsova, Maria M.; Ryumina, Alina P.; Turchin, Ilya V.; Sergeeva, Ekaterina A.; Ignatova, Nadezhda I.; Klementieva, Natalia V.; Lukyanov, Konstantin A.; Lukyanov, Sergey A.; Zagaynova, Elena V.
Despite of the success of photodynamic therapy (PDT) in cancer treatment, the problems of low selective accumulation of a photosensitizer in a tumor and skin phototoxicity have not resolved yet. The idea of encoding of a photosensitizer in genome of cancer cells is attractive, particularly because it can provide highly selective light induced cell killing. This work is aimed at the development of new approach to PDT of cancer, namely to using genetically encoded photosensitizers. A phototoxicity of red fluorescent GFP-like protein KillerRed and FMN-binding protein miniSOG was investigated on HeLa tumor xenografts in nude mice. The tumors were generated by subcutaneous injection of HeLa cells stably expressing the phototoxic proteins. The tumors were irradiated with 594 nm or 473 nm laser at 150 mW/cm2 for 20 or 30 min, repeatedly. Fluorescence intensity of the tumors was measured in vivo before and after each treatment procedure. Detailed pathomorphological analysis was performed 24 h after the therapy. On the epi-fluorescence images in vivo photobleaching of both proteins was observed indicating photodynamic reaction. Substantial pathomorphological abnormalities were found in the treated KillerRed-expressing tumor tissue, such as vacuolization of cytoplasm, cellular and nuclear membrane destruction, activation of apoptosis. In contrast, miniSOG-expressing tumors displayed no reaction to PDT, presumably due to the lack of FMN cofactor needed for fluorescence recovery of the flavoprotein. The results are of interest for photodynamic therapy as a proof of possibility to induce photodamages in cancer cells in vivo using genetically encoded photosensitizers.
Full Text Available Natural killer (NK cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors (KIR, NK Group 2 member D (NKG2D, NKG2A/CD94, NKp46 and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols.Cytokine-induced killer (CIK cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming.NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.
Hilda C P Morana
Full Text Available OBJETIVO: Apresentar as características básicas dos diversos transtornos específicos de personalidade, mas centrando-se no transtorno de personalidade anti-social, fazendo sua diferenciação com psicopatia. O estudo ainda se propõe a abordar a figura do serial killer, apontando a presença de aspectos psicopáticos no homicídio seriado. MÉTODO: Uma revisão bibliográfica foi feita no sentido de se abordar convergências e divergências entre diversos autores sobre um assunto tão polêmico, sobretudo quanto à viabilidade de tratamento dessa clientela forense. RESULTADOS: Enquanto o transtorno de personalidade anti-social é um diagnóstico médico, pode-se entender o termo "psicopatia", pertencente à esfera psiquiátrico-forense, como um "diagnóstico legal". Não se pode falar ainda de tratamento eficaz para os chamados "serial killers". CONCLUSÃO: Os transtornos de personalidade, especialmente o tipo anti-social, representam ainda hoje um verdadeiro desafio para a psiquiatria forense. O local mais adequado e justo para seus portadores, bem como recomendação homogênea e padronizada de tratamento são questões ainda não respondidas.OBJECTIVE: To illustrate the basic characteristics of several specific personality disorders, focusing mainly in antisocial personality disorder. The differences between antisocial personality disorder and psychopathy are highlighted. Serial killers and its psychopathic aspects are also discussed. METHOD: A bibliographic review was completed in order to outline convergences and divergences among different authors about this controversial issue, especially those concerning the possibility of treatment. RESULTS: While anti-social personality disorder is a medical diagnosis, the term "psychopathy" (which belongs to the sphere of forensic psychiatry may be understood as a "legal diagnosis". It is not still possible to identify an effective treatment for serial killers. CONCLUSION: Personality disorders
Mehmet Emin Demirkol
Conclusion: Although medical treatments and drug industry develop day by day, there have been no changes in the treatment adherence ratios in the past years. To generate possible solutions, treatment adherence should be assessed in all clinical interviews and if patient is non-adherent this issue should be handled seriously. [Cukurova Med J 2015; 40(3.000: 555-568
Full Text Available In the 40 years since the discovery of Natural Killer (NK cells it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue resident NK cells with distinct phenotypical and functional characteristics have been identified. Here we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.
National Oceanic and Atmospheric Administration, Department of Commerce — Patterns of seasonal occurrence of Southern Resident Killer Whales (SRKW) throughout their range. Southern Resident Killer Whales are listed as a Distinct...
Satoh, J; Kim, S U; Kastrukoff, L F
The cytotoxic activity of killer (K) cells against enriched cultures of bovine oligodendrocytes (BOL) was investigated in multiple sclerosis (MS) and controls. Human K cells mediated cytotoxicity to primary cultures of BOL in the presence of anti-BOL antiserum in all study groups, while BOL were resistant to human natural killer (NK) cells. Cytotoxic activity was significantly reduced in MS when compared to age-matched normal controls but not when compared to other neurologic disease (OND) patients. K cell-mediated lysis of BOL could also be induced with anti-galactocerebroside antibody but not with other antibodies including those specific for OL antigens (myelin basic protein, proteolipid apoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase). Enrichment of the effector population indicated that antibody-dependent cell-mediated cytotoxicity (ADCC) to BOL was mediated by large granular lymphocytes, and the effector population was further characterized by flow cytometry. The effector cells mediating ADCC could be inhibited by protein A of Staphylococcus aureus, and by K562 cells in cold competition assay. These observations indicate that oligodendrocytes are resistant to NK cells but are susceptible to cytolysis mediated by K cells. This may represent a potentially important immune mechanism in the pathogenesis of MS.
Lehmann, D.; Spanholtz, J.; Osl, M.; Tordoir, M.; Lipnik, K.; Bilban, M.; Schlechta, B.; Dolstra, H.; Hofer, E.
Ex vivo differentiation systems of natural killer (NK) cells from CD34+ hematopoietic stem cells are of potential importance for adjuvant immunotherapy of cancer. Here, we analyzed ex vivo differentiation of NK cells from cord blood-derived CD34+ stem cells by gene expression profiling, real-time RT
Full Text Available Aurel O Iuga,1,2 Maura J McGuire3,4 1Johns Hopkins Bloomberg School of Public Health, 2Johns Hopkins University, 3Johns Hopkins Community Physicians, 4Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Medication nonadherence is an important public health consideration, affecting health outcomes and overall health care costs. This review considers the most recent developments in adherence research with a focus on the impact of medication adherence on health care costs in the US health system. We describe the magnitude of the nonadherence problem and related costs, with an extensive discussion of the mechanisms underlying the impact of nonadherence on costs. Specifically, we summarize the impact of nonadherence on health care costs in several chronic diseases, such as diabetes and asthma. A brief analysis of existing research study designs, along with suggestions for future research focus, is provided. Finally, given the ongoing changes in the US health care system, we also address some of the most relevant and current trends in health care, including pharmacist-led medication therapy management and electronic (e-prescribing. Keywords: patient, medication, adherence, compliance, nonadherence, noncompliance, cost
Ma, Wu; O'Shaughnessy, Thomas; Chang, Eddie
Neuronal networks have been widely used for neurophysiology, drug discovery and toxicity testing. An essential prerequisite for future widespread application of neuronal networks is the development of efficient cryopreservation protocols to facilitate their storage and transportation. Here is the first report on cryopreservation of mammalian adherent neuronal networks. Dissociated spinal cord cells were attached to a poly-d-lysine/laminin surface and allowed to form neuronal networks. Adherent neuronal networks were embedded in a thin film of collagen gel and loaded with trehalose prior to transfer to a freezing medium containing DMSO, FBS and culture medium. This was followed by a slow rate of cooling to -80 degrees C for 24 h and then storage for up to 2 months in liquid nitrogen at -196 degrees C. The three components: DMSO, collagen gel entrapment and trehalose loading combined provided the highest post-thaw viability, relative to individual or two component protocols. The post-thaw cells with this protocol demonstrated similar neuronal and astrocytic markers and morphological structure as those detected in unfrozen cells. Fluorescent dye FM1-43 staining revealed active recycling of synaptic vesicles upon depolarizing stimulation in the post-thaw neuronal networks. These results suggest that a combination of DMSO, collagen gel entrapment and trehalose loading can significantly improve conventional slow-cooling methods in cryopreservation of adherent neuronal networks.
Bager, Palle; Julsgaard, Mette; Vestergaard, Thea;
different aspects of adherence and to identify predictors of non-adherence, including the quality of care, for outpatients with IBD. MATERIALS AND METHODS: An anonymous electronic questionnaire was used to investigate different aspects of adherence, the quality of care, patient involvement and shared...... decision making among 377 IBD outpatients. RESULTS: Three hundred (80%) filled in the questionnaire. The overall adherence rate was 93%. Young age (< 35 years old) and smoking were significantly associated with non-adherence (prevalence odds ratio (POR) 2.98, 95% CI 1.04-8.52, p < 0.05 and POR 3.88, 95% CI...
... killer whale (Orcinus orca). 226.206 Section 226.206 Wildlife and Fisheries NATIONAL MARINE FISHERIES... CRITICAL HABITAT § 226.206 Critical habitat for the Southern Resident killer whale (Orcinus orca). Critical habitat is designated for the Southern Resident killer whale as described in this section. The...
Pedersen, M. N.
In real political life "killer amendments" are very rare. William H. Riker was the first political scientist to draw systematic attention to this special "heresthetic" phenomenon, but he was himself only able to identify a handful of successful "killer amendments". Subsequent systematic empirical...... Constitution. The motion was defeated by means of what looks like a nicely orchestrated "killer amendment"....
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Coutinho, S D; Paula, C R
The killer phenomenon has been used as epidemiological marker for Candida albicans, where hundreds of biotypes can be obtained. The objective of this study is to observe the behaviour of 30 strains of Malassezia pachydermatis isolated from dogs with otitis (15) or dermatitis (15) against 9 killer yeasts, which, when grouped in triplets produced a 3 digit code (biotype). The growth inhibition of the 30 strains of M. pachydermatis due to the effect of the killer yeasts used permitted the determination of the following biotypes: 888 (33.3%), 212 (26.7%), 111 (16.7%), 312 (6.7%), 512 (6.7%), 242 (3.3%), 311 (3.3%) and 411 (3.3%). Biotypes 888, 212 and 111 occurred most frequently in both ear canal and skin samples. PMID:17655416
Full Text Available Abstract Natural killer cells have been demonstrated to play a major role in mediating an anti-leukemia effect in patients given a T-cell depleted allogeneic hematopoietic stem cell transplantation from an HLA-haploidentical family donor. In particular, donor-derived natural killer cells, which are alloreactive (i.e. KIR/HLA mismatched towards recipient cells, significantly contribute to the eradication of leukemia blasts escaping the preparative regimen to transplantation. A recent study on high-risk pediatric acute lymphoblastic leukemia refractory to chemotherapy further highlighted the importance of donors with alloreactive natural killer cells in haploidentical hematopoietic stem cell transplantation, as it demonstrated that these cells can emerge starting from the fourth-fifth month after the allograft and persist for many months. This study represents a major breakthrough in the cure of otherwise fatal leukemias, providing information on the best criteria for choosing the optimal donor.
Full Text Available Natural Killer (NK cells are important in the host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to prevent autoimmunity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the PI3K signaling pathway have defective development, natural killer cell repertoire expression (NKRR and effector function. Here we review the role of inositol phospholipid signaling in NK cell biology.
Massoud, Tarik F; Kalnins, Aleksandrs
We present the unusual appearance on brain magnetic resonance imaging of a glioblastoma with an uncanny shape of a rabbit. By invoking fearsome "killer" rabbits depicted in the art and literature of the Middle Ages, this image is an eerie reminder of the current lethality of this disease. There is a pressing need for more effective treatments for glioblastoma. PMID:27157288
Menopause evolved in humans and whales, presumably because older females can help their kin. But how do they help? New research shows that post-menopausal female killer whales lead foraging groups. This leadership is most significant when food is scarce. PMID:25784039
Klarlund, K; Pedersen, B K; Theander, T G;
Natural killer (NK) cell activity against K562 target cells was measured in patients within 24 h of acute myocardial infarction (AMI) and regularly thereafter for 6 weeks. NK cell activity was suppressed on days 1, 3, and 7 (P less than 0.01), day 14 (P less than 0.05) and at 6 weeks (P = 0...
Menopause evolved in humans and whales, presumably because older females can help their kin. But how do they help? New research shows that post-menopausal female killer whales lead foraging groups. This leadership is most significant when food is scarce.
Masihi, K N; Lange, W; Rohde-Schulz, B
The effect on natural killer (NK) cytotoxicity of splenic cells from BALB/c mice pretreated i.v. with squalane-in-water preparations of muramyl dipeptide (MDP), trehalose dimycolate (TDM), or the combination of MDP-plus-TDM was investigated. MDP or TDM augmented the NK cytotoxicity which peaked 48 h after the pretreatment whereas the combination of MDP and TDM induced an inhibition of the NK activity. Infection with influenza virus, a potent stimulator of NK cells, after the pretreatment with biological response modifiers resulted in a markedly enhanced NK activity on day 2 in MDP and control groups. Mice pretreated with TDM or the combination of MDP and TDM showed only moderate NK activity which peaked on day 3 after influenza infection. The NK activity was susceptible to asialo GM1 and complement treatment. The cytotoxicity of MDP-plus-TDM cells could be significantly enhanced after treatment with anti-macrophage monoclonal antibody and complement. NK activity induced by MDP or TDM was reduced by mixing MDP-plus-TDM cells. Addition of adherent cell-depleted MDP-plus-TDM suspension to MDP or TDM cells had a NK restorative effect. Splenic cells from mice pretreated 2 days earlier with MDP or TDM, but not MDP-plus-TDM, generated enhanced levels of luminol-dependent chemiluminescence.
Moreno, M.; Molling, J.W.; Mensdorff-Pouilly, S von; Verheijen, R.H.; Blomberg, B.M.E. von; Eertwegh, A.J. van den; Scheper, R.J.; Bontkes, H.J.
Invariant natural killer T (iNKT) cells play a pivotal role in cancer immunity through trans-activation of effector cells via swift cytokine secretion. In mice, iNKT cell activation by alpha-galactosylceramide (alpha-GC) induces potent NK cell-mediated anti-tumour effects. Here we investigated wheth
Full Text Available BACKGROUND: Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear. METHODOLOGY: The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions. PRINCIPAL FINDINGS: P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours. SIGNIFICANCE: Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.
Goldstein, Irit; Grefat, Rami; Ephros, Moshe; Rishpon, Shmuel
Malaria infects 30,000 travelers annually worldwide. At greatest risk are those who travel for long duration. Prevention of malaria includes chemoprophylaxis. This prospective study on 121 travelers who visited two travel clinics shows that adherence to prophylactic treatment was low, especially in long duration trips, and that adherence rate could be predicted by the much more available intent-to-adhere rate.
Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli
Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, ... prescribed fixed-combination therapy (ICS and long-acting β2 agonists). Good adherence was associated with higher FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations, less use of oral corticosteroids, and lower mortality rate. Overall, 24% of exacerbations and 60% of asthma...
Modi, Avani C.; Zeller, Meg H.; Xanthakos, Stavra A.; Jenkins, Todd M.; Inge, Thomas H.
Adolescents with extreme obesity, who have undergone bariatric surgery, must adhere to many lifestyle and nutritional recommendations, including multivitamin therapy. Little is know about multivitamin adherence following adolescent bariatric surgery. The present study aims to document self-reported and electronically-monitored adherence to multivitamins, determine convergence between self-report and electronic monitoring adherence for multivitamins, and identify barriers to multivitamin adher...
Tønnesen, E; Mickley, H; Grunnet, N
Natural killer (NK) cell activity of peripheral blood mononuclear cells was measured against K-562 target cells in a 51Cr release assay in eight patients undergoing total hip replacement surgery. Eight consecutive blood samples were taken from each patient. A significant increase of NK cell...... days. The findings of this study indicate that premedication, anaesthesia and surgery cause a rapid and transient increase in NK cell activity, followed by a decline in activity postoperatively. The transient increase in activity may be explained by mobilization of natural killer cells from extravasal...... activity was observed after premedication with diazepam per os. The activity increased further during a combined anaesthesia (thiopentone + N2O + O2 + buprenorphene + pancuronium) and remained increased during surgery. Postoperatively, NK cell activity fell and remained depressed for a period of at least 5...
JianhongZhang; BAnneCroy; ZhigangTian
Uterine natural killer (uNK) cells, sharing many characters with peripheral blood natural killer (pNK) cells, are a major uterine lymphocyte population at early gestational stages during normal pregnancy in placental mammals. The functions of uNK cells include cytokine production and cytotoxcity that are regulated by signals through activating and inhibitory receptors. UNK cells differ from pNK cells however and contribute to the structural changes that accompany the differentiation of the maternal-fetal interface. Immunological mechanisms must provide a balanced environment for uNK cell proliferation, differentiation and activation through intricate signaling pathways. An improved knowledge of mechanisms regulating uNK cells development and the cytokine network at the maternal-fetal interface of mice and humans might be useful to harness the power of these cells for maintenance of pregnancy. Cellular & Molecular Immunology. 2005;2(2):123-129.
Jianhong Zhang; B Anne Croy; Zhigang Tian
Uterine natural killer (uNK) cells, sharing many characters with peripheral blood natural killer (pNK) cells, are a major uterine lymphocyte population at early gestational stages during normal pregnancy in placental mammals.The functions of uNK cells include cytokine production and cytotoxcity that are regulated by signals through activating and inhibitory receptors. UNK cells differ from pNK cells however and contribute to the structural changes that accompany the differentiation of the maternal-fetal interface. Immunological mechanisms must provide a balanced environment for uNK cell proliferation, differentiation and activation through intricate signaling pathways. An improved knowledge of mechanisms regulating uNK cells development and the cytokine network at the maternal-fetal interface of mice and humans might be useful to harness the power of these cells for maintenance of pregnancy. Cellular & Molecular Immunology. 2005;2(2):123-129.
Moura, A E; Kenny, J G; Chaudhuri, R R; Hughes, M A; Reisinger, R R; de Bruyn, P J N; Dahlheim, M E; Hall, N; Hoelzel, A R
For many highly mobile species, the marine environment presents few obvious barriers to gene flow. Even so, there is considerable diversity within and among species, referred to by some as the 'marine speciation paradox'. The recent and diverse radiation of delphinid cetaceans (dolphins) represents a good example of this. Delphinids are capable of extensive dispersion and yet many show fine-scale genetic differentiation among populations. Proposed mechanisms include the division and isolation of populations based on habitat dependence and resource specializations, and habitat release or changing dispersal corridors during glacial cycles. Here we use a phylogenomic approach to investigate the origin of differentiated sympatric populations of killer whales (Orcinus orca). Killer whales show strong specialization on prey choice in populations of stable matrifocal social groups (ecotypes), associated with genetic and phenotypic differentiation. Our data suggest evolution in sympatry among populations of resource specialists.
Full Text Available Killer yeasts are able to produce toxins that antagonize the growth of susceptible yeasts cells of the same species or the ones that are related to them. Killer strains are resistant to their own toxins but can be sensitive to killer proteins of other yeasts. The killer proteins of Pichia spp. are known for its broad spectrum of antifungal activity including pathogens such as Candida albicans. The aim of the study was to investigate the potential of the partly purified killer toxins to inhibit the growth of selected yeast strains which can contribute to wine spoilage. Three Pichia killer yeast strains (CBS 1982, CBS 5759, CBS 7373 were used in the study. The killer protein secreted by Pichia anomala CBS 1982 was characterized by the highest antifungal activity. The most pronounced effect of the reduction of cell proliferation by killer toxin preparations was found after 2 and 20 h cultivation. Among the 13 tested strains, all Pichia killer toxin preparations inhibited the growth of Rhodotorula graminis Rg, Rhodotorula mucilaginosa Rm and Schizosaccharomyces pombe DSM 70576. Killer toxins produced by Pichia anomala CBS 1982 (K8 and CBS 5759 (K4 limited the growth of Candida pulcherrima K5 and Hanseniaspora guillermondii DSM 3432 after 2, 20 and 168 h of incubation. A significant reduction of Debaryomyces hansenii DSM 3428 biomass was observed in medium with the addition of one toxin preparation (Pichia anomala CBS 1982. The growth limitation of Candida glabrata DSM 6425, Hanseniaspora uvarum DSM 2768, Metchnikowia pulcherrima DSM 70321 and Cryptococcus laurentii DSM 70766 was noticed only after 2 hours cultivation in presence of killer protein preparations. The killer toxins could be used in the food industry as selective tools to control infections during the fermentation of wine and improve the quality of the final product.
Behnood-Rod, Azin; Rabbanifar, Omid; Pourzargar, Pirouz; Rai, Alireza; Saadat, Zahra; Saadat, Habibollah; Moharamzad, Yashar; Morisky, Donald E
Introduction. Appropriate adherence to medication is still a challenging issue for hypertensive patients. We determined adherence to antihypertensive(s) and its associated factors among 280 Iranian patients. Methods. They were recruited consecutively from private and university health centers and pharmacies in four cities. The validated Persian version of the 8-item Morisky Medication Adherence Scale (MMAS-8) was administered to measure adherence. Results. Mean (±SD) overall MMAS-8 score was 5.75 (±1.88). About half of the sample (139 cases, 49.6%) showed low adherence (MMAS-8 score emergency services due to hypertensive crisis (B = -0.79, P = 0.001), and getting medication directly from drugstore without refill prescription in hand (B = -0.51, P = 0.04) were factors recognized to have statistically significant association with the MMAS-8 score. Conclusion. Antihypertensive adherence was unsatisfactory. We suggest that health care providers pay special attention and make use of the aforementioned findings in their routine visits of hypertensive patients to recognize those who are vulnerable to poor adherence. PMID:27069676
Full Text Available Introduction. Appropriate adherence to medication is still a challenging issue for hypertensive patients. We determined adherence to antihypertensive(s and its associated factors among 280 Iranian patients. Methods. They were recruited consecutively from private and university health centers and pharmacies in four cities. The validated Persian version of the 8-item Morisky Medication Adherence Scale (MMAS-8 was administered to measure adherence. Results. Mean (±SD overall MMAS-8 score was 5.75 (±1.88. About half of the sample (139 cases, 49.6% showed low adherence (MMAS-8 score < 6. There was a negative linear association between the MMAS-8 score and systolic BP (r=-0.231, P<0.001 as well as diastolic BP (r=-0.280, P<0.001. In linear regression model, overweight/obesity (B=-0.52, P=0.02, previous history of admission to emergency services due to hypertensive crisis (B=-0.79, P=0.001, and getting medication directly from drugstore without refill prescription in hand (B=-0.51, P=0.04 were factors recognized to have statistically significant association with the MMAS-8 score. Conclusion. Antihypertensive adherence was unsatisfactory. We suggest that health care providers pay special attention and make use of the aforementioned findings in their routine visits of hypertensive patients to recognize those who are vulnerable to poor adherence.
Approved for public release; distribution is unlimited In this thesis, we present a Markov-based probability model for a human operated system of aerial hunter-killers attacking time-sensitive targets. We explore the effect of two resources -- time and supply of munitions -- and some cognitive aspects of the human operator on the performance of the system in different operational scenarios. We model the combat mission as a sequence of engagements; each of which includes a classificati...
Singh, Bhoopendra; Singh, Prakash Raj; Mohanty, Manoj Kumar
The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant base...
Desbois, Mélanie; Rusakiewicz, Sylvie; Locher, Clara; Zitvogel, Laurence; Chaput, Nathalie
Natural killer (NK) cells belong to the innate immune system and were initially described functionallywise by their spontaneous cytotoxic potential against transformed or virus-infected cells. A delicate balance between activating and inhibiting receptors regulates NK cell tolerance. A better understanding of tissue resident NK cells, of NK cell maturation stages and migration patterns has evolved allowing a thoughtful evaluation of their modus operandi. While evidence has been brought up for...
The question of serial homicides and their perpetrators poses a considerable problem of both a definitional and practical nature. T R. Bundy is the first perpetrator who was officially termed a "serial killer". Since that time, this concept has been commonly used and sometimes even overused, e.g. in reference to mass murderers. However, the definitions established for Bundy's case have been preserved and continue to be used in practice.
Gumbleton, Matthew; Kerr, William G.
Natural killer (NK) cells are important for host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the inositol ph...
Jamil, K M; Hydes, T.J.; Cheent, K.S.; Cassidy, S A; Traherne, J. A.; Jayaraman, J.; Trowsdale, J.; Alexander, G J; Little, A M; McFarlane, H.; Heneghan, M. A.; Purbhoo, M.A.; Khakoo, S I
Objective: Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. Design: Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using ...
Caut, Stéphane; Laran, Sophie; Garcia-Hartmann, Emmanuel; Das, Krishna
There is currently a great deal of interest in using stable-isotope methods to investigate diet, trophic level and migration movement in wild cetaceans. Fundamental to the interpretation of these methods is the need to understand how diet isotopic values are reflected in consumer tissues. In this study, we investigated patterns of isotopic discrimination between diet and blood constituents of two species of cetaceans (killer whale, Orcinus orca and 19 bottlenose dolphin, Tursiops truncutus) f...
Yupanun WUTTI-IN; Preeyanat VONGCHAN; Thananchai, Hathairat
Background: Natural killer (NK) cells are important guards of the innate immune system, which act by performing as primary effector cells in viral infections. NK cell function is regulated by the engagement of activating and/or inhibitory receptors on individual NK cell surfaces. Subsequent to activation, the release of preformed cytolytic granules or cytokines occurs. Recently, the polyfunctionality of NK cells has been described as a potent NK cell subset that mediates antiviral response in...
Lester, David; White, John
In a sample of 483 serial killers, 6.2% were documented to have committed suicide. Those who committed suicide were found to come from more dysfunctional homes characterized by more psychiatric disturbance in the parents. The sexual acts involved in the murders by the suicides seemed to be more deviant in some aspects, such as committing more bizarre sexual acts or more often taping the murder.
Jentzen, J; Palermo, G; Johnson, L T; Ho, K C; Stormo, K A; Teggatz, J
We were involved as forensic experts in the case of the serial killer Jeffrey Dahmer. We discuss the scene and victim autopsy findings, with a brief consideration of the basic emotion of hostility. These findings support the thesis that at the basis of this serial killer's behavior were primary unconscious feelings of hate that he had channeled into a sadistic programmed destruction of 17 young men. The interview of the serial killer, the photographic scene documentation, and the autopsy findings stress the ambivalent homosexuality of the killer, his sexual sadism, his obsessive fetishism, and his possible cannibalism and necrophilia.
Kasahara, S; Ben Inoue, S; Mio, T; Yamada, T; Nakajima, T; Ichishima, E; Furuichi, Y; Yamada, H
HM-1 killer toxin secreted from Hansenula mrakii inhibits the growth of Saccharomyces cerevisiae cells by interfering with beta-1,3-glucan synthesis. We found that HM-1 killer toxin killed intact cells but not protoplasts. In addition, cells lacking the functional KRE6 allele (kre6 delta) became resistant to higher concentration of HM-1 killer toxin. As reported by Roemer and Bussey [(1991) Proc. Natl. Acad. Sci. 88 11295-11299], cells lacking functional KRE6 had a reduced level of the cell wall beta-1,6-glucan compared to that in cells harboring the normal KRE6. These results suggest that the cell wall beta-glucan is involved in the action of HM-1 killer toxin. Addition of HM-1 killer toxin with several kinds of oligosaccharides revealed that either beta-1,3- or beta-1,6-glucan blocked the cytocidal action of HM-1 killer toxin whereas alpha-1,4-glucan and chitin did not. Mannan also interfered with HM-1 killer toxin action, but this inhibitory effect was much weaker than that observed with beta-1,3- or beta-1,6-glucans. Thus, it appears that the cell wall beta-glucan interacts with HM-1 killer toxin, and that this toxin-beta-glucan commitment is required for the action of HM-1 killer toxin. PMID:8026578
Ausloos, M.; Petroni, F.
Religious adherence can be considered as a degree of freedom, in a statistical physics sense, for a human agent belonging to a population. The distribution, performance and life time of religions can thus be studied having in mind heterogeneous interacting agent modeling in mind. We present a comprehensive analysis of 58 so called religion (to be better defined in the main text) evolutions, as measured through their number of adherents between 1900 and 2000, - data taken from the World Christ...
Griffiths, P G; Elliot, T. S.; McTaggart, L
We have demonstrated, with an in vitro model, that Staphylococcus epidermidis is able to colonise intraocular lenses. Adherent organisms were quantitated by light microscopy, scanning electron microscopy, and viable counting. Bacterial adherence was associated with production of a polysaccharide glycocalyx. Organisms which were attached to the lenses were resistant to apparently bactericidal concentrations of antibiotics, as determined by conventional testing. We speculate on the role of colo...
Jones Gareth; Hawkins Kim; Mullin Rebecca; Nepusz Tamás; Naughton Declan P; Sheeran Paschal; Petróczi Andrea
Abstract Background The extent to which patients follow treatments as prescribed is pivotal to treatment success. An exceptionally high level (> 95%) of HIV medication adherence is required to suppress viral replication and protect the immune system and a similarly high level (> 80%) of adherence has also been suggested in order to benefit from prescribed exercise programmes. However, in clinical practice, adherence to both often falls below the desirable level. This project aims to investiga...
Full Text Available After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1 Adherence measurement in clinical trials, (2 Comprehension of use instructions/Instructions for use, (3 Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4 Partner influence on use, (5 Retention and continuation and (6 Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.
Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044
Spontaneous and ultraviolet-induced changeabilities of wine yeasts from the killer state to sensitive one have been studied. Observed often spontaneous changes of killer and neutral phenotypes under laboratory store conditions as well as high mutation frequency of genetic elements responsible for the killer indication on ultraviolet irradiation testify that often encounterability in nature and in the production of sensitive yeasts is attributed to high frequency of mutation changes of the killer and neutral phenotypes to the sensitive state
Schafer, Jamie L; Ries, Moritz; Guha, Natasha; Connole, Michelle; Colantonio, Arnaud D; Wiertz, EJ; Wilson, Nancy A; Kaur, Amitinder; Evans, David T
Natural killer (NK) cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex (MHC) class I ligands on target cells. We previously reporte
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Gildo Almeida da Silva
Full Text Available The aim of this work was to study the production of functional protein in yeast culture. The cells of Saccharomyces cerevisiae Embrapa 1B (K+R+ killed a strain of Saccharomyces cerevisiae Embrapa 26B (K-R-in grape must and YEPD media. The lethal effect of toxin-containing supernatant and the effect of aeration upon functional killer production and the correlation between the products of anaerobic metabolism and the functional toxin formation were evaluated. The results showed that at low sugar concentration, the toxin of the killer strain of Sacch. cerevisiae was only produced under anaerobic conditions . The system of killer protein production showed to be regulated by Pasteur and Crabtree effects. As soon as the ethanol was formed, the functional killer toxin was produced. The synthesis of the active killer toxin seemed to be somewhat associated with the switch to fermentation process and with concomitant alcohol dehydrogenase (ADH activity.
Lee, Hyubn Jin; Lee, Sang Wook; Suh, Cheol Won; Huh, Joo Ryung; Yoon, Sang Min; Kim, Young Seok; Kim, Su San; Kim, Jong Hoon; Choi, Eun Kyung; Ahn, Seung Do [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
To evaluate the radiotherapy treatment outcome of patients in stage IE and IIE nasal natural killer/T-cell lymphoma. From August 1999 to August 2009, 46 patients with stage IE and IIE nasal natural killer/T-cell lymphoma were treated by definitive radiotherapy and chemotherapy. 33 patients were treated with chemotherapy followed by radiotherapy (CT + RT) and they received 50.4 Gy in 28 fractions. 13 patients were treated with concurrent chemoradiotherapy (CCRT) and they received 40 Gy in 20 fractions. The median follow-up period was 4.6-137.6 months (median, 50.2 months) for all patients. The 4-year overall survival was 68.6% and 4-year disease free survival (DFS) was 61.9%. The 4-year locoregional recurrence free survival was 65.0%, and 4-year distant metastasis free survival (DMFS) was 66.2%. For patients treated with CT + RT, 15 patients (45.5%) achieved complete response after chemotherapy, and 13 patients (39.4%) achieved partial response. 13 patients (81.8%) achieved complete response after radiotherapy, and 6 patients (18.2%) achieved partial response. For patients treated with CCRT, 11 patients (84.6%) achieved complete response, and one patient (7.7%) achieved partial response. In univariate analysis, presence of cervical lymph node metastasis was only significant prognostic factor for DFS and DMFS. This study did not show satisfactory overall survival rate and disease free survival rate of definitive radiotherapy and chemotherapy for stage IE and IIE nasal natural killer/T-cell lymphoma. For patients with cervical lymph node metastasis, further investigation of new chemotherapy regimens is necessary to reduce the distant metastasis.
Zschocke, Ina; Mrowietz, Ulrich; Lotzin, Annett; Karakasili, Eleni; Reich, Kristian
Medication adherence rates strongly depend on favorable disease outcomes. It is known that medication adherence rates are lower for topical treatment than for systemic treatment. However, to date no validated instrument for the assessment of adherence factors in topical treatment is available. The aim of this study was to develop a new questionnaire to assess adherence risk factors in topical treatment. The development of the Topical Therapy Adherence Questionnaire (TTAQ) and Patient Preference Questionnaire (PPQ) was based on a systematic literature review, and qualitative patient focus interviews and expert focus groups' input. The psychometric properties and comprehensibility of the TTAQ and PPQ were assessed in a feasibility study with 59 psoriasis patients. Our first preliminary results indicate that the TTAQ and PPQ are psychometrically sound and reliable measures for the assessment of factors influencing topical treatment adherence. The questionnaires are currently being further developed and various parameters (e.g., time point of assessment) are currently being tested in an exploratory pilot study with ca. 2,000 psoriasis patients receiving topical treatment in a European clinical trial. The use of the final versions of TTAQ and PPQ in clinical practice may facilitate the early identification of specific non-adherence factors in patients under topical treatment, which could enable designing and applying adherence-enhancing interventions according to the patient's individual needs.
Kaul, Sunil C; Deocaris, Custer C; Wadhwa, Renu
Mortalin was first cloned as a mortality factor that existed in the cytoplasmic fractions of normal, but not in immortal, mouse fibroblasts. A decade of efforts have expanded its persona from a house keeper protein involved in mitochondrial import, energy generation and chaperoning of misfolded proteins, to a guardian of stress that has multiple binding partners and to a killer protein that contributes to carcinogenesis on one hand and to old age disorders on the other. Being proved to be an attractive target for cancer therapy, it also warrants attention from the perspectives of management of old age diseases and healthy aging.
Do you have a Facebook profile? How about a Google+ page? Which do you prefer: Facebook or Google+? You may have both, but not use one as often as the other. You may have just one while waiting for the right time to join the other. The question is: When is the right time? Are you waiting to see which one is the better product? This issue has been the talk of the cybersphere since Google+ was released - will it be the Facebook killer that a number of other social media sites in the past have failed to become?
Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells(IKDCs).IKDCs not only secret type I and type II interferons to recognize and kill tumor cells effectively, but also express MHC-II molecules to present antigens.Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.
DAI Wei; ZHONG Ming; SHEN Wei; ZOU Ke; BAI Chen-guang
Natural killer T-cell lymphoma (NKTL) is a malignant neoplasm which usually involves the nasal cavity or paranasal sinuses,while an orbit origin is extremely rare.Here we report the clinical,radiological and histopathologic features of a patient with NKTL originating from the orbit.We analyzed the clinical and radiologic records in the whole course of the disease.We also reviewed the morphology and immunohistochemistry of the neoplasm biopsy,including the presence of CD56,CD3 and cytotoxic molecules.This case demonstrated that nasal-type NKTL with a poor prognosis can originate from the orbit.
李建中; 章竹君; 金伯泉; 田方
A new time-resolved fluorimetric method for the measurement of natural killer (NK) cell cytotoxicity has been developed by labelling the target cell K562 with a new synthesized fluorescence marker KLUK. The method has advantages of higher sensitivity, time-saving, good reproducibility and has no radioactivity problems. A satisfactory result is obtained by comparing it with 51Cr release method. It demonstrates that the new marker provides an alternative to currently used radioactive markers for the assessment of in vitro cellular cytotoxicity.
WANG JiongKun; XING FeiYue
Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells (IKDCs). IKDCs not only secret type Ⅰ and type Ⅱ interferons to recognize and kill tumor cells effectively, but also express MHC-Ⅱ molecules to present antigens. Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.
POLONELLI, L.; Morace, G
Anti-idiotypic antibodies (anti-Ids) were raised in a rabbit against a murine monoclonal antibody (MAb) neutralizing the yeast killer toxin produced by a strain of Pichia (Hansenula) anomala. In an immunodiffusion test, the anti-Ids produced in the rabbit recognized the antigen-binding site of the MAb used as the immunogen (KT4) but not that of another heterologous MAb. The absence of any significant cross-reactivity among the anti-Ids raised in a rabbit for a heterologous MAb suggested that ...
Hedegaard, Ulla; Kjeldsen, Lene Juel; Pottegård, Anton;
BACKGROUND: and Purpose: In patients with hypertension, medication adherence is often suboptimal, thereby increasing the risk of ischemic heart disease and stroke. In a randomized trial, we investigated the effectiveness of a multifaceted pharmacist intervention in a hospital setting to improve...... medication adherence in hypertensive patients. Motivational interviewing was a key element of the intervention. METHODS: Patients (N=532) were recruited from 3 hospital outpatient clinics and randomized to usual care or a 6-month pharmacist intervention comprising collaborative care, medication review......, tailored adherence counselling including motivational interviewing and telephone follow-ups. The primary outcome was composite medication possession ratio (MPR) to antihypertensive and lipid-lowering agents, at one-year follow-up, assessed by analyzing pharmacy records. Secondary outcomes at 12 months...
Cooperman, Nina A.; Heo, Moonseong; Berg, Karina M.; Li, Xuan; Litwin, Alain H.; Nahvi, Shadi; Arnsten, Julia H.
Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence couns...
Abdulmajid Ahmed Ali
Full Text Available To The Editor: It is estimated that 1.26 million people worldwide died in 2000 from road traffic accidents, 90% of them in low and middle-income countries. In 2000, the road traffic injury mortality rate for the world was 20.8 per 100,000 populations (30.8 in males, 11.0 in females .The Arab population constitutes 3.6% of the world’s population and it owns 1% of the world’s vehicles. Its human losses as a result of road traffic accidents (RTA account for 4.8% of that of the world’s losses . It is estimated that the annual cost of road crashes is about 1% of the Gross National Product (GNP in developing countries, 1.5 in transitional countries and 2% in highly motorised countries .In Libya the situation is worse. It is a sad fact that road traffic accidents are the number one killer in Libya. As a matter of fact I consider it to be an ‘epidemic’ in all sectors of the Libyan society. There is not a day that goes by in Libya without us hearing about families, young men, women and children getting killed in horrific car accidents.It is alarming that young children are knocked down on a daily basis by speeding young drivers, whose understanding of driving skills may have been acquired from "playstation games"! (You can watch some of the shameful video clips sent by some of these drivers on this link http://www.youtube.com/watch?v=doWEDjiHlVoI feel it is our responsibility as physicians observing the situation to raise awareness about the scale of the problem, possible causes, and how to tackle it. POSSIBLE CAUSES:• A driving licence in Libya is not issued on the basis of how much you know. Therefore the majority of drivers know little or nothing about the law.• Wearing seat belts is not compulsory in most parts of Libya. In some places, especially in the Eastern part of Libya, you could be penalised for wearing one. I was stopped many years ago by the traffic police in the Eastern part of Libya because I was wearing sunglasses
Bauwens, Marine; Schneider, Marie-paule; Nanchen, David
Statins are an established treatment for dyslipidemia, because they were shown to decrease the cardiovascular risk by 25%. However, one third of patients using statins don't take them regularly. Statin intolerance is an important risk factor for nonadherence, but health literacy and lack of education regarding the cardiovascular benefits are also important triggers for poor adherence to statins. A better communication between the caregiver and his patient, by taking patient's perspectives into account could help find effective solutions. This article reviews the issue of statins adherence and suggests solutions to improve it. PMID:27089601
Full Text Available Many receptors on natural killer (NK cells recognize major histocompatibility complex class I molecules in order to monitor unhealthy tissues, such as cells infected with viruses, and some tumors. Genes encoding families of NK receptors and related sequences are organized into two main clusters in humans: the natural killer complex on Chromosome 12p13.1, which encodes C-type lectin molecules, and the leukocyte receptor complex on Chromosome 19q13.4, which encodes immunoglobulin superfamily molecules. The composition of these gene clusters differs markedly between closely related species, providing evidence for rapid, lineage-specific expansions or contractions of sets of loci. The choice of NK receptor genes is polarized in the two species most studied, mouse and human. In mouse, the C-type lectin-related Ly49 gene family predominates. Conversely, the single Ly49 sequence is a pseudogene in humans, and the immunoglobulin superfamily KIR gene family is extensive. These different gene sets encode proteins that are comparable in function and genetic diversity, even though they have undergone species-specific expansions. Understanding the biological significance of this curious situation may be aided by studying which NK receptor genes are used in other vertebrates, especially in relation to species-specific differences in genes for major histocompatibility complex class I molecules.
The L/sub A/ and M double-stranded (ds) RNA segments of the cytoplasmically inherited killer virus of Saccharomyces cerevisiae are encapsidated in virions that contain a DNA-independent transcriptase activity. This enzyme catalyzes the synthesis of full-length (+) stranded copies of the genomic dsRNA segments, denoted l/sub A/ and m. The L/sub A/ dsRNA segment appears to encode the major capsid protein in which both dsRNA molecules are encapsidated, while M dsRNA encodes products responsible for the two killer phenotypes of toxin production and resistance to toxin. Proteins extracted from transcriptionally active virions fail to cross-react with antibody to yeast DNA-dependent RNA polymerases, suggesting that none of the subunits of the host cell polymerases are active in viral transcription. Sequence analysis of the in vitro transcripts reveals neither to be 3'-terminally polyadenylated, although m contains an apparent internal polyA-like tract. In the presence of any three ribonucleoside triphosphates (0.5 mM), the fourth ribonucleoside triphosphate shows an optimal rate of incorporation into transcript at a concentration of 20 μM. However, in a 3-hour reaction, the yield of a product RNA increases with the concentration of the limiting ribonucleotide up to 0.5 mM. Gel electrophoresis of the reaction products reveals that increasing the substrate concentration accelerates the appearance of radioactivity in full-length l/sub A/ and m transcripts
Wolkers, Hans; Corkeron, Peter J; Van Parijs, Sofie M; Similä, Tiu; Van Bavel, Bert
Blubber tissue of one subadult and eight male adult killer whales was sampled in Northern Norway in order to assess the degree and type of contaminant exposure and transfer in the herring-killer whale link of the marine food web. A comprehensive selection of contaminants was targeted, with special attention to toxaphenes and polybrominated diphenyl ethers (PBDEs). In addition to assessing exposure and food chain transfer, selective accumulation and metabolism issues also were addressed. Average total polychlorinated biphenyl (PCB) and pesticide levels were similar, approximately 25 microg/g lipid, and PBDEs were approximately 0.5 microg/g. This makes killer whales one of the most polluted arctic animals, with levels exceeding those in polar bears. Comparing the contamination of the killer whale's diet with the diet of high-arctic species such as white whales reveals six to more than 20 times higher levels in the killer whale diet. The difference in contaminant pattern between killer whales and their prey and the metabolic index calculated suggested that these cetaceans have a relatively high capacity to metabolize contaminants. Polychlorinated biphenyls, chlordanes, and dichlorodiphenyldichloro-ethylene (DDE) accumulate to some degree in killer whales, although toxaphenes and PBDEs might be partly broken down.
Samarra, Filipa I P; Deecke, Volker B; Miller, Patrick J O
Killer whale acoustic behavior has been extensively investigated; however, most studies have focused on pulsed calls and whistles. This study reports the production of low-frequency signals by killer whales at frequencies below 300 Hz. Recordings were made in Iceland and Norway when killer whales were observed feeding on herring and no other marine mammal species were nearby. Low-frequency sounds were identified in Iceland and ranged in duration between 0.14 and 2.77 s and in frequency between 50 and 270 Hz, well below the previously reported lower limit for killer whale tonal sounds of 500 Hz. Low-frequency sounds appeared to be produced close in time to tail slaps, which are indicative of feeding attempts, suggesting that these sounds may be related to a feeding context. However, their precise function is unknown, and they could be the by-product of a non-vocal behavior rather than a vocal signal deliberately produced by the whales. Although killer whales in Norway exhibit similar feeding behavior, this sound has not been detected in recordings from Norway to date. This study suggests that, like other delphinids, killer whales produce low-frequency sounds, but further studies will be required to understand whether similar sounds exist in other killer whale populations. PMID:27036251
Cellular immune response is a major barrier to xenotransplantation. Human tumor necrosis factor-α (hTNF-α) possesses cross-species activity and directly amplifies the immune rejection via the upregulation of adhesion molecules on porcine endothelium. We investigated the role of protein tyrosine phosphorylation in the induction of expression of E-sclectin and vascular cell adhesion molecule-1 (VCAM-1), and the augmentation of adhesion of human peripheral blood monocytes (PBMo) and natural killer cells (PBNK), after rhTNF-α-stimulation of porcine aortic endothelial cells (PAEC) in vitro, rhTNF-α-increased adhesiveness of PAEC for both PBMo and PBNK was dose-dependently reduced by pretreatment of PAEC with the selective protein tyrosine kinase (PTK) inhibitor genistein. The inhibitory effect occurred at the early time of PAEC activation triggered by rhTNF-α, and was completely reversible. PTK activity assay indicated that genistein also suppressed rhTNF-α stimulated activation of protein tyrosine kinases (PTKs) in PAEC in a dose-dependent manner. Flow cytometric analysis showed that genistein inhibited the upregulation of E-selectin and VCAM-1 by rhTNF-α. These results suggest that PTKs may regulate the expression of E-selectin and VCAM-1 on PAEC and the adherence of PBMo and PBNK induced by rhTNF-α. Moreover, dietary genistein, used as an adhesion antagonist, may contribute to managing the cell-mediated rejection in the clinical application.
van Beers Hans
Full Text Available Abstract Background Clinical guidelines are considered important instruments to improve quality in health care. In physiotherapy, insight in adherence to guidelines is limited. Knowledge of adherence is important to identify barriers and to enhance implementation. Purpose of this study is to investigate the ability to adherence to recommendations of the guideline Acute ankle injury, and to identify patient characteristics that determine adherence to the guideline. Methods Twenty-two physiotherapists collected data of 174 patients in a prospective cohort study, in which the course of treatment was systematically registered. Indicators were used to investigate adherence to recommendations. Patient characteristics were used to identify prognostic factors that may determine adherence to the guideline. Correlation between patient characteristics and adherence to outcome-indicators (treatment sessions, functioning of patient, accomplished goals was calculated using univariate logistic regression. To calculate explained variance of combined patient characteristics, multivariate analysis was performed. Results Adherence to individual recommendations varied from 71% to 100%. In 99 patients (57% the physiotherapists showed adherence to all indicators. Adherence to preset maximum of six treatment sessions for patients with severe ankle injury was 81% (132 patients. The odds to receive more than six sessions were statistically significant for three patient characteristics: females (OR:3.89; 95%CI: 1.41–10.72, recurrent sprain (OR: 6.90; 95%CI: 2.34 – 20.37, co-morbidity (OR: 25.92; 95% CI: 6.79 – 98.93. All factors together explained 40% of the variance. Inclusion of physiotherapist characteristics in the regression model showed that work-experience reduced the odds to receive more than six sessions (OR: 0.2; 95%CI: 0.06 – 0.77, and increased explained variance to 45%. Conclusion Adherence to the clinical guideline Acute ankle sprain showed that the
Waldemar Waldeck, Gabriele Mueller, Manfred Wiessler, Katalin Tóth, Klaus Braun
Full Text Available Fluorescent proteins (FPs are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED, used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS resulting in photokilling processes. It is a given that the extent of the KRED's cell toxicity depends on its subcellular localization. Evidences are documented that the nuclear lamina as well as especially the chromatin are critical targets for KRED-mediated ROS-based DNA damaging. Here we investigated the damaging effects of the KRED protein fused to the nuclear lamina and to the histone H2A DNA-binding protein. We detected a frequency of DNA strand breaks, dependent first on the illumination time, and second on the spatial distance between the localization at the chromatin and the site of ROS production. As a consequence we could identify defined DNA bands with 200, 400 and (600 bps as most prominent degradation products, presumably representing an internucleosomal DNA cleavage induced by KRED. These findings are not restricted to the detection of programmed cell death processes in the therapeutic field like PDT, but they can also contribute to a better understanding of the structure-function relations in the epigenomic world.
Waldeck, Waldemar; Mueller, Gabriele; Wiessler, Manfred; Tóth, Katalin; Braun, Klaus
Fluorescent proteins (FPs) are established tools for new applications, not-restricted to the cell biological research. They could also be ideal in surgery enhancing the precision to differentiate between the target tissue and the surrounding healthy tissue. FPs like the KillerRed (KRED), used here, can be activated by excitation with visible day-light for emitting active electrons which produce reactive oxygen species (ROS) resulting in photokilling processes. It is a given that the extent of the KRED's cell toxicity depends on its subcellular localization. Evidences are documented that the nuclear lamina as well as especially the chromatin are critical targets for KRED-mediated ROS-based DNA damaging. Here we investigated the damaging effects of the KRED protein fused to the nuclear lamina and to the histone H2A DNA-binding protein. We detected a frequency of DNA strand breaks, dependent first on the illumination time, and second on the spatial distance between the localization at the chromatin and the site of ROS production. As a consequence we could identify defined DNA bands with 200, 400 and (600) bps as most prominent degradation products, presumably representing an internucleosomal DNA cleavage induced by KRED. These findings are not restricted to the detection of programmed cell death processes in the therapeutic field like PDT, but they can also contribute to a better understanding of the structure-function relations in the epigenomic world. PMID:21278894
Feldman, S.R.; Horn, E.J.; Balkrishnan, R.; Basra, M.K.; Finlay, A.Y.; McCoy, D.; Menter, A.; Kerkhof, P.C.M. van de
Topical therapy has an important role in psoriasis treatment. It is efficacious and has a favorable safety profile as demonstrated in clinical trials. However, poor treatment outcomes from topical therapy regimens likely result from poor adherence and ineffective use of the medication. The Internati
Wagner, Stefan Rahr; Toftegaard, Thomas Skjødeberg; Bertelsen, Olav W.
. Methods: Key concepts related to self-care and adherence were defined, discussed, and implemented as part of the ASEF framework. ASEF was applied to seven self-care case studies, and the perceived usefulness and feasibility of ASEF was evaluated in a questionnaire study by the case study participants...
Bregnballe, Vibeke; Schiøtz, Peter Oluf
Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack...
Full Text Available ABSTRACT: BACKGROUND: In spite of any number of medicines will not be of use unless patient takes’ them. After diagnosing the disease, the next most i mportant step is to follow the instructions of physician in terms of treatment. The doctor’s respons ibility does not end with writing prescription, assuming patient will adhere to it. He/ she should cross check the behavior of patient for drug compliance and see that patient follo ws it and get the benefit. Non compliance is the main barrier for the effective delivery of the medical care. This will have greater implications on the economic burde n on the country in terms of frequent hospitalization, use of expensive medicines in case o f relapse due to non adherence.Though the terms compliance and adherence are used synonymously , they differ in the delivery of quality of the medicare as the former implicates the passive fol lowing of the physician instruction, while in the later, patient actively participates in the dev elopment of the treatment plan, which will improves outcome of the treatment. Adherence is the preferred term over compliance by WHO.
Morgan, William P.; Dishman, Rod K.
Introduces a collection of papers on adherence to exercise programs and physical activity from the 2000 American Academy of Kinesiology and Physical Education conference, which included research on middle school boys and girls, college men and women, and men and women in the later years, as well as on the more traditional subject of middle aged…
Although eHealth technologies and especially web-based interventions for the promotion of health and health related behavior have been shown to be effective, the impact is hindered by non-adherence: while many eHealth interventions reach a large group of participants, not all of these participants c
Linnet, Kristján; Halldórsson, Matthías; Thengilsdóttir, Gudrún;
Primary non-adherence refers to the patient not redeeming a prescribed medication at some point during drug therapy. Research has mainly focused on secondary non-adherence. Prior to this study, the overall rate of primary non-adherence in general practice in Iceland was not known.......Primary non-adherence refers to the patient not redeeming a prescribed medication at some point during drug therapy. Research has mainly focused on secondary non-adherence. Prior to this study, the overall rate of primary non-adherence in general practice in Iceland was not known....
von Zons, P; Crowley-Nowick, P; Friberg, D; Bell, M.; Koldovsky, U; Whiteside, T L
Natural killer (NK) and lymphokine-activated killer (LAK) cell activities were measured in peripheral blood obtained from healthy women to compare a standard 51Cr release assay with a nonradioactive europium (Eu3+) release assay based on time-resolved fluorescence. The two types of cytotoxicity assays were first compared in paired determinations performed on 28 samples of peripheral blood mononuclear cells obtained from healthy women who had normal pap smears or no biopsy evidence of cervical...
Peremarch, C Perez-Jorge; Tanoira, R Perez; Arenas, M A; Matykina, E; Conde, A; De Damborenea, J J; Gomez Barrena, E; Esteban, J, E-mail: firstname.lastname@example.org
The aim of this study was to evaluate Staphylococcus sp adhesion to modified surfaces of anodized titanium alloy (Ti-6Al-4V). Surface modification involved generation of fluoride-containing titanium oxide nanotube films. Specimens of Ti-6Al-4V alloy 6-4 ELI-grade 23- meets the requirements of ASTM F136 2002A (AMS 2631B class A1) were anodized in a mixture of sulphuric/hydrofluoric acid at 20 V for 5 and 60 min to form a 100 nm-thick porous film of 20 nm pore diameter and 230 nm-thick nanotube films of 100 nm in diameter. The amount of fluorine in the oxide films was of 6% and of 4%, respectively. Collection strains and six clinical strains each of Staphylococcus aureus and Staphylococcus epidermidis were studied. The adherence study was performed using a previously published protocol by Kinnari et al. The experiments were performed in triplicates. As a result, lower adherence was detected for collection strains in modified materials than in unmodified controls. Differences between clinical strains were detected for both species (p<0.0001, Kruskal-Wallis test), although global data showed similar results to that of collection strains (p<0.0001, Kruskal-Wallis test). Adherence of bacteria to modified surfaces was decreased for both species. The results also reflect a difference in the adherence between S. aureus and S. epidermidis to the modified material. As a conclusion, not only we were able to confirm the decrease of adherence in the modified surface, but also the need to test multiple clinical strains to obtain more realistic microbiological results due to intraspecies differences.
J. Valentín Quiroga
Full Text Available Introducción: En el momento actual, los tumores sólidos refractarios al tratamiento convencional constituyen la principal causa de muerte en la edad pediátrica. Por tanto, es necesario desarrollar y consolidar nuevos tratamientos. Las células Natural Killer (NK constituyen la primera línea de defensa del sistema inmune frente al desarrollo de células tumorales. Planteamos una nueva estrategia de terapia celular antitumoral en niños con cánceres refractarios, inmunoterapia con células NK estimuladas con interleucina 15 (IL-15. Pacientes y Métodos: En 22 pacientes pediátricos con tumores sólidos refractarios y en controles sanos determinamos mediante citometría de flujo multiparamétrica y fluorescencia resuelta en el tiempo, el fenotipo y la actividad citotóxica de las células NK, respectivamente. En ratones inmunodeficientes desarrollamos un modelo de neuroblastoma metastático muy agresivo y terapia de rescate con células Natural Killer estimuladas con IL-15. Resultados: Los pacientes pediátricos con cáncer refractario tienen un mayor porcentaje de células NK bright y una menor actividad citotóxica. La estimulación con IL-15 mejora la citotoxicidad in vitro y disminuye la carga tumoral in vivo. Conclusiones: Las células NK estimuladas con IL-15 constituyen una prometedora estrategia antitumoral.Introduction: Refractory solid tumours lead children deaths. To change this statement, new treatments should be developed. Natural Killer cells constitute the first line of defence against tumour cells. We propose a new strategy for antitumor cell therapy in children with refractory solid malignancies: IL-15 stimulated NK cells. Patients and methods: 22 paediatric patients suffering refractory solid tumours participate in this study. We compare NK cell subsets and K562 cytotoxicity in patients and sex-age pair's healthy controls. We use multiparametric flow and time-resolved fluorescent, respectively. In immunocompromised mice we
Matzner, Shari; Fu, Tao; Ren, Huiying; Deng, Zhiqun; Sun, Yannan; Carlson, Thomas J.
For the planned tidal turbine site in Puget Sound, WA, the main concern is to protect Southern Resident Killer Whales (SRKW) due to their Endangered Species Act status. A passive acoustic monitoring system is proposed because the whales emit vocalizations that can be detected by a passive system. The algorithm for detection is implemented in two stages. The first stage is an energy detector designed to detect candidate signals. The second stage is a spectral classifier that is designed to reduce false alarms. The evaluation presented here of the detection algorithm incorporates behavioral models of the species of interest, environmental models of noise levels and potential false alarm sources to provide a realistic characterization of expected operational performance.
Ren, Yulin; Yuan, Chunhua; Deng, Youcai; Kanagasabai, Ragu; Ninh, Tran Ngoc; Tu, Vuong Tan; Chai, Hee-Byung; Soejarto, Djaja D.; Fuchs, James R.; Yalowich, Jack C.; Yu, Jianhua; Kinghorn, A. Douglas
A dichapetalin-type triterpenoid and a dibenzylbutyrolactone-type lignan, together with five known lignans, a known aromatic diterpenoid, and a known acylated phytosterol, were isolated from the aerial parts of Phyllanthus songboiensis, collected in Vietnam. Their structures were determined by interpretation of the spectroscopic data, and the inhibitory activity toward the HT-29 human colon cancer cells of all isolates was evaluated by a cytotoxicity assay. The known arylnaphthalene lignan, (+)-acutissimalignan A, was highly cytotoxic toward HT-29 cells, with an IC50 value of 19 nM, but this compound was inactive as a DNA topoisomerase IIα (topo IIα) poison. The known phytosterol, (−)-β-sitosterol-3-O-β-D-(6-O-palmitoyl)glucopyranoside, was found to stimulate natural killer (NK) cells at a concentration of 10 μM in the presence of interleukin 12 (IL-12). PMID:25596805
Heiberg, Ida Louise; Laura J., Pallett; Winther, Thilde Nordmann;
Natural Killer (NK) cells exhibit dysregulated effector function in adult chronic HBV infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK...... cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell IFN-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells...... suggests a role of impaired NK-Dendritic Cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of antiviral therapy...
Bossi, Giovanna; Trambas, Christina; Booth, Sarah; Clark, Richard; Stinchcombe, Jane; Griffiths, Gillian M
Cytotoxic T lymphocytes (CTLs) destroy their targets by a process involving secretion of specialized granules. The interactions between CTLs and target can be very brief; nevertheless, adhesion and signaling proteins segregate into an immunological synapse. Secretion occurs in a specialized secretory domain. Use of live and fixed cell microscopy allows this secretory synapse to be visualized both temporally and spatially. The combined use of confocal and electron microscopy has produced some surprising findings, which suggest that the secretory synapse may be important both in delivering the lethal hit and in facilitating membrane transfer from target to CTL. Studies on the secretory synapse in wild-type and mutant CTLs have been used to identify proteins involved in secretion. Further clues as to the signals required for secretion are emerging from comparisons of inhibitory and activating synapses formed by natural killer cells.
Kallian, M; Bar-el, Y C; Durst, R; Witztum, E
This paper describes a rare forensic psychiatric syndrome which has been the subject of massive publicity in the last decade. Despite the widespread interest, the psychodynamic process whereby a person becomes a serial murderer remains largely unknown. "Jacob" was convicted of a series of murders that he carried out over a decade. The case material is based on the psychiatric reports that were presented to the court and the many articles published in the local press at the time. Despite the limitations imposed by the material, the available information on "Jacob" bears some similarity to the phenomenological and psychodynamic models described in the literature. An attempt is made to understand the transformation of a person into a serial killer considering the life events, psychopathology and stressors that lead to the emergence from the world of imagination and fantasy of a potential murderer to the deeds that comprise the syndrome.
JIANG Yong-jun; SHANG Hong; ZHANG Zi-ning; DIAO Ying-ying; GENG Wen-qing; DAI Di; LIU Jing; WANG Ya-nan; ZHANG Min; HAN Xiao-xu
@@ Natural killer (NK) cells are bone marrow derived,large granular lymphocytes, comprising approximately 10% to 20% of the mononuclear cell fraction in normal peripheral blood. They form a part of the first line defense mechanism against tumoural and viral spreading.1-4 Unlike T and B cells, NK cells do not require gene rearrangement for assembly of their receptor genes; rather, NK cells discriminate potential target cells based on the levels of self major histocompatibility complex (MHC) class Ⅰ expression on such cells.5,6 There are two kinds of NK cell receptors.2,7,8 Inhibitory receptors recognize MHC class Ⅰ molecules and deliver a downregulatory signal that inactivates the lyric machinery of NK cells. Stimulatory receptors expressed by NK cells deliver an activation signal.
Steatosis is a common feature of many liver diseases, namely non-alcoholic steatohepatitis (NASH) and hepatitis C virus (HCV) infection, but the pathogenic mechanisms differ. Insulin resistance (IR), a key feature of metabolic syndrome, is crucial for NASH development, associated with many underlying genetically determined or acquired mitochondrial and metabolic defects and culminates to inflammation and progression to fibrosis. This may have potential implications for new drug therapy. In HCV-related disease, steatosis impacts both fibrosis progression and response to treatment. Steatosis in HCV-related disease relates to both viral factors (HCV genotype 3), and host factors (alcohol consumption, overweight, hyperlipidemia, diabetes). Among others, IR is a recognized factor. Hepatic steatosis is reported to be associated with disturbance in the signaling cascade of interferon and downregulation of its receptors. Thus, hepatic steatosis should not be considered a benign feature, but rather a silent killer.
Full Text Available Natural killer (NK cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I and Class I-like molecules, classical co-stimulatory ligands and cytokines. The ability of NK cells to be very rapidly activated by inflammatory cytokines, to secrete effector cytokines and to kill infected or stressed host cells, suggests that they may be among the very early responders during infection. Recent studies have also identified a small number of pathogen-derived ligands that can bind to NK cell surface receptors and directly induce their activation. Here we review recent studies that have begun to elucidate the various pathways by which viral, bacterial and parasite pathogens activate NK cells. We also consider two emerging themes of NK cell-pathogen interactions, namely their contribution to adaptive immune responses and their potential to take on regulatory and immunomodulatory functions.
Levin, Jennifer B; Krivenko, Anna; Howland, Molly; Schlachet, Rebecca; Sajatovic, Martha
Poor medication adherence is a pervasive problem that causes disability and suffering as well as extensive financial costs among individuals with bipolar disorder (BD). Barriers to adherence are numerous and cross multiple levels, including factors related to bipolar pathology and those unique to an individual's circumstances. External factors, including treatment setting, healthcare system, and broader health policies, can also affect medication adherence in people with BD. Fortunately, advances in research have suggested avenues for improving adherence. A comprehensive review of adherence-enhancement interventions for the years 2005-2015 is included. Specific bipolar adherence-enhancement approaches that target knowledge gaps, cognitive patterns, specific barriers, and motivation may be helpful, as may approaches that capitalize on technology or novel drug-delivery systems. However, much work remains to optimally facilitate long-term medication adherence in people with BD. For adherence-enhancement approaches to be widely adapted, they need to be easily accessible, affordable, and practical. PMID:27435356
Full Text Available Natural killer (NK cells, key members of a distinct hempatopoietic lineage, innate lymphoid cells (ILCs, are critical effectors that mediate cytotoxicity toward tumor and virally-infected cells but also regulate inflammation, antigen presentation and the adaptive immune response. It has been shown that NK cells can regulate the development and activation of many other components of the immune response such as dendritic cells, which in turn, modulate the function of NK cells in multiple synergistic feed back loops driven by cell-cell contact and the secretion of cytokines and chemokines that control effector function and migration of cells to sites of immune activation. The Signal Transducer and Activator of Transcription (STAT-3 is involved in driving almost all of the pathways that control NK cytolytic activity as well as the reciprocal regulatory interactions between NK cells and other components of the immune system. In the context of tumor immunology, NK cells are a first line of defense that eliminates pre-cancerous and transformed cells early in the process of carcinogenesis, through a mechanism of immune surveillance. Even after tumors become established, NK cells are critical components of anti-cancer immunity: dysfunctional NK cells are often found in the peripheral blood of cancer patients and the lack of NK cells in the tumor microenvironment often correlates with poor prognosis. The pathways and soluble factors activated in tumor-associated NK cells, cancer cells, and regulatory myeloid cells which determine the outcome of cancer immunity are all critically regulated by STAT3. Using the tumor microenvironment as a paradigm, we present here an overview of the research that has revealed fundamental mechanisms through which STAT3 regulates all aspects of natural killer cell biology, including NK development, activation, target cell killing, and fine tuning of the innate and adaptive immune responses.
Gharehbaghian, Ahmad; Haque, K M Gausul; Truman, Carol; Newman, John; Bradley, Benjamin A
A technique was developed to measure the frequency of natural killer cell precursors (NKpf) in human peripheral blood mononuclear cell (PBMC) samples. Functional maturity of NK cells was reflected in their ability to lyse target cells from the K562 cell line. During the development of the technique, venous blood was taken from one healthy adult and assayed at different times to avoid individual variation. The technique was based on the principle of limiting dilution analysis. The NKpf assay was set up with a range of cell dilutions from 40,000 to 625 per 100 microl/well in 96-well culture plates. At the end of the culture period, the K562 cell line labelled with europium (Eu-K562) was added and the Eu-release was measured in culture supernatants using time-resolved fluorometry. The NKpf value differed between individuals and was influenced by the length of time in culture, being maximal at day 5. Maturation of NKp required the continuous presence of recombinant interleukin 2 (rIL-2), or rIL-15, both being equally effective. In the absence of cytokines, the functional NK cells declined rapidly beyond 24 h in culture. Irradiated allogeneic cells appeared to substitute in part for cytokines, but the numbers of allo-activated NKpf were lower than those observed when allo-activated NKpf were cultured with rIL-2. This suggested selective activation by the allogeneic stimulus of subsets of NKp or rIL-2-rescue of NKp subsets destined for apoptotic cell death. Alternatively, the increased frequency could have been attributable to activation of precursors of natural killer-T cells (NK-Tp). This assay is suitable for estimating the total number of precursors of functional NK cells in the blood of patients. PMID:11792377
... Hepatitis C Now Leading Infectious Disease Killer in U.S. CDC notes that nearly 20,000 Americans died ... deaths in 2014, according to preliminary data from U.S. Centers for Disease Control and Prevention. Those tragically ...
Muntner, Paul; Mann, Devin M.; Woodward, Mark; Choi, James W.; Stoler, Robert C; Shimbo, Daichi; Farkouh, Michael E.; Kim, Michael C.
Few data are available on factors associated with low adherence or early clopidogrel discontinuation following percutaneous coronary intervention (PCI). Patients (n=284) were evaluated prior to hospital discharge following PCI to identify factors associated with low adherence to clopidogrel 30 days later. Pre-PCI adherence to daily medications was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low, medium, or high (scores
Lindsley Carol B
Full Text Available Abstract Poor adherence to medical regimens can compromise the efficacy of treatments for children and adolescents with juvenile rheumatoid arthritis (JRA. The purpose of this review is to describe medical regimens for the treatment of JRA and the rates of adherence to these regimens. We also summarize and critically the few research studies aimed at improving adherence to regimens for JRA. Finally, we summarize strategies for enhancing adherence in clinical practice.
Kooij, M. J.
For many patients it is not easy to adhere to the agreed treatment with medication. Adherence has been defined as “the extent to which a person’s behaviour - taking medication - corresponds with agreed recommendations from a health care provider”. Numerous factors influence this taking behaviour and non-adherence must not be seen as the patients’ problem only. Health care providers, including pharmacists, should support patients to adhere. The overall aim of this thesis was to evaluate interv...
Patton, Susana R.
This paper reviewed current findings on dietary adherence in youth with type 1 diabetes mellitus (T1DM), discussed factors predicting dietary adherence, and presented directions for future research. The search terms were: type 1 diabetes mellitus; youth (0-22 years); diet; dietary adherence; nutrition; dietary intake; obesity; and complications. The studies involved youth with T1DM, presented dietary adherence data specifically, and/or described usual dietary patterns in youth. Articles that ...
Full Text Available Abstract Background The extent to which patients follow treatments as prescribed is pivotal to treatment success. An exceptionally high level (> 95% of HIV medication adherence is required to suppress viral replication and protect the immune system and a similarly high level (> 80% of adherence has also been suggested in order to benefit from prescribed exercise programmes. However, in clinical practice, adherence to both often falls below the desirable level. This project aims to investigate a wide range of psychological and personality factors that may lead to adherence/non-adherence to medical treatment and exercise programmes. Methods HIV positive patients who are referred to the physiotherapist-led 10-week exercise programme as part of the standard care are continuously recruited. Data on social cognitive variables (attitude, intention, subjective norms, self-efficacy, and outcome beliefs about the goal and specific behaviours, selected personality factors, perceived quality of life, physical activity, self-reported adherence and physical assessment are collected at baseline, at the end of the exercise programme and again 3 months later. The project incorporates objective measures of both exercise (attendance log and improvement in physical measures such as improved fitness level, weight loss, improved circumferential anthropometric measures and medication adherence (verified by non-invasive hair analysis. Discussion The novelty of this project comes from two key aspects, complemented with objective information on exercise and medication adherence. The project assesses beliefs about both the underlying goal such as following prescribed treatment; and about the specific behaviours such as undertaking the exercise or taking the medication, using both implicit and explicit assessments of patients’ beliefs and attitudes. We predict that i the way people think about the underlying goal of their treatments explains medication and exercise
Yassine, Mohammad; Al-Hajje, Amal; Awada, Sanaa; Rachidi, Samar; Zein, Salam; Bawab, Wafa; Bou Zeid, Mayssam; El Hajj, Maya; Salameh, Pascale
Controlling hypertension is essential in cardiovascular diseases. Poor medication adherence is associated with poor disease outcomes, waste of healthcare resources, and contributes to reduced blood pressure control. This study evaluates treatment adherence to antihypertensive therapy in Lebanese hypertensive patients by estimating the proportion of adherent hypertensive patients using a validated tool and investigates what factors predict this behavior. A questionnaire-based cross-sectional study was conducted on a random sample of 210 hypertensive outpatients selected from clinics located in tertiary-care hospitals and from private cardiology clinics located in Beirut. Adherence level was measured using a validated 8-item Modified Morisky Medication Adherence Scale (MMMAS). Among 210 patients, 50.5% showed high adherence, 27.1% medium adherence, and 22.4% low adherence to medication. Mean MMMAS score was 6.59±2.0. In bivariate analyses, having controlled blood pressure (p=0.003) and taking a combination drug (p=0.023) were predictors of high adherence. Forgetfulness (p<0.01), complicated drug regimen (p=0.001), and side effects (p=0.006) were predictors of low adherence after multiple liner regression. Logistic regression results showed that calcium channel blockers (p=0.030) were associated with increased adherence levels. In conclusion, developing multidisciplinary intervention programs to address the factors identified, in addition to educational strategies targeting healthcare providers, are necessary to enhance patient adherence. PMID:26232704
Wessel, S. W.; Chen, Y.; Maitra, A.; van den Heuvel, E. R.; Slomp, A. M.; Busscher, H. J.; van der Mei, H. C.
The oral microbiome consists of a planktonic microbiome residing in saliva and an adhering microbiome (the biofilm adhering to oral hard and soft tissues). Here we hypothesized that possible differences in microbial composition of the planktonic and adhering oral microbiome on teeth can be related t
Naar-King, S; Frey, M; Harris, M; Arfken, C
Parent, child, physician report and pill counts were used to measure adherence in paediatric HIV. Relationships to viral load were assessed. Pill counts were considered invalid. Adherence measures did not correlate with one another. Physicians reported lower adherence than parents, but parent and physician report correlated with viral load. The clinical and research utility of the various measures are discussed.
Xu, Jinshan; Deng, Zhiqun; Carlson, Thomas J.; Moore, Brian
A major criterion for tidal power licensing in Washington’s Puget Sound is the management of the risk of injury to killer whales due to collision with moving turbine blades. An active monitoring system is being proposed for killer whale detection, tracking, and alerting that links to and triggers temporary turbine shutdown when there is risk of collision. Target strength (TS) modeling of the killer whale is critical to the design and application of any active monitoring system. A 1996 study performed a high-resolution measurement of acoustic reflectivity as a function of frequency of a female bottlenose dolphin (2.2 m length) at broadside aspect and TS as a function of incident angle at 67 kHz frequency. Assuming that killer whales share similar morphology structure with the bottlenose dolphin, we extrapolated the TS of an adult killer whale 7.5 m in length at 67 kHz frequency with -8 dB at broadside aspect and -28 dB at tail side. The backscattering data from three Southern Resident killer whales were analyzed to obtain the TS measurement. These data were collected at Lime Kiln State Park using a split-beam system deployed from a boat. The TS of the killer whale at higher frequency (200 kHz) was estimated based on a three-layer model for plane wave reflection from the lung of the whale. The TS data of killer whales were in good agreement with our model. In this paper, we also discuss and explain possible causes for measurement estimation error.
Full Text Available Ecosystem-based management (EBM of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca and their primary prey, Chinook salmon (Oncorhynchus tshawytscha. Both species have at-risk conservation status and transboundary (Canada-US ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of
The Soft Killer background subtraction method removes the softest particles up to a certain transverse momentum cut-off threshold in an event. The applied threshold is determined dynamically on an event-by-event basis. The aim of this project was to implement the Soft Killer subtraction method within the AliROOT framework and to study the performance in the LHC energy regime for p-p and Pb-Pb collision systems.
Campbell, Jeffrey I; Eyal, Nir; Musiimenta, Angella; Haberer, Jessica E
Electronic adherence monitors (EAMs) record and report an array of health behaviors, ranging from taking daily medications to wearing medical devices. EAMs are utilized in research worldwide and are being investigated for clinical use. However, there is also growing popular concern about the extent to which electronic devices may be used to monitor individuals, including allegations in the media that EAMs represent a move towards "Big Brother" in medicine. Here, we highlight the unique benefits as well as the potential ethical challenges that electronic adherence monitoring generates. These challenges surround autonomy, privacy and confidentiality, trust, and ancillary care obligations. We describe key questions within each of these domains that warrant further investigation, and present potential solutions to many of the concerns raised. PMID:26358284
Donati, Alessia; Gupta, Swati; Reviakine, Ilya
Understanding how platelet activation is regulated is important in the context of cardiovascular disorders and their management with antiplatelet therapy. Recent evidence points to different platelet subpopulations performing different functions. In particular, procoagulant and aggregating subpopulations have been reported in the literature in platelets treated with the GPVI agonists. How the formation of platelet subpopulations upon activation is regulated remains unclear. Here, it is shown that procoagulant and aggregating platelet subpopulations arise spontaneously upon adhesion of purified platelets on clean glass surfaces. Calcium ionophore treatment of the adhering platelets resulted in one platelet population expressing both the procoagulant and the adherent population markers phosphatidylserine and the activated form of GPIIb/IIIa, while all of the platelets expressed CD62P independently of the ionophore treatment. Therefore, all platelets have the capacity to express all three activation markers. It is concluded that platelet subpopulations observed in various studies reflect the dynamics of the platelet activation process. PMID:27338300
Leutwyler, Heather C; Fox, Patrick J; Wallhagen, Margaret
Older adults with schizophrenia are a growing segment of the population, yet their physical and mental health status is extremely poor. This article presents findings from a qualitative study that explored the understanding older adults with schizophrenia have of their physical health status. The study was conducted among 28 older adults with schizophrenia from a variety of settings using semi-structured interviews and participant observation. Self-management of psychiatric and non-psychiatric medications and its effect on participants' health status was one of the central themes that emerged from the study. Different styles of medication adherence were identified and factors associated with each style are presented. The findings provide insights into the design of clinical interventions aimed at promoting medication adherence among older adults with schizophrenia.
Full Text Available Pollen killer genes disable noncarrier pollens, and are responsible for male sterility and segregation distortion in hybrid populations of distantly related plant species. The genetic networks and the molecular mechanisms underlying the pollen killer system remain largely unknown. Two pollen killer genes, S24 and S35, have been found in an intersubspecific cross of Oryza sativa ssp. indica and japonica. The effect of S24 is counteracted by an unlinked locus EFS. Additionally, S35 has been proposed to interact with S24 to induce pollen sterility. These genetic interactions are suggestive of a single S24-centric genetic pathway (EFS–S24–S35 for the pollen killer system. To examine this hypothetical genetic pathway, the S35 and the S24 regions were further characterized and genetically dissected in this study. Our results indicated that S35 causes pollen sterility independently of both the EFS and S24 genes, but is dependent on a novel gene close to the S24 locus, named incentive for killing pollen (INK. We confirmed the phenotypic effect of the INK gene separately from the S24 gene, and identified the INK locus within an interval of less than 0.6 Mb on rice chromosome 5. This study characterized the genetic effect of the two independent genetic pathways of INK–S35 and EFS–S24 in indica–japonica hybrid progeny. Our results provide clear evidence that hybrid male sterility in rice is caused by several pollen killer networks with multiple factors positively and negatively regulating pollen killer genes.
Orentaite, Irma; Poranen, Minna M; Oksanen, Hanna M; Daugelavicius, Rimantas; Bamford, Dennis H
Saccharomyces cerevisiae cells produce killer toxins, such as K1, K2 and K28, that can modulate the growth of other yeasts giving advantage for the killer strains. Here we focused on the physiological changes induced by K2 toxin on a non-toxin-producing yeast strain as well as K1, K2 and K28 killer strains. Potentiometric measurements were adjusted to observe that K2 toxin immediately acts on the sensitive cells leading to membrane permeability. This correlated with reduced respiration activity, lowered intracellular ATP content and decrease in cell viability. However, we did not detect any significant ATP leakage from the cells treated by killer toxin K2. Strains producing heterologous toxins K1 and K28 were less sensitive to K2 than the non-toxin producing one suggesting partial cross-protection between the different killer systems. This phenomenon may be connected to the observed differences in respiratory activities of the killer strains and the non-toxin-producing strain at low pH. This might also have practical consequences in wine industry; both as beneficial ones in controlling contaminating yeasts and non-beneficial ones causing sluggish fermentation. PMID:26818855
Richard H Chapman
Full Text Available Richard H Chapman1, Elise M Pelletier1, Paula J Smith1, Craig S Roberts21US Health Economics and Outcomes Research, IMS Health, Falls Church, VA, USA; 2Global Outcomes Research, Pfizer Inc, New York, NY, USAObjective: To compare adherence with statin therapy in patients switching to single-pill amlodipine besylate/atorvastatin calcium with patients adding a separate statin to their amlodipine regimen.Methods: We identified hypertensive patients prescribed amlodipine who switched to amlodipine/atorvastatin (switch or added a statin to their amlodipine regimen (add-on from July 2004 to June 2007. Propensity score matching (1 switch:3 add-on was applied based on ‘nearest neighbor’ approach. The primary adherence measure was patients with proportion of days covered (PDC ≥0.80 at 180 days; secondary measures included mean PDC and persistence. A sensitivity analysis was performed, accounting for total statin/amlodipine exposure.Results: Among 4556 matched patients (n = 1139 switch; n = 3417 add-on, mean age was 53.9 years and 52.1% were male. After 180 days, adherence with statin therapy was higher for the switch vs add-on cohort (50.8% vs 44.3%; P < 0.001. After adjusting for pre-index amlodipine adherence, the switch cohort was more likely to be adherent than the add-on cohort (odds ratio: 1.64 [95% confidence interval: 1.42 to 1.89]. Persistence was higher in the switch than the add-on cohort (127.6 vs 117 days; P < 0.001.Conclusion: Hypertensive patients taking amlodipine who initiated statin therapy via single-pill amlodipine/atorvastatin were more likely to remain adherent to their statin than patients adding a separate statin to their antihypertensive regimen.Keywords: adherence, amlodipine, atorvastatin, cardiovascular disease, persistence, single-pill
Shi, Lizheng; Liu, Jinan; Koleva, Yordanka; Fonseca, Vivian; Kalsekar, Anupama; Pawaskar, Manjiri
The primary objective of this review was to identify and examine the literature on the association between medication adherence self-reported questionnaires (SRQs) and medication monitoring devices. The primary literature search was performed for 1980-2009 using PubMed, PubMed In Process and Non-Indexed, Ovid MEDLINE, Ovid MEDLINE In-Process, PsycINFO (EBSCO), CINAHL (EBSCO), Ovid HealthStar, EMBASE (Elsevier) and Cochrane Databases and using the following search terms: 'patient compliance', 'medication adherence', 'treatment compliance', 'drug monitoring', 'drug therapy', 'electronic', 'digital', 'computer', 'monitor', 'monitoring', 'drug', 'drugs', 'pharmaceutical preparations', 'compliance' and 'medications'. We identified studies that included SRQs and electronic monitoring devices to measure adherence and focused on the SRQs that were found to be moderately to highly correlated with the monitoring devices. Of the 1679 citations found via the primary search, 41 full-text articles were reviewed for correlation between monitoring devices and SRQs. A majority (68%) of articles reported high (27%), moderate (29%) or significant (12%) correlation between monitoring devices (37 using Medication Event Monitoring System [MEMS®] and four using other devices) and SRQs (11 identified and numerous other unnamed SRQs). The most commonly used SRQs were the Adult/Pediatric AIDS Clinical Trial Group (AACTG/PACTG; 24.4%, 10/41) followed by the 4-item Morisky (9.8%, 4/41), Brief Medication Questionnaire (9.8%, 4/41) and visual analogue scale (VAS; 7.3%, 3/41). Although study designs differed across the articles, SRQs appeared to report a higher rate of medication adherence (+14.9%) than monitoring devices. In conclusion, several medication adherence SRQs were validated using electronic monitoring devices. A majority of them showed high or moderate correlation with medication adherence measured using monitoring devices, and could be considered for measuring patient
Roghmann, M C; Sexton, M
Adherence to asthma practice guidelines is low. Improved compliance could potentially improve care of patients with asthma. The purpose of this study was to determine if patients managed in a general practice with an associated asthma clinic are more likely to use asthma medications according to clinical practice guidelines than patients managed in the general surgery of the practice. A cross-sectional study of adult asthmatics, aged 18-55 years, was conducted in six British general practices. Prescription data on all asthma medication was collected for a 6-month period. Information on asthma clinic attendance, age, sex, employment status, other medical illness, and how patients used their inhaled beta2-agonist was collected through questionnaire. The prescription data for asthma medication and patient use of inhaled beta2-agonist were compared to the British Thoracic Society's (BTS) Guidelines for Management of Asthma in Adults to determine if the patient's asthma medication regimen was appropriate. There was no significant association found between appropriate asthma medication and asthma clinic attendance or other patient characteristics. Adherence to the BTS guidelines was low. Fifty-eight percent of the asthma patients used asthma medication regimens that were not consistent with the BTS guidelines published 1 year earlier. Adherence to the BTS guidelines was low regardless of patient characteristics, including asthma clinic attendance, age, sex, employment status, other medical illness, or individual practice. These findings underscore the need to document the utility of clinical practice guidelines which may improve physician compliance.
You, Shaodi; Tan, Robby T; Kawakami, Rei; Mukaigawa, Yasuhiro; Ikeuchi, Katsushi
Raindrops adhered to a windscreen or window glass can significantly degrade the visibility of a scene. Modeling, detecting and removing raindrops will, therefore, benefit many computer vision applications, particularly outdoor surveillance systems and intelligent vehicle systems. In this paper, a method that automatically detects and removes adherent raindrops is introduced. The core idea is to exploit the local spatio-temporal derivatives of raindrops. To accomplish the idea, we first model adherent raindrops using law of physics, and detect raindrops based on these models in combination with motion and intensity temporal derivatives of the input video. Having detected the raindrops, we remove them and restore the images based on an analysis that some areas of raindrops completely occludes the scene, and some other areas occlude only partially. For partially occluding areas, we restore them by retrieving as much as possible information of the scene, namely, by solving a blending function on the detected partially occluding areas using the temporal intensity derivative. For completely occluding areas, we recover them by using a video completion technique. Experimental results using various real videos show the effectiveness of our method. PMID:26485475
Liekens, S; Hulshagen, L; Dethier, M; Laekeman, G; Foulon, V
Medication adherence in chronic conditions such as asthma, type 2 diabetes, heart failure, HIV and cancer appears to be a frequent problem. However, the literature on adherence in patients who use inhaled corticosteroids (ICS), oral hypoglycemic agents, drugs for heart failure, antiretrovirals or oral chemotherapy, contains little or no relevant data for Belgium. In the context of a Master thesis in Pharmaceutical care at KU Leuven, a quantitative study was performed to determine the prevalence of adherence to chronic medication in Belgium. This retrospective, cross-sectional study used a database containing refill data of a regional pharmacists' association (KLAV). Out of the 603 pharmacies affiliated with this association, all 50 pharmacies where HIV medication was delivered, were selected. Dispensing data from the selected pharmacies were collected from 01/07/2008 to 31/12/2009 for five pathologies, i.e.; asthma, type 2 diabetes, heart failure, HIV and cancer. Adherence (TT) was calculated with the Medication Refill Adherence (MRA) method. In order to determine whether there were associations between age, gender, drug class and adherence, Chi-square tests were used. Compared with the other patients, cancer patients were the most adherent in taking their drugs (median adherence rate = 88%). In addition, this was the only group in which the median adherence rate was above the set limit of 80%. The patients who were prescribed inhaled corticosteroids were the least adherent (median adherence rate = 38%). More than 50% of patients with asthma/COPD, heart failure and diabetes were classified as "under-users". Furthermore, the results showed a significant association within asthma patients between gender and adherence. In asthma, type 2 diabetes, heart failure and HIV patients there was a significant relationship between age and adherence and drug class and adherence. As the current study has some limitations, the results should be handled with caution. Nevertheless
Evers, A.W.M.; Klusmann, V.; Schwarzer, R.; Heuser, I.
Objective. Adherence to behavioural intervention programmes is a necessary condition for beneficial outcomes to be achieved. This study tested whether social cognitive variables and coping plans predict adherence. Design and methods. Adherence was examined in a randomized controlled trial with healt
Vestbo, J; Anderson, J A; Calverley, P M A;
between adherence and mortality remained unchanged and statistically significant after adjusting for other factors related to prognosis (hazard ratio 0.40 (95% CI 0.35 to 0.46), p... adherence and hospital admission remained unchanged and significant in a multivariate analysis (rate ratio 0.58 (95% CI 0.44 to 0.73, p... was more pronounced in patients with good adherence than in those with poor adherence. CONCLUSION: Adherence to inhaled medication is significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD. Further research is needed to understand these strong...
GUO Zongqi; Michel Rigaud
Based on the sandwich test, adherence mechanisms of cement clinker on various basic bricks were tackled by microstructural observations with help of cathodoluminescence technique. Doloma based bricks offer sufficient lime to react with clinker, forming C3 S rich layer and initializing superior adherence. However, clinker with low silica ratio leads to MgO agglomeration at the interface of doloma bricks, which reduces adherence strength. On magnesia spinel bricks, fine, crystalline spinel easily reacts with lime containing phases from clinker to form lowmelting phases and belite zone, which shows high adherence performance. Lack of fine spinel in magnesia spinel bricks results in poor adherence.
Full Text Available Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by which H pylori causes disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence of H pylori to the gastric mucosa is summarized. Topics discussed are the mechanism of H pylori adherence; in vitro and in vivo models of H pylori infection; and adherence and potential adhesins and receptors for H pylori.
Full Text Available A random survey of 100 representative mosques in the U.S. was conducted to measure the correlation between Sharia adherence and dogma calling for violence against non-believers. Of the 100 mosques surveyed, 51% had texts on site rated as severely advocating violence; 30% had texts rated as moderately advocating violence; and 19% had no violent texts at all. Mosques that presented as Sharia adherent were more likely to feature violence-positive texts on site than were their non-Sharia-adherent counterparts. In 84.5% of the mosques, the imam recommended studying violence-positive texts. The leadership at Sharia-adherent mosques was more likely to recommend that a worshipper study violence-positive texts than leadership at non-Sharia-adherent mosques. Fifty-eight percent of the mosques invited guest imams known to promote violent jihad. The leadership of mosques that featured violence-positive literature was more likely to invite guest imams who were known to promote violent jihad than was the leadership of mosques that did not feature violence-positive literature on mosque premises.
Durban, J. W.; Pitman, R. L.
Killer whales (Orcinus orca) are important predators in high latitudes, where their ecological impact is mediated through their movements. We used satellite telemetry to provide the first evidence of migration for killer whales, characterized by fast (more than 12 km h−1, 6.5 knots) and direct movements away from Antarctic waters by six of 12 type B killer whales tagged when foraging near the Antarctic Peninsula, including all tags transmitting for more than three weeks. Tags on five of these...
Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra T; McBain, James; Dold, Christopher; Stott, Jeffrey L
Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify "insults" and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The immunologic
Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra; McBain, James; Dold, Christopher; Stott, Jeffrey L.
Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify “insults” and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The
Deng, Zhiqun; Carlson, Thomas J.; Xu, Jinshan; Martinez, Jayson J.; Weiland, Mark A.; Mueller, Robert P.; Myers, Joshua R.; Jones, Mark E.
Before final approval is given to the Snohomish County Public Utility District No. 1 for deploying the first tidal power devices in the United States in an open water environment, a system to manage the potential risk of injury to killer whales due to collision with moving turbine blades must be demonstrated. The Pacific Northwest National Laboratory (PNNL) is tasked with establishing the performance requirements for, constructing, and testing a prototype marine animal alert system for triggering temporary turbine shutdown when there is risk of collision with a killer whale. To develop a system that relies on active sonar two critical areas must be investigated - the target strength of killer whales and the frequency content of commercially available active sonar units. PNNL studied three target strength models: a simple model, the Fourier matching model, and the Kirchoff-ray mode model. Using target strength measurements of bottlenose dolphins obtained by previous researchers and assuming killer whales share similar morphology and structure, PNNL extrapolated the target strength of an adult killer whale 7.5 m in length at a frequency of 67 kHz. To study the frequency content of a commercially available sonar unit, direct measurements of the signal transmitted by the sonar were obtained by using a hydrophone connected to a data acquisition system in both laboratory and field conditions. The measurements revealed that in addition to the primary frequency of 200 kHz, there is a secondary frequency component at 90 kHz, which is within the hearing range of killer whales. The amplitude of the 90-kHz frequency component is above the hearing threshold of killer whales but below the threshold for potential injuries.
It was found that the marine yeast strain YF07b could secrete a large amount of killer toxin against a pathogenic yeast strain WCY which could cause milky disease in Portunus trituberculatus. The marine yeast strain YF07b was identified to be Pichia anomala according to the results of routine yeast identification and 18S rDNA and ITS sequences. The gene encoding killer toxin in the marine yeast strain YF07b was amplified by PCR technology. After sequencing, the results show that an open reading frame, consisting of 1 281 bp, encoded a presumed protein of 427 amino acids. The sequence of the cloned gene was found to have 99% match with that of the gene encoding killer toxin in Pichia anomalas strain K. A signal peptide including 17 amino acids appeared in the N-terminal domain of the killer toxin. Therefore, the mature protein consisted of 410 amino acids, its molecular mass was estimated to be 47.4 ku and its isoelctronic point was 4.5.
Full Text Available Background: Acquired immune deficiency syndrome (AIDS is now considered as a manageable chronic illness. There has been a dramatic reduction in human immunodeficiency virus (HIV related morbidity and mortality due to antiretroviral therapy. A high level of adherence (>95% is required for antiretroviral therapy to be effective. There are many barriers to adherence in both developed and developing countries. Aim: The aim of our study was to determine adherence levels and factors influencing adherence to antiretroviral therapy among people living with HIV. Materials and Methods: Using a cross-sectional study design, 116 HIV positive patients receiving antiretroviral therapy for at least 1 year were interviewed using a semi structured questionnaire. The collected data was analyzed using Statistical Product and Service Solutions (SPSS version 11.5. Chi-square test was done. A P value of < 0.05 was considered statistically significant. Results: Of 116 participants, 63.7% reported adherence ≥ 95%. Mean adherence index was 91.25%. Financial constraints, forgetting to take medication, lack of family care, depression, alcohol use, social stigma and side effects to antiretroviral therapy were barriers for adherence in our study. Conclusion: Adherence to antiretroviral therapy in south India is suboptimal. Intensive adherence counseling should be provided to all patients before initiation ofantiretroviral therapy. Health care providers must identify possible barriers to adherence at the earliest and provide appropriate solutions.
Baguso, Glenda N; Gay, Caryl L; Lee, Kathryn A
Medication adherence is linked to health outcomes among adults with HIV infection. Transgender women living with HIV (TWLWH) in the US report suboptimal adherence to medications and are found to have difficulty integrating HIV medication into their daily routine, but few studies explore the factors associated with medication adherence among transgender women. Thus, the purpose of this paper is to examine demographic and clinical factors related to self-reported medication adherence among transgender women. This secondary analysis is based on data collected from the Symptom and Genetic Study that included a convenience sample of 22 self-identified transgender women, 201 non-transgender men, and 72 non-transgender women recruited in northern California. Self-reported medication adherence was assessed using the AIDS Clinical Trials Group Adherence Questionnaire. Gender differences in demographic and clinical variables were assessed, as were differences between transgender women reporting high and low adherence. Transgender women had lower adherence to medications compared to non-transgender males and non-transgender females (p = .028) and were less likely to achieve viral suppression (p = .039). Within the transgender group, Black/African-Americans reported better adherence than participants who were Whites/Caucasian or other races (p = .009). Adherence among transgender women was unrelated to medication count and estrogen therapy, but consistent with other reports on the HIV population as a whole; transgender women with high adherence were more likely to achieve viral suppression compared to the transgender women with low adherence. Despite the high incidence of HIV infection in the transgender population, few studies focus on TWLWH, either in regard to their adherence to antiretroviral therapies or to their healthcare in general. To address ongoing health disparities, more studies are needed focusing on the transgender population's continuum of care in
William H. D. Hallett; William J. Murphy
Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.
Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T
Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states. PMID:26967308
Michael C Horowitz
Full Text Available The possibility that today’s drones could become tomorrow’s killer robots has attracted the attention of people around the world. Scientists and business leaders, from Stephen Hawking to Elon Musk, recently signed a letter urging the world to ban autonomous weapons. Part of the argument against these systems is that they violate the public conscience provision of the Martens Clause due to public opposition, making them illegal under international law. What, however, does the US public think of these systems? Existing research suggests widespread US public opposition, but focused on support for autonomous weapons in a vacuum. This paper uses two survey experiments to test the conditions in which public opposition rises and falls. The results demonstrate that public opposition to autonomous weapons is contextual. Fear of other countries or non-state actors developing these weapons makes the public significantly more supportive of developing them. The public also becomes much more willing to actually use autonomous weapons when their use would protect US forces. Beyond contributing to ongoing academic debates about casualty aversion, the microfoundations of foreign policy, and weapon systems, these results suggest the need for modesty when making claims about how the public views new, unknown technologies such as autonomous weapons.
Cemile AKYILDIZ ERCAN
Full Text Available Myths have remained popular in every field of art since ancient times till today. Lilith, who is mentioned as the first wife of Adam in Sumerian mythology, revolts against patriarchal structure, but is labelled as child killer in following generations and thus punished by patriarchal culture. Frequently encountered in literary works, Lilith is regarded as the first woman who started the war between woman and men by the feminists. Lamia and Medea, the two mythological figures who share the some destiny with Lilith have also been accused of child killing and punished by the patriarchal society because of their revolt against patriarchal structure.It is examined in this study how the norms as imposed to women by the patriarchal structure and those who challenge these norms are shaped and how these are reflected onto myths. The traces of the revolt by Lilith, who is considered to be first women to start the gender conflict between men and women, are followed in the study of this myth. In addition, the figures of Lamia and Medea in Greek myths are mentioned as they are found in the myths and their truthfulness is explored. It is detected in the study that the position of women has not changed in much myths as in real life.
龚伊红; R.R.Hcrberman; C.W.Reynolds
Antisexum against purified cytoplasmic granules from rat LGL tumor cells, and protein A-gold inmmnoelec-tron microscopy were used to study the secretory events in lysis of YAC-1 tumor cells by rat LGL tumor cells or by isolated LGL from normal rats. After 30 min incubation of effector and target cells together, gold-labeled cyto-plasmic granules were often seen concentrated in the area of the LGL adjacent to the ~ YAC-1 Within 60min,the grantees were observed to move to the cell border near the conjugazed site. At this point, fine granules were fused with file cell membrane, and subsequently released file gold-labeled contents into the junction between the LGL and the target cell. Gold particles could be seen at the B-T interface, on the surface,or sometimes on the target cell surface.These data provide direct evidence for the hypothesis that under conditions of active cytotoxicity,natural killer cells secrete their cytoplasmic granule contents leading to the deposition of granule material on the target cell surface and the eventual lysis of the cell.
Desbois, Mélanie; Rusakiewicz, Sylvie; Locher, Clara; Zitvogel, Laurence; Chaput, Nathalie
Natural killer (NK) cells belong to the innate immune system and were initially described functionallywise by their spontaneous cytotoxic potential against transformed or virus-infected cells. A delicate balance between activating and inhibiting receptors regulates NK cell tolerance. A better understanding of tissue resident NK cells, of NK cell maturation stages and migration patterns has evolved allowing a thoughtful evaluation of their modus operandi. While evidence has been brought up for their relevance as gate keepers in some hematopoietic malignancies, the role of NK cells against progression and dissemination of solid tumors remains questionable. Hence, many studies pointed out the functional defects of the rare NK cell infiltrates found in tumor beds and the lack of efficacy of adoptively transferred NK cells in patients. However, several preclinical evidences suggest their anti-metastatic role in a variety of mouse tumor models. In the present review, we discuss NK cell functions according to their maturation stage and environmental milieu, the receptor/ligand interactions dictating tumor cell recognition and recapitulate translational studies aimed at deciphering their prognostic or predictive role against human solid malignancies. PMID:23269924
Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.
Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A
For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field.
Chi, Chau-Hwa; Wang, Yu-Shan; Yang, Chieh-Han; Chi, Kwan-Hwa
We investigated whether natural killer (NK) cells in the tumor microenvironment have a radiosensitization effect. The radiosensitization effect of combined CpG and Herceptin((R)) (Genentech, Inc., South San Francisco, CA) (CpG/Herceptin), given before or after radiation, was evaluated by using a murine colon cancer cell line overexpressing human HER2/neu, CT26HER2/neu. In vitro radiosensitization effects were investigated by coculture of CT26HER2/neu with splenocytes, CpG, and Herceptin before applying radiation. Tumor cells, cocultured with CpG-pretreated splenocytes and Herceptin, were more vulnerable to radiation damage. In BALB/c mice injected with CT26HER2/neu, CpG/Herceptin administered before radiotherapy was associated with a better retardation of tumor growth than when administered after radiotherapy. The radiosensitization effect was significantly abrogated by NK-cell depletion, indicating that NK cells play an essential role in it. Further, surviving mice treated with CpG or CpG/Herceptin and reverse transcriptase were resistant to renewed tumor challenge, suggesting the presence of an induced immune response to the tumor. Neoadjuvant immunotherapy with CpG/Herceptin may improve response to radiotherapy of HER2/neu-expressing tumors. PMID:20187795
Brian L. Anderson
Full Text Available Natural killer T (NKT cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive research by chemists and immunologists to understand how glycolipids are recognized, possible responses by NKT cells, and the structural features of glycolipids necessary for stimulatory activity. The presence of this cell type in humans and most mammals suggests that it plays critical roles in antigen recognition and the interface between innate and adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells have been identified, and it is likely that glycolipid antigens remain to be discovered. Multiple series of structurally varied glycolipids have been synthesized and tested for stimulatory activity. The structural features of glycolipids necessary for NKT cell stimulation are moderately well understood, and designed compounds have proven to be much more potent antigens than their natural counterparts. Nevertheless, control over NKT cell responses by designed glycolipids has not been optimized, and further research will be required to fully reveal the therapeutic potential of this cell type.
Kast, Alene; Klassen, Roland; Meinhardt, Friedhelm
Virus like dsDNA elements (VLE) in yeast were previously shown to encode the killer toxins PaT and zymocin, which target distinct tRNA species via specific anticodon nuclease (ACNase) activities. Here, we characterize a third member of the VLE-encoded toxins, PiT from Pichia inositovora, and identify PiOrf4 as the cytotoxic subunit by conditional expression in Saccharomyces cerevisiae. In contrast to the tRNA targeting toxins, however, neither a change of the wobble uridine modification status by introduction of elp3 or trm9 mutations nor tRNA overexpression rescued from PiOrf4 toxicity. Consistent with a distinct RNA target, expression of PiOrf4 causes specific fragmentation of the 25S and 18S rRNA. A stable cleavage product comprising the first ∼ 130 nucleotides of the 18S rRNA was purified and characterized by linker ligation and subsequent reverse transcription; 3'-termini were mapped to nucleotide 131 and 132 of the 18S rRNA sequence, a region showing some similarity to the anticodon loop of tRNA(Glu)(UUC), the zymocin target. PiOrf4 residues Glu9 and His214, corresponding to catalytic sites Glu9 and His209 in the ACNase subunit of zymocin are essential for in vivo toxicity and rRNA fragmentation, raising the possibility of functionally conserved RNase modules in both proteins. PMID:24308908
Paula Cristina de Andrade Pires Olympio
Full Text Available Backgound and Objectives: Psychoneuroimmunology is one of the areas in charge of nurses, as it provides the implementation of an individualized and humanistic practice, perceiving the patient as a whole and aiming at physical and psychological aspects. The objective of this study was to evaluate the activity of Natural Killer (NK cells in women with breast cancer when the relaxation technique was used in nursing interventions and assess the association between the activity of NK cells and the pattern of behavior for stress and coping. Method: This is an experimental study with a quantitative approach, carried out with mastectomized women submitted to chemotherapy. Results: It was observed that NK cell levels, at the 1st measurement, were not statistically different between the control and experimental groups, demonstrating that the control and experimental groups were initially homogeneous. However, the same groups showed significant differences at the 2nd measurement. Conclusion: The nursing intervention using the relaxation technique modified the activity of NK cells, as the women in the experimental group showed increased activity after learning and practicing relaxation techniques.
Campbell, Kerry S; Hasegawa, Jun
Natural killer (NK) cells constitute a minor subset of normal lymphocytes that initiate innate immune responses toward tumor and virus-infected cells. They can mediate spontaneous cytotoxicity toward these abnormal cells and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses. Significant progress has been made in the past 2 decades to improve our understanding of NK cell biology. Here we review recent discoveries, including a better comprehension of the "education" of NK cells to achieve functional competence during their maturation and the discovery of "memory" responses by NK cells, suggesting that they might also contribute to adaptive immunity. The improved understanding of NK cell biology has forged greater awareness that these cells play integral early roles in immune responses. In addition, several promising clinical therapies have been used to exploit NK cell functions in treating patients with cancer. As our molecular understanding improves, these and future immunotherapies should continue to provide promising strategies to exploit the unique functions of NK cells to treat cancer, infections, and other pathologic conditions.
Full Text Available In contrast to donor T cells, natural killer (NK cells are known to mediate anti-cancer effects without the risk of inducing graft-versus-host disease (GvHD. In order to improve cytotoxicity against resistant cancer cells, auspicious efforts have been made with chimeric antigen receptor (CAR expressing T- and NK cells. These CAR-modified cells express antigen receptors against tumor-associated surface antigens, thus redirecting the effector cells and enhancing tumor-specific immunosurveillance. However, many cancer antigens are also expressed on healthy tissues, potentially leading to off tumor/ on target toxicity by CAR-engineered cells. In order to control such potentially severe side effects, the insertion of suicide genes into CAR-modified effectors can provide a means for efficient depletion of these cells. While CAR-expressing T cells have entered successfully clinical trials, experience with CAR-engineered NK cells is mainly restricted to pre-clinical investigations and predominantly to NK cell lines. In this review we summarize the data on CAR expressing NK cells focusing on the possible advantage using these short-lived effector cells and discuss the necessity of suicide switches. Furthermore, we address the compliance of such modified NK cells with regulatory requirements as a new field in cellular immunotherapy.
Stradner, Martin H; Cheung, Kitty P; Lasorella, Anna; Goldrath, Ananda W; D’Cruz, Louise M
While the invariant natural killer T (iNKT)-cell response to primary stimulation with the glycolipid, α-galactosylceramide (αGalCer), is robust, the secondary response to this stimulus is muted resulting in a hyporesponsive state characterized by anti-inflammatory interleukin-10 (IL-10) production and high expression of programmed cell death 1 (PD1) and neuropilin 1 (NRP1). The E protein transcription factors and their negative regulators, the Id proteins, have previously been shown to regulate iNKT cell thymic development, subset differentiation and peripheral survival. Here, we provide evidence that the expression of the transcriptional regulator Id2 is downregulated upon stimulation of iNKT cells with their cognate antigen. Moreover, loss of Id2 expression by iNKT cells resulted in a hyporesponsive state, with splenic Id2-deficient iNKT cells expressing low levels of TBET, high levels of PD1 and NRP1 and production of IL-10 upon stimulation. We propose that downregulation of Id2 expression is an essential component of induction of the anti-inflammatory, hyporesponsive state in iNKT cells. PMID:26880074
Regina Celia Cândido
Full Text Available Foi estudado o efeito killer de 9 cepas padrão de leveduras sobre 146 amostras de Candida albicans isoladas dos seguintes espécimes clínicos: mucosa bucal, fezes, lavado brônquico, escarro, secreção vaginal, urina, lesão de pele, lesão de unha e sangue. Usando este sistema foi possível diferenciar 23 biotipos de C. albicans. Os biotipos 211, 111 e 811 foram os mais freqüentemente isolados. A maioria das amostras de C. albicans (98,6% foi sensível a pelo menos uma ou mais das 9 cepas killer. Empregando- se este sistema foi possível demonstrar que 2 pacientes albergavam mesmo biotipo killer, respectivamente, 111 e 211, em diferentes espécimes clínicos, e em outro paciente, o mesmo biotipo (211 foi isolado de hemoculturas realizadas em ocasiões distintas. O uso do sistema killer para diferenciar os tipos entre as espécies de leveduras patogênicas, pode ser um método útil para estabelecer a eventual fonte de infecção, constituindo uma ajuda valiosa para o controle e vigilância de infecções nosocomiais causadas por leveduras.The authors studied the killer effect of nine standard strains of yeasts on 146 samples of Candida albicans isolated from the following clinical specimens: oral mucosa, feces, bronchial wash, sputum, vaginal secretion, urine, skin lesion, nail lesion and blood. Using this system it was possible to differentiate 23 biotypes of Candida albicans. The biotypes 211, 111 and 811 were most frequently isolated. Most of the samples of C. albicans (98.6% were sensitive to at least one or more of the nine killer strains. Using the killer system it was possible to show that two patients harbored the same killer biotypes, 111 and 211, respectively, in different clinical specimens and another patient harbored the same biotype (211 in blood cultures effected in different ocasions. The utilization of the killer system to differentiate types among species of pathogenic yeasts can be a useful method to stablish the eventual
Brand, Paul L. P.; Klok, Ted; Kaptein, Adrian A.
Nonadherence to maintenance medication is common in paediatric chronic conditions. Despite the common belief that nonadherence is therapy-resistant, and the apparent lack of evidence for successful interventions to improve adherence, there is, in fact, a considerable body of evidence suggesting that
Vervoort, Sigrid C. J. M.; Grypdonck, Mieke H. F.; de Grauwe, Annelies; Hoepelman, Andy I. M.; Borleffs, Jan C. C.
In order to explore and clarify the underlying processes which lead to (non)-adherence behavior in patients treated with highly active antiretroviral therapy (HAART), a qualitative study was conducted. Thirty-seven in-depth interviews were held with 30 Caucasian HIV-positive patients. Additional dat
Youoku, Sachihiro; Suto, Yoshinori; Ando, Moritoshi; Ito, Akio
We have developed an automated microinjection system that can handle more than 500 cells an hour. Microinjection injects foreign agents directly into cells using a micro-capillary. It can randomly introduce agents such as DNA, proteins and drugs into various types of cells. However, conventional methods require a skilled operator and suffer from low throughput. The new automated microinjection techniques we have developed consist of a Petri dish height measuring method and a capillary apex position measuring method. The dish surface height is measured by analyzing the images of cells that adhere to the dish surface. The contrast between the cell images is minimized when the focus plane of an object lens coincides with the dish surface. We have developed an optimized focus searching method with a height accuracy of +/-0.2 um. The capillary apex position detection method consists of three steps: rough, middle, and precise. These steps are employed sequentially to cover capillary displacements of up to +/-2 mm, and to ultimately accomplish an alignment accuracy of less than one micron. Experimental results using this system we developed show that it can introduce fluorescent material (Alexa488) into adherent cells, HEK293, with a success rate of 88.5%.
Ausloos, M; Ausloos, Marcel; Petroni, Filippo
Religiosity is one of the most important sociological aspects of populations. All religions may evolve in their beliefs and adapt to the society developments. A religion is a social variable, like a language or wealth, to be studied like any other organizational parameter. Several questions can be raised, as considered in this study: e.g. (i) from a ``macroscopic'' point of view : How many religions exist at a given time? (ii) from a ``microscopic'' view point: How many adherents belong to one religion? Does the number of adherents increase or not, and how? No need to say that if quantitative answers and mathematical laws are found, agent based models can be imagined to describe such non-equilibrium processes. It is found that empirical laws can be deduced and related to preferential attachment processes, like on evolving network; we propose two different algorithmic models reproducing as well the data. Moreover, a population growth-death equation is shown to be a plausible modeling of evolution dynamics in a...
Bliddal, Henning; Eriksen, Stine A; Christensen, Robin;
Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis....../contact, with at least one prescription of MTX (L04AX03), were included. Results. A total of 18,703 (47.6%) patients had ever used MTX among 39,286 with a diagnosis of RA; among the MTX users, 16,503 (88.2%) had filed more than one MTX prescription. The median time from diagnosis to first MTX prescription was 0.66 (IQR...... 0.26-1.80) years. In those who filed more than one MTX prescription, the mean adherence time for ≥7.5 mg MTX per week was 1,925 (IQR 467-3,056) days for patients treated in private practice versus 1,892 (IQR 452-3,316) days for patients treated in hospital. The main determinants of nonadherence were...
Full Text Available Zhe Hui Hoo,1,2 Rachael Curley,1,2 Michael J Campbell,1 Stephen J Walters,1 Daniel Hind,3 Martin J Wildman1,2 1School of Health and Related Research (ScHARR, University of Sheffield, 2Sheffield Adult Cystic Fibrosis Centre, Northern General Hospital, 3Sheffield Clinical Trials Research Unit, University of Sheffield, Sheffield, UK Background: Preventative inhaled treatments in cystic fibrosis will only be effective in maintaining lung health if used appropriately. An accurate adherence index should therefore reflect treatment effectiveness, but the standard method of reporting adherence, that is, as a percentage of the agreed regimen between clinicians and people with cystic fibrosis, does not account for the appropriateness of the treatment regimen. We describe two different indices of inhaled therapy adherence for adults with cystic fibrosis which take into account effectiveness, that is, “simple” and “sophisticated” normative adherence. Methods to calculate normative adherence: Denominator adjustment involves fixing a minimum appropriate value based on the recommended therapy given a person’s characteristics. For simple normative adherence, the denominator is determined by the person’s Pseudomonas status. For sophisticated normative adherence, the denominator is determined by the person’s Pseudomonas status and history of pulmonary exacerbations over the previous year. Numerator adjustment involves capping the daily maximum inhaled therapy use at 100% so that medication overuse does not artificially inflate the adherence level. Three illustrative cases: Case A is an example of inhaled therapy under prescription based on Pseudomonas status resulting in lower simple normative adherence compared to unadjusted adherence. Case B is an example of inhaled therapy under-prescription based on previous exacerbation history resulting in lower sophisticated normative adherence compared to unadjusted adherence and simple normative adherence
Danilo Santana Alessio Franceschi
Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.
White, John H; Lester, David; Gentile, Matthew; Rosenbleeth, Juliana
Movies and nightly television shows appear to emphasize highly efficient regimens in forensic science and criminal investigative analysis (profiling) that result in capturing serial killers and other perpetrators of homicide. Although some of the shows are apocryphal and unrealistic, they reflect major advancements that have been made in the fields of forensic science and criminal psychology during the past two decades that have helped police capture serial killers. Some of the advancements are outlined in this paper. In a study of 200 serial killers, we examined the variables that led to police focusing their attention on specific suspects. We developed 12 categories that describe how serial killers come to the attention of the police. The results of the present study indicate that most serial killers are captured as a result of citizens and surviving victims contributing information that resulted in police investigations that led to an arrest. The role of forensic science appears to be important in convicting the perpetrator, but not necessarily in identifying the perpetrator. PMID:21333473
Eskesen, Ida; Wahlberg, Magnus; Simon, Malene;
The source characteristics of biosonar signals from sympatric killer whales and long-finned pilot whales in a Norwegian fjord were compared. A total of 137 pilot whale and more than 2000 killer whale echolocation clicks were recorded using a linear four-hydrophone array. Of these, 20 pilot whale...... clicks and 28 killer whale clicks were categorized as being recorded on-axis. The clicks of pilot whales had a mean apparent source level of 196 dB re 1 lPa pp and those of killer whales 203 dB re 1 lPa pp. The duration of pilot whale clicks was significantly shorter (23 ls, S.E.¼1.3) and the centroid...... frequency significantly higher (55 kHz, S.E.¼2.1) than killer whale clicks (duration: 41 ls, S.E.¼2.6; centroid frequency: 32 kHz, S.E.¼1.5). The rate of increase in the accumulated energy as a function of time also differed between clicks from the two species. The differences in duration, frequency...
Brent G. Young
Full Text Available We identified individual killer whales (Orcinus orca using recent (2004–09 photographs to obtain a minimum count of whales that use eastern Canadian Arctic waters. Fifty-three individuals were identified from nine different sightings; 11 individuals from western Hudson Bay sightings and 42 from the areas around northern and eastern Baffin Island. One whale was re-sighted: an adult female or large juvenile photographed 17 days and 375 km apart at Churchill, Manitoba, and off-shore of Rankin Inlet, Nunavut, in August 2007. With only one individual re-sighted, the number of individuals that use this area is likely much larger. No re-sightings occurred between Arctic killer whales and individuals photographed off the coast of Newfoundland. Our results represent the minimum number of killer whales sighted in eastern Canadian Arctic waters and provide the foundation for further killer whale research. Little is known about Arctic killer whales and, as a top predator, it is unclear what effect they have on Arctic marine ecosystems.
White, John H; Lester, David; Gentile, Matthew; Rosenbleeth, Juliana
Movies and nightly television shows appear to emphasize highly efficient regimens in forensic science and criminal investigative analysis (profiling) that result in capturing serial killers and other perpetrators of homicide. Although some of the shows are apocryphal and unrealistic, they reflect major advancements that have been made in the fields of forensic science and criminal psychology during the past two decades that have helped police capture serial killers. Some of the advancements are outlined in this paper. In a study of 200 serial killers, we examined the variables that led to police focusing their attention on specific suspects. We developed 12 categories that describe how serial killers come to the attention of the police. The results of the present study indicate that most serial killers are captured as a result of citizens and surviving victims contributing information that resulted in police investigations that led to an arrest. The role of forensic science appears to be important in convicting the perpetrator, but not necessarily in identifying the perpetrator.
Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita
Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.
Similä, Tiu; Holst, Jens Christian; Christensen, Ivar
Our objectives were to investigate the seasonal occurrence of photoidentified killer whale pods in relation to the distribution of Norwegian spring-spawning herring and whether or not pod-specific differences in the occurrence or diet of killer whales could be demonstrated. In a 4-year study, the killer whales occurred in different areas during the summer and the fall–winter, and these areas coincided with the distribution areas of herring. Killer whales were encountered most freq...
Sieben, Angelien; Bredie, S J H Bas; van Laarhoven, C J H M Kees; Schoonhoven, Lisette; Burger, David M; van Onzenoort, Hein A W
Poor adherence to medication is one of the most important determinants in the treatment of patients with chronic disorders. e-Health-based interventions may be able to improve treatment adherence. This article gives an overview of the available e-Health interventions and the extent to which they can improve adherence. We searched in the PubMed, Cinahl, PsycInfo, and Embase databases for e-Health interventions that aimed at improving adherence to treatment. Of the 16 included studies, 15 used a website and one used an app. Ten studies showed a significant improvement in treatment adherence by using the intervention. e-Health interventions were generally complex. Simple interventions were the most successful in improving treatment adherence.
Full Text Available Purpose: Natural killer (NK cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS; however, histocytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Immunohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.
Osborn, Chandra Y; Cavanaugh, Kerri; Wallston, Kenneth A.; Kripalani, Sunil; White, Richard O.; Elasy, Tom A.; Rothman, Russell L.
While low health literacy and suboptimal medication adherence are more prevalent in racial/ethnic minority groups than Whites, little is known about the relationship between these factors in adults with diabetes, and whether health literacy or numeracy might explain racial/ethnic disparities in diabetes medication adherence. Previous work in HIV suggests health literacy mediates racial differences in adherence to anti-retroviral treatment, but no study to date has explored numeracy as a media...
Weerkamp, A H; McBride, B C
The adherence and aggregation properties of 46 human oral Streptococcus salivarius isolates were examined. A total of 41% of the isolates aggregated with whole human saliva, 50% aggregated with human erythrocytes, and 85% adhered to human buccal epithelial cells. Strains that aggregated with saliva and erythrocytes usually reacted with Streptococcus group K typing serum whereas the non-hemagglutinating strains did not. K+ strains also adhered more strongly to human buccal epithelial cells tha...
Carbone, Loretta; Zebrack, Bradley; Plegue, Melissa; Joshi, Sucheta; Shellhaas, Renée
Treatment adherence is often suboptimal among adolescents with epilepsy. Yet knowledge is lacking regarding factors that affect adherence. Empirical studies and theories of human development suggest that self-management skills, self-efficacy, and sense of control are related to adherence. Eighty-eight adolescents with epilepsy, and their parents, completed standardized measures assessing epilepsy knowledge and expectations, treatment self-management, sense of control, and self-efficacy. Bette...
Clyne, M.; Drumm, B
Helicobacter pylori adheres only to gastric cells in vivo. However, the organism adheres to a wide variety of nongastric cells in vitro. In this study, we have used flow cytometry to assess the adherence of H. pylori to primary epithelial cells isolated from gastric, duodenal, and colonic biopsy specimens by collagenase digestion. After incubation of bacteria and cells together and subsequent staining with a two-stage fluorescein isothiocyanate-labelled H. pylori antibody method, cells with a...
Aldebot, Stephanie; Weisman de Mamani, Amy G.
Antipsychotics are often the first line of treatment for individuals with schizophrenia (Fialko et al., 2008). One challenge to effective treatment is lack of adherence to prescribed medication. Lower rates of adherence are associated with considerably higher rates of relapse and poorer course of illness. Therefore studying characteristics that may be related to medication adherence is important. Coping styles may be one such factor. Individuals utilize a variety of coping mechanisms to manag...
Elhamy Rifky Abdel Khalek; Laila M Sherif; Naglaa Mohamed Kamal; Gharib, Amal F.; H M Shawky
Background, Aims, Settings and Design: Poor adherence to oral maintenance chemotherapy can cause relapse of acute lymphoblastic leukemia (ALL). A multicenter study for the evaluation of adherence to oral 6-mercaptopurine (6-MP) maintenance chemotherapy for childhood ALL in Egypt to identify contributing factors and possible steps to promote adherence. Materials and Methods: The study included 129 children with ALL in complete remission receiving 6-MP single daily oral dose in the evening....
Mehler Phillip S
Full Text Available Abstract Background Therapy with 3-Hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors (statins improve outcomes in a broad spectrum of patients with hyperlipidemia. However, effective therapy requires ongoing medication adherence; restrictive pharmacy policies may represent a barrier to successful adherence, particularly among vulnerable patients. In this study we sought to assess the relationship between the quantity of statin dispensed by the pharmacy with patient adherence and total cholesterol. Methods We analyzed a cohort of 3,386 patients receiving more than one fill of statin medications through an integrated, inner-city health care system between January 1, 2000 and December 31, 2002. Our measure of adherence was days of drug acquisition divided by days in the study for each patient, with adequate adherence defined as ≥ 80%. Log-binomial regression was used to determine the relative risk of various factors, including prescription size, on adherence. We also assessed the relationship between adherence and total cholesterol using multiple linear regression. Results After controlling for age, gender, race, co-payment, comorbidities, and insurance status, patients who obtained a majority of fills as 60-day supply compared with 30-day supply were more likely to be adherent to their statin medications (RR 1.41, 95% CI 1.28–1.55, P Conclusion In a healthcare system serving predominantly indigent patients, the provision of a greater quantity of statin medication at each prescription fill contributes to improved adherence and greater drug effectiveness.
Full Text Available Sarah D Fenerty1, Cameron West1, Scott A Davis1, Sebastian G Kaplan3, Steven R Feldman1,2,41Center for Dermatology Research, Department of Dermatology, 2Department of Pathology, 3Department of Psychiatry and Behavioral Medicine, 4Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USABackground: Patient adherence is an important component of the treatment of chronic disease. An understanding of patient adherence and its modulating factors is necessary to correctly interpret treatment efficacy and barriers to therapeutic success.Purpose: This meta-analysis aims to systematically review published randomized controlled trials of reminder interventions to assist patient adherence to prescribed medications.Methods: A Medline search was performed for randomized controlled trials published between 1968 and June 2011, which studied the effect of reminder-based interventions on adherence to self-administered daily medications.Results: Eleven published randomized controlled trials were found between 1999 and 2009 which measured adherence to a daily medication in a group receiving reminder interventions compared to controls receiving no reminders. Medication adherence was measured as the number of doses taken compared to the number prescribed within a set period of time. Meta-analysis showed a statistically significant increase in adherence in groups receiving a reminder intervention compared to controls (66.61% versus 54.71%, 95% CI for mean: 0.8% to 22.4%. Self-reported and electronically monitored adherence rates did not significantly differ (68.04% versus 63.67%, P = 1.0. Eight of eleven studies showed a statistically significant increase in adherence for at least one of the reminder group arms compared to the control groups receiving no reminder intervention.Limitations: The data are limited by imperfect measures of adherence due to variability in data collection methods. It is also likely
Read, T; Mijch, A; Fairley, C K
Adherence to antiretroviral therapy is a powerful predictor of response to therapy. For optimal antiretroviral therapy response, individuals need to take more than 95% of their prescribed medication. The most widely used method for measuring adherence is self-report of the number of missed doses and this should be done at every clinic visit. There are several well-recognized predictors of poor adherence, such as illicit drug use, depression, limited knowledge or ambivalence about starting treatment. Adherence can be improved by addressing these issues or through other means such as pill boxes or electronic reminders. PMID:12752896
Sandra Regina Ceccato-Antonini
Full Text Available Twenty-four yeasts out of 342 isolated from the fermentative process showed killer activity and three of them were selected for the fermentative efficiency evaluation in batch system with cell recycle, flask and fermentor experiments. The selected three killer strains did not present similar results to those of pressed (baking yeast concerning ethanol (0.07-0.18; 0.12-0.20; 0.10-0.13; 0.22-0.25 g/g, respectively and biomass (0.19-0.26; 0.33-0.39; 0.13-0.27; 0.47-0.61 g/g, respectively yields and fermentative efficiency (12.3-36.3; 21.0-40.0; 19.3-26.3; 47.6-54.0 %, respectively in sugarcane juice, in flasks. In fermentor, similar behaviour was observed. However, the selected strains showed high cellular viability and killer activity (using cell-free filtrate along the fermentative cycles, in spite of the unfavourable conditions of the medium, like high pH variation of the medium (from 5.5-6.0 to 3.0-4.0, low aeration and higher temperature (30º C, which were not the ideal ones for the production/activity of killer toxins. A Pichia strain (CCA 510 showed the best results among the killer yeasts tested, exhibiting a killer activity against 92% of isolated fermentative yeasts of the process and against the pressed (baking ferment. It also demonstrated killer activity (using crude toxin preparation at higher temperatures (38ºC and low pH (4.0 after 72 hours of incubation, under proliferative and non-proliferative conditions. The results indicated that the killer activity should be a characteristic to be looked for in the strain selection for ethanolic fermentation, beside other important productivity-based characteristics, since it assure the permanence of the selected strain during the process.A atividade 'killer' poderia garantir às leveduras fermentativas uma vantagem competitiva sobre outras linhagens durante a fermentação etanólica, no entanto, pouco se sabe sobre o papel do sistema 'killer' nesse tipo de fermentação alcoólica. A sele
Full Text Available Abstract Background The adherence to long tuberculosis (TB treatment is a key factor in TB control programs. Always some patients abandon the treatment or die. The objective of this study is to identify factors associated with defaulting from or dying during antituberculosis treatment. Methods Prospective study of a large cohort of TB cases diagnosed during 2006-2007 by 61 members of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR. Predictive factors of completion outcome (cured plus completed treatment vs. defaulters plus lost to follow-up and fatality (died vs. the rest of patients were based on logistic regression, calculating odds ratios (OR and 95% confidence intervals (CI. Results Of the 1490 patients included, 29.7% were foreign-born. The treatment outcomes were: cured 792 (53.2%, completed treatment 540 (36.2%, failure 2 (0.1%, transfer-out 33 (2.2%, default 27 (1.8%, death 27 (1.8%, lost to follow-up 65 (4.4%, other 4 (0.3%. Completion outcome reached 93.5% and poor adherence was associated with: being an immigrant (OR = 2.03; CI:1.06-3.88, living alone (OR = 2.35; CI:1.05-5.26, residents of confined institutions (OR = 4.79; CI:1.74-13.14, previous treatment (OR = 2.93; CI:1.44-5.98, being an injecting drug user (IDU (OR = 9.51; CI:2.70-33.47 and treatment comprehension difficulties (OR = 2.93; CI:1.44-5.98. Case fatality was 1.8% and it was associated with the following variables: age 50 or over (OR = 10.88; CI:1.12-105.01, retired (OR = 12.26;CI:1.74-86.04, HIV-infected (OR = 9.93; CI:1.48-66.34, comprehension difficulties (OR = 4.07; CI:1.24-13.29, IDU (OR = 23.59; CI:2.46-225.99 and Directly Observed Therapy (DOT (OR = 3.54; CI:1.07-11.77. Conclusion Immigrants, those living alone, residents of confined institutions, patients treated previously, those with treatment comprehension difficulties, and IDU patients have poor adherence and should be targeted for DOT. To reduce fatality rates, stricter monitoring is required
Beck, Suzanne; Kuningas, Sanna; Esteban, Ruth;
-eating ecotype than the more phylogenetically distant Pacific mammal-eating ecotype. Our study suggests that sociality in killer whales is to some extent plastic and can be adapted to the local ecological conditions. Key words: ecology, killer whale, orca, orcinus, sociality.......The persistence and size of social groups can be plastic and governed by ecological selection or be under greater genetic control and constrained by phylogenetic inertia. Comparing sociality of phylogenetically divergent populations under the same ecolog- ical conditions or between groups within...... a population under different ecological conditions can identify the relative influence of ecological selection on group formation. Here, we compare the size and persistence of social groups within a community of Atlantic killer whales, comparing between data collected from an area around Scotland where...
Morin, Phillip A; Archer, Frederick I; Foote, Andrew D;
Killer whales (Orcinus orca) currently comprise a single, cosmopolitan species with a diverse diet. However, studies over the last 30 yr have revealed populations of sympatric "ecotypes" with discrete prey preferences, morphology, and behaviors. Although these ecotypes avoid social interactions...... and are not known to interbreed, genetic studies to date have found extremely low levels of diversity in the mitochondrial control region, and few clear phylogeographic patterns worldwide. This low level of diversity is likely due to low mitochondrial mutation rates that are common to cetaceans. Using killer whales...... as a case study, we have developed a method to readily sequence, assemble, and analyze complete mitochondrial genomes from large numbers of samples to more accurately assess phylogeography and estimate divergence times. This represents an important tool for wildlife management, not only for killer whales...
Castle, Tammy; Hensley, Christopher
Scholars have endeavored to study the motivation and causality behind serial murder by researching biological, psychological, and sociological variables. Some of these studies have provided support for the relationship between these variables and serial murder. However, the study of serial murder continues to be an exploratory rather than explanatory research topic. This article examines the possible link between serial killers and military service. Citing previous research using social learning theory for the study of murder, this article explores how potential serial killers learn to reinforce violence, aggression, and murder in military boot camps. As with other variables considered in serial killer research, military experience alone cannot account for all cases of serial murder. Future research should continue to examine this possible link.
Wolf, Barbara C; Lavezzi, Wendy A
Although research into the phenomenon of serial murder has revealed that serial killers frequently do not fit the initially described paradigm in terms of their physical and psychological profiles, backgrounds, and motives to kill, the media continues to sensationalize the figures of such killers and the investigators who attempt to analyze them on the basis of aspects of their crimes. Although the so-called "typical" profile of the serial murderer has proven accurate in some instances, in many other cases the demographics and behaviors of these killers have deviated widely from the generalized assumptions. This report details two unusual cases in which five and eight murders were committed in upstate New York. The lives and crimes of these offenders illustrate the wide spectrum of variations in the backgrounds, demographics, motivations, and actions witnessed among serial murderers, and highlight the limitations and dangers of profiling based on generalities. PMID:17209938
Castle, Tammy; Hensley, Christopher
Scholars have endeavored to study the motivation and causality behind serial murder by researching biological, psychological, and sociological variables. Some of these studies have provided support for the relationship between these variables and serial murder. However, the study of serial murder continues to be an exploratory rather than explanatory research topic. This article examines the possible link between serial killers and military service. Citing previous research using social learning theory for the study of murder, this article explores how potential serial killers learn to reinforce violence, aggression, and murder in military boot camps. As with other variables considered in serial killer research, military experience alone cannot account for all cases of serial murder. Future research should continue to examine this possible link. PMID:12150084
Wolf, Barbara C; Lavezzi, Wendy A
Although research into the phenomenon of serial murder has revealed that serial killers frequently do not fit the initially described paradigm in terms of their physical and psychological profiles, backgrounds, and motives to kill, the media continues to sensationalize the figures of such killers and the investigators who attempt to analyze them on the basis of aspects of their crimes. Although the so-called "typical" profile of the serial murderer has proven accurate in some instances, in many other cases the demographics and behaviors of these killers have deviated widely from the generalized assumptions. This report details two unusual cases in which five and eight murders were committed in upstate New York. The lives and crimes of these offenders illustrate the wide spectrum of variations in the backgrounds, demographics, motivations, and actions witnessed among serial murderers, and highlight the limitations and dangers of profiling based on generalities.
Lynch, Lydia A
With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight-management clinic and 11 lean healthy controls. Patients were classified into metabolically "healthy obese" (n = 26; mean age 42.6 years, mean BMI 46.8 kg\\/m(2)) or "unhealthy obese" (n = 26; mean age 45 years, mean BMI 47.5 kg\\/m(2)) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.
Hsueh, C M; Lorden, J F; Hiramoto, R N; Ghanta, V K
An increase in natural killer (NK) cell activity can be conditioned with a one trial learning paradigm to demonstrate the interaction between the central nervous system (CNS) and the immune system. In order to demonstrate learning possibilities during 'non-conscious' state, mice were anesthetized with a ketamin/rompun mixture and underwent one trial learning with odor cue as the conditioned stimulus (CS) preceding the unconditioned stimulus (US). The results indicated that mice that were exposed to camphor odor cue under the influence of anesthesia can associate the signal with the poly I:C unconditioned stimulus and were able to recall the conditioned response upon reexposure to the CS. Secondly, the conditioned association made in a conscious state can be recalled by exposure to the same olfactory odor cue in a 'non-conscious' state. The increase in the conditioned change in NK cell activity of both situations was significantly higher than the control group. The results demonstrate that learning can take place and the learned response can be recalled under the reduced awareness caused by anesthesia. The findings we report are unusual and novel in that they demonstrate that the CNS can learn new associations under conditions where the host is apparently unaware of the signals being linked. Anesthesia combined with the long interstimulus interval indicates that certain neuronal pathways in the CNS are receptive to second signals (elicited by the US) even when the second signal is separated by one day. This means the conditioned learning of a physiological response can take place unconsciously at a separate level and under situations where the host is totally unaware of the events which the brain is processing and linking as incoming information.
Nabavi Nouri, N.
Previous data generated by Murphy and McDaniel indicate that normal murine nylon wool nonadherent splenic cells, with the characteristics of natural killer (NK) cells, effectively inhibit the in vitro growth of Cryptococcus neoformans, a yeast-like pathogen. Nylon wood nonadherent cells from spleens of 7-8 week old mice were further fractionated on discontinuous Percoll gradients. The enrichment of NK cells in Percoll fractions 1 and 2 was confirmed by morphological examination, immunofluorescent staining, and by assessing the cytolytic activity of each Percoll cell fraction against YAC-1 targets in the 4 h /sup 51/Cr release assay. Cells isolated from each Percoll fraction were tested for growth inhibitory activity against C neoformans, using an in vitro 18 h growth inhibition assay. The results showed that NK cell enrichment was concomitant with the enrichment of anti-cryptococcal activity the Percoll fractions 1 and 2. An immunolabeling method combined with scanning electron microscopy was used to demonstrate that the effector cells attached to C. neoformans were asialo GM/sub 1/ positive and, therefore, had NK cell characteristics. NK cells have Fc receptors on their surfaces , and are capable of antibody-dependent cell-mediated cytotoxicity (ADCC) against IgG-coated target cells. The author examined the effects of the IgG fraction of rabbit anti-cryptococcal antibody on the NK cell-mediated growth inhibition of C. neoformans. The data indicated that the effector cells involved in antibody-dependent growth inhibition of cryptococci are either NK cells or copurify and coexist in the same population with NK cells.
Segerstrom, Suzanne C; Al-Attar, Ahmad; Lutz, Charles T
Psychosocial factors may influence aspects of immunological aging. The present study tested the hypothesis that psychosocial resources correlate with the expression of the cell surface maker CD57 on natural killer (NK) immune cells. CD57 is a marker of terminal maturation and senescence in this cell subset. The study further tested the relative contribution of specific resources in the social, psychological, financial, and status-skill domains, given the potential differential value of different resources for younger and older adults, and the contribution of relative versus absolute resources. Younger (n = 38) and older (n = 34) women completed measures of relative and absolute resources and had blood drawn. Examined both between groups and within the older women, older age and fewer total relative resources were associated with more CD57 expression on NK cells. One SD in resources was the equivalent of 5 years of aging among the older women. Among the specific resource types, a preponderance of financial resources, both relative and absolute, was associated with less CD57 expression on NK cells, and these relationships did not significantly vary between younger and older women. There was no evidence that depressive symptoms mediated the effects of resources on CD57 expression on NK cells. These findings provide support for the hypothesis that the sense that one has substantial resources, particularly with regard to finances and possessions, may retard age-associated aspects of the microenvironment in which NK cells develop and mature, independent of effects on distress, and this process may begin in younger adulthood. PMID:22708535
Full Text Available Background: Natural killer (NK cells are important guards of the innate immune system, which act by performing as primary effector cells in viral infections. NK cell function is regulated by the engagement of activating and/or inhibitory receptors on individual NK cell surfaces. Subsequent to activation, the release of preformed cytolytic granules or cytokines occurs. Recently, the polyfunctionality of NK cells has been described as a potent NK cell subset that mediates antiviral response in HIV-infected slow progressors. Objectives: To evaluate the polyfunctional NK cells in healthy individuals. Methods: Peripheral blood mononuclear cells (PBMCs were separated from 41 healthy blood donors by Ficoll-Hypaque gradient centrifugation. Multicolor flow cytometry was used to investigate the expression of function markers (degranulation marker (CD107a, IFN-γ, and TNF-a on NK cells following PMA/Ionomycin or K562 stimulation. Results: The percentage of NK cells expressing CD107a, IFN-γ, or TNF-a in response to PMA/Ionomycin were 17.85, 10.56, and 2.66 %, respectively. The NK cells expressing CD107a, IFN-γ, or TNF-a in response to K562 stimulation were 6.43, 2.09, and 0.57 %, respectively. The capability of NK cells to perform polyfunctions was 6.19 % of the total NK cells following PMA/Ionomycin stimulation, while 1.06 % was observed following K562 stimulation. The trifunctional CD107a+ / IFN-γ+ / TNF-a + NK cell subset was found to be 0.95 and 0.04 % following PMA/Ionomycin and K562 stimulation, respectively. Conclusion: A small fraction of NK cells was capable of performing polyfunctions following stimulation, with less than 1 % being able to perform trifunctions in this study setting.
Mehta, S. K.; Kaur, I.; Grimm, E. A.; Smid, C.; Feeback, D. L.; Pierson, D. L.
Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+) (NMHC) killer cells and cell surface marker expression of peripheral blood mononuclear cells were determined before and after spaceflight. Ten astronauts (9 men, 1 woman) from two space shuttle missions (9- and 10-day duration) participated in the study. Blood samples were collected 10 days before launch, within 3 h after landing, and 3 days after landing. All peripheral blood mononuclear cell preparations were cryopreserved and analyzed simultaneously in a 4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were considered as one study group, NMHC killer cell numbers did not change significantly during the three sampling periods, but at landing lytic activity had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten astronauts had decreased lytic activity immediately after flight. NMHC killer cell cytotoxicity of only three astronauts returned toward preflight values by 3 days after landing. Consistent with decreased NMHC killer cell cytotoxicity, urinary cortisol significantly increased after landing compared with preflight levels. Plasma cortisol and ACTH levels at landing were not significantly different from preflight values. No correlation of changes in NMHC killer cell function or hormone levels with factors such as age, gender, mission, or spaceflight experience was found. After landing, expression of the major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by flow cytometric analysis, did not show any consistent changes from measurements made before flight.
Megan J Peterson
Full Text Available Killer whale (Orcinus orca depredation (whales stealing or damaging fish caught on fishing gear adversely impacts demersal longline fisheries for sablefish (Anoplopoma fimbria, Pacific halibut (Hippoglossus stenolepis and Greenland turbot (Reinhardtius hippoglossoides in the Bering Sea, Aleutian Islands and Western Gulf of Alaska. These interactions increase direct costs and opportunity costs associated with catching fish and reduce the profitability of longline fishing in western Alaska. This study synthesizes National Marine Fisheries Service observer data, National Marine Fisheries Service sablefish longline survey and fishermen-collected depredation data to: 1 estimate the frequency of killer whale depredation on longline fisheries in Alaska; 2 estimate depredation-related catch per unit effort reductions; and 3 assess direct costs and opportunity costs incurred by longliners in western Alaska as a result of killer whale interactions. The percentage of commercial fishery sets affected by killer whales was highest in the Bering Sea fisheries for: sablefish (21.4%, Greenland turbot (9.9%, and Pacific halibut (6.9%. Average catch per unit effort reductions on depredated sets ranged from 35.1-69.3% for the observed longline fleet in all three management areas from 1998-2012 (p<0.001. To compensate for depredation, fishermen set additional gear to catch the same amount of fish, and this increased fuel costs by an additional 82% per depredated set (average $433 additional fuel per depredated set. In a separate analysis with six longline vessels in 2011 and 2012, killer whale depredation avoidance measures resulted in an average additional cost of $494 per depredated vessel-day for fuel and crew food. Opportunity costs of time lost by fishermen averaged $522 per additional vessel-day on the grounds. This assessment of killer whale depredation costs represents the most extensive economic evaluation of this issue in Alaska to date and will help
Ulrik, Charlotte Suppli; Sørensen, Tina Brandt; Højmark, Torben Brunse;
BACKGROUND: The general practitioner (GP) is often the first healthcare contact for patients with chronic obstructive pulmonary disease (COPD). AIMS: To determine whether participating in a standardised educational programme delivered in the GP's own practice is associated with adherence to COPD...... guidelines. METHODS: A nationwide register-based observational before and after study was undertaken with a control group of propensity-matched practices (follow-up period 6 months). COPD was defined as age 40+ years and at least two prescriptions for inhaled medication. The educational programme consisted...... were used to compare the rate of spirometry testing, preventive consultations, and influenza vaccinations provided to COPD patients and the rate of spirometry testing in non-COPD individuals, assumed to reflect diagnostic activity. RESULTS: Data for 102 participating GP practices were analysed...
Sister Carrie is one of the most controversial characters in American literature.Thought as a "fallen woman" firstly,she was defined as a "new woman" by some critics later. However, by digging into the motivaton behind the whole process of Carrie's "success", the relationship between Carrie and her creator (the author), the social conditions of then American, it can be found that Carrie has never been free-standing on her thought and she has never found her real-sdf even after becoming a famous actress. In a society dominated by mass consumerism Carrie is only an adherent of her own desires. She also is a representative of all those country girls flooded into cities, a symbol and a sacrifice of the urbanization of America in a time countryside was overcome by cities.
Foote, Andrew David; Morin, PA; JW, Durban;
Killer whales (Orcinus orca) are the most widely distributed marine mammals and have radiated to occupy a range of ecological niches. Disparate sympatric types are found in the North Atlantic, Antarctic and North Pacific oceans, however, little is known about the underlying mechanisms driving...... reconstructions and a clinal decrease in diversity suggest a North Pacific to North Atlantic founding event, and the later return of killer whales to the North Pacific. Therefore, ecological divergence could have occurred during the allopatric phase through drift or selection and/or may have either commenced...
Full Text Available Natural killer (NK cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta, we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results showed that the absolute number of total NK cells in the blood increased in response to MPXV infection at a magnitude of 23-fold, manifested by increases in CD56+, CD16+, CD16-CD56- double negative, and CD16+CD56+ double positive NK cell subsets. Similarly, the frequency and NK cell numbers in the lymph nodes also largely increased with the total NK cell number increasing 46.1-fold. NK cells both in the blood and lymph nodes massively proliferated in response to MPXV infection as measured by Ki67 expression. Chemokine receptor analysis revealed reduced expression of CXCR3, CCR7, and CCR6 on NK cells at early time points (days 2 and 4 after virus inoculation, followed by an increased expression of CXCR3 and CCR5 at later time points (days 7-8 of infection. In addition, MPXV infection impaired NK cell degranulation and ablated secretion of interferon-γ and tumor necrosis factor-α. Our data suggest a dynamic model by which NK cells respond to MPXV infection of rhesus macaques. Upon virus infection, NK cells proliferated robustly, resulting in massive increases in NK cell numbers. However, the migrating capacity of NK cells to tissues at early time points might be reduced, and the functions of cytotoxicity and cytokine secretion were largely compromised. Collectively, the data may explain, at least partially, the pathogenesis of MPXV infection in rhesus macaques.
Drotar, Dennis; Greenley, Rachel Neff; Demeter, Christine A.; McNamara, Nora K.; Stansbrey, Robert J.; Calabrese, Joseph R.; Stange, Jonathan; Vijay, Priya; Findling, Robert L.
Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase. Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of…
Dulmen, S. van; Sluijs, E.; Dijk, L. van; Ridder, D. de; Heerdink, R.; Bensing, J.
BACKGROUND: Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the e
Braam, R.L.; Uum, S.H.M. van; Lenders, J.W.M.; Thien, Th.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Insufficient drug adherence is an important reason for inadequate blood pressure control. Currently, methods that measure drug adherence objectively are lacking. Objective methods are needed to help improve blood pressure control and outcome in hypertensive
van Boven, Job F. M.; Trappenburg, Jaap C. A.; van der Molen, Thys; Chavannes, Niels H.
In this paper, we aim to emphasise the need for a more comprehensive and tailored approach to manage the broad nature of non-adherence, to personalise current asthma management. Although currently several methods are available to measure the extent of asthma patients' adherence, the vast majority do
Haagen, Esther C; Nelen, Willianne L D M; Grol, Richard P T M; Braat, Didi D M; Hermens, Rosella P M G; Kremer, Jan A M
Health-care delivery according to clinical practice guidelines is thought to be critical in achieving optimal outcomes. This study aimed to assess the extent to which practice performance in intrauterine insemination (IUI) care is consistent with guideline recommendations and to evaluate the association between guideline adherence and outcome of IUI care. In a retrospective cohort study, 1100 infertile couples who underwent IUI treatment at 10 Dutch hospitals were asked to grant access to their medical record for assessment of guideline adherence using 25 systematically developed guideline-based performance indicators. A total of 558 couples who started 2334 IUI cycles participated. Guideline adherence regarding 20 process and five structure aspects of IUI care was often substandard and varied considerably between hospitals. Out of 10 possible associations investigated, guideline adherence regarding sperm quality and guideline adherence regarding the total number of IUI cycles were associated with improved ongoing pregnancy rates after IUI. Thus, guideline adherence in IUI care is far from optimal and varies substantially between hospitals. As associations between guideline adherence and ongoing pregnancy after IUI were mainly non-significant, further research is needed to evaluate associations between guideline adherence and other outcomes of IUI care besides ongoing pregnancy, such as patient safety and cost effectiveness. PMID:20129823
... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Adherence to original budget estimates. 1260.72 Section 1260.72 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Post-Award Requirements § 1260.72 Adherence to original budget estimates....
Mol, PGM; Gans, ROB; Panday, PVN; Degener, JE; Laseur, M; Haaijer-Ruskamp, FM
Assessment procedures for adherence to a guideline must be reliable and credible. The aim of this study was to explore the reliability of assessment of adherence, taking account of the professional backgrounds of the observers. A secondary analysis explored the impact of case characteristics on asse
... 42 Public Health 4 2010-10-01 2010-10-01 false Adherence to upper limits; FFP. 447.304 Section 447... Noninstitutional Services § 447.304 Adherence to upper limits; FFP. (a) The Medicaid agency must not pay more than... payments may be made only up to the reasonable charge under Medicare. (c) FFP is not available for a...
Roder, E.; Berger, M. Y.; de Groot, H.; van Wijk, R. Gerth
Background Adherence is essential for effective treatment. Although several trials on the efficacy of sublingual immunotherapy (SLIT) in youngsters have been published, few contain data on medication intake. Objective We aimed to quantify adherence both to study protocol and medication intake as wel
Objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are freeliving. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs)of expected weight loss ca...
Objective measures are needed to quantify dietary adherence during caloric restriction (CR) while participants are freeliving. One method to monitor adherence is to compare observed weight loss to the expected weight loss during a prescribed level of CR. Normograms (graphs) of expected weight loss c...
Safren, Steven A.; Hendriksen, Ellen S.; Mayer, Kenneth H.; Mimiaga, Matthew J.; Pickard, Robert; Otto, Michael W.
For patients with HIV, depression is a common, distressing condition that can interfere with a critical self-care behavior--adherence to antiretroviral therapy. The present study describes a cognitive-behavioral treatment designed to integrate cognitive-behavioral therapy for depression with our previously tested approach to improving adherence to…
Sameer Bhaskar GOKHALE
Full Text Available Low patient adherence remains a major public health challenge globally and imposes a considerable economic burden on healthcare systems. It is critical to develop an effective intervention to improve patient adherence. Factors such as physician-patient relation, patient's health literacy, attitude, cultural variations, and patient’s involvement in decision making are responsible for improving adherence. Information technology has revolutionized almost all industries including healthcare but its use has not shown its full promise to boost adherence. Recent developments in smart phone market penetration, gamification, and easy to navigate user experience have made it possible for healthcare providers to effectively connect with patients using innovative ways enabled by technology. Leveraging on this fact, healthcare industry should be focusing on development and use of interactive health games. Indication-wise games can be developed in collaboration with physicians, academics, thought leaders and experienced media companies. In summary, gamification mayeffectively be used to improve patient adherence.
Costa, Elísio; Giardini, Anna; Savin, Magda; Menditto, Enrica; Lehane, Elaine; Laosa, Olga; Pecorelli, Sergio; Monaco, Alessandro; Marengoni, Alessandra
Medication adherence and persistence is recognized as a worldwide public health problem, particularly important in the management of chronic diseases. Nonadherence to medical plans affects every level of the population, but particularly older adults due to the high number of coexisting diseases they are affected by and the consequent polypharmacy. Chronic disease management requires a continuous psychological adaptation and behavioral reorganization. In literature, many interventions to improve medication adherence have been described for different clinical conditions, however, most interventions seem to fail in their aims. Moreover, most interventions associated with adherence improvements are not associated with improvements in other outcomes. Indeed, in the last decades, the degree of nonadherence remained unchanged. In this work, we review the most frequent interventions employed to increase the degree of medication adherence, the measured outcomes, and the improvements achieved, as well as the main limitations of the available studies on adherence, with a particular focus on older persons. PMID:26396502
Dirk Michael Zajonc
Full Text Available T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the Major Histocompatibility (MHC family (MHC I and II, lipids, glycolipids and lipopeptides can be presented by the non-classical MHC member CD1. The best studied subset of lipid-reactive T cells are Type I Natural killer T (iNKT cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi the causative agents of Lyme disease and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR, leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18 and TCR stimulation. Many microbes carry TLR antigens and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here we will review the molecular basis of iNKT cell
Jensen, L S; Andersen, A J; Christiansen, P M;
The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measure...
Eissens, D.N.; Michelo, C.M.; Preijers, F.W.M.B.; Cranenbroek, B. van; Houwelingen, K.P. van; Meer, A. van der; Joosten, I.
In allogeneic stem cell transplantation (SCT), natural killer (NK) cells lacking their cognate inhibitory ligand can induce graft-versus-leukemia responses, without the induction of severe graft-versus-host disease (GVHD). This feature can be exploited for cellular immunotherapy. In this study, we e
Timonen, T T; Palva, I P
Acute leukaemia is known to develop in many cases of benzene-induced pancytopenia . This is a report of the development of acute leukaemia in a patient who had apparently recovered from pancytopenia after chronic exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid. PMID:6769284
... a False Killer Whale Take Reduction Team and Meeting, 75 FR 2853, January 19, 2010), the Team's... of this FKWTRP were provided in the proposed rule (76 FR 42082, July 18, 2011) and are not repeated... Team (75 FR 2853, January 19, 2010), the American Samoa stock was not included in the scope of the...
Foote, Andrew D; Newton, Jason; Piertney, Stuart B;
promoting divergence. Here we use morphological traits, nitrogen stable isotope ratios and tooth wear to characterize two disparate types of North Atlantic killer whale. We find a highly specialist type, which reaches up to 8.5 m in length and a generalist type which reaches up to 6.6 m in length...
Foote, Andrew David; Newton, Jason; Avila Arcos, Maria del Carmen;
and investigate the evolutionary outcomes. Isotopic ratios were measured from tissue samples of sympatric killer whale Orcinus orca lineages from the North Sea, spanning over 10 000 years. Isotopic ratios spanned a range similar to the difference in isotopic values of two known prey items, herring Clupea harengus...
Spel, Lotte; Boelens, Jaap Jan; Van Der Steen, Dirk M.; Blokland, Nina J G; van Noesel, Max M.; Molenaar, Jan J.; Heemskerk, Mirjam H M; Boes, Marianne; Nierkens, Stefan
Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20-40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neurobla
New electronic tablet devices are often referred to as either saviours of newspapers or killers of traditional print media. These crude statements are based on a naive concept of media substitution and an overestimation of the actual use of new media for news consumption. It is much more likely that
Oleson, J. C.
As part of my Ph.D. research on criminal genius, I conducted 44 semi-structured interviews. One of the 44 subjects, in particular, stood out. This noteworthy individual claimed that he had killed 15 people. His story was particularly interesting because--unlike most social research involving serial killers--he claimed that he had never been…
Saadoun, Samira; Bridges, Leslie R; Verkman, A S; Papadopoulos, Marios C
Neuromyelitis optica is a severe inflammatory demyelinating disease of the central nervous system. Most patients with neuromyelitis optica have circulating immunoglobulin G (IgG) antibodies against the astrocytic water channel protein aquaporin-4 (AQP4), which are pathogenic. Anti-AQP4 IgG-mediated complement-dependent astrocyte toxicity is a key mechanism of central nervous system damage in neuromyelitis optica, but the role of natural killer and cytotoxic T cells is unknown. Our objective was to determine whether natural killer and cytotoxic T cells play a role in human neuromyelitis optica lesions. We immunostained four actively demyelinating lesions, obtained from patients with anti-AQP4 IgG positive neuromyelitis optica, for Granzyme B and Perforin. The inflammatory cells were perivascular neutrophils, eosinophils and macrophages, with only occasional Granzyme B+ or Perforin+ cells. Greater than 95% of inflamed vessels in each lesion had no surrounding Granzyme B+ or Perforin+ cells. Granzyme B+ or Perforin+ cells were abundant in human spleen (positive control). Although natural killer cells produce central nervous system damage in mice injected with anti-AQP4 IgG, our findings here indicate that natural killer-mediated and T cell-mediated cytotoxicity are probably not involved in central nervous system damage in human neuromyelitis optica.
Stopiglia, Cheila Denise Ottonelli; Heidrich, Daiane; Sorrentino, Julia Medeiros; Vieira, Fabiane Jamono; Landell, Melissa Fontes; Valente, Patrícia; Scroferneker, Maria Lúcia
The Sporothrix schenckii complex is the etiologic agent of sporotrichosis, a subacute or chronic mycosis which can affect humans and animals. Killer yeasts have been used in the medical field for development of novel antimycotics and biotyping of pathogenic fungi. The action of 18 killer yeasts on the growth of 88 characterized S. schenckii, Sporothrix globosa, Sporothrix brasiliensis, and Sporothrix mexicana clinical and environmental isolates was evaluated. Killer studies were performed on Petri dishes containing cheese black starch agar. The yeasts Candida catenulata (QU26, QU31, QU127, LV102); Trichosporon faecale (QU100); Trichosporon japonicum (QU139); Kluyveromyces lactis (QU30, QU99, QU73); Kazachstania unispora (QU49), Trichosporon insectorum (QU89), and Kluyveromyces marxianus (QU103) showed activity against all strains of the S. schenckii complex tested. Observation by optical microscopy of S. brasiliensis 61 within the inhibition haloes around the colonies of the killer yeasts QU100, QU139, and LV102 showed that there was no conidiation, but there was hyphal proliferation. The toxins were fungistatic against S. brasiliensis 61. There was no difference in susceptibility to the toxins among the S. schenckii species complex. Further investigations are necessary to clearly establish the mechanism of action of the toxins.
Nielsen, Hans Jørgen; Pedersen, B K; Moesgaard, F;
hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper...
Cure, C.; Antunes, R.; Samarra, F.; Alves, A.C.; Visser, F.; Kvadsheim, P.H.; Miller, P.J.O.
In cetaceans’ communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans’ behavior. Killer whales (Orcinus orca) ar
Villalba, María Leticia; Susana Sáez, Julieta; Del Monaco, Silvana; Lopes, Christian Ariel; Sangorrín, Marcela Paula
Microbiological spoilage is a major concern throughout the wine industry, and control tools are limited. This paper addresses the identification and partial characterization of a new killer toxin from Torulaspora delbrueckii with potential biocontrol activity of Brettanomyces bruxellensis, Pichia guilliermondii, Pichia manshurica and Pichia membranifaciens wine spoilage. A panel of 18 different wine strains of T. delbrueckii killer yeasts was analysed, and the strain T. delbrueckii NPCC 1033 (TdKT producer) showed a significant inhibitory effect on the growth of all different spoilage yeasts evaluated. The TdKT toxin was then subjected to a partial biochemical characterization. Its estimated molecular weight was N30 kDa and it showed glucanase and chitinase enzymatic activities. The killer activity was stable between pH 4.2 and 4.8 and inactivated at temperature above 40 °C. Pustulan and chitin — but not other cell wall polysaccharides — prevented sensitive yeast cells from being killed by TdKT, suggesting that those may be the first toxin targets in the cell wall. TdKT provoked an increase in necrosis cell death after 3 h treatment and apoptotic cell death after 24 h showing time dependence in its mechanisms of action. Killer toxin extracts were active at oenological conditions, confirming their potential use as a biocontrol tool in winemaking. PMID:26513248
Pedersen, B K; Beyer, J M; Rasmussen, A; Klarlund, K; Pedersen, B N; Helin, P
Natural killer (NK) cell activity was studied in 8 patients with classic or definite rheumatoid arthritis (RA) by investigating the killing of K 562 cells by peripheral blood lymphocytes before, during, and after intravenous methylprednisolone pulse therapy (MPPT). MPPT produced a considerable fall in NK activity and after 3 months NK activity was less than half that before MPPT. PMID:6516854
Funk, Brian K.; Castelli, Jonathan C.; Watkins, Adam S.; McCubbin, Christopher B.; Marshall, Steven J.; Barton, Jeffrey D.; Newman, Andrew J.; Peterson, Cammy K.; DeSena, Jonathan T.; Dutrow, Daniel A.; Rodriguez, Pedro A.
The Johns Hopkins University Applied Physics Laboratory deployed and demonstrated a prototype Cooperative Hunter Killer (CHK) Unmanned Aerial System (UAS) capability and a prototype Upstream Data Fusion (UDF) capability as participants in the Joint Expeditionary Force Experiment 2010 in April 2010. The CHK capability was deployed at the Nevada Test and Training Range to prosecute a convoy protection operational thread. It used mission-level autonomy (MLA) software applied to a networked swarm of three Raven hunter UAS and a Procerus Miracle surrogate killer UAS, all equipped with full motion video (FMV). The MLA software provides the capability for the hunter-killer swarm to autonomously search an area or road network, divide the search area, deconflict flight paths, and maintain line of sight communications with mobile ground stations. It also provides an interface for an operator to designate a threat and initiate automatic engagement of the target by the killer UAS. The UDF prototype was deployed at the Maritime Operations Center at Commander Second Fleet, Naval Station Norfolk to provide intelligence analysts and the ISR commander with a common fused track picture from the available FMV sources. It consisted of a video exploitation component that automatically detected moving objects, a multiple hypothesis tracker that fused all of the detection data to produce a common track picture, and a display and user interface component that visualized the common track picture along with appropriate geospatial information such as maps and terrain as well as target coordinates and the source video.
Villalba, María Leticia; Susana Sáez, Julieta; Del Monaco, Silvana; Lopes, Christian Ariel; Sangorrín, Marcela Paula
Microbiological spoilage is a major concern throughout the wine industry, and control tools are limited. This paper addresses the identification and partial characterization of a new killer toxin from Torulaspora delbrueckii with potential biocontrol activity of Brettanomyces bruxellensis, Pichia guilliermondii, Pichia manshurica and Pichia membranifaciens wine spoilage. A panel of 18 different wine strains of T. delbrueckii killer yeasts was analysed, and the strain T. delbrueckii NPCC 1033 (TdKT producer) showed a significant inhibitory effect on the growth of all different spoilage yeasts evaluated. The TdKT toxin was then subjected to a partial biochemical characterization. Its estimated molecular weight was N30 kDa and it showed glucanase and chitinase enzymatic activities. The killer activity was stable between pH 4.2 and 4.8 and inactivated at temperature above 40 °C. Pustulan and chitin — but not other cell wall polysaccharides — prevented sensitive yeast cells from being killed by TdKT, suggesting that those may be the first toxin targets in the cell wall. TdKT provoked an increase in necrosis cell death after 3 h treatment and apoptotic cell death after 24 h showing time dependence in its mechanisms of action. Killer toxin extracts were active at oenological conditions, confirming their potential use as a biocontrol tool in winemaking.
Santucci, M.; Pimpinelli, N; Massi, D; Kadin, ME; Meijer, C.J.L.M.; Muller-Hermelink, HK; Paulli, M; Wechsler, J.; Willemze, R.; Audring, H; Bernengo, MG; Cerroni, L.; Chimenti, S.; Chott, A.; Diaz-Perez, J.L.; Dippel, E; Duncan, LM; Feller, AC; Geerts, M.L.; Hallermann, C; Kempf, W; Russell-Jones, R; Sander, C; Berti, E.
BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases o
Puppels, G.J.; Garritsen, H.S.P.; Kummer, J.A.; Greve, Jan
The presence and subcellular location of carotenoids in human lymphocyte sub-populations (CD4+, CD8+, T-cell receptor-γδ+, and CD19+ ) and natural killer cells (CD16+ ) were studied by means of Raman microspectroscopy. In CD4+ lymphocytes a high concentration (10-3M) of carotenoids was found in the
Multhoff, G; Mizzen, L; Winchester, CC; Milner, CM; Wenk, S; Eissner, G; Kampinga, HH; Laumbacher, B; Johnson, J
We previously demonstrated that lysis of tumor cells that express Hsp70, the highly stress-inducible member of the HSP70 family, on their plasma membrane is mediated by natural killer (NK) cells. Here, we studied the effects of different proteins of the HSP70 family in combination with interleukin 2
Filatova, Olga A; Miller, Patrick J O
The killer whale is one of the few animal species with vocal dialects that arise from socially learned group-specific call repertoires. We describe a new agent-based model of killer whale populations and test a set of vocal-learning rules to assess which mechanisms may lead to the formation of dialect groupings observed in the wild. We tested a null model with genetic transmission and no learning, and ten models with learning rules that differ by template source (mother or matriline), variation type (random errors or innovations) and type of call change (no divergence from kin vs. divergence from kin). The null model without vocal learning did not produce the pattern of group-specific call repertoires we observe in nature. Learning from either mother alone or the entire matriline with calls changing by random errors produced a graded distribution of the call phenotype, without the discrete call types observed in nature. Introducing occasional innovation or random error proportional to matriline variance yielded more or less discrete and stable call types. A tendency to diverge from the calls of related matrilines provided fast divergence of loose call clusters. A pattern resembling the dialect diversity observed in the wild arose only when rules were applied in combinations and similar outputs could arise from different learning rules and their combinations. Our results emphasize the lack of information on quantitative features of wild killer whale dialects and reveal a set of testable questions that can draw insights into the cultural evolution of killer whale dialects.
Kuningas, S.; Kvadsheim, P.H.; Lam, F.P.A.; Miller, P.J.O.
In this study, retrospective data on naval sonar activity and prey abundance were correlated with killer whale sightings within a fjord basin in northern Norway. In addition, passive acoustic and visual marine mammal surveys were conducted before, during, and after a specific navy exercise in 2006.
Regina Celia Cândido
Full Text Available Foi estudado o efeito killer de 9 cepas padrão de leveduras sobre 146 amostras de Candida albicans isoladas dos seguintes espécimes clínicos: mucosa bucal, fezes, lavado brônquico, escarro, secreção vaginal, urina, lesão de pele, lesão de unha e sangue. Usando este sistema foi possível diferenciar 23 biotipos de C. albicans. Os biotipos 211, 111 e 811 foram os mais freqüentemente isolados. A maioria das amostras de C. albicans (98,6% foi sensível a pelo menos uma ou mais das 9 cepas killer. Empregando- se este sistema foi possível demonstrar que 2 pacientes albergavam mesmo biotipo killer, respectivamente, 111 e 211, em diferentes espécimes clínicos, e em outro paciente, o mesmo biotipo (211 foi isolado de hemoculturas realizadas em ocasiões distintas. O uso do sistema killer para diferenciar os tipos entre as espécies de leveduras patogênicas, pode ser um método útil para estabelecer a eventual fonte de infecção, constituindo uma ajuda valiosa para o controle e vigilância de infecções nosocomiais causadas por leveduras.
Fracture mechanics is used to identify criteria under which uniform oxide scales may be expected to fail due to rapidly applied strains. The most common failure mode occurs when the strain, ε, builds up in the scale until the strain energy density per unit area exceeds the fracture surface energy, γ, of the oxide. This produces spalling when ε > (2γ/hE)1/2, where h is the scale thickness and E is the oxide Youngs modulus. In thin scales, as the external strain is applied to the oxide via the metal substrate, it is clear that no further strain can be applied to the oxide if the substrate has itself been strained beyond yield. This gives rise to extended oxide adherence in which the oxide cracks and forms a series of islands but remains attached to the deformed metal. When the oxide thickness is less than its comminution limit, the flaw size necessary for brittle fracture exceeds the oxide thickness and the oxide yields in a ductile manner without cracking. The results are presented as maps of failure strain versus oxide thickness for various oxide systems such as Fe3O4, Cr2O3, Al2O3, SiO2 and NiO. The observed cases of spalling are found to lie within the predicted regions. (author)
Full Text Available To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC "call types". The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population.
Huang, Jen-Ying; Chen, Hsing-Mei
Pharmacotherapy plays an important role in the management of chronic diseases. However, many patients with chronic disease do not adhere to their medication regimen. This results in worsening symptoms and frequent re-hospitalizations. As a result, healthcare providers may view these patients as bad. Medication adherence is a complex concept. Analyzing this concept may assist nurses to improve patient-centered care. This paper uses Walker & Avant's method to conduct a concept analysis of medication adherence. Results show the defining attributes of medication adherence as: (1) knowing and agreeing to the medication; (2) communicating and negotiating the regimen; and (3) active, continuous involvement in and appraisal of the treatment effect. Identified antecedents of medication adherence included the patient having: (1) a prescribed medication regimen; (2) cognitive and action abilities in her / his role as a patient; and (3) level of preparation for medication treatment. Identified consequences of medication adherence include: (1) improving symptom control; (2) decreasing re-hospitalizations and mortality; (3) reducing medical care costs; (4) restoring self-esteem; and (5) diminishing depression. It is hoped that this concept analysis provides a reference for nurses to achieve a better understanding of medication adherence and further improve nursing practice. PMID:24899565
Full Text Available Manuela Casula,1 Elena Tragni,1 Alberico Luigi Catapano1,21Epidemiology and Preventive Pharmacology Centre (SEFAP, Department of Pharmacological Sciences, University of Milan, Milan, Italy; 2IRCCS MultiMedica, Sesto San Giovanni, ItalyAbstract: Despite the widespread prescription of highly effective lipid-lowering medications, such as the HMG-CoA reductase inhibitors (statins, a large portion of the population has lipid levels higher than the recommended goals. Treatment failures have been attributed to a variety of causes but the most important is likely to be poor adherence to therapy in the form of irregular or interrupted intake and the high frequency of discontinuation or lack of persistence. Adherence is a multidimensional phenomenon determined by the interplay of patient factors, physician factors, and health care system factors. Patients' knowledge and beliefs about their illness, motivation to manage it, confidence in their ability to engage in illness-management behaviors, and expectations regarding the outcome of treatment and the consequences of poor adherence interact to influence adherence behavior. Patient-related factors account for the largest incremental explanatory power in predicting adherence. This article provides an overview of this critical issue, focusing on patient role in determining adherence level to lipid-lowering therapy.Keywords: hyperlipidemia/drug therapy, medication adherence, patient preference, health behavior
Bainbridge, Jacquelyn L; Ruscin, J Mark
Patient adherence to a medication regimen is critical to treatment outcome, quality of life and future healthcare costs. For elderly patients with Parkinson's disease, obstacles to adherence can be particularly complex. Beyond age-related and economic factors, elderly patients with Parkinson's disease often require complicated dosing or titration schedules and have multiple co-morbidities that necessitate administration of therapies from multiple drug classes. In addition, neuropsychiatric disturbances and cognitive impairment, which are often part of the disease process, can affect adherence, as can variable responses to anti-parkinsonian agents as the disease progresses. Several recent studies in patients with Parkinson's disease point to the need for establishing good adherence patterns early and maintaining these throughout the course of treatment. To achieve optimal adherence in elderly patients with Parkinson's disease, a combination of pharmacological and non-pharmacological approaches appears to be the best strategy for success. Examples include a strong provider-patient relationship, educational intervention by phone or face-to-face contact, simplified dosing and administration schedules, management and understanding of medication adverse events, and the use of adherence aids such as pill boxes and hour-by-hour organizational charts. Research into new avenues that include improved drug monitoring, pharmacogenetics and neuroprotective regimens may give rise to better adherence in elderly patients with Parkinson's disease in the future. PMID:19220071
Link, Lilli B; Jacobson, Judith S
The purpose of this study was to evaluate adherence and identify predictors of adherence to a raw vegan diet (i.e., uncooked plant foods) following a stay at a raw vegan institute. In this cohort study of guests at a raw vegan institute, subjects completed written questionnaires upon arrival and 12 weeks later. Of 107 eligible guests, 84 participated. Mean age was 54 years, 23 were male, and 73 white. Fifty-one completed the 12-week follow-up. Eight (16%) reported their diet to be 80% raw vegan at baseline and 14 (28%) at follow-up. Based on a raw vegan dietary adherence score (range 0-42) created for this study, mean adherence (SD) increased from 15.1 (5.4) to 17.0 (5.8) over 12 weeks (p=0.03). Baseline predictors of adherence included: education (beta=0.95), severity of disease (beta=0.98), and self-efficacy to adhere (beta=0.72). Future interventions that evaluate this diet should address self-efficacy, an important, potentially remediable predictor of adherence.
Full Text Available Teresa L Kauf1, Keith L Davis2, Stephanie R Earnshaw2, E Anne Davis31Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, 2RTI Health Solutions, Research Triangle Park, NC, 3Independent consultant, Pittsboro, NC, USAAbstract: The impact of fixed-dose combination (FDC products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI backbone consisting of the FDC Epzicom®, GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group versus NRTI combinations taken as two separate pills (NRTI Combo group using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR. Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001. In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03. None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.Keywords
Kolewe, Kristopher W; Peyton, Shelly R; Schiffman, Jessica D
Clinically, biofilm-associated infections commonly form on intravascular catheters and other hydrogel surfaces. The overuse of antibiotics to treat these infections has led to the spread of antibiotic resistance and underscores the importance of developing alternative strategies that delay the onset of biofilm formation. Previously, it has been reported that during surface contact, bacteria can detect surfaces through subtle changes in the function of their motors. However, how the stiffness of a polymer hydrogel influences the initial attachment of bacteria is unknown. Systematically, we investigated poly(ethylene glycol) dimethacrylate (PEGDMA) and agar hydrogels that were 20 times thicker than the cumulative size of bacterial cell appendages, as a function of Young's moduli. Soft (44.05-308.5 kPa), intermediate (1495-2877 kPa), and stiff (5152-6489 kPa) hydrogels were synthesized. Escherichia coli and Staphylococcus aureus attachment onto the hydrogels was analyzed using confocal microscopy after 2 and 24 h incubation periods. Independent of hydrogel chemistry and incubation time, E. coli and S. aureus attachment correlated positively to increasing hydrogel stiffness. For example, after a 24 h incubation period, there were 52 and 82% fewer E. coli adhered to soft PEGDMA hydrogels than to the intermediate and stiff PEGDMA hydrogels, respectively. A 62 and 79% reduction in the area coverage by the Gram-positive microbe S. aureus occurred after 24 h incubation on the soft versus intermediate and stiff PEGDMA hydrogels. We suggest that hydrogel stiffness is an easily tunable variable that could potentially be used synergistically with traditional antimicrobial strategies to reduce early bacterial adhesion and therefore the occurrence of biofilm-associated infections.
Cohn, Robert C.
Background: A patient's adherence to an appropriate treatment regimen is necessary to minimize morbidity and mortality associated with childhood asthma. Many factors influence the success of treatment adherence.
Alava, Juan José; Ross, Peter S; Gobas, Frank A P C
Resident killer whale populations in the NE Pacific Ocean are at risk due to the accumulation of pollutants, including polybrominated diphenyl ethers (PBDEs). To assess the impact of PBDEs in water and sediments in killer whale critical habitat, we developed a food web bioaccumulation model. The model was designed to estimate PBDE concentrations in killer whales based on PBDE concentrations in sediments and the water column throughout a lifetime of exposure. Calculated and observed PBDE concentrations exceeded the only toxicity reference value available for PBDEs in marine mammals (1500 μg/kg lipid) in southern resident killer whales but not in northern resident killer whales. Temporal trends (1993-2006) for PBDEs observed in southern resident killer whales showed a doubling time of ≈5 years. If current sediment quality guidelines available in Canada for polychlorinated biphenyls are applied to PBDEs, it can be expected that PBDE concentrations in killer whales will exceed available toxicity reference values by a large margin. Model calculations suggest that a PBDE concentration in sediments of approximately 1.0 μg/kg dw produces PBDE concentrations in resident killer whales that are below the current toxicity reference value for 95 % of the population, with this value serving as a precautionary benchmark for a management-based approach to reducing PBDE health risks to killer whales. The food web bioaccumulation model may be a useful risk management tool in support of regulatory protection for killer whales. PMID:26289814
Incubation of resting lymphoid cells with recombinant interleukin 2 (IL- 2) in vitro leads to the generation of lymphokine activated killer (LAK) cells capable of lysing fresh tumor cell suspensions in short- term chromium-release assays. Our previous studies (7) have demonstrated that the injection of LAK cells plus low doses of recombinant IL-2 were capable of inhibiting the growth of pulmonary metastases. We have now explored the ability of high doses of recombinant IL-2, administered syst...
National Oceanic and Atmospheric Administration, Department of Commerce — In this study, vocal compensation is being investigated in Southern Resident killer whale (SRKW) calls to determine the degree to which whales can adjust to...
Objective To explore the influence of the killer cell immunoglobulin like receptor(KIR)gene polymorphism on cytomegalovirus(CMV)infection and pathogenesis after hematopoietic stem cell transplantation(HSCT)
Palu, Tiit, 1970-
Vanemuises esietenduvad 19. mail Arthur Milleri 'Sööst kuristikku' (lavastaja Andrus Allikvee) ja 20. mail Tracy Lettsi 'Killer Joe' (lavastaja Tiit Palu). Postimehe küsitlus lavastajatele (vastavad samadele küsimustele)
Brown, E. E.
Anodic treatment of titanium alloy enables electroplating of tightly adherent coatings of copper and nickel on the alloy. The alloy is treated in a solution of hydrofluoric and acetic acids, followed by the electroplating process.
Hebert, Elizabeth A; Vincent, Norah; Lewycky, Samantha; Walsh, Kaitlyn
This study examined the ability of the Theory of Planned Behavior (TPB; Ajzen, 1985) and the Transtheoretical Model of Behavior Change (TTM; Prochaska & DiClemente, 1983) to explain adherence and attrition in an online treatment program for chronic insomnia. Responses to questionnaire measures of the TPB and TTM were used to predict adherence and dropout over the subsequent 5 weeks of treatment. Results showed that there was a 17% dropout rate and that perceived behavioral control, social support, and intention to complete the program were significantly associated with adherence to sleep hygiene homework. Attrition was predicted only by symptom severity and psychiatric comorbidity. Implications are that these models should be considered to maximize adherence. PMID:20582757
individualised interventions and team-based care, e.g. integrating a clinical pharmacist with particular focus on patients’ drug-related problems. One approach with growing evidence of improving medication adherence is motivational interviewing (MI). So far, no clinical pharmacist intervention using MI has......-based patient interview and three follow-up telephone calls. There was no difference in the primary outcome, the composite medication possession ratio (MPR) for antiplatelets, anticoagulants and statins during the year after hospitalisation, as assessed by analysing prescription refill records. At 12 months...... to the one in the first study, except that the patient interview was more structured using the Drug Adherence Work-up (DRAW) tool and an adherence questionnaire for identifying potential adherence and lifestyle-related problems. At 12 months, 20.3% of the patients in the intervention group (N=231) were non...
Hawley-Hague, Helen; Horne, Maria; Skelton, Dawn A; Todd, Chris
Exercise classes provide a range of benefits for older adults, but adherence levels are poor. We know little of instructors' experiences of delivering exercise classes to older adults. Semistructured interviews, informed by the Theory of Planned Behavior (TPB), were conducted with instructors (n = 19) delivering multicomponent exercise classes to establish their perspectives on older adults' uptake and adherence to exercise classes. Analysis revealed 'barriers' to uptake related to identity, choice/control, cost, and venue, and 'solutions' included providing choice/control, relating exercise to identity, a personal touch, and social support. Barriers to adherence included unrealistic expectations and social influences, and solutions identified were encouraging commitment, creating social cohesion, and an emphasis on achieving outcomes. Older adults' attitudes were an underlying theme, which related to all barriers and solutions. The instructor plays an important, but not isolated, role in older adults' uptake and adherence to classes. Instructors' perspectives help us to further understand how we can design successful exercise classes. PMID:26214265
In one aspect, a method for detaching adherent cells can include adding a cell lifting solution to the media including a sample of adherent cells and incubating the sample of adherent cells with the cell lifting solution. No scraping or pipetting is needed to facilitate cell detachment. The method do not require inactivation of cell lifting solution and no washing of detaching cells is required to remove cell lifting solution. Detached cells can be stained with dye in the presence of cell lifting solution and are further analyzed using flow cytometer. The method has been tested using 6 different cell lines, 4 different assays, two different plate formats (96 and 384 well plates) and two different flow cytometry instruments. The method is simple to perform, less time consuming, with no cell loss and makes high throughput flow cytometry on adherent cells a reality.
Hawley-Hague, Helen; Horne, Maria; Skelton, Dawn A; Todd, Chris
Exercise classes provide a range of benefits for older adults, but adherence levels are poor. We know little of instructors' experiences of delivering exercise classes to older adults. Semistructured interviews, informed by the Theory of Planned Behavior (TPB), were conducted with instructors (n = 19) delivering multicomponent exercise classes to establish their perspectives on older adults' uptake and adherence to exercise classes. Analysis revealed 'barriers' to uptake related to identity, choice/control, cost, and venue, and 'solutions' included providing choice/control, relating exercise to identity, a personal touch, and social support. Barriers to adherence included unrealistic expectations and social influences, and solutions identified were encouraging commitment, creating social cohesion, and an emphasis on achieving outcomes. Older adults' attitudes were an underlying theme, which related to all barriers and solutions. The instructor plays an important, but not isolated, role in older adults' uptake and adherence to classes. Instructors' perspectives help us to further understand how we can design successful exercise classes.
Full Text Available Zhanglin Cui, Yang Zhao, Diego Novick, Douglas FariesEli Lilly and Company, Indianapolis, IN, USAObjectives: Adherence to medication for the treatment of fibromyalgia (FM is predictive of lower overall health-care costs, and thus a lower burden on both patients and providers. The objectives of this study were to examine the predictors of adherence to and persistence with duloxetine therapy among commercially insured FM patients, and to identify subgroups of patients with high duloxetine persistence and adherence.Study design: This cross-sectional, retrospective study analyzed medical and pharmacy records over 1 year for patients in the US aged 18–64 years with FM who initiated (no prior 90-day use duloxetine treatment in 2008.Methods: Adherence to duloxetine was measured by medication possession ratio (MPR, with high adherence defined as MPR ≥ 0.8. Persistence was defined as the duration of therapy from the index date to the earliest of: the ending date of the last prescription, the date of the first gap of >15 days between prescriptions, or the end of the study period (12 months. Demographic and clinical predictors of adherence were examined via multiple logistic regression (MLR, and subgroups of duloxetine-persistent and -adherent patients were identified using classification and regression trees (CART.Results: Among 4660 duloxetine patients, 33% achieved high adherence. Factors associated with high adherence from MLR included older age, North Central and Northeast regions, prior venlafaxine, pregabalin, selective serotonin reuptake inhibitor (SSRI, or other antidepressant use, or comorbid dyslipidemia or osteoarthritis (all P < 0.05. CART analysis revealed that patients with prior antidepressant use, aged ≥46, or prior osteoarthritis had higher MPR (all P < 0.05, and patients aged ≥45 with a history of SSRI, venlafaxine, or anticonvulsant use had longer duration of therapy (all P < 0.05.Conclusions: Patients with high adherence to and
Svendsen, Mathias Tiedemann; Andersen, Flemming; Hansen, Jakob;
OBJECTIVE: Topical corticosteroids and corticosteroid combinations are the principal treatments in psoriasis. The aim of this study was to investigate published literature dealing with medical adherence to topical corticosteroid or corticosteroid combinations in patients with psoriasis. MATERIALS...... health outcome in topical treatment of psoriasis, further studies should be conducted addressing determinants of nonadherence and test interventions to improve adherence. Validated measurements of medical nonadherence, prescription registers, or medication-weight are needed....
Dhaliwal P; Wagg A
Prabhpreet Dhaliwal, Adrian Wagg Department of Medicine, University of Alberta, Edmonton, Canada Abstract: Overactive bladder is a common, debilitating condition for many patients who may benefit from pharmacological management of their condition. However, adherence to medication in this condition is markedly worse than other chronic medical conditions. This review explores what is known about persistence and the factors which influence medication adherence for overactive bladder, those fac...
Verma, S.; Madarnas, Y.; Sehdev, S.; Martin, G; Bajcar, J.
Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider–related. To date, there is a gap in the literature concerning a comprehensive...
Full Text Available Medication adherence is defined as patient's adherence to take their medications as prescribed and continue to take the prescribed medication for stipulated time frame. Medication non-adherence is a growing concern to physicians, healthcare systems, and other stakeholders (e.g., payers and there is an increasing evidence of its prevalence and is associated with adverse clinical outcomes eventually resulting into higher costs of care. The cost of non-adherence has been estimated at $100 billion to $300 billion annually, including costs from avoidable hospitalizations, nursing home admissions, and premature deaths. Improving adherence to medication is critical to improve the quality of health care, to encourage better chronic care management, and promote better health outcomes. Reasons for non-adherence are multiple and complex. Studies have reported that poor adherence to drug dosage is due to patient perception that the disease is non-significant, adverse drug effects, lack of treatment effectiveness, and the patient's poor or incomplete knowledge of the disease and (cost. A multifactorial approach is required to tackle this complex problem as a single approach will be ineffective for all patients. The most effective intervention is to use a combination of approaches and address literacy, behavior, and organizational issues. There are challenges as well as opportunities in addressing the public health issue of medication adherence. Changing healthcare reforms, advances in digital health media, social media and modern technologies can now provide alternatives to tackle this issue. [Int J Basic Clin Pharmacol 2014; 3(5.000: 748-754
In renal transplantation, immunosuppressants are prescribed to patients to prevent graft loss. Although the extent of adherence required for such treatment to prevent graft loss has not been determined, it is thought to be high. Despite this, research suggests adherence rates for renal transplant recipients to be only between 50% and 95%. Considering the impact of graft loss on the renal patient, the national healthcare budget and on the limited resource of donor organs, it is important to id...
Sulaiman, Imran; Cushen, Breda; Greene, Garrett; Seheult, Jansen; Seow, Dexter; Rawat, Fiona; MacHale, Elaine; Mokoka, Matshediso; Moran, Catherine Nora; Bhreathnach, Aoife Sartini; MacHale, Philippa; Tappuni, Shahed; Deering, Brenda; Jackson, Mandy; McCarthy, Hannah
RATIONALE: Objective adherence to inhaled therapy by patients with COPD has not been reported. OBJECTIVES: The aim of this study was to objectively quantify adherence to preventer DiskusTM inhaler therapy by patients with COPD with an electronic audio recording device (INCATM). METHODS: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCATM device attached. Analysis of this audio quantified the frequency...
Throughout life, a patient with severe haemophilia is confronted with many treatment-related challenges. Insight into self-management and non-adherence could improve the quality of care for these patients. The aim of this thesis was to provide an overview of a series of studies on self-management and adherence to prophylaxis in haemophilia. Based on series of studies, aspects of treatment were explored: learning and performing self-infusion, achieving self-management skills in adolescence, ad...
Brodtkorb, Eylert; Samsonsen, Christian; Sund, Janne Kutschera; Bråthen, Geir; Helde, Grethe; Reimers, Arne
Non-adherence to antiepileptic drug treatment strongly affects the outcome of epilepsy and is frequently clinically unrecognized. This review addresses current knowledge on medication-taking behavior in people with epilepsy, as well as the importance of tailoring interventions to the individual patterns of non-adherence. Non-adherence can be categorized as non-initiation, poor execution (accidental or intentional) or non-persistence and are related to clinical characteristics and health care barriers. All available methods to assess adherence are hampered by shortcomings. Self-reports are indirect and subjective. Pill-counts, electronic bottle-tops and pharmacy records are objective, but indirect measures of drug ingestion. Therapeutic drug monitoring is both direct and objective, but pharmacokinetic and diurnal variability must be taken into account. Young adults with generalized epilepsy may be particularly vulnerable to non-adherence. The drug burden in the form of polytherapy, multiple dosing and side effects are obvious obstacles. Poor understanding of the principles of prophylactic treatment as well as drug costs may be important in people with low socioeconomic status. Depression is also associated with low adherence. In people with multihandicaps, failed oral intake may be due to behavioral or physical problems, as well as insufficient education of the caregivers. Non-adherence often results in seizure breakthrough and hospital admissions, but the consequences may be more dramatic. It is the leading cause of status epilepticus in people with epilepsy, and the association with sudden death (SUDEP) is clear. The management of poor drug-taking behavior should be based on the identification of the specific causes in each individual and corresponding multiprofessional interventions. Non-adherence to antiepileptic drugs needs more clinical and scientific attention. PMID:26897547
Full Text Available This paper explores the monetary expectations induced to the managers of Romanian firms by adheration. It is based on an investigation among twenty Romanian executives regarding the impact on adheration over monetary aspects: inflation, exchange rates and adoption of euro. We conclude that the results of the monetary policy in the last years made the executives confident that the Romanian authorities could maintain the monetary stability after theadheration.
Latif Gachkar; Gelareh Asadzadeh-Totonchi; Mohammadreza Alaei; Shirin Farivar
Objective:There are several problems associated to the management of patients with phenylketonuria (PKU). Social status could be one of the affecting factors on dietary adherence in these patients. The aim of this study was to evaluate family social status and dietary adherence of PKU patients in Iranian population. Methods: In a cross-sectional study, we studied 105 Iranian PKU patients (born 1984 to 2010), treated and followed at Mofid Childrens Hospital, Tehran. Social status was defined b...
Corral, Pedro Del; Bryan, David R.; Garvey, W. Timothy; Gower, Barbara A.; Gary R. Hunter
This study examined the relationship between previous dietary adherence during a low-calorie diet weight loss intervention and subsequent weight change during a 2-year follow-up for weight maintenance. One hundred and sixteen healthy, recently weight reduced (lost ~12 kg, BMI 22–25 kg/m2) premenopausal women were studied. Dietary adherence was assessed by doubly labeled water (DLW) and body composition change. Comparisons were made between the upper and lower tertiles for previous dietary adh...
Beny Spira; Gerson Moura Ferreira; Luiz Gustavo de Almeida
Enteropathogenic Escherichia coli (EPEC) is a known causative agent of diarrhea in children. In the process of colonization of the small intestine, EPEC synthesizes two types of adhesins, the bundle-forming pilus (BFP) and intimin. The BFP pilus is an adhesin associated with the initial stages of adherence of EPEC to epithelial cells, while the outer membrane protein intimin carries out the intimate adherence that takes place at the third stage of infection. BFP is encoded by the bfp operon l...
Kuçi, Selim; Rettinger, Eva; Voß, Bernhard; Weber, Gerrit; Stais, Miriam; Kreyenberg, Hermann; Willasch, Andre; Kuçi, Zyrafete; Koscielniak, Ewa; Klöss, Stephan; Laer, Dorothee von; Klingebiel, Thomas; Bader, Peter
Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and has a poor prognosis. Here we assessed the capability of ex vivo expanded cytokine-induced killer cells to lyse both alveolar and embryonic rhabdomyosarcoma cell lines and investigated the mechanisms involved. Design and Methods: Peripheral blood mononuclear cells from six healthy donors were used to generate and expand cytokine-induced killer cells. The phenotype and composition of these cells were deter...
Similä, Tiu; Christensen, Ivar
Killer whales (Orcinus orca) have been pohotoidentified around Lofoten and Vesterålen islands northern Norway during fall-winter (October-February) and summer (June-August) in 1990 and 1991. Some background data exists from 1983-1989. To date 302 killer whale individuals belonging to 44 different groups have been identified. The yearly distribution and abundance of whales is closely related to the distribution of springspawning herring (Clupea harengus) in the area. Since...
Ciro da Silva Portes; Andriélen Virke de Oliveira; Patrícia Simer; Alessandra Machado Lunkes; Alexandre Rodrigo Coelho
This work evaluated the antagonism of killer positive yeast strains (isolated from 11 samples of different frozen fruit pulps) against the strains of Penicillium expansum and Aspergillus ochraceus. Of the total 41 killer yeasts tested in YM agar, 19 showed antibiosis against P. expansum and A. ochraceus, with inhibition zone ranging from 10 to 18 mm and 10 to 19 mm, respectively. In the following step, the extracellular activity of Kluyveromyces sp. FP4(13) was tested performing the assay in ...
Grebner, Dawn M.
The scientific goal of this dissertation was to carefully study the signal structure of killer whale communications and vocal complexity and link them to behavioral circumstances. The overall objective of this research sought to provide insight into killer whale call content and usage which may be conveying information to conspecifics in order to maintain group cohesion. Data were collected in the summers of 2006 and 2007 in Johnstone Strait, British Columbia. For both individuals and small groups, vocalizations were isolated using a triangular hydrophone array and the behavioral movement patterns were captured by a theodolite and video camera positioned on a cliff overlooking the hyrophone locations. This dissertation is divided into four analysis chapters. In Chapter 3, discriminant analysis was used to validate the four N04 call subtypes which were originally parsed due to variations in slope segments. The first two functions of the discriminant analysis explained 97% of the variability. Most of the variability for the N04 call was found in the front convex and the terminal portions of the call, while very little variability was found in the center region of the call. This research revealed that individual killer whales produced multiple subtypes of the N04 call. No correlations of behaviors to acoustic parameters obtained were found. The aim of the Chapter 4 was to determine if killer whale calling behavior varied prior to and after the animals had joined. Pulsed call rates were found to be greater pre- compared to post-joining events. Two-way vocal exchanges were more common occurring 74% of the time during pre-joining events. In Chapter 5, initiated and first response to calls varied between age/sex class groups when mothers were separated from an offspring. Solo mothers and calves initiated pulsed calls more often than they responded. Most of the no vocal responses were due to mothers who were foraging. Finally, observations of the frequency split in N04
Taylor, Bernadette C; Brotheridge, Rory M; Jessup, David A; Stott, Jeffrey L
Killer whales and sea otters maintained in captivity are the subjects of routine health monitoring programs, and interest in immunologic studies in sea otters has been rising recently in response to potential impacts from infectious disease and environmental pollution on the threatened southern sea otter population. Development of species-specific reagents for immunologic studies in these two marine mammals is currently in its infancy. In this study, killer whale and sea otter immunoglobulin-specific polyclonal antibodies were generated, and used to develop tests for serum Ig concentration in the killer whale (Orcinus orca) and the southern (Enhydra lutris nereis) and northern sea otter (Enhydra lutris lutris). Killer whale serum IgG was purified using caprylic acid/ammonium sulfate precipitation. Sea otter plasma IgG was purified using protein-A-agarose. Polyclonal anti-Ig antisera were produced in rabbits, and specificity confirmed by immunoelectrophoresis. Radial immunodiffusion was used to measure Ig concentration in serum or plasma samples derived from 21 captive killer whales, 18 wild and 4 captive southern sea otters and 15 wild and 4 captive northern sea otters grouped by age. Mean killer whale serum Ig concentration (+/-95% confidence interval) ranged from 15.04 +/- 3.97 g/l for animals aged 0-5 years to 26.65 +/- 9.8 g/l for animals aged >10 years. Mean sea otter serum Ig concentration (+/-95% confidence interval) ranged from 28.39 +/- 11.00 g/l for southern sub-adults to 32.76 +/- 11.58 g/l for southern adults. No significant difference in serum Ig concentration was found between southern and northern sea otters. Serum Ig concentrations in two northern sea otter pups were low compared to those of adult sea otters. The two serum Ig quantitation assays produced were highly specific and reproducible and will be useful additions to the limited number of tests available for immune function in these marine mammal species. PMID:12383650
Gebremedhin Berhe Gebregergs
Full Text Available Household contacts of active tuberculosis cases are at high risk of getting tuberculosis disease. Tuberculosis detection rate among contacts of household members is high. Hence, this study investigated household contact screening adherence and associated factors among tuberculosis patients in Amhara region, Ethiopia.A cross-sectional study was conducted from April 10 - June 30, 2013 in five urban districts of Amhara region, where 418 patients receiving treatment at tuberculosis clinic were interviewed. All patients were interviewed using structured and pre-tested questionnaire. Bringing at least one household contact to TB clinic was regarded as adherent to household contacts screening. Bivariate and multiple logistic regressions were used to investigate association.The overall adherence to household contact screening in Amhara region was 33.7%. Adherence was higher among Muslims than Christians. Adherence was high if patient took health education from Health Care Worker [AOR: 3.22, 95% CI: 1.88 to 5.51] and 2.17 times higher if patient had sufficient knowledge on tuberculosis [AOR: 2.17, 95% CI: 1.29 to 3.67] during interview. Relationship with contact was a significant [AOR: 0.4, 95% CI: 0.2 to 0.9] social related factor.One third of tuberculosis patients adhered to household contact screening in health facilities during their treatment course. Promoting knowledge of tuberculosis in the community and continuous health education to tuberculosis patients are recommended.
Robeck, Todd R; Nollens, Hendrik H
Gestation and lactation result in metabolic alterations of the dam because of varying demands of the fetus and offspring during the different stages of development. Despite killer whales (Orcinus orca) having one of the longest gestations and highest birth weights of all mammals in human care, these metabolic alterations, and their impact on the physiology of the dam have not been measured. The objectives of this analysis were to determine if physiologic demands on the killer whale during pregnancy and lactation have measurable effects on hematology and biochemical analytes and if detectable, to compare these changes to those which are observed in other mammalian species. Forty hematologic and biochemical analytes from seven female killer whales (22 pregnancies, 1,507 samples) were compared between the following stages: (1) non-pregnant or lactating (control); (2) gestation; and (3) the first 12 months of lactation. Decreased hematocrit, hemoglobin, and red blood cell counts were indicative of plasma volume expansion during mid and late gestation. The killer whales exhibited a progressively increasing physiologic inflammatory state leading up to parturition. Gestation and lactation caused significant shifts in the serum lipid profiles. Gestation and lactation cause significant physiologic changes in the killer whale dam. The last 12 months of gestation had greater physiological impact than lactation, but changes associated with and immediately following parturition were the most dramatic. During this period, killer whales may experience increased susceptibility to illness, and anthropogenic and environmental disturbances. PMID:23813680
Sharpe, Deborah Lynn
Apex predators are important indicators of ecosystem health, but little is known about the population structure of Bigg's killer whales ( Orcinus orca; i.e. 'transient' ecotype) in western Alaska. Currently, all Bigg's killer whales in western Alaska are ascribed to a single broad stock for management under the US Marine Mammal Protection Act. However, recent nuclear microsatellite and mitochondrial DNA analyses indicate that this stock is likely comprised of genetically distinct sub-populations. In accordance with what is known about killer whale vocal dialects in other locations, I sought to evaluate Bigg's killer whale population structure by examining the spatial distribution of group-specific call types in western Alaska. Digital audio recordings were collected from 33 encounters with Bigg's killer whales throughout the Aleutian and Pribilof Islands in the summers of 2001-2007 and 2009-2010. Recorded calls were perceptually classified into discrete types and then quantitatively described using 12 structural and time-frequency measures. Resulting call categories were objectively validated using a random forest approach. A total of 36 call types and subtypes were identified across the entire study area, and regional patterns of call type usage revealed three distinct dialects, each of which corresponding to proposed genetic delineations. I suggest that at least three acoustically and genetically distinct subpopulations are present in western Alaska, and put forth an initial catalog for this area describing the regional vocal repertoires of Bigg's killer whale call types.
Heo, D.S.; Park, J.G.; Hata, K.; Day, R.; Herberman, R.B.; Whiteside, T.L. (Univ. of Pittsburgh School of Medicine, PA (USA))
A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay was developed and compared with 51Cr release from different adherent tumor cell targets (human squamous cell carcinoma lines of the head and neck established in our laboratory, melanoma, and colorectal carcinoma) using 5-7-day human lymphokine-activated killer cells and monocyte-depleted peripheral blood lymphocytes as effectors. With adherent tumor cell targets, MTT colorimetry was more sensitive than the 51Cr release assay in measuring the antitumor activity of effectors: median, 4385 (range, 988-8144) versus median, 1061 (range, 582-7294) lytic units (the number of effector cells required to lyse 20% of 5 x 10(3) targets)/10(7) effectors (P less than 0.01). Background effects (without effector cells) were comparable in 4-h assays (9% versus 10%) between MTT colorimetry and 51Cr release. In 24-h assays, MTT colorimetry showed higher antitumor activity (70-100% versus 40-60% lysis at 1:1 effector:target cell ratio) but lower background effects (6% versus 38%) than 51Cr release assay. Thus, MTT colorimetry was more sensitive, did not use radiolabeled targets, required fewer effector cells, and was easier, less expensive, and better adaptable to serial monitoring of effector cell function in cancer patients. This colorimetric assay is especially well suited to adherent tumor cell targets. The use of adherent tumor cell monolayers, as opposed to trypsinized single cell suspensions, provides an opportunity to measure interactions of effector cells with enzymatically unaltered solid tumor targets. Because of the greater sensitivity of the colorimetric assay, the transformation of MTT data into lytic units, as commonly used for 51Cr release assays, required an adjustment to avoid the extrapolation based on the exponential fit equation.
Riber, U; Espersen, F; Kharazmi, A
The ability to consume complement and activate neutrophils was investigated for staphylococci adherent to silicone surfaces and non-adherent staphylococci. Staphylococcus epidermidis strain ATCC 14990 and Staphylococcus aureus strain E 2371 were used in this study. The bacteria were allowed...... at 37 degrees C. The bacteria consumed complement to approximately the same extent when adherent to the catheter segments, but more slowly in comparison with planktonic bacteria. When planktonic bacteria were compared, complement was consumed more quickly by S. epidermidis than by S. aureus. Measuring...... the induction of chemiluminescence by planktonic bacteria, S. epidermidis induced a lower response than S. aureus, while when adherent to the catheter segments the bacteria induced similar responses. These responses were only 15 to 20% of those induced by planktonic bacteria and only slightly higher than...
Full Text Available Connie T Kekwaletswe,1 Neo K Morojele1,21Alcohol and Drug Abuse Research Unit, Medical Research Council, Pretoria, 2School of Public Health, University of the Witwatersrand, Johannesburg, South AfricaBackground: The primary objectives of this study were to determine the association between alcohol and antiretroviral therapy (ART adherence and the perceived appropriateness and acceptability of elements of an adherence counseling program with a focus on alcohol-related ART nonadherence among a sample of ART recipients in human immunodeficiency virus (HIV clinics in Tshwane, South Africa.Methods: We conducted a cross-sectional study with purposive sampling. The sample comprised 304 male and female ART recipients at two President's Emergency Plan For AIDS Relief-supported HIV clinics. Using an interview schedule, we assessed patients' alcohol use (Alcohol Use Disorders Identification Test, other drug use, level of adherence to ART, and reasons for missing ART doses (AIDS Clinical Trials Group adherence instrument. Additionally, patients’ views were solicited on: the likely effectiveness of potential facilitators; the preferred quantity, duration, format, and setting of the sessions; the usefulness of having family members/friends attend sessions along with the patient; and potential skill sets to be imparted.Results: About half of the male drinkers’ and three quarters of the female drinkers’ Alcohol Use Disorders Identification Test scores were suggestive of hazardous or harmful drinking. Average self-reported ART adherence was 89.7%. There was a significant association between level of alcohol use and degree of ART adherence. Overall, participants perceived two clinic-based sessions, each of one hour’s duration, in a group format, and facilitated by a peer or adherence counselor, as most appropriate and acceptable. Participants also had a favorable attitude towards family and friends accompanying them to the sessions. They also favored an
Pedersen, B K; Bygbjerg, Ib Christian; Svenson, M
Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the cont......Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while...... that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis....
Full Text Available Abstract Purpose To evaluate the efficacy of cytokine-induced killer (CIK cell therapy in the treatment of hepatocellular carcinoma. Materials and methods Randomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells". Results The analysis showed significant survival benefit (one-year survival, p p p p p p +, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p Conclusions CIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.
Full Text Available Natural killer cells participate in the early immune response against melanoma and also contribute to the development of an adequate adaptive immune response by their crosstalk with dendritic cells and cytokine secretion. Melanoma resistance to conventional therapies together with its high immunogenicity justifies the development of novel therapies aimed to stimulate effective immune responses against melanoma. However, melanoma cells frequently escape to CD8 T cell recognition by the down-regulation of major histocompatibility complex class I molecules. In this scenario, Natural killer cells emerge as potential candidates for melanoma immunotherapy due to their capacity to recognize and destroy melanoma cells expressing low levels of major histocompatibility complex class I molecules. In addition, the possibility to combine immune checkpoint blockade with other NK cell potentiating strategies (e.g. cytokine induction of activating receptors has opened new perspectives in the potential use of adoptive NK cell-based immunotherapy in melanoma.
Marina López Martínez
Full Text Available This article deals with the figure of the serial killer, a character whose extreme violence has constituted it as the maximum exponent of evilness in our cultural representations. My main interest is to see the treatment that some French police novel writers reserve to him: Brigitte Aubert, Maud Tabachnik, Fred Vargas and Virginie Despentes. The cinematographic adaptation of Despente’s Baise-moi (2000 is specially revealing: while the bloodthirsty murders of Hannibal Lecter or other masculine serial killers receive the approval of the great public and the critic in general, the crimes committed by the two heroins of Virginie Despentes have been put under the censorship. I try to demonstrate from this example that the use of violent women is still disturbing, a taboo after which remains old generic prejudices.
Reisner, Andrew D; McGee, Mark; Noffsinger, Stephen G
The authors present the case of a man who was hospitalized after claiming that he was about to become a serial killer. The patient presented with extensive written homicidal fantasies and homicidal intentions without evidence of actual homicidal acts. In addition to routine assessments, hospital staff members used case conferences, psychological testing, outside forensic consultation, and a forensic review process to make decisions regarding diagnosis, treatment planning, and discharge. The patient was discharged after 8 months of inpatient treatment and was apparently free of homicidal impulses or symptoms of severe mental illness. A 2-year court commitment allowed for the enactment and potential enforcement of a discharge plan that was endorsed by the patient, the hospital, and community care providers. The authors review diagnostic and risk management issues. Comparisons with known features of typical serial killers are made.
Reisner, Andrew D; McGee, Mark; Noffsinger, Stephen G
The authors present the case of a man who was hospitalized after claiming that he was about to become a serial killer. The patient presented with extensive written homicidal fantasies and homicidal intentions without evidence of actual homicidal acts. In addition to routine assessments, hospital staff members used case conferences, psychological testing, outside forensic consultation, and a forensic review process to make decisions regarding diagnosis, treatment planning, and discharge. The patient was discharged after 8 months of inpatient treatment and was apparently free of homicidal impulses or symptoms of severe mental illness. A 2-year court commitment allowed for the enactment and potential enforcement of a discharge plan that was endorsed by the patient, the hospital, and community care providers. The authors review diagnostic and risk management issues. Comparisons with known features of typical serial killers are made. PMID:12613432
Williams, Rob; Erbe, Christine; Ashe, Erin; Beerman, Amber; Smith, Jodi
Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arbitrary decision about severity threshold indicating a response. Subtle responses were observed around broadband received levels of 130 dB re 1 μPa (rms); more severe responses are hypothesized to occur at received levels beyond 150 dB re 1 μPa, where our study lacked data. Avoidance responses are expected to carry minor energetic costs in terms of increased energy expenditure, but future research must assess the potential for reduced prey acquisition, and potential population consequences, under these noise levels. PMID:24373666
Barnig, C.; Cernadas, M; Dutile, S.; Liu, X.; Perrella, M A; Kazani, S.; Wechsler, M.E.; Israel, E; Levy, B.D.
Asthma is a prevalent disease of chronic inflammation in which endogenous counter-regulatory signaling pathways are dysregulated. Recent evidence suggests that innate lymphoid cells (ILCs), including natural killer (NK) cells and type 2 innate lymphoid cells (ILC2), can participate in the regulation of allergic airways responses, in particular airway mucosal inflammation. Here, we have identified both NK cells and ILC2 in human lung and peripheral blood in healthy and asthmatic subjects. NK c...
Alam, Shahabuddin; Katakura, Yoshinori; Shirahata, Sanetaka
We have succeeded in establishing a method to reproducibly immortalize human T cells by oncogene(s) transfection (Alam, 1997). This study was based on our previous discoveries that these immortalized T cell lines contained T cells which showed cytotoxicity against K562 cells in MHC-nonrestricted manner. Then we attempted to obtain human T cell clones exhibiting natural killer-like activity. Here, we tried to establish clones from these immortalized T cell lines by limiting dilution after stim...
Ebere Anyanwu; Campbell, Andrew W.; Joseph Jones; Ehiri, John E; Akpan I. Akpan
Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological signif...
Ni, Jing; Cerwenka, Adelheid
Natural killer cells (NK) are commonly considered to be potent antitumor effector cells. The study by Gotthardt and colleagues challenges this concept and reveals that STAT5-deficient/inhibited NK cells induce angiogenesis and promote tumor progression. These unexpected findings shed new light on potential adverse effects of JAK-STAT inhibitors in the clinics.Cancer Discov; 6(4); 347-9. ©2016 AACRSee related article by Gotthardt et al., p. 414. PMID:27045017
Yoder, Jeffrey A.; Gary W. Litman
Natural killer (NK) cells effect a form of innate immunity that recognizes and eliminates cells that are infected with certain viruses or have undergone malignant transformation. In mammals, this recognition can be mediated through immunoglobulin- (Ig) and/or lectin-type NK receptors (NKRs). NKR genes in mammals range from minimally polymorphic single copy genes to complex multigene families that exhibit high levels of haplotypic complexity and exhibit significant interspecific variation. Cer...
The prevalence and severity of allergic diseases are increasing in western countries. Known pathophysiological mechanisms involve the induction of Th2 response by dendritic cells, leading to IgE production and inflammation. The innate immunity was recently highlighted in the control of adaptive immunity, which is antigen specific. However, the role of Natural Killer (NK) cells, innate cells mainly known for their anti-tumoral and anti-microbial functions, is still unknown in allergic patholog...
Pham, Betty; Piard-Ruster, Karine; Silva, Richard; Gallo, Amy; Esquivel, Carlos O.; Martinez, Olivia M.; Krams, Sheri M.
Natural killer (NK) cells are important in the immune response against tumors and virally infected cells. A balance of inhibitory and activating receptors controls the effector functions of NK cells. We examined the fate of circulating NK cells and the expression of the NK cell activating receptors in pediatric liver transplant recipients. Blood specimens were collected from 38 pediatric liver transplant recipients before transplant, and at 1 week, 1, 3, 6, and 9 months, and 1 year post-trans...
Williams, Rob; Krkošek, Martin; Ashe, Erin; Branch, Trevor A; Clark, Steve; Hammond, Philip S.; Hoyt, Erich; Noren, Dawn P; Rosen, David; Winship, Arliss
Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada–US) ranges. We modele...
Williams, Robert; Krkošek, Martin; Ashe, Erin; Branch, Trevor A; Clark, Stephen; Hammond, Philip Steven; Hoyt, Eric; Noren, Dawn P; Rosen, David; Winship, Arliss
Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada–US) ranges. We modele...
Brent, Lauren J N; Franks, Daniel W; Foster, Emma A; Balcomb, Kenneth C; Cant, Michael A; Croft, Darren P
Classic life-history theory predicts that menopause should not occur because there should be no selection for survival after the cessation of reproduction . Yet, human females routinely live 30 years after they have stopped reproducing . Only two other species-killer whales (Orcinus orca) and short-finned pilot whales (Globicephala macrorhynchus) [3, 4]-have comparable postreproductive lifespans. In theory, menopause can evolve via inclusive fitness benefits [5, 6], but the mechanisms by which postreproductive females help their kin remain enigmatic. One hypothesis is that postreproductive females act as repositories of ecological knowledge and thereby buffer kin against environmental hardships [7, 8]. We provide the first test of this hypothesis using a unique long-term dataset on wild resident killer whales. We show three key results. First, postreproductively aged females lead groups during collective movement in salmon foraging grounds. Second, leadership by postreproductively aged females is especially prominent in difficult years when salmon abundance is low. This finding is critical because salmon abundance drives both mortality and reproductive success in resident killer whales [9, 10]. Third, females are more likely to lead their sons than they are to lead their daughters, supporting predictions of recent models  of the evolution of menopause based on kinship dynamics. Our results show that postreproductive females may boost the fitness of kin through the transfer of ecological knowledge. The value gained from the wisdom of elders can help explain why female resident killer whales and humans continue to live long after they have stopped reproducing. PMID:25754636
Martens, Willem H J
In this article the psychodynamic link between loneliness and sadism is examined on basis of a case report of the sadistic and cannibalistic serial killer Jeffery Dahmer. Envy, shame/rage mechanism, a disturbed oral-sadistic development, castration fear and severe feelings of inferiority, the conviction of being unlovable and unacceptable, need to diminish tension, powerful and sadistic fantasies as a consequence of inadequate and frustrated parenting, and reality distortion appear to be involved in sadistic etiology.
David Nau; Nora Altmayer; Jochen Mattner
Mucosal surfaces in the airways and the gastrointestinal tract are critical for the interactions of the host with its environment. Due to their abundance at mucosal tissue sites and their powerful immunomodulatory capacities, the role of innate lymphoid cells (ILCs) and natural killer T (NKT) cells in the maintenance of mucosal tolerance has recently moved into the focus of attention. While NKT cells as well as ILCs utilize distinct transcription factors for their development and lineage dive...
Cooper, Megan A.; Colonna, Marco; Yokoyama, Wayne M.
Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells and producing immunoregulatory cytokines. Herein, we discuss recent studies that indicate that NK cells span the conventional boundaries between innate and adaptive immunity. For example, it was recently discovered that NK cells have the capacity for memory-like responses, a property that was previously thought to be limited to adaptive immunity. NK cells have also been identified in multiple tissues, and ...
Kay, Alexander W; Strauss-Albee, Dara M; Blish, Catherine A
Mass cytometry is a novel platform for high-dimensional phenotypic and functional analysis of single cells. This system uses elemental metal isotopes conjugated to monoclonal antibodies to evaluate up to 42 parameters simultaneously on individual cells with minimal overlap between channels. The platform can be customized for analysis of both phenotypic and functional markers. Here, we will describe methods to stain, collect, and analyze intracellular functional markers and surface phenotypic markers on natural killer cells. PMID:27177653
Filatova, Olga A; Miller, Patrick J O
The killer whale is one of the few animal species with vocal dialects that arise from socially learned group-specific call repertoires. We describe a new agent-based model of killer whale populations and test a set of vocal-learning rules to assess which mechanisms may lead to the formation of dialect groupings observed in the wild. We tested a null model with genetic transmission and no learning, and ten models with learning rules that differ by template source (mother or matriline), variation type (random errors or innovations) and type of call change (no divergence from kin vs. divergence from kin). The null model without vocal learning did not produce the pattern of group-specific call repertoires we observe in nature. Learning from either mother alone or the entire matriline with calls changing by random errors produced a graded distribution of the call phenotype, without the discrete call types observed in nature. Introducing occasional innovation or random error proportional to matriline variance yielded more or less discrete and stable call types. A tendency to diverge from the calls of related matrilines provided fast divergence of loose call clusters. A pattern resembling the dialect diversity observed in the wild arose only when rules were applied in combinations and similar outputs could arise from different learning rules and their combinations. Our results emphasize the lack of information on quantitative features of wild killer whale dialects and reveal a set of testable questions that can draw insights into the cultural evolution of killer whale dialects. PMID:25817037
Brent, Lauren J N; Franks, Daniel W; Foster, Emma A; Balcomb, Kenneth C; Cant, Michael A; Croft, Darren P
Classic life-history theory predicts that menopause should not occur because there should be no selection for survival after the cessation of reproduction . Yet, human females routinely live 30 years after they have stopped reproducing . Only two other species-killer whales (Orcinus orca) and short-finned pilot whales (Globicephala macrorhynchus) [3, 4]-have comparable postreproductive lifespans. In theory, menopause can evolve via inclusive fitness benefits [5, 6], but the mechanisms by which postreproductive females help their kin remain enigmatic. One hypothesis is that postreproductive females act as repositories of ecological knowledge and thereby buffer kin against environmental hardships [7, 8]. We provide the first test of this hypothesis using a unique long-term dataset on wild resident killer whales. We show three key results. First, postreproductively aged females lead groups during collective movement in salmon foraging grounds. Second, leadership by postreproductively aged females is especially prominent in difficult years when salmon abundance is low. This finding is critical because salmon abundance drives both mortality and reproductive success in resident killer whales [9, 10]. Third, females are more likely to lead their sons than they are to lead their daughters, supporting predictions of recent models  of the evolution of menopause based on kinship dynamics. Our results show that postreproductive females may boost the fitness of kin through the transfer of ecological knowledge. The value gained from the wisdom of elders can help explain why female resident killer whales and humans continue to live long after they have stopped reproducing.
Sirota, L.; Straussberg, R; Notti, I.; Bessler, H
The effect of human colostrum on the production of interleukin-2 (IL-2) and on natural killer (NK) cell activity by peripheral blood mononuclear cells (PBMC) was investigated in 50 healthy women. At concentrations as low as 0.5%, human colostrum stimulated IL-2 production; at a higher concentration (10%), IL-2 secretion was inhibited. A time and dose dependent inhibitory effect of colostrum on NK cytotoxicity was also observed. This inhibition could be reversed by the addition of human recomb...
Carpenter, Roger; Gilleland, Diana
Adherence to exercise is one of the most problematic health behaviors. This pilot study describes the impact of an exercise program on adherence to exercise and fitness indicators for overweight and obese adults enrolled in an insurance reimbursed exercise plan. Chart reviews were conducted retrospectively in a convenience sample of 77 subjects from a human performance lab (HPL) at a large southern university. Charts from 2004 to 2009 were reviewed for health history, fitness indicators (fitness level, weight, BMI, hip/waist ratio, % body fat, BP, HR, cholesterol), and adherence (number of exercise sessions/month). Exercise supervision was operationalized in two phases over 12 months: Phase I (3 months supervised exercise) and Phase II (9 months unsupervised exercise). Fifty-eight participants completed Phase I, and 8 completed Phase II. Six-nine percent of those completing Phase I visited the gym at least 8 times/month with significant (α=.05) improvement in all fitness indicators. Those visiting fitness level, weight, BMI, and % body fat. Twenty-four subjects continued into Phase II, with only eight completing Phase II. Of those eight, only one subject visited the HPL at least 8 times/month. Health history data including co-morbidities, symptoms, habits, perceived tension, job stress, and fitness level were not associated with adherence. Symptoms of swollen, stiff, painful joints, and swollen ankles and legs were associated with decreased adherence to exercise. Supervised exercise was positively related to adherence and improved fitness indicators. Adults with joint symptoms may require more support. Based on these pilot data, designing a study with a larger sample and the inclusion of barriers and facilitators for adherence to self-directed exercise would allow additional analysis. Innovative interventions are needed that mimic the supervised environment, shifting responsibility for the exercise plan from the supervisor to those exercising.
Ebben, Remco; Vloet, Lilian; Mintjes, Joke; Achterberg, Theo van
Adherence to ambulance and ED protocols is often suboptimal. Insight into factors influencing adherence is a requisite for improvement of adherence. This study aims to gain an in-depth understanding of factors that influence ambulance and emergency nurses’ adherence to protocols.
Ebben, R.H.A.; Vloet, L.C.M.; Schalk, D.M.; Mintjes-de Groot, J.; Achterberg, T. van
INTRODUCTION: Adherence to ambulance and ED protocols is often suboptimal. Insight into factors influencing adherence is a requisite for improvement of adherence. This study aims to gain an in-depth understanding of factors that influence ambulance and emergency nurses' adherence to protocols. METHO
Bosma, Otto H.; Vermeulen, Karin M.; Verschuuren, Erik A.; Erasmus, Michiel E.; van der Bij, Wim
BACKGROUND: Adherence to medication is a favourable with regard to survival after kidney, heart and liver transplantation. Little is known about adherence to medication in lung transplant recipients. To determine the prevalence of adherence and identify risk factors of non-adherence (NA) we evaluate
A.M. Knops; M.N. Storm-Versloot; A.P.M. Mank; D.T. Ubbink; H. Vermeulen; P.M.M. Bossuyt; A. Goossens
After successful implementation, adherence to hospital guidelines should be sustained. Long-term adherence to two hospital guidelines was audited. The overall aim was to explore factors accounting for their long-term adherence or non-adherence. A fluid balance guideline (FBG) and body temperature gu
Rehn, Nicola; Filatova, Olga A.; Durban, John W.; Foote, Andrew D.
Facial and vocal expressions of emotion have been found in a number of social mammal species and are thought to have evolved to aid social communication. There has been much debate about whether such signals are culturally inherited or are truly biologically innate. Evidence for the innateness of such signals can come from cross-cultural studies. Previous studies have identified a vocalisation (the V4 or `excitement' call) associated with high arousal behaviours in a population of killer whales in British Columbia, Canada. In this study, we compared recordings from three different socially and reproductively isolated ecotypes of killer whales, including five vocal clans of one ecotype, each clan having discrete culturally transmitted vocal traditions. The V4 call was found in recordings of each ecotype and each vocal clan. Nine independent observers reproduced our classification of the V4 call from each population with high inter-observer agreement. Our results suggest the V4 call may be universal in Pacific killer whale populations and that transmission of this call is independent of cultural tradition or ecotype. We argue that such universality is more consistent with an innate vocalisation than one acquired through social learning and may be linked to its apparent function of motivational expression.
Full Text Available In cetaceans' communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans' behavior. Killer whales (Orcinus orca are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas. Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways.
Kalian, M; Birger, M; Witztum, E
The current study re-examines an exceptional case of a serial killer incarcerated since a decade ago. "Jacob" is the first serial killer apprehended in Israel. His known actions were committed during the eighties of the last century, and continued for eleven years. The victims were elderly individuals, including both his parents. Shortly after incarceration he became overtly schizophrenic and underwent five hospitalisations. The case is re-examined in view of changes, both in the perpetrator's diagnosis and criminal legislation. Was Jacob doomed to become a serial killer, or could his fate be avoided through early professional intervention? Were the killings presenting symptoms of a psychotic or pre-psychotic phase? Should he be eligible for a retrial? What would have been his position with the current law in view of the new 300A(a) clause ("Reduced Punishment") of the Israeli Criminal Code? Could he ever be released back to the community? These are some of the questions to be addressed.
de Lima, Jaqueline Rabelo; Gonçalves, Luciana Rocha Barros; Brandão, Luciana Rocha; Rosa, Carlos Augusto; Viana, Francisco Marto Pinto
A total of 580 yeasts strains, isolated from Ceara State of Brasil, were evaluated for their ability to produce killer toxin. Of these strains, 29 tested positive for the killer phenotype and were further evaluated for their ability to control Colletotrichum gloeosporioides germination in vitro. All yeast strains that expressed the killer phenotype were characterized by sequencing the D1/D2 regions of the large subunit of the rRNA gene. Five yeast strains provided a significant reduction in mycelial growth and conidial germination of C. gloeosporioides in vitro, especially Meyerozyma guilliermondii, which was able to reduce the fungal mycelial growth on solid medium (potato dextrose agar (PDA)) by 60% and block 100% of conidia germination in liquid media (potato dextrose broth (PDB)). Filtering and autoclaving the liquid cultures had no effect on the growth of the pathogen. These results indicate the potential use of antagonist yeasts isolated from tropical fruits in the control of anthracnose caused by C. gloeosporioides in papaya. Further elucidation of main mechanisms involved on anthracnose control by these yeasts could be helpful for the development of biocontrol techniques related to the management of this disease in tropical fruits. PMID:22915228
Riera, Amalis; Ford, John K; Ross Chapman, N
Killer whales in British Columbia are at risk, and little is known about their winter distribution. Passive acoustic monitoring of their year-round habitat is a valuable supplemental method to traditional visual and photographic surveys. However, long-term acoustic studies of odontocetes have some limitations, including the generation of large amounts of data that require highly time-consuming processing. There is a need to develop tools and protocols to maximize the efficiency of such studies. Here, two types of analysis, real-time and long term spectral averages, were compared to assess their performance at detecting killer whale calls in long-term acoustic recordings. In addition, two different duty cycles, 1/3 and 2/3, were tested. Both the use of long term spectral averages and a lower duty cycle resulted in a decrease in call detection and positive pod identification, leading to underestimations of the amount of time the whales were present. The impact of these limitations should be considered in future killer whale acoustic surveys. A compromise between a lower resolution data processing method and a higher duty cycle is suggested for maximum methodological efficiency. PMID:23968036
Full Text Available The study of cetacean vocalizations is usually based on spectrogram analysis. The feature extraction is obtained from 2D methods like the edge detection algorithm. Difficulties appear when signal-to-noise ratios are weak or when more than one vocalization is simultaneously emitted. This is the case for acoustic observations in a natural environment and especially for the killer whales which swim in groups. To resolve this problem, we propose the use of the Hilbert-Huang transform. First, we illustrate how few modes (5 are satisfactory for the analysis of these calls. Then, we detail our approach which consists of combining the modes for extracting the time-varying frequencies of the vocalizations. This combination takes advantage of one of the empirical mode decomposition properties which is that the successive IMFs represent the original data broken down into frequency components from highest to lowest frequency. To evaluate the performance, our method is first applied on the simulated chirp signals. This approach allows us to link one chirp to one mode. Then we apply it on real signals emitted by killer whales. The results confirm that this method is a favorable alternative for the automatic extraction of killer whale vocalizations.
Huth, T. K.; Brenu, E. W.; Staines, D. R.; Marshall-Gradisnik, S. M.
Killer cell immunoglobulin-like receptor (KIR) genes encode for activating and inhibitory surface receptors, which are correlated with the regulation of Natural Killer (NK) cell cytotoxic activity. Reduced NK cell cytotoxic activity has been consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients, and KIR haplotypes and allelic polymorphism remain to be investigated. The aim of this article was to conduct a pilot study to examine KIR genotypes, haplotypes, and allelic polymorphism in CFS/ME patients and nonfatigued controls (NFCs). Comparison of KIR and allelic polymorphism frequencies revealed no significant differences between 20 CFS/ME patients and 20 NFCs. A lower frequency of the telomeric A/B motif (P < 0.05) was observed in CFS/ME patients compared with NFCs. This pilot study is the first to report the differences in the frequency of KIR on the telomeric A/B motif in CFS/ME patients. Further studies with a larger CFS/ME cohort are required to validate these results. PMID:27346947
Full Text Available Kimberly M Shuler Shuler Counseling and Consulting, Fayetteville, AR, USA Purpose: In patients with schizophrenia, nonadherence to prescribed medications increases the risk of patient relapse and hospitalization, key contributors to the costs associated with treatment. The objectives of this review were to evaluate the impact of nonadherence to pharmacotherapy in patients with schizophrenia as it relates to health care professionals, particularly social workers, and to identify effective team approaches to supporting patients based on studies assessing implementation of assertive community treatment teams. Materials and methods: A systematic review of the medical literature was conducted by searching the Scopus database to identify articles associated with treatment adherence in patients with schizophrenia. Articles included were published from January 1, 2003, through July 15, 2013, were written in English, and reported findings concerning any and all aspects of nonadherence to prescribed treatment in patients with schizophrenia. Results: Of 92 unique articles identified and formally screened, 47 met the inclusion criteria for the systematic review. The burden of nonadherence in schizophrenia is significant. Factors with the potential to affect adherence include antipsychotic drug class and formulation, patient-specific factors, and family/social support system. There is inconclusive evidence suggesting superior adherence with an atypical versus typical antipsychotic or with a long-acting injectable versus an oral formulation. Patient-specific factors that contribute to adherence include awareness/denial of illness, cognitive issues, stigma associated with taking medication, substance abuse, access to health care, employment/poverty, and insurance status. Lack of social or family support may adversely affect adherence, necessitating the assistance of health care professionals, such as social workers. Evidence supports the concept that an
Full Text Available Introduction: Adherence to antiretroviral therapy (ART plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh in the first 24 months of ART in an Asian HIV cohort. Methods: As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i 14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results: Out of 1316 patients, 32% ever reported 2 assessments per patient per year had an odds ratio (OR=0.7 (95% confidence interval (CI (0.55 to 0.90, p=0.006, compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs (OR=1.92, 95% CI (1.23 to 3.00, p=0.004 and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71, p<0.001. Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67, p=0.001 compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI combination. SubAdh decreased with increasing time on ART (all p<0.001. Similar associations were found with adherence <95% as the outcome. Conclusions: We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social
Full Text Available Abstract Background Adherence with tobramycin inhalation solution (TIS during routine cystic fibrosis (CF care may differ from recommended guidelines and affect health care utilization. Methods We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to Results Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54 received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84. High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423 and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768. Conclusions Use of TIS did not reflect recommended guidelines and may impact other health care utilization.
Giannetti, Vincent J; Kamal, Khalid M
There is an extensive literature regarding nonadherence with both therapeutic regimens and medication. This literature includes reviews of empirical research regarding the factors associated with nonadherence. Health care system, provider, and patient factors as well as the nature of the illness and therapeutic regimen all effect adherence rates. Different behavioral models for adherence counseling such as the Health Belief Model, the Theory of Reasoned Action, the Medication Interest Model, and Motivational Interviewing have also been reported in the research literature. This article will discuss the development of a brief model for patient counseling with specific techniques illustrated for pharmacists based on empirical findings that have demonstrated effectiveness in the adherence research literature. In addition, the article will address the measurement of the economic impact of medication nonadherence and propose a framework for assessing the cost-effectiveness of pharmacist counseling to increase adherence. The problem of nonadherence has significant effects upon health care expenditures through increase in physician's visits, emergency department incidents, rehospitalizations, and nursing home readmissions. Thus, the overall goal is to assist the pharmacist in developing a brief adherence counseling program in community pharmacy and evaluating the economic feasibility of the intervention demonstrating the value-added proposition of pharmacist intervention. PMID:25292442
Lopez-Lopez, G; Pascual, A; Perea, E J
The kinetics of adherence of single isolates of Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Escherichia coli to catheters made of polyvinyl chloride (PVC), Teflon, siliconised latex, polyurethane and Vialon was evaluated by a radiometric assay. Radiolabelled bacteria (10(8) cfu/ml) were incubated in vials containing 1-cm lengths of catheter for up to 3 days. The peak of maximal adherence to each biomaterial was reached after 24 h for P. aeruginosa and after 72 h for the other strains. Bacterial adherence to PVC and siliconised latex was significantly higher (2-6 times; p less than 0.05) than to the other biomaterials for all the strains. The lowest values of adherence were observed with polyurethane and Vialon for the staphylococci but with Teflon for E. coli and P. aeruginosa. Bacterial viability and growth was evaluated in eluates obtained from incubation of segments of each catheter in buffer for 24 h. None of the eluates affected the viability of the staphylococci. However, all of them, significantly increased the growth of E. coli and P. aeruginosa with the exception of the eluate from siliconised latex, in which the inoculum count was reduced to an undetectable level for E. coli. We conclude that bacterial adherence to catheters may depend in part on the nature of the biomaterial and that certain substances eluted from the catheters may affect the viability and growth of different micro-organisms. PMID:1905357
Full Text Available Purpose. We hypothesized that socioeconomic factors and a language barrier would impact adherence with continuous positive airway pressure (CPAP among Hispanics with obstructive sleep apnea (OSA. Methods. Patients with OSA who were prescribed CPAP for at least 1 year and completed a questionnaire evaluating demographic data, socioeconomic status, and CPAP knowledge and adherence participated in the study. Results. Seventy-nine patients (26 males; 53±11 yrs; body mass index (BMI=45±9 kg/m2 with apnea-hypopnea index (AHI 33±30 events/hr completed the study. Included were 25 Hispanics, 39 African Americans, and 15 Caucasians, with no difference in age, AHI, CPAP use, or BMI between the groups. While there was a difference in educational level (P=0.006, income level (P<0.001, and employment status (P=0.03 between the groups, these did not influence CPAP adherence. Instead, overall improvement in quality of life and health status and perceived benefit from CPAP influenced adherence, both for the group as a whole (P=0.03, P=0.004, and P=0.001, resp., as well as in Hispanics (P=0.02, P=0.02, P=0.03, resp.. Conclusion. In Hispanic patients with OSA, perceived benefit with therapy, rather than socioeconomic status or a language barrier, appears to be the most important factor in determining CPAP adherence.
Full Text Available OBJECTIVE: Previous research has shown that a better therapeutic relationship (TR predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia. METHODS: 134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity. RESULTS: Patient and clinician ratings of the TR were weakly inter-correlated (r(s = 0.13, p = 0.004, but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%. After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%. CONCLUSIONS: A better TR is associated with better adherence to medication among patients with schizophrenia. Patients' and clinicians' perspectives of the TR are both important, but may reflect distinct aspects.
Ramadhani, Habib O.; Muiruri, Charles; Maro, Venance P.; Omondi, Michael; Mushi, Julian B.; Lirhunde, Eileen S.; Bartlett, John A.
Background Adherence to Antiretroviral Therapy (ART) is critical piece in the management of HIV infected patients. Despite the benefits of ART, non-adherence to ART persists. This study explores association between patient’s knowledge of the ART line of treatment, availability of future treatment options and adherence. Methods A cross sectional survey of HIV infected adolescent and adults was conducted. Cumulative optimal and sub-optimal adherence was defined as percentage adherence of ≥ 95 %...
Kimura, L H; Pearsall, N N
A strong correlation was shown between germination and increased adherence of Candida albicans to human buccal epithelial cells, indicating that germination or other changes in the fungi accompanying germination were responsible for enhanced adherence. Partial inhibition of germination by cysteine resulted in a comparably lower adherence. Preferential adherence of germinated fungi occurred in competition assays with nongerminated and germinated fungi. The enhanced adherence to human mucosal c...
Key findings. (1) Value-based insurance design (VBID) improves medication adherence by 1 to 3 percent in the first year after implementation; (2) Improvements in adherence were sustained and amplified in the second year post-implementation, ranging from 2 to 5 percent; (3) Adherence improvements varied according to VBID participants' baseline adherence, with greatest improvements evident in those with poorer baseline adherence
Full Text Available Anecdotal data suggest that some South Africans living with HIV who receive disability grants from the state deliberately default on their antiretroviral medication in an attempt to lower their CD4 count to remain eligible for grants. No actual empirical data however exist to show that disability grants act as such perverse incentives and are a valid reason for non-adherence. This article examines some of the complexities of antiretroviral adherence in the context of a resource-constrained environment. The multitude of structural barriers, including sometimes difficult patient-doctor conversations about the renewal of disability grants, shape patients’ experiences of the clinic environment and influence their adherence to care.
Mazure, R A; Cancer, E; Martínez Olmos, M A; De Castro, M L; Abilés, V; Abilés, J; Bretón, I; Álvarez, V; Peláez, N; Culebras, J M
A correct treatment of obesity needs a program of habits modification regardless of the selected technique, especially if it is minimally invasive as the intragastric balloon (BIG). The adherence of the obese patients with regard to recommended drugs measures to medium- and long-term is less than 50%. Given that the results obtained using the technique of gastric balloon must be seen influenced by adherence to the modification of habits program and its fulfillment, we reviewed series published in attention to the program proposed with the BIG. The series published to date provide few details about the used Therapeutic Programs as well as the adherence of patients to them, and even less concerning the Monitoring Plan and the loyalty of the patient can be seen. We conclude the convenience to agree on a follow-up strategy, at least the 6 months during which the BIG remain in the stomach. PMID:24483961
Buus, Niels; Johannessen, Helle; Stage, Kurt Bjerregaard
analysed thematically with "explanatory models" as the starting point. RESULTS: Patients had ambiguous experiences of depression and antidepressants. Patients explained their illness and the medical treatment in experience-near terms. Explanations of the reasons for depression were psychosocial and biology......BACKGROUND: Adherence to antidepressant medication is a challenging clinical issue, which reduces treatment efficacy: 30-60% of all patients commencing treatment with antidepressants are estimated to stop taking the medication within the first 12 weeks. Patients' personal beliefs about depression...... and antidepressants are regarded as central influences on adherence. OBJECTIVES: The aim was to gain detailed insight into patients' personal accounts of depression and use of antidepressant medication and to relate these accounts to the patients' self-reported level of adherence. METHODS: In-depth, qualitative...
Diniz, Normélia Maria Freire; de Almeida, Lílian Conceição Guimarães; dos S Ribeiro, Bárbara Cristina; de Macêdo, Valéria Góes
This study aimed to investigate the adherence of women victims of sexual violence, to AIDS chemoprevention treatment. A quantitative study was carried out at a care service to victims of sexual violence in Salvador (Bahia, Brazil). Study participants were 172 women. Data were collected through interviews with forms and consultation of patient files. The results showed that 45.4% of the abused women were teenagers and 40.7% of the attended women were raped. Only 54% of the women were advised to use antiretrovirals to prevent HIV. Adherence to treatment occurred in 57.4% of cases and discontinuity corresponded to 42.6%. Non-adherence to treatment was attributed to psychological or emotional disorders and non-understanding of the established treatment. Therefore, it is important that professionals pay careful attention in order to perceive the conditions that might increase women's vulnerability to the infection. PMID:17375226
Vera Lúcia da Silveira
Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.
James R Warren
Full Text Available Deficiencies in medication adherence are a major barrier to effectiveness of chronic condition management. Continuity of primary care may promote adherence. We assessed the association of continuity of primary care with adherence to long-term medication as exemplified by statins.We linked data from a prospective study of 267,091 Australians aged 45 years and over to national data sets on prescription reimbursements, general practice claims, hospitalisations and deaths. For participants having a statin dispense within 90 days of study entry, we computed medication possession ratio (MPR and usual provider continuity index (UPI for the subsequent two years. We used multivariate Poisson regression to calculate the relative risk (RR and 95% confidence interval (CI for the association between tertiles of UPI and MPR adjusted for socio-demographic and health-related patient factors, including age, gender, remoteness of residence, smoking, alcohol intake, fruit and vegetable intake, physical activity, prior heart disease and speaking a language other than English at home. We performed a comparison approach using propensity score matching on a subset of the sample.36,144 participants were eligible and included in the analysis among whom 58% had UPI greater than 75%. UPI was significantly associated with 5% increased MPR for statin adherence (95% CI 1.04-1.06 for highest versus lowest tertile. Dichotomised analysis using a cut-off of UPI at 75% showed a similar effect size. The association between UPI and statin adherence was independent of socio-demographic and health-related factors. Stratification analyses further showed a stronger association among those who were new to statins (RR 1.33, 95% CI 1.15-1.54.Greater continuity of care has a positive association with medication adherence for statins which is independent of socio-demographic and health-related factors.
Cai, Tommaso; Verze, Paolo; Brugnolli, Anna;
Escherichia coli to piperacillin/tazobactam (9.1% vs. 5.4%; p=0.03), gentamicin (18.3% vs. 11.2%; p=0.02), and ciprofloxacin (32.3% vs. 19.1%; p=0.03) decreased significantly after protocol introduction. The defined daily dose (DDD) use of ciprofloxacin fell from 4.2 to 0.2 DDD per 100 patient-days after....... We found that adherence to the guidelines reduced the rate of bacterial resistance, in particular against piperacillin/tazobactam, gentamicin, and ciprofloxacin, and reduced costs without increasing the risk of postoperative infection after urologic procedures. We recommend adherence to the...
Full Text Available Background: Adherence is critical for the effectiveness of antiretroviral HIV therapy (ART, accordingly decreasing the opportunistic diseases and increasing the quality of life. Neurocognitive disorders (NCD are still frequent in ART era and could impair the adherence, but how ethical is to refer ART in patients with NCD? Objective: To assess the relation between NCD and adherence in HIV Romanian patients. Material and methods: Cross-sectional screening study on 151 patients under ART, no drug users, from HIV Clinic - Galati, assessed by HIV-Associated Dementia Scale (HDS, Hospital Anxiety and Depression Scale (HADS , ART CNS-effectiveness Letendre scores  and adherence assessment questionnaire CNLAS- Romania. Normal values: HDS >10; anxiety/ depression <8. Statistical analysis performed: Chi-square test and Mann-Whitney test, with 5% significance level. Results: Characteristics of the patients: median age 22 [20; 56] years old; sex ratio F/M 1.17; median educational level 8 [0; >12] years; HBV co-infection 27.8%; AIDS stage 85.3%; current median CD4 526/mm3 [8; 1605] and 65% undetectable HIV-RNA levels. 49.6% (75/151 patients attain HDS scores <10 and imply probable NCD. Scores below 8 for anxiety are more frequent than for depression: 24% vs 13%. The median ART CNS penetration score is 8 [5; 12]. Adherence is considered for 66% patients and is correlating with CD4 number (p=0.001, educational level >4 years (p=0.001; OR=4.2, HDS >10 (p=0.01; OR=2.4 and ART-CNS penetration score >7 (p=0.023; OR=2.4. Low HDS are influenced by old age (p=0.003, depression (p=0.02 and ART-CNS penetration scores <7 (p=0.01. Anxiety is related neither with adherence nor with NCD by HDS, but females are obvious anxious than males (p<0.001. Conclusions: Basic educational level is sufficient for developing ART adherence. High scores of HDS screening should be predictors for ART adherence. Referring ART as well to patients with low HDS scores is rational and
Hawley-Hague, H. Horne, S. Skelton, D.A. Todd, C
Exercise classes provide a range of benefits for older adults, but adherence levels are poor. We know little of instructorsÃ¢ÂÂ experiences of delivering exercise classes to older adults. Semi-structured interviews,informed by the Theory of Planned Behaviour (TPB), were conducted with instructors (n=19) delivering multi-component exercise classes to establish their perspectives on older adultsÃ¢ÂÂ uptake and adherence to exercise classes. Analysis revealed Ã¢ÂÂbarriersÃ¢ÂÂ related t...
M Y H Moosa
Full Text Available Aim. To determine changes in adherence to antiretroviral therapy (ART in HIV-positive patients with depression, following treatment with an antidepressant or psychotherapy. Methods. The study was prospective, randomised and controlled. Consenting volunteers aged ≥18 years and stable on ART for ≥6 months were included in the study. Sociodemographic data were obtained, and a clinical diagnostic evaluation and the Hamilton Depression rating scale (HAMD were performed on all subjects at entry to and at the end of the study. Participants found to be depressed were randomly assigned antidepressant treatment (20 mg citalopram or interpersonal psychotherapy (IPT (5 sessions. Medication was dispensed at each visit and patients were asked to return all unused medication to determine ART adherence. The study was approved by the University of the Witwatersrand. Results. Sixty-two HIV-positive persons receiving ART participated; 30 were not depressed (control group and 32 were depressed (patient group. No significant differences in demographic characteristics existed between the control and patient groups. Mean ART adherence at the start of the study was 99.5% (standard error (SE ±0.46 and 92.1% (SE ±1.69 in the control and patients groups, respectively. Mean ART adherence at the end of the study changed marginally in the control group (99.7%; SE ±0.46 and increased significantly in the patient group (99.5%; SE± 0.13 (p>0.05. The mean ART adherence rate of patients who received pharmacotherapy increased from 92.8% to 99.5%, and of those who received psychotherapy increased from 91.1% to 99.6% (p>0.05. There was no significant association between the increased adherence in the patient group and baseline demographic and clinical characteristics, irrespective of antidepressant therapy or IPT (p>0.05. Conclusion. Successful treatment of depression with an antidepressant or psychotherapy was associated with improved ART adherence, independent of the type
Link, Lilli B.; Jacobson, Judith S.
The purpose of this study was to evaluate adherence and identify predictors of adherence to a raw vegan diet (i.e., uncooked plant foods) following a stay at a raw vegan institute. In this cohort study of guests at a raw vegan institute, subjects completed written questionnaires upon arrival and 12 weeks later. Of 107 eligible guests, 84 participated. Mean age was 54 years, 23 were male, and 73 white. Fifty-one completed the 12-week follow-up. Eight (16%) reported their diet to be ≥80% raw ve...
Velázquez, Rocío; Zamora, Emiliano; Álvarez, Manuel; Álvarez, María L; Ramírez, Manuel
The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. The effect was faster under high-pressure than under low-pressure conditions. Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. PMID:27375256
Full Text Available Stephen Jones,1 Nathan Babiker,2 Emma Gardner,2,3 Jane Royle,2 Rachael Curley,3,4 Zhe Hui Hoo,3,4 Martin J Wildman3,4 1Psychology Department, University of Sheffield, 2Psychological Services, Sheffield Teaching Hospitals NHS Foundation Trust, 3Adult Cystic Fibrosis Unit, Northern General Hospital, 4School of Health and Related Research (ScHARR, University of Sheffield, Sheffield, UK Background: Cystic fibrosis (CF health care professionals recognize the need to motivate people with CF to adhere to nebulizer treatments, yet little is known about how best to achieve this. We aimed to produce motivational posters to support nebulizer adherence by using social marketing involving people with CF in the development of those posters. Methods: The Sheffield CF multidisciplinary team produced preliminary ideas that were elaborated upon with semi-structured interviews among people with CF to explore barriers and facilitators to the use of nebulized therapy. Initial themes and poster designs were refined using an online focus group to finalize the poster designs. Results: People with CF preferred aspirational posters describing what could be achieved through adherence in contrast to posters that highlighted the adverse consequences of nonadherence. A total of 14 posters were produced through this process. Conclusion: People with CF can be engaged to develop promotional material to support adherence, providing a unique perspective differing from that of the CF multidisciplinary team. Further research is needed to evaluate the effectiveness of these posters to support nebulizer adherence. Keywords: behavior change, social marketing, patient participation, nebulizers, medication adherence
Full Text Available Abstract Background The goal of this study is to observe changes in HBcAg-specific cytotoxic T lymphocytes (CTLs, natural killer (NK and natural killer T (NKT cells from peripheral blood and to relate such changes on viral clearance and liver injury in patients with acute hepatitis B (AHB. Methods Dynamic profiles on the frequency of HLA-A0201-restricted HBcAg18-27 pentamer complex (MHC-Pentamer-specific CTLs and lymphocyte subsets in AHB patients were analyzed in addition to liver function tests, HBV serological markers, and HBV DNA levels. ELISPOT was used to detect interferon-gamma (INF-γ secretion in specific CTLs stimulated with known T cell epitope peptides associated with HBV surface protein, polymerase, and core protein. Results HBV-specific CTL frequencies in AHB patients were much higher than in patients with chronic hepatitis B (CHB (p +CD8+ T cell numbers in AHB patients was more than observed in the healthy control group from the first to the fourth week after admission (p = 0.008 and 0.01, respectively; the number of CD3+CD8+ T cells and frequency of HBcAg18-27-specific CTLs in AHB patients reached peak levels at the second week after admission. NK and NKT cell numbers were negatively correlated with the frequency of HBcAg-specific CTLs (r = -0.266, p = 0.05. Conclusions Patients with AHB possess a higher frequency of HBcAg-specific CTLs than CHB patients. The frequency of specific CTLs in AHB patients is correlated with HBeAg clearance indicating that HBV-specific CTLs play an important role in viral clearance and the self-limited process of the disease. Furthermore, NK and NKT cells are likely involved in the early, non-specific immune response to clear the virus.
Paul Lioy was simultaneously a staunch adherent to the scientific method and an innovator of new ways to conduct science, particularly related to human exposure. Current challenges to science and the application of the scientific method are presented as they relate the approaches...
Full Text Available Rosa Dolz-Marco,1 Roberto Gallego-Pinazo,1 Manuel Díaz-Llopis,2 Emmett T Cunningham Jr,3–6 J Fernando Arévalo7,8 1Unit of Macula, Department of Ophthalmology, University and Polytechnic Hospital La Fe, 2Faculty of Medicine, University of Valencia, Spain; 3Department of Ophthalmology, California Pacific Medical Center, San Francisco, 4Department of Ophthalmology, Stanford University School of Medicine, Stanford, 5The Francis I Proctor Foundation, University of California San Francisco Medical Center, 6West Coast Retina Medical Group, San Francisco, CA, USA; 7Vitreoretina Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 8Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Noninfectious uveitis includes a heterogenous group of sight-threatening ocular and systemic disorders. Significant progress has been made in the treatment of noninfectious uveitis in recent years, particularly with regard to the effective use of corticosteroids and non-corticosteroid immunosuppressive drugs, including biologic agents. All of these therapeutic approaches are limited, however, by any given patient’s ability to comply with and adhere to their prescribed treatment. In fact, compliance and adherence are among the most important patient-related determinants of treatment success. We discuss strategies to optimize compliance and adherence. Keywords: noninfectious uveitis, intraocular inflammation, immunosuppressive treatment, adherence, compliance, therapeutic failure
Escobar Zapata, Edna V.; Martinez Perez, Carlos A.; Rodriguez Gonzalez, Claudia A.; Castro Carmona, Javier S. [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico); Quevedo Lopez, Manuel A. [Departamento de Polimeros y Materiales, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora (Mexico); Garcia-Casillas, Perla E., E-mail: email@example.com [Instituto de Ingenieria y Tecnologia, Universidad Autonoma de Ciudad Juarez, Ave. Del Charro 610 norte, Col. Partido Romero, C.P. 32320, Cd. Juarez Chihuahua (Mexico)
Highlights: Black-Right-Pointing-Pointer Chitosan silica magnetite adsorbs antineoplastic drug. Black-Right-Pointing-Pointer Silica coating improve the drug adherence. - Abstract: Cancer treatment is a big challenge in medicine where chemotherapies and radiotherapies are aggressive and poorly effective having side effects as delirium, fatigue, insomnia, nausea and vomiting which are common problems for cancer patients. For this reason, during the last two decades, many researchers have developed several techniques to improve the current therapies; one of them is the functionalization of magnetic nanoparticles for drug delivery. In this work, magnetic nanoparticles with an average crystallite size 21.8 nm were covered in a core/shell type; magnetite/silica, magnetite/chitosan, and a double shell magnetite/silica/chitosan were developed for attaching an antineoplastic drug. The mechanism for the functionalization of the nanoparticles with a single and double shell was studied with Fourier transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The adherence of an antineoplastic drug, paclitaxel, onto functionalized nanoparticles was analyzed with a UV-Visible spectroscopy at a wavelength of 253 nm. It was found that the adherence of the drug is improved up to 18% when magnetite nanoparticles are coated with a single chitosan shell, and when the nanoparticles are coated with a silica/chitosan shell the adherence increases up to 29%.
Presents a framework and some practical examples for using rigorous implementation research to inform program outcomes and foster program development for developmental interventions. Focuses on: (1) role of process research, specifically developing developmental interventions; (2) characteristics of adherence process research; and (3)…
Phillips, Frances H; Barnes, Donelle M
Among United States (U.S.) veterans, the prevalence of chronic hepatitis C infection is three times that of the general U.S. population. Treatment success is proportionate to the degree of treatment adherence. There has been little research dedicated to the systematic exploration of issues related to treatment adherence. The purpose of this study was to describe factors that influenced adherence in infected military veterans. Phenomenological research emphasizes a rich description. A convenience sample of 21 veterans was recruited from a clinic in north Texas. One-time in-depth interviews explored reasons for remaining in treatment despite difficult side effects. Analysis included immersion, data transformation, thematic analysis, and summary. Cognitive strategies to stay on medication include making a commitment to treatment, "not ready to leave this world," conserving energy and staying busy, looking forward, and starting over. Veterans utilize previously learned military discipline to stay on medications and follow providers' orders. They are not ready to die and have plans for life after treatment. Patient education should focus on side effect management, rather than on genotypes or viral load. Treatment teams should include substance abuse specialists and gastroenterology providers. Future studies need to develop a measurement tool for adherence during antiviral treatment. PMID:26825560
As one of the most significant American Jewish writers in the 20th century, Saul Bellow was influenced by the Jewish tradition and American mainstream thoughts in his writing creations. The conflicts and amalgamation between these two different cultures in his novels indicate that Bellow not only adheres to the Jewish traditional culture, but also breaks through the narrow-mindedness of it.
... HUMAN SERVICES Food and Drug Administration ``Script Your Future'' Medication Adherence Campaign AGENCY... medicine as directed to treat an illness or disease in order to get the best health outcome possible for...) called ``Script Your Future''. To continue and enhance this important public health initiative,...
Full Text Available Enteropathogenic Escherichia coli (EPEC is a known causative agent of diarrhea in children. In the process of colonization of the small intestine, EPEC synthesizes two types of adhesins, the bundle-forming pilus (BFP and intimin. The BFP pilus is an adhesin associated with the initial stages of adherence of EPEC to epithelial cells, while the outer membrane protein intimin carries out the intimate adherence that takes place at the third stage of infection. BFP is encoded by the bfp operon located in plasmid EAF, present only in typical EPEC isolates, while eae, the gene that encodes intimin is situated in the LEE, a chromosomal pathogenicity island. Transcription of bfp and eae is regulated by the products of the perABC operon, also present in plasmid EAF. Here we show that deletion of relA, that encodes a guanosine penta and tetraphosphate synthetase impairs EPEC adherence to epithelial cells in vitro. In the absence of relA, the transcription of the regulatory operon perABC is reduced, resulting in lower levels of BFP and intimin. Bacterial adherence, BFP and intimin synthesis and perABC expression are restored upon complementation with the wild-type relA allele.
Fish, Laura J.; Moorman, Patricia G.; Wordlaw-Stintson, Lashawn; Vidal, Adriana; Smith, Jennifer S.; Hoyo, Cathrine
Background: Understanding the gaps in knowledge about human papilloma virus (HPV) infection, transmission, and health consequences and factors associated with the knowledge gap is an essential first step for the development of interventions to improve adherence to follow-up among women with abnormal Pap smears. Purpose: To examine the relationship…
Van Wijk, Boris L G; Klungel, Olaf H; Heerdink, Eibert R; de Boer, Anthonius
BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to
Rauscher, Laura Anne
Paradigm adherence has been developed as a meta-theoretical approach to organize and to classify the multitude of different theories of counseling and psychotherapy. Four paradigms have been identified in the literature: The Organic-Medical, The Psychological, The Systemic-Relational, and the Social Constructivist paradigms. Only one other study…
Ratynskaia, S.; Tolias, P.; I. Bykov,; Rudakov, D.; de Angeli, M.; Vignitchouk, L.; Ripamonti, D.; Riva, G.; Bardin, S.; van der Meiden, H.; Vernimmen, J.; Bystrov, K.; De Temmerman, G.
The first study of the interaction of metallic dust (tungsten, aluminum) adhered on tungsten substrates with transient plasma heat loads is presented. Experiments were carried out in the Pilot-PSI linear device with transient heat fluxes up to 550 MW m −2 and in the DIII-D divertor tokamak. The cent
O'Quin, K. E.; Semalulu, T.; Orom, H.
Medication mismanagement is a growing public health concern, especially among elders. Annually, it is a major contributor to emergency hospitalization and nursing home placement. Elders and their caregivers, as healthcare consumers and stakeholders in this issue, are uniquely qualified to inform strategies to improve medication adherence. We…
Ebben, R.H.A.; Vloet, L.C.M.; Groot, J.M. de; Achterberg, T. van
The objective of this study was to identify factors that influence emergency nurses' adherence to an emergency department national protocol (EDNP). A survey of emergency nurses (n=200) and physicians with medical end responsibility on an emergency department (n=103) was carried out. Emergency nurses
Full Text Available Abstract Patient adherence to treatment is an important factor in the effectiveness of antiretroviral regimens. Adherence to treatment could be monitored by estimation of antiretroviral drugs in biological fluids. We aimed to obtain information on the quantity and duration of excretion of lamivudine in urine following oral administration of a single dose of 300 mg and to assess its suitability for adherence monitoring purposes. Spot urine samples were collected before dosing and at 4, 8, 12, 24, 28, 32, 48, 72, and 96 hours post dosing from 10 healthy subjects, and lamivudine was estimated by high-pressure liquid chromatography (HPLC. Lamivudine values were expressed as a ratio of urine creatinine. About 91% of the ingested drug was excreted by 24 hours, and the concentration thereafter in urine was very negligible. A lamivudine value of 0.035 mg/mg creatinine or less at 48 hours is suggestive of a missed dose in the last 24 hours. The study findings showed that estimation of urine lamivudine in spot specimens could be useful in monitoring patient adherence to antiretroviral treatment. However, this needs to be confirmed on a larger sample size and among patients on once-daily and twice-daily treatment regimens.
Shah, Pranjul Jaykumar; Vedarethinam, Indumathi; Kwasny, Dorota;
Microfluidic bioreactors (μBR) are becoming increasingly popular for cell culture, sample preparation and analysis in case of routine genetic and clinical diagnostics. We present a novel μBR for non-adherent cells designed to mimic in vivo perfusion of cells based on diffusion of media through...
M.J. Kikkert; A.H. Schene; M.W.J. Koeter; D. Robson; A. Born; H. Helm; M. Nose; C. Goss; G. Thornicroft; R.J. Gray
One of the major clinical problems in the treatment of people with schizophrenia is suboptimal medication adherence. Most research focusing on determinants of nonadherence use quantitative research methods. These studies have some important limitations in exploring the decision-making process of pat
Brown, Ian; Sheeran, Paschal; Reuber, Markus
Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (Pintention intervention may be an easy-to-administer and effective means of promoting AED adherence. PMID:19864187
Javadekar, V S; SivaRaman, H; Gokhale, D V
Conditions were optimized for rapid release and improved regeneration of protoplasts of Saccharomyces cerevisiae NCIM 3458. Rapid protoplast release was also obtained with representatives of several other yeast genera under the modified conditions of treatment. The application of the procedure in construction of a highly flocculent Saccharomyces cerevisiae with a killer character is described. Fusion was effected between UV-killed protoplasts of S. cerevisiae NCIM 3578 with a killer character and live protoplasts of the highly flocculent S. cerevisiae NCIM 3528 in the presence of polyethylene glycol (PEG) 6000. Fusants were selected using benomyl resistance as marker, the killer toxin producer rather than the highly flocculent yeast being resistant to the fungicide at a concentration of 100 micrograms ml-1. Fusants were also characterized by their DNA contents, capacity for ethanolic fermentation of molasses sugar and levels of invertase, alcohol dehydrogenase and pyruvate decarboxylase activities. PMID:7576466
Gregorian, S K; Battisto, J R
In our companion paper we have reported that cell-mediated immunity of mice bearing renal cell carcinoma is profoundly suppressed. The non-responsiveness of such animals was found to be attributable to Renca cells themselves and to splenic lymphoid cells that down-regulate other fully capable lymphoid cells. In this communication the lymphoid cell source of suppression within Renca-bearing mice has been explored with the aim of identifying phenotypes of the responsible cells, the manner by which suppression is mediated, and initial ways by which suppression may be eliminated. A plastic-adherent cell bearing the Thy1.2 surface marker as well as the Lyt1 and Lyt2 antigens has been found to operate, perhaps in conjunction with macrophages, to down-regulate lymphokine-activated killer (LAK) cell development for natural killer (NK) and non-NK targets that include Renca cells themselves. The splenic suppressor cells lost the capacity to suppress the NK response of normal recipient mice upon shallow irradiation (250 rad) prior to adoptive transfer. Spleen cells, presumably macrophages, from Renca-bearing mice were found to suppress the generation of LAK and NK cells in vitro by synthesizing prostaglandins. Indomethacin, a prostaglandin synthetase inhibitor, blocked the induction of suppression both in vitro and in vivo, suggesting the presence of endogenous prostaglandins in Renca-bearing mice. The suppression seen in Renca-bearing mice that derives from multiple sources and has been prevented by two separate methods has been discussed from the viewpoint of the inter-relatedness of the sources. PMID:1974826
Pamela L. Ostby
Full Text Available Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL, a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing progressive swelling and infection. The aim of this review of contemporary literature published from 2005–2015 is to examine the complexities of BCRL self-management, to identify adherence-focused studies relevant to BCRL, and to summarize barriers to self-management of BCRL. Six electronic indices were searched from which 120 articles were retrieved; 17 were BCRL-focused; and eight met inclusion criteria. Seventeen of 120 articles identified barriers to self-management of BCRL such as complexities of treatment regimens, symptom burden, balance of time for treatment and life demands, and lack of education and support; however, only eight studies included outcome measures of adherence to BCRL treatment regimens with a subsequent improvement in reduced limb volumes and/or perceptions of self-efficacy and self-regulation. A major limitation is the few number of rigorously developed outcome measures of BCRL adherence. In addition, randomized studies are needed with larger sample sizes to establish adequate levels of evidence for establishing best practice standards for improving adherence to BCRL self-management treatment regimens.
Full Text Available Objective: The scope of this article is to describe the background for and content of an adherence counselling programme with a specific focus on an individualised, multi-dimensional adherence model for patients with a potential adherence problem (a so-called ‘individualised systems model’.Methods: An intervention programme based on WHO’s systems model for adherence was developed for implementation in primary health care and tested in a development project in Danish pharmacies in 2004-2005 in three pharmacies and 4 GP practices by 27 patients. Data were collected from the participants by registration forms, questionnaires, and focus groups. Since the programme was to support patients in the self-management process regarding choice and implementation of medication treatment, various strategies were used and different theoretical assumptions and choices made prior to setting up the study. These strategies include distinguishing between different types of non-adherence, a model for stages of change, self-efficacy, narratives, motivating interviewing strategies and coaching techniques. These strategic and theoretical choices are described in the article. Results: The strategies and theoretical reflections formed the platform for the creation of a counselling programme, which was tested in two forms, a basic and an extended version - provided by either a pharmaconomist or a pharmacist. The result section also describes a toolbox of instruments to enable pharmacy staff and GPs to tailor a counselling programme for patients individually called ‘Safe and effective use of medicines’. Besides, the results include a description of how the WHO-model is transformed into an individualised counselling model.
Full Text Available Dominique Larrey,1,2 Marie-Pierre Ripault,1 Georges-Philippe Pageaux11Département d'Hépato-Gastroentérologie et Transplantation, Hôpital Saint Eloi, 2IRB-INSERM1040, Montpellier, FranceAbstract: The current standard-of-care treatments for chronic hepatitis C, based on a bitherapy that combines peginterferon alpha-2a or -2b and ribavirin for all genotypes, and on a triple therapy with the addition of an antiprotease specifically for genotype 1, are associated with a limited adherence that decreases their efficacy. The main factors limiting adherence are difficulties in taking the treatment and side effects that worsen the quality of life of the patients. Programs of therapeutic education are essential to improve adherence, quality of life, likelihood of viral suppression, improvement of liver disease, and decrease of late complications. Therapeutic education should be understood as an acquisition of decisional, technical, and social competency with the purpose of making the patient able to make health choices, realize their own life plans, and use health care resources in the best manner. The patient should be placed in the center of an organization, comprising various care workers who include social service professionals and medical staff. For hepatitis C, therapeutic education may be separated into three phases: a first phase corresponding to the educative diagnosis; a second phase corresponding to support during treatment; and the third phase corresponding to support after treatment. Therapeutic education is performed using various instruments and methods specifically adapted to the needs and expectations of individual patients. Upcoming treatments for hepatitis C, with evidence for high efficacy, few side effects, and shorter duration, will certainly change the landscape of adherence and the management of therapeutic education.Keywords: adherence to treatment, quality of life, therapeutic education, hepatitis C
Ostby, Pamela L; Armer, Jane M
Breast cancer survivors are at increased risk for breast cancer-related lymphedema (BCRL), a chronic, debilitating, condition that is progressive and requires lifelong self-management. Up to 40% of 3 million breast cancer survivors in the US will develop BCRL, which has no cure, is irreversible, and requires self-management with regimens that may include multiple components. The complexities of treatment can negatively affect adherence to BCRL self-management which is critical to preventing progressive swelling and infection. The aim of this review of contemporary literature published from 2005-2015 is to examine the complexities of BCRL self-management, to identify adherence-focused studies relevant to BCRL, and to summarize barriers to self-management of BCRL. Six electronic indices were searched from which 120 articles were retrieved; 17 were BCRL-focused; and eight met inclusion criteria. Seventeen of 120 articles identified barriers to self-management of BCRL such as complexities of treatment regimens, symptom burden, balance of time for treatment and life demands, and lack of education and support; however, only eight studies included outcome measures of adherence to BCRL treatment regimens with a subsequent improvement in reduced limb volumes and/or perceptions of self-efficacy and self-regulation. A major limitation is the few number of rigorously developed outcome measures of BCRL adherence. In addition, randomized studies are needed with larger sample sizes to establish adequate levels of evidence for establishing best practice standards for improving adherence to BCRL self-management treatment regimens. PMID:26580657
In 1931 an unknown murderer of little girls (Peter Lorre) is terrorizing the city of Berlin. We see him entice a new victim, the little Elsie Beckmann, who is coming home from school: whistling a tune by Grieg, he buys her a balloon from a blind beggar. When her corpse is discovered, the police undertake a major mobilization aimed at seeking the serial killer in the criminal underworld; meanwhile, the ever more terrified population starts to see the dangerous murderer in everyone. Since the roundups and incursions into the seediest parts of town disturb the gangsters' activities, the leaders of organized crime, headed by Schränker (Gustav Gründgens), take it upon themselves also to hunt down the solitary child-killer, engaging the community of beggars. Every corner of the city is catalogued and sifted by the dual activity of the police and the gangsters. The 'monster', a former psychiatric patient, mild and harmless in manner, is finally tracked down via two parallel routes: the clue of a cigarette packet enables Inspector Lohmann (Otto Wernicke) to track down the serial killer's address, while the blind beggar recognizes the whistled tune. The murderer is identified by a 'slap' from a young criminal which leaves an M marked in chalk on a shoulder of the man's overcoat. Thus he is caught and undergoes a kind of trial at the hands of the gangsters who tie him up in order to lynch him, but they are interrupted by the arrival of the forces of law and order.
In 1931 an unknown murderer of little girls (Peter Lorre) is terrorizing the city of Berlin. We see him entice a new victim, the little Elsie Beckmann, who is coming home from school: whistling a tune by Grieg, he buys her a balloon from a blind beggar. When her corpse is discovered, the police undertake a major mobilization aimed at seeking the serial killer in the criminal underworld; meanwhile, the ever more terrified population starts to see the dangerous murderer in everyone. Since the roundups and incursions into the seediest parts of town disturb the gangsters' activities, the leaders of organized crime, headed by Schränker (Gustav Gründgens), take it upon themselves also to hunt down the solitary child-killer, engaging the community of beggars. Every corner of the city is catalogued and sifted by the dual activity of the police and the gangsters. The 'monster', a former psychiatric patient, mild and harmless in manner, is finally tracked down via two parallel routes: the clue of a cigarette packet enables Inspector Lohmann (Otto Wernicke) to track down the serial killer's address, while the blind beggar recognizes the whistled tune. The murderer is identified by a 'slap' from a young criminal which leaves an M marked in chalk on a shoulder of the man's overcoat. Thus he is caught and undergoes a kind of trial at the hands of the gangsters who tie him up in order to lynch him, but they are interrupted by the arrival of the forces of law and order. PMID:26463110
Morin, Phillip A; Archer, Frederick I; Foote, Andrew D; Vilstrup, Julia; Allen, Eric E; Wade, Paul; Durban, John; Parsons, Kim; Pitman, Robert; Li, Lewyn; Bouffard, Pascal; Abel Nielsen, Sandra C; Rasmussen, Morten; Willerslev, Eske; Gilbert, M Thomas P; Harkins, Timothy
Killer whales (Orcinus orca) currently comprise a single, cosmopolitan species with a diverse diet. However, studies over the last 30 yr have revealed populations of sympatric "ecotypes" with discrete prey preferences, morphology, and behaviors. Although these ecotypes avoid social interactions and are not known to interbreed, genetic studies to date have found extremely low levels of diversity in the mitochondrial control region, and few clear phylogeographic patterns worldwide. This low level of diversity is likely due to low mitochondrial mutation rates that are common to cetaceans. Using killer whales as a case study, we have developed a method to readily sequence, assemble, and analyze complete mitochondrial genomes from large numbers of samples to more accurately assess phylogeography and estimate divergence times. This represents an important tool for wildlife management, not only for killer whales but for many marine taxa. We used high-throughput sequencing to survey whole mitochondrial genome variation of 139 samples from the North Pacific, North Atlantic, and southern oceans. Phylogenetic analysis indicated that each of the known ecotypes represents a strongly supported clade with divergence times ranging from approximately 150,000 to 700,000 yr ago. We recommend that three named ecotypes be elevated to full species, and that the remaining types be recognized as subspecies pending additional data. Establishing appropriate taxonomic designations will greatly aid in understanding the ecological impacts and conservation needs of these important marine predators. We predict that phylogeographic mitogenomics will become an important tool for improved statistical phylogeography and more precise estimates of divergence times. PMID:20413674
Deecke, Volker B.; Barrett-Lennard, Lance G.; Spong, Paul; Ford, John K. B.
A few species of mammals produce group-specific vocalisations that are passed on by learning, but the function of learned vocal variation remains poorly understood. Resident killer whales live in stable matrilineal groups with repertoires of seven to 17 stereotyped call types. Some types are shared among matrilines, but their structure typically shows matriline-specific differences. Our objective was to analyse calls of nine killer whale matrilines in British Columbia to test whether call similarity primarily reflects social or genetic relationships. Recordings were made in 1985-1995 in the presence of focal matrilines that were either alone or with groups with non-overlapping repertoires. We used neural network discrimination performance to measure the similarity of call types produced by different matrilines and determined matriline association rates from 757 encounters with one or more focal matrilines. Relatedness was measured by comparing variation at 11 microsatellite loci for the oldest female in each group. Call similarity was positively correlated with association rates for two of the three call types analysed. Similarity of the N4 call type was also correlated with matriarch relatedness. No relationship between relatedness and association frequency was detected. These results show that call structure reflects relatedness and social affiliation, but not because related groups spend more time together. Instead, call structure appears to play a role in kin recognition and shapes the association behaviour of killer whale groups. Our results therefore support the hypothesis that increasing social complexity plays a role in the evolution of learned vocalisations in some mammalian species.
Santos, Antonio; Navascués, Eva; Bravo, Enrique; Marquina, Domingo
Brettanomyces bruxellensis is one of the most damaging species for wine quality, and tools for controlling its growth are limited. In this study, thirty-nine strains belonging to Saccharomyces cerevisiae and B. bruxellensis have been isolated from wineries, identified and then tested against a panel of thirty-nine killer yeasts. Here, for the first time, the killer activity of Ustilago maydis is proven to be effective against B. bruxellensis. Mixed cultures in winemaking conditions show that U. maydis CYC 1410 has the ability to inhibit B. bruxellensis, while S. cerevisiae is fully resistant to its killer activity, indicating that it could be used in wine fermentation to avoid the development of B. bruxellensis without undesirable effects on the fermentative yeast. The characterization of the dsRNAs isolated and purified from U. maydis CYC 1410 indicated that this strain produces a KP6-related toxin. Killer toxin extracts were active against B. bruxellensis at pH values between 3.0 and 4.5 and temperatures comprised between 15 °C and 25 °C, confirming their biocontrol activity in winemaking and wine aging conditions. Furthermore, small amounts (100 AU/ml) of killer toxin extracts from U. maydis significantly reduced the amount of 4-ethylphenol produced by B. bruxellensis, indicating that in addition to the growth inhibition observed for high killer toxin concentrations (ranging from 400 to 2000 AU/ml), small amounts of the toxin are able to reduce the production of volatile phenols responsible for the aroma defects in wines caused by B. bruxellensis.
Flamand, L.; Stefanescu, I.(Argonne National Laboratory, Argonne, IL, 60439, USA); Menezes, J.
The marked tropism of human herpesvirus-6 (HHV-6) for natural killer (NK) cells and T lymphocytes has led us to investigate the effect of HHV-6 on cellular cytotoxicity. We describe here how HHV-6 infection of peripheral blood mononuclear cells (PBMC) leads to upregulation of their NK cell cytotoxicity. The induction of NK cell activity by HHV-6 was abrogated by monoclonal antibodies (mAbs) to IL-15 but not by mAbs to other cytokines (IFN-alpha, IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-12) su...
Korsgren, Magnus; Persson, Carl G.A.; Sundler, Frank; Bjerke, Torbjörn; Hansson, Tony; Chambers, Benedict J.; Hong, Seokmann; Van Kaer, Luc; Ljunggren, Hans-Gustaf; Korsgren, Olle
The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1+ T cells (NKT cells), and γ/δ T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1+ cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3+ T cell infiltration as well as in...
This paper reports on the alteration of natural killer(NK) cells and their responsiveness to IL-2 observed in 125 atomic-bomb survivors. It is found no difference in the number and activity of NK cells among different dose groups with the same age ATB. But there was of difference in NK activity in different age ATB groups with same dose, especially in the g roups 25 years, the old with doses of 0.01-1 Gy (P < 0.05). This result suggests that there is an obvious late effect of ionizing radiation on activity of NK cells in children
Hackett, J; Bosma, G C; Bosma, M J; Bennett, M.; Kumar, V
We have utilized a mouse mutant (C.B-17 scid) that lacks functional T and B lymphocytes to examine the relationship among transplantable progenitors of natural killer (NK) cells, T cells, and B cells. The NK-progenitor cells contained in the bone marrow were detected by their ability to generate mature NK cells, following transfer of bone marrow cells into NK cell-depleted and lethally irradiated mice. Regeneration of NK activity in the recipient mice was monitored by two different assays: th...