A novel mutation in EROS (CYBC1) causes chronic granulomatous disease.

Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterised by opportunistic infection and sterile granulomatous inflammation. CGD is caused by a failure of reactive oxygen species (ROS) production by the phagocyte NADPH oxidase. Mutations in the genes encoding phagocyte NADPH oxidase subunits cause CGD. We and others have described a novel form of CGD (CGD5) secondary to lack of EROS (CYBC1), a highly selective chaperone for gp91phox. EROS-deficient cells express minimal levels of gp91phox and its binding partner p22phox, but EROS also controls the expression of other proteins such as P2X7. The full nature of CGD5 is currently unknown. We describe a homozygous frameshift mutation in CYBC1 leading to CGD. Individuals who are heterozygous for this mutation are found in South Asian populations (allele frequency = 0.00006545), thus it is not a private mutation. Therefore, it is likely to be the underlying cause of other cases of CGD.

Quantum Unique Ergodicity for Cayley Graphs of Quasirandom Groups.

A finite group G is called C-quasirandom (by Gowers) if all non-trivial irreducible complex representations of G have dimension at least C. For any unit ℓ2 function on a finite group we associate the quantum probability measure on the group given by the absolute value squared of the function. We show that if a group is highly quasirandom, in the above sense, then any Cayley graph of this group has an orthonormal eigenbasis of the adjacency operator such that the quantum probability measures of the eigenfunctions put close to the correct proportion of their mass on suitably selected subsets of the group that are not too small.

Hematotoxic Snakebite Victim with Trauma: The Role of Guided Transfusion, Rotational Thromboelastometry, and Tranexamic Acid.

Hematotoxic snake bite is a leading cause of mortality in South India. However, it is rare for the emergency physician to encounter a patient with trauma associated with snakebite. Management of such a patient differs substantially from the routine management of either a trauma patient or a snakebite victim. A 59-y-old man was bitten by a snake, after which he lost consciousness, fell, and sustained facial trauma. He was rushed to the emergency department within 30 min and was discovered to have ongoing oromaxillofacial bleeding. His respiratory distress and gasping respirations warranted orotracheal intubation and ventilation. He was treated with anti-snake venom and underwent viscoelastometry-guided transfusion to correct coagulopathy. Hemostasis was achieved after administration of tranexamic acid and bilateral posterior nasal packing. Imaging studies revealed craniomaxillofacial trauma with intracranial hemorrhage. He underwent a delayