Phytoestrogens

Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens

The Escape Problem for Irreversible Systems

The problem of noise-induced escape from a metastable state arises in physics, chemistry, biology, systems engineering, and other areas. The problem is well understood when the underlying dynamics of the system obey detailed balance. When this assumption fails many of the results of classical transition-rate theory no longer apply, and no general method exists for computing the weak-noise asymptotics of fundamental quantities such as the mean escape time. In this paper we present a general technique for analysing the weak-noise limit of a wide range of stochastically perturbed continuous-time nonlinear dynamical systems. We simplify the original problem, which involves solving a partial differential equation, into one in which only ordinary differential equations need be solved. This allows us to resolve some old issues for the case when detailed balance holds. When it does not hold, we show how the formula for the mean escape time asymptotics depends on the dynamics of the system along the most probable escape path. We also present new results on short-time behavior and discuss the possibility of focusing along the escape path.Comment: 24 pages, APS revtex macros (version 2.1) now available from PBB via `get oldrevtex.sty

Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation

<p>Abstract</p> <p>Background</p> <p>Lung ischemia-reperfusion (IR) injury leads to significant morbidity and mortality which remains a major obstacle after lung transplantation. However, the role of various subset(s) of lung cell populations in the pathogenesis of lung IR injury and the mechanisms of cellular protection remain to be elucidated. In the present study, we investigated the effects of adenosine A_2Areceptor (A_2AAR) activation on resident lung cells after IR injury using an isolated, buffer-perfused murine lung model.</p> <p>Methods</p> <p>To assess the protective effects of A_2AAR activation, three groups of C57BL/6J mice were studied: a sham group (perfused for 2 hr with no ischemia), an IR group (1 hr ischemia + 1 hr reperfusion) and an IR+ATL313 group where ATL313, a specific A_2AAR agonist, was included in the reperfusion buffer after ischemia. Lung injury parameters and pulmonary function studies were also performed after IR injury in A_2AAR knockout mice, with or without ATL313 pretreatment. Lung function was assessed using a buffer-perfused isolated lung system. Lung injury was measured by assessing lung edema, vascular permeability, cytokine/chemokine activation and myeloperoxidase levels in the bronchoalveolar fluid.</p> <p>Results</p> <p>After IR, lungs from C57BL/6J wild-type mice displayed significant dysfunction (increased airway resistance, pulmonary artery pressure and decreased pulmonary compliance) and significant injury (increased vascular permeability and edema). Lung injury and dysfunction after IR were significantly attenuated by ATL313 treatment. Significant induction of TNF-α, KC (CXCL1), MIP-2 (CXCL2) and RANTES (CCL5) occurred after IR which was also attenuated by ATL313 treatment. Lungs from A_2AAR knockout mice also displayed significant dysfunction, injury and cytokine/chemokine production after IR, but ATL313 had no effect in these mice.</p> <p>Conclusion</p> <p>Specific activation of A_2AARs provides potent protection against lung IR injury via attenuation of inflammation. This protection occurs in the absence of circulating blood thereby indicating a protective role of A_2AAR activation on resident lung cells such as alveolar macrophages. Specific A_2AAR activation may be a promising therapeutic target for the prevention or treatment of pulmonary graft dysfunction in transplant patients.</p

How does online postal self-sampling (OPSS) shape access to testing for sexually transmitted infections (STIs)? A qualitative study of service users

