HIV seroprevalence and its effect on outcome of moderate to severe burn injuries: A Ugandan experience

\ud \ud HIV infection in a patient with burn injuries complicates the care of both the patient and the treating burn team. This study was conducted to establish the prevalence of HIV among burn patients in our setting and to compare the outcome of these patients who are HIV positive with those who are HIV negative. This was a prospective cohort study involving burn injury patients admitted to Mulago Hospital between November 2005 and February 2006. Patients were stratified into HIV positive (exposed) group and HIV-negative (unexposed) group. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software version 11.5. Of the 130 patients included in the study, 17 (13.1%) patients tested HIV positive and this formed the study (exposed) group. The remaining 113 patients (86.9%) formed the control (unexposed) group. In the HIV positive group, females outnumbered males by a ratio of 1.4:1 and the mean age was 28.4 ± 21.5 years (range 3 months-34 years). 64.7% of HIV positive patients reported to have risk factors for HIV infection. Of these, multiple sexual partners [Odds Ratio 8.44, 95% C.I. (3.87-143.23), P = 0.011] and alcoholism [Odds Ratio 8.34, 95% C.I. (5.76-17.82), P = 0.002] were found to be independently and significantly associated with increased risk to HIV infection. The mean CD4 count for HIV positive and HIV negative patients were 394 ± 328 cells/μL and 912 ± 234 cells/μL respectively which is statistically significant (P = 0.001). There was no difference in the bacteria cultured from the wounds of HIV positive and negative patients (P = 0.322). Patients with clinical signs of sepsis had lower CD4+ counts compared to patients without sepsis (P < 0.001). ). Skin grafting was carried out in 35.3% of HIV negative patients and 29.4% of HIV positive patients with no significant difference in skin graft take and the degree of healed burn on discharge was the same (P = 0.324). There was no significant difference in hospital stay between HIV positive and negative patients (P = 0.674). The overall mortality rate was 11.5%. Using multivariate logistic regression analysis, mortality rate was found to be independently and significantly related to the age of the patient, HIV positive with stigmata of AIDS, CD4 count, inhalation injury, %TBSA and severity of burn (p-value < 0.001). HIV infection is prevalent among burn injury patients in our setting and thus presents an occupational hazard to health care workers who care for these patients. All burn health care workers in this region need to practice universal precautions in order to reduce the risk of exposure to HIV infection and post-exposure prophylaxis should be emphasized. The outcome of burn injury in HIV infected patients is dependent upon multiple variables such as age of the patient, inhalation injury and %TBSA and not the HIV status alone

Secluded Dark Matter Coupled to a Hidden CFT

Models of secluded dark matter offer a variant on the standard WIMP picture and can modify our expectations for hidden sector phenomenology and detection. In this work we extend a minimal model of secluded dark matter, comprised of a U(1)'-charged dark matter candidate, to include a confining hidden-sector CFT. This provides a technically natural explanation for the hierarchically small mediator-scale, with hidden-sector confinement generating m_{gamma'}>0. Furthermore, the thermal history of the universe can differ markedly from the WIMP picture due to (i) new annihilation channels, (ii) a (potentially) large number of hidden-sector degrees of freedom, and (iii) a hidden-sector phase transition at temperatures T << M_{dm} after freeze out. The mediator allows both the dark matter and the Standard Model to communicate with the CFT, thus modifying the low-energy phenomenology and cosmic-ray signals from the secluded sector.Comment: ~50p, 8 figs; v2 JHEP versio

Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia.

Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). This complex orchestrates the attachment of the GPI anchor to the C terminus of precursor proteins in the endoplasmic reticulum. Here, we report bi-allelic mutations in GPAA1 in ten individuals from five families. Using whole-exome sequencing, we identified two frameshift mutations (c.981_993del [p.Gln327Hisfs∗102] and c.920delG [p.Gly307Alafs∗11]), one intronic splicing mutation (c.1164+5C>T), and six missense mutations (c.152C>T [p.Ser51Leu], c.160_161delinsAA [p.Ala54Asn], c.527G>C [p.Trp176Ser], c.869T>C [p.Leu290Pro], c.872T>C [p.Leu291Pro], and c.1165G>C [p.Ala389Pro]). Most individuals presented with global developmental delay, hypotonia, early-onset seizures, cerebellar atrophy, and osteopenia. The splicing mutation was found to decrease GPAA1 mRNA. Moreover, flow-cytometry analysis of five available individual samples showed that several GPI-anchored proteins had decreased cell-surface abundance in leukocytes (FLAER, CD16, and CD59) or fibroblasts (CD73 and CD109). Transduction of fibroblasts with a lentivirus encoding the wild-type protein partially rescued the deficiency of GPI-anchored proteins. These findings highlight the role of the transamidase complex in the development and function of the cerebellum and the skeletal system

The epigenetic regulator Histone Deacetylase 1 promotes transcription of a core neurogenic programme in zebrafish embryos

<p>Abstract</p> <p>Background</p> <p>The epigenetic regulator Histone Deacetylase 1 (Hdac1) is required for specification and patterning of neurones and myelinating glia during development of the vertebrate central nervous system (CNS). This co-ordinating function for Hdac1 is evolutionarily conserved in zebrafish and mouse, but the mechanism of action of Hdac1 in the developing CNS is not well-understood.</p> <p>Results</p> <p>A genome-wide comparative analysis of the transcriptomes of Hdac1-deficient and wild-type zebrafish embryos was performed, which identified an extensive programme of gene expression that is regulated by Hdac1 in the developing embryo. Using time-resolved expression profiling of embryos, we then identified a small subset of 54 genes within the Hdac1-regulated transcriptome that specifically exhibit robust and sustained Hdac1-dependent expression from early neurogenesis onwards. 18 of these 54 stringently Hdac1-regulated genes encode DNA-binding transcription factors that are implicated in promoting neuronal specification and CNS patterning, including the proneural bHLH proteins Ascl1a and Ascl1b, as well as Neurod4 and Neurod. Relatively few genes are strongly repressed by Hdac1 but expression of the Notch target gene <it>her6 </it>is attenuated by Hdac1 in specific sub-regions of the developing CNS, from early stages of neurogenesis onwards. Selected members of the stringently Hdac1-regulated group of genes were tested for Hdac1 binding to their promoter-proximal <it>cis</it>-regulatory elements. Surprisingly, we found that Hdac1 is specifically and stably associated with DNA sequences within the promoter region of <it>ascl1b </it>during neurogenesis, and that this Hdac1-<it>ascl1b </it>interaction is abolished in <it>hdac1 </it>mutant embryos.</p> <p>Conclusions</p> <p>We conclude that Hdac1 regulates histone acetylation and methylation in the developing zebrafish embryo and promotes the sustained, co-ordinate transcription of a small set of transcription factor genes that control expansion and diversification of cell fates within the developing CNS. Our <it>in vivo </it>chromatin immunoprecipitation results also suggest a specific function for Hdac1 in directly regulating transcription of a key member of this group of genes, <it>ascl1b</it>, from the beginning of neurogenesis onwards. Taken together, our observations indicate a novel role for Hdac1 as a positive regulator of gene transcription during development of the vertebrate CNS, in addition to its more well-established function in transcriptional repression.</p

Physical activity inversely associated with the presence of depression among urban adolescents in regional China

<p>Abstract</p> <p>Background</p> <p>An inverse relationship between physical activity (PA) and depression among adolescents has been reported in developed communities without consideration of sedentary behaviors (SB, including sitting for course study, viewing TV, and sleeping). We explored the association between recreational PA time (hr/wk) and depression after adjustment with SB and other possible confounders among Chinese adolescents.</p> <p>Methods</p> <p>A population-based cross-sectional study was conducted in Nanjing municipality of China in 2004 using a multi-stage cluster sampling approach. A total of 72 classes were randomly selected from 24 urban junior high schools and all students completed the structured questionnaire. Adolescent depression was examined by the Children's Depression Inventory (CDI) of Chinese version with cutoff point value of 20 or above as the presence of depression. Recreational PA time was measured by a question on weekly hours of PA outside of school. Descriptive statistics, multivariate logistic and linear regression models were used in analysis.</p> <p>Results</p> <p>The overall prevalence of depression was 15.7% (95%CI: 14.3%, 17.1%) among 2,444 eligible participants. It was found that physical activity was negatively associated with depression. After adjustment for sedentary behaviors and other potential confounders, participants who spent 1–7 hr/wk, 8–14 hr/wk and 15+ hr/wk for recreational PA, respectively, had odds ratios of 0.70 (95% CI = 0.57, 0.86), 0.68 (95% CI = 0.53, 0.88) and 0.66 (95% CI = 0.50, 0.87) for likelihood of being depressive, compared to their counterparts who spent 0–0.9 hr/wk for PA. This inverse relationship between PA time and depression remained statistically significant by gender and grade.</p> <p>Conclusion</p> <p>This study, conducted among Chinese adolescents, strengthened the evidence that physical activity was inversely associated with depression. Our study has important implications for health officers and public health professionals to pay much attention to the relationship between physical activity and depression in Mainland China.</p

VLPs and particle strategies for cancer vaccines

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The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease