Effects of Global Warming on Gonadal Functions, Cellular Apoptosis, and Oxidative Stress in the American Oyster

Global warming due to climate change is predicted to intensify the heat stress in marine and coastal organisms, affecting their development, growth and reproductive functions. In this study. I analyzed gonadal development, heat shock protein 70 (HSP70), nitrotyrosine protein (NTP), dinitrophenyl (DNP) expressions, cellular apoptosis, and coelomic fluid (CF) conditions in American oyster. Oysters were placed in six aquariums and exposed to control (24°C), medium (28°C), and high (32°C) temperatures for one week. Higher temperature significantly decreased the number of eggs and sperm. CF protein concentrations also declined compared to control. In contrast, CF pH and HSP70 expression in gonad increased after heat-exposure, consistent with increased gonadal apoptosis. The enhanced apoptosis in gonads of heat-exposed oysters was associated with increased NTP and DNP expressions in gametes. Collectively, these results suggest that higher temperatures drastically increased oxidative stress leading to increased cellular apoptosis, which subsequently declined gonadal functions in American oyster

Post-immunization leucocytosis and its implications for the management of febrile infants.

AIMS: Clinical guidelines for management of infants with fever but no evident focus of infection recommend that those aged 1-3 months with a white cell count >15 × 109/l have a full septic screen and be admitted for parenteral antibiotics. However, there is limited information about leucocyte changes following routine immunization, a common cause of fever. We investigated white cell counts shortly after routine immunization in Ugandan infants under 3 months of age. METHODS: White cell counts were measured in 212 healthy infants following routine immunizations (DTwP-HepB-Hib, oral polio and pneumococcal conjugate 7 vaccines) received prior to 3 months of age. RESULTS: Mean leucocyte counts increased from 9.03 × 109/l (95% confidence interval 8.59-9.47 × 109/l) pre-immunizations to 16.46 × 109/l (15.4-17.52 × 109/l) at one-day post-immunizations at 6 weeks of age, and 15.21 × 109/l (14.07-16.36 × 109/l) at one-day post-immunizations at 10 weeks of age. The leucocytosis was primarily a neutrophilia, with neutrophil percentages one-day post-immunization of 49% at 6 weeks of age and 46% at 10 weeks of age. White cell parameters returned to baseline by two-days post-immunization. No participant received antibiotics when presenting with isolated fever post-immunization and all remained well at follow-up. CONCLUSIONS: In our study almost half the children <3 months old presenting with fever but no evident focus of infection at one-day post-immunization met commonly used criteria for full septic screen and admission for parenteral antibiotics, despite having no serious bacterial infection. These findings add to the growing body of literature that questions the utility of white blood cell measurement in identification of young infants at risk of serious bacterial infections, particularly in the context of recent immunizations, and suggest that further exploration of the effect of different immunization regimes on white cell counts is needed. This observational work was nested within a clinical trial, registration number ISRCTN59683017

Iminosugar idoBR1 isolated from Cucumber Cucumis sativus reduces inflammatory activity

Cucumbers have been anecdotally claimed to have anti-inflammatory activity for a long time, but the active principle was not identified. idoBR1, (2R,3R,4R,5S)-3,4,5-trihydroxypiperidine-2-carboxylic acid, is an iminosugar amino acid isolated from fruits of certain cucumbers, Cucumis sativus (Cucurbitaceae). It has no chromophore and analytically behaves like an amino acid making detection and identification difficult. It has anti-inflammatory activity reducing lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) in THP-1 cells and ex vivo human blood. It showed selective inhibition of human α-l-iduronidase and sialidases from both bacteria (Tannerella forsythia) and human THP-1 cells. idoBR1 and cucumber extract reduced the binding of hyaluronic acid (HA) to CD44 in LPS-stimulated THP-1 cells and may function as an anti-inflammatory agent by inhibiting induced sialidase involved in the production of functionally active HA adhesive CD44. Similar to the related iminosugars, idoBR1 is excreted unchanged in urine following consumption. Its importance in the diet should be further evaluated

Developing a COVID-19 Medical Respite Unit for Adults Experiencing Homelessness: Lessons Learned from an Interdisciplinary Community-Academic Partnership

Individuals experiencing homelessness are at particularly high risk for infection, severe illness, and death from COVID19. Local public health initiatives to address the pandemic should include medical respite services for individuals experiencing homelessness with documented or suspected COVID-19 infection, who are well enough to not be admitted to the hospital. We are a group of public health officials, clinicians, academics, and non-profit leaders who partnered with the City of New Haven, Connecticut to develop a COVID-19 medical respite program for people experiencing homelessness in our community. We seek to describe the key processes and challenges inherent to designing the COVID-19 respite including: the balance between patient autonomy and a public health agenda, how to deliver trauma informed, equitable, patient-centered, high quality care with low resources, and approaches to program evaluation.There is no funding specific to this article. This publication was made possible by the Yale National Clinician Scholars Program and by CTSA Grant Number TL1 TR001864 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.https://deepblue.lib.umich.edu/bitstream/2027.42/155396/1/Nash main article.pdfDescription of Nash main article.pdf : Main articl

An assessment of routine primary care health information system data quality in Sofala Province, Mozambique

<p>Abstract</p> <p>Background</p> <p>Primary health care is recognized as a main driver of equitable health service delivery. For it to function optimally, routine health information systems (HIS) are necessary to ensure adequate provision of health care and the development of appropriate health policies. Concerns about the quality of routine administrative data have undermined their use in resource-limited settings. This evaluation was designed to describe the availability, reliability, and validity of a sample of primary health care HIS data from nine health facilities across three districts in Sofala Province, Mozambique. HIS data were also compared with results from large community-based surveys.</p> <p>Methodology</p> <p>We used a methodology similar to the Global Fund to Fight AIDS, Tuberculosis and Malaria data verification bottom-up audit to assess primary health care HIS data availability and reliability. The quality of HIS data was validated by comparing three key indicators (antenatal care, institutional birth, and third diptheria, pertussis, and tetanus [DPT] immunization) with population-level surveys over time.</p> <p>Results and discussion</p> <p>The data concordance from facility clinical registries to monthly facility reports on five key indicators--the number of first antenatal care visits, institutional births, third DPT immunization, HIV testing, and outpatient consults--was good (80%). When two sites were excluded from the analysis, the concordance was markedly better (92%). Of monthly facility reports for immunization and maternity services, 98% were available in paper form at district health departments and 98% of immunization and maternity services monthly facility reports matched the Ministry of Health electronic database. Population-level health survey and HIS data were strongly correlated (R = 0.73), for institutional birth, first antenatal care visit, and third DPT immunization.</p> <p>Conclusions</p> <p>Our results suggest that in this setting, HIS data are both reliable and consistent, supporting their use in primary health care program monitoring and evaluation. Simple, rapid tools can be used to evaluate routine data and facilitate the rapid identification of problem areas.</p

Aberrant \u3ci\u3eAZIN2\u3c/i\u3e and Polyamine Metabolism Precipitates Tau Neuropathology

Tauopathies display a spectrum of phenotypes from cognitive to affective behavioral impairments; however, mechanisms promoting tau pathology and how tau elicits behavioral impairment remain unclear. We report a unique interaction between polyamine metabolism, behavioral impairment, and tau fate. Polyamines are ubiquitous aliphatic molecules that support neuronal function, axonal integrity, and cognitive processing. Transient increases in polyamine metabolism hallmark the cell’s response to various insults, known as the polyamine stress response (PSR). Dysregulation of gene transcripts associated with polyamine metabolism in Alzheimer’s disease (AD) brains were observed, and we found that ornithine decarboxylase antizyme inhibitor 2 (AZIN2) increased to the greatest extent. We showed that sustained AZIN2 overexpression elicited a maladaptive PSR in mice with underlying tauopathy (MAPT P301S; PS19). AZIN2 also increased acetylpolyamines, augmented tau deposition, and promoted cognitive and affective behavioral impairments. Higher-order polyamines displaced microtubule-associated tau to facilitate polymerization but also decreased tau seeding and oligomerization. Conversely, acetylpolyamines promoted tau seeding and oligomers. These data suggest that tauopathies launch an altered enzymatic signature that endorses a feed-forward cycle of disease progression. Taken together, the tau-induced PSR affects behavior and disease continuance, but may also position the polyamine pathway as a potential entry point for plausible targets and treatments of tauopathy, including AD

A new family of giardial cysteine-rich non-VSP protein genes and a novel cyst protein

© 2006 Davids et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The definitive version was published in PLoS ONE 1 (2006): e44, doi:10.1371/journal.pone.0000044.Since the Giardia lamblia cyst wall is necessary for survival in the environment and host infection, we tested the hypothesis that it contains proteins other than the three known cyst wall proteins. Serial analysis of gene expression during growth and encystation revealed a gene, “HCNCp” (High Cysteine Non-variant Cyst protein), that was upregulated late in encystation, and that resembled the classic Giardia variable surface proteins (VSPs) that cover the trophozoite plasmalemma. HCNCp is 13.9% cysteine, with many “CxxC” tetrapeptide motifs and a transmembrane sequence near the C-terminus. However, HCNCp has multiple “CxC” motifs rarely found in VSPs, and does not localize to the trophozoite plasmalemma. Moreover, the HCNCp C-terminus differed from the canonical VSP signature. Full-length epitope-tagged HCNCp expressed under its own promoter was upregulated during encystation with highest expression in cysts, including 42 and 21 kDa C-terminal fragments. Tagged HCNCp targeted to the nuclear envelope in trophozoites, and co-localized with cyst proteins to encystation-specific secretory vesicles during encystation. HCNCp defined a novel trafficking pathway as it localized to the wall and body of cysts, while the cyst proteins were exclusively in the wall. Unlike VSPs, HCNCp is expressed in at least five giardial strains and four WB subclones expressing different VSPs. Bioinformatics identified 60 additional large high cysteine membrane proteins (HCMp) containing ≥20 CxxC/CxC's lacking the VSP-specific C-terminal CRGKA. HCMp were absent or rare in other model or parasite genomes, except for Tetrahymena thermophila with 30. MEME analysis classified the 61 gHCMp genes into nine groups with similar internal motifs. Our data suggest that HCNCp is a novel invariant cyst protein belonging to a new HCMp family that is abundant in the Giardia genome. HCNCp and the other HCMp provide a rich source for developing parasite-specific diagnostic reagents, vaccine candidates, and subjects for further research into Giardia biology

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

A sequence-based survey of the complex structural organization of tumor genomes

Tumors and cancer cell lines were surveyed with end-sequencing profiling, yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent

Dual Testing Algorithm of BED-CEIA and AxSYM Avidity Index Assays Performs Best in Identifying Recent HIV Infection in a Sample of Rwandan Sex Workers

To assess the performance of BED-CEIA (BED) and AxSYM Avidity Index (Ax-AI) assays in estimating HIV incidence among female sex workers (FSW) in Kigali, Rwanda. Eight hundred FSW of unknown HIV status were HIV tested; HIV-positive women had BED and Ax-AI testing at baseline and ≥12 months later to estimate assay false-recent rates (FRR). STARHS-based HIV incidence was estimated using the McWalter/Welte formula, and adjusted with locally derived FRR and CD4 results. HIV incidence and local assay window periods were estimated from a prospective cohort of FSW. At baseline, 190 HIV-positive women were BED and Ax-AI tested; 23 were classified as recent infection (RI). Assay FRR with 95% confidence intervals were: 3.6% (1.2-8.1) (BED); 10.6% (6.1-17.0) (Ax-AI); and 2.1% (0.4-6.1) (BED/Ax-AI combined). After FRR-adjustment, incidence estimates by BED, Ax-AI, and BED/Ax-AI were: 5.5/100 person-years (95% CI 2.2-8.7); 7.7 (3.2-12.3); and 4.4 (1.4-7.3). After CD4-adjustment, BED, Ax-AI, and BED/Ax-AI incidence estimates were: 5.6 (2.6-8.6); 9.7 (5.0-14.4); and 4.7 (2.0-7.5). HIV incidence rates in the first and second 6 months of the cohort were 4.6 (1.6-7.7) and 2.2 (0.1-4.4). Adjusted incidence estimates by BED/Ax-AI combined were similar to incidence in the first 6 months of the cohort. Furthermore, false-recent rate on the combined BED/Ax-AI algorithm was low and substantially lower than for either assay alone. Improved assay specificity with time since seroconversion suggests that specificity would be higher in population-based testing where more individuals have long-term infectio