Background: Sexually transmitted infections (STIs) are a serious public health issue in many countries. Online postal self-sampling (OPSS) is increasingly used to test for STIs, a trend accelerated by the COVID-19 pandemic. There remains limited understanding of how service users experience OPSS and what leads them to access it over clinic-based services, or vice versa. This research seeks to address these gaps, by undertaking a large qualitative study which sits within the ASSIST study, a mixed-methods, realist evaluation of OPSS. Methods: Participants were recruited via clinic-based and online sexual health services in three case study areas in England. Purposive sampling was used to over-represent populations disproportionately affected by poor sexual health: young people; people of colour; men who have sex with men; and trans and non-binary people. Semi-structured interviews were analysed using Levesque’s conceptual framework of access to healthcare. Results: We interviewed 100 service users. Participants typically became aware of OPSS from sexual health services, the internet or word of mouth. Acceptability of OPSS was facilitated by the perceived privacy it offered over clinic-based services, which some participants found embarrassing to access. OPSS also enabled participants to overcome barriers to reaching clinic-based services, such as a lack of appointment availability, although difficulty obtaining OPSS kits in some areas undermined this. As all services in our case study areas were free to use, affordability did not significantly shape access, although OPSS enabled some participants to avoid costs associated with travelling to clinic-based services. Participants were usually able to engage with OPSS, finding it easy to use and reliable, although blood self-sampling was challenging for most. Participants valued the support offered by clinic-based services beyond STI testing, including the opportunity to access contraception or ask staff questions, and felt this was more appropriate when they had specific concerns about their sexual health, such as STI symptoms. Conclusions: Our findings constitute one of the largest qualitative studies to have explored OPSS and offer valuable insights to providers. OPSS shapes access to STI testing in a number of ways, including facilitating access in many circumstances, but users also want to retain access to clinic-based services, particularly for when they believe they need support beyond STI testing

Precision exercise medicine: understanding exercise response variability

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability. In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability531811411153The consensus meeting that led to the writing of this manuscript was held with the financial support of the Pennington Biomedical Research Foundation, the Pennington Biomedical Research Center Division of Education, the LSU Boyd Professorship and the John W. Barton, Sr. Chair in Genetics and Nutrition. No funding and/or honorarium was provided to any member of the writing group for the production of this manuscrip

The impact of changes to heroin supply on blood-borne virus notifications and injecting related harms in New South Wales, Australia

BACKGROUND: In early 2001 Australia experienced a sudden and unexpected disruption to heroin availability, know as the 'heroin shortage'. This 'shortage has been linked to a decrease in needle and syringe output and therefore possibly a reduction in injecting drug use. We aimed to examine changes, if any, in blood-borne viral infections and presentations for injecting related problems related to injecting drug use following the reduction heroin availability in Australia, in the context of widespread harm reduction measures. METHODS: Time series analysis of State level databases on HIV, hepatitis B, hepatitis C notifications and hospital and emergency department data. Examination of changes in HIV, hepatitis B, hepatitis C notifications and hospital and emergency department admissions for injection-related problems following the onset of the heroin shortage; non-parametric curve-fitting of number of hepatitis C notifications among those aged 15–19 years. RESULTS: There were no changes observed in hospital visits for injection-related problems. There was no change related to the onset heroin shortage in the number of hepatitis C notifications among persons aged 15–19 years, but HCV notifications have subsequently decreased in this group. No change occurred in HIV and hepatitis B notifications. CONCLUSION: A marked reduction in heroin supply resulted in no increase in injection-related harm at the community level. However, a delayed decrease in HCV notifications among young people may be related. These changes occurred in a setting with widespread, publicly funded harm reduction initiatives

Experienced stressors and coping strategies among Iranian nursing students

<p>Abstract</p> <p>Background</p> <p>College students are prone to stress due to the transitional nature of college life. High levels of stress are believed to affect students' health and academic functions. If the stress is not dealt with effectively, feelings of loneliness, nervousness, sleeplessness and worrying may result. Effective coping strategies facilitate the return to a balanced state, reducing the negative effects of stress.</p> <p>Methods</p> <p>This descriptive cross-sectional study was performed to determine sources of stress and coping strategies in nursing students studying at the Iran Faculty of Nursing & Midwifery. All undergraduate nursing students enrolled in years 1-4 during academic year 2004-2005 were included in this study, with a total of 366 questionnaires fully completed by the students. The Student Stress Survey and the Adolescent Coping Orientation for Problem Experiences Inventory (ACOPE) were used for data collection.</p> <p>Results</p> <p>Most students reported "finding new friends" (76.2%), "working with people they did not know" (63.4%) as interpersonal sources of stress, "new responsibilities" (72.1%), "started college" (65.8%) as intrapersonal sources of stress more than others. The most frequent academic source of stress was "increased class workload" (66.9%) and the most frequent environmental sources of stress were being "placed in unfamiliar situations" (64.2%) and "waiting in long lines" (60.4%). Interpersonal and environmental sources of stress were reported more frequently than intrapersonal and academic sources. Mean interpersonal (P=0.04) and environmental (P=0.04) sources of stress were significantly greater in first year than in fourth year students. Among coping strategies in 12 areas, the family problem solving strategies, "trying to reason with parents and compromise" (73%) and "going along with family rules" (68%) were used "often or always" by most students. To cope with engaging in demanding activity, students often or always used "trying to figure out how to deal with problems" (66.4%) and "trying to improve themselves" (64.5%). The self-reliance strategy, "trying to make their own decisions" (62%); the social support strategies, "apologizing to people" (59.6%), "trying to help other people solve their problems" (56.3%), and "trying to keep up friendships or make new friends" (54.4%); the spiritual strategy, "praying" (65.8%); the seeking diversions strategy, "listening to music" (57.7%), the relaxing strategy "day dreaming" (52.5%), and the effort to "be close with someone cares about you" (50.5%) were each used "often or always" by a majority of students. Most students reported that the avoiding strategies "smoking" (93.7%) and "drinking beer or wine" (92.9%), the ventilating strategies "saying mean things to people" and "swearing" (85.8%), the professional support strategies "getting professional counseling" (74.6%) and "talking to a teacher or counselor" (67.2%) and the humorous strategy "joking and keeping a sense of humor" (51.9%) were used "seldom or never".</p> <p>Conclusion</p> <p>First year nursing students are exposed to a variety of stressors. Establishing a student support system during the first year and improving it throughout nursing school is necessary to equip nursing students with effective coping skills. Efforts should include counseling helpers and their teachers, strategies that can be called upon in these students' future nursing careers.</p

Protein phosphatase beta, a putative type-2A protein phosphatase from the human malaria parasite Plasmodium falciparum.

Protein phosphatases play a critical role in the regulation of the eukaryotic cell cycle and signal transduction. A putative protein serine/threonine phosphatase gene has been isolated from the human malaria parasite Plasmodium falciparum. The gene has an unusual intron that contains four repeats of 32 nucleotides and displays a high degree of size polymorphism among different strains of P. falciparum. The open reading frame reconstituted by removal of the intron encodes a protein of 466 amino acids with a predicted molecular mass of approximately 53.7 kDa. The encoded protein, termed protein phosphatase beta (PP-beta), is composed of two distinct domains. The C-terminal domain comprises 315 amino acids and exhibits a striking similarity to the catalytic subunits of the type-2A protein phosphatases. Database searches revealed that the catalytic domain has the highest similarity to Schizosaccharomyces pombe Ppa1 (58% identity and 73% similarity). However, it contains a hydrophilic insert consisting of five amino acids. The N-terminal domain comprises 151 amino acid residues and exhibits several striking features, including high levels of charged amino acids and asparagine, and multiple consensus phosphorylation sites for a number of protein kinases. An overall structural comparison of PP-beta with other members of the protein phosphatase 2A group revealed that PP-beta is more closely related to Saccharomyces cerevisiae PPH22. Southern blots of genomic DNA digests and chromosomal separations showed that PP-beta is a single-copy gene and is located on chromosome 9. A 2800-nucleotide transcript of this gene is expressed specifically in the sexual erythrocytic stage (gametocytes). The results indicate that PP-beta may be involved in sexual stage development

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort

CONTEXT: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. OBJECTIVE: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. RESEARCH DESIGN AND METHODS: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. RESULTS: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. CONCLUSIONS: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment