Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) mutation and EBV-associated T-cell lymphoproliferative disorder of the thyroid

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%–50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein–Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation

Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

Relayed FSO Communication with Aperture Averaging Receivers and Misalignment Errors

In this paper, the performance of decode-and-forward relay-assisted free-space-optical (FSO) communication systems under atmospheric turbulence induced fading and misalignment errors is investigated. To mitigate the adverse effects of the atmospheric turbulence, the aperture averaging receivers are considered both at the relay and destination sides. The atmospheric turbulence induced fading is modeled via the exponentiated-Weibull distribution, which has recently been proposed to characterize an FSO link in the presence of finite-sized receiver aperture. The expression for the moment generating function (MGF) of the instantaneous signal-to-noise ratio is derived. Further, new closed form expression for the outage probability is obtained. Moreover, the new expression for the average symbol error rate of the subcarrier intensity modulated M-ary phase shift keying is obtained using the MGF-based approach. Finally, numerical examples are discussed and all the derived analytical results are corroborated by Monte-Carlo simulations. Relayed FSO Communication with Aperture Averaging Receivers and Misalignment Errors. Available from: https://www.researchgate.net/publication/307931308_Relayed_FSO_Communication_with_Aperture_Averaging_Receivers_and_Misalignment_Errors [accessed Nov 10, 2016]

An observational study on stress and sleep variation among paramedical students during Covid-19 lockdown

Background-Enforcement of nationwide lockdown to prevent the further spread of Covid-19 infection, the advisory of social distancing and isolation has imposed mental health challenges to the students. This abrupt onset of changes leads to fear, stress, and anxiety in all the concerned paramedical students. Objectives: To evaluate the association between sleep onset and perceived stress score in paramedical students. Material and Methods- An observational study was done on 134 first year paramedical students of the Government Medical College of Jabalpur( Madhya Pradesh) who participated in the study. The data was collected through online questionnaires. Data was analyzed using the chi-square test. Results- The mean age of the participants was 19.98± 1.21years and body mass index (BMI) was 20.93 ±3.40 Kg/m2. The Mean Perceived Stress Score Scale (PSS Score) was 18.19 ± 11.19. The association between difficulty in falling asleep and PSS Score was found to be non significant (p=0.157). 24.62% of students pursued art/painting,7.46% dance,15.67% exercise, 25.37% music, and 14.18% yoga as their hobbies to cope up with the stress. Conclusion- Covid 19 lockdown has a substantial impact on the paramedical students in terms of the increased level of stress

Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells

T cells are a major cell type involved in systemic lupus erythematosus (SLE). Here, the authors use promoter capture-C and ATAC-seq in human follicular T helper cells to identify SLE genes distant from GWAS loci (via 3D interaction) and validate the function of key regulatory elements and genes in vitro

Hydroxymethylation profile of cell-free DNA is a biomarker for early colorectal cancer.

Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study of over two thousand individual blood samples, we created, tested and explored the properties of a 5-hydroxymethylcytosine-based classifier to detect colorectal cancer (CRC). In an independent validation sample set, the classifier discriminated CRC samples from controls with an area under the receiver operating characteristic curve (AUC) of 90% (95% CI [87, 93]). Sensitivity was 55% at 95% specificity. Performance was similar for early stage 1 (AUC 89%; 95% CI [83, 94]) and late stage 4 CRC (AUC 94%; 95% CI [89, 98]). The classifier could detect CRC even when the proportion of tumor DNA in blood was undetectable by other methods. Expanding the classifier to include information about cell-free DNA fragment size and abundance across the genome led to gains in sensitivity (63% at 95% specificity), with similar overall performance (AUC 91%; 95% CI [89, 94]). We confirm that 5-hydroxymethylcytosine can be used to detect CRC, even in early-stage disease. Therefore, the inclusion of 5-hydroxymethylcytosine in multianalyte testing could improve sensitivity for the detection of early-stage cancer