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1 times more frequently (р less then 0.02), predominantly inductivity disorders. We found signs of hyperactivation proportionate to the ASA level (p less then 0.001). DNA fragmentation was more highly expressed and was 1.6 and 1.3 times more frequent compared with the fertile and the ASA-negative patients, respectively (p less then 0.001 and p less then 0.05). We found signs of oxidative stress (OS) ROS generation by washed ASA-positive spermatozoa was 3.7 times higher than in the fertile men (p less then 0.00001) and depended on the ASA levels (R=0.5; p less then 0.0001). The ASA correlation with ROS generation in native sperm was weak (R=0.2; р less then 0.001). We concluded that autoimmune reactions against spermatozoa are accompanied by a fertility decrease in normozoospermia. This results from AR and capacitation disorders and DNA fragmentation. The pathogenesis of sperm abnormalities in immune infertility is associated with the OS of spermatozoa.The presence of patient heterogeneity in dose finding studies is inherent (i.e. groups with different maximum tolerated doses). When this type of heterogeneity is not accounted for in the trial design, subjects may be exposed to toxic or suboptimal doses. Options to handle patient heterogeneity include conducting separate trials or splitting the trial into arms. However, cost and/or lack of resources may limit the feasibility of these options. If information is shared between the groups, then both of these options do not benefit from using the shared information. Extending current dose finding designs to handle patient heterogeneity maximizes the utility of existing methods within a single trial. We propose a modification to the time-to-event continual reassessment method to accommodate two groups using a two-parameter model and maximum likelihood estimation. The operating characteristics of the design are investigated through simulations under different scenarios including the scenario where one conducts two separate trials, one for each group, using the one-sample time-to-event continual reassessment method.There is increasing evidence that adult attachment plays a role in the development and perseverance of symptoms of posttraumatic stress disorder (PTSD). This meta-analysis aims to synthesise this evidence and investigate the relationship between adult attachment styles and PTSD symptoms. A random-effects model was used to analyse 46 studies (N=9268) across a wide range of traumas. Results revealed a medium association between secure attachment and lower PTSD symptoms (ρˆ=-.27), and a medium association, in the opposite direction, between insecure attachment and higher PTSD symptoms (ρˆ=.26). Attachment categories comprised of high levels of anxiety most strongly related to PTSD symptoms, with fearful attachment displaying the largest association (ρˆ=.44). Dismissing attachment was not significantly associated with PTSD symptoms. The relationship between insecure attachment and PTSD was moderated by type of PTSD measure (interview or questionnaire) and specific attachment category (e.g. secure, fearful). Results have theoretical and clinical significance.Electron microscopy is commonly employed to determine the subunit organization of large macromolecular assemblies. However, the field lacks a robust molecular labeling methodology for unambiguous identification of constituent subunits. We present a strategy that exploits the unique properties of an unnatural amino acid in order to enable site-specific attachment of a single, readily identifiable protein label at any solvent-exposed position on the macromolecular surface. Using this method, we show clear labeling of a subunit within the 26S proteasome lid subcomplex that has not been amenable to labeling by traditional approaches.It is well known that long-term exposure to arsenite leads to human skin cancer, but the underlying mechanisms of carcinogenesis remain obscure. The transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism; however, emerging data suggest that constitutive activation of Nrf2 is associated with cancer development and chemotherapy resistance. The reasons Nrf2 continuously accumulates in cancer cells remain to be fully understood. By establishing transformed human keratinocyte cells via chronic arsenite treatment, we observed a continuous reduction in reactive oxygen species levels and enhanced levels of Nrf2 and its target antioxidant enzymes in the later stage of arsenite-induced cell transformation. We also revealed that hypermethylation of the Keap1 gene promoter region induced by DNA methyltransferase-3 leading to inactivation of its function was responsible for constitutive activation of Nrf2 and its target enzymes. To validate these observations, the expression of Keap1 protein was restored in arsenite-transformed cells by treatment with a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-Aza-dC), and protein levels of Nrf2 and colony formation were then determined after these treatments. Results showed that enhancement of Keap1 expression by 5-Aza-dC significantly reduced Nrf2 and its target antioxidant enzyme levels, and that in turn suppressed cell proliferation and colony formation of the transformed cells. Taken together, the present study strongly suggests that loss of Keap1 function by hypermethylation of its promoter region leading to Nrf2 nuclear accumulation appears to play a role in arsenite-induced human keratinocyte transformation.
To improve access to contraceptives in remote and rural areas, sub-Saharan African countries are allowing community health workers (CHWs) to distribute hormonal contraceptives. Before offering hormonal contraceptives, CHWs must determine pregnancy status but often lack a reliable way to do so. No studies have evaluated the impact of providing CHWs with urine pregnancy test kits. We assessed the impact of giving CHWs free pregnancy test kits on the number of new clients purchasing hormonal contraceptives from CHWs.

We implemented a randomized experiment in Eastern Madagascar among CHWs who sell injectable and oral hormonal contraceptives. A total of 622 CHWs were stratified by region and randomly assigned at the individual level. Treatment-group CHWs were given free pregnancy tests to distribute (n analyzed=272) and control-group CHWs did not receive the tests (n analyzed=263). We estimated an ordinary least-squares regression model, with the monthly number of new hormonal contraceptive clients per CHW as including these tests among CHWs' services.
No study has evaluated the impact of giving CHWs free urine pregnancy test kits for distribution to improve provision of hormonal contraceptives. Poly(vinylalcohol) Giving CHWs free pregnancy test kits significantly increases the number of clients to whom they sell hormonal contraceptives. Community-based distribution programs should consider including these tests among CHWs' services.Few ideas are as inexorable as the arrow of causation causes must precede their effects. Explicit or implicit knowledge about this causal order permits humans and other animals to predict and control events in order to produce desired outcomes. The sense of agency is deeply linked with representation of causation, since it involves the experience of a self-capable of acting on the world. Since causes must precede effects, the perceived temporal order of our actions and subsequent events should be relevant to the sense of agency. The present study investigated whether the ability to predict the outcome of an action would impose the classical cause-precedes-outcome pattern on temporal order judgements. Participants indicated whether a visual stimulus (dots moving upward or downward) was presented either before or after voluntary actions of the left or right hand. Crucially, the dot motion could be either congruent or incongruent with an operant association between hand and motion direction learned in a previous learning phase. When the visual outcome of voluntary action was congruent with previous learning, the motion onset was more often perceived as occurring after the action, compared to when the outcome was incongruent. This suggests that the prediction of specific sensory outcomes restructures our perception of timing of action and sensory events, inducing the experience that congruent effects occur after participants' actions. Interestingly, this bias to perceive events according to the temporal order of cause and outcome disappeared when participants knew that motion directions were automatically generated by the computer. This suggests that the reorganisation of time perception imposed by associative learning depends on participants' causal beliefs.Pressure difference is an accepted clinical biomarker for cardiovascular disease conditions such as aortic coarctation. Currently, measurements of pressure differences in the clinic rely on invasive techniques (catheterization), prompting development of non-invasive estimates based on blood flow. In this work, we propose a non-invasive estimation procedure deriving pressure difference from the work-energy equation for a Newtonian fluid. Spatial and temporal convergence is demonstrated on in silico Phase Contrast Magnetic Resonance Image (PC-MRI) phantoms with steady and transient flow fields. The method is also tested on an image dataset generated in silico from a 3D patient-specific Computational Fluid Dynamics (CFD) simulation and finally evaluated on a cohort of 9 subjects. The performance is compared to existing approaches based on steady and unsteady Bernoulli formulations as well as the pressure Poisson equation. The new technique shows good accuracy, robustness to noise, and robustness to the image segmentation process, illustrating the potential of this approach for non-invasive pressure difference estimation.Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplantation services may improve outcomes.Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft.
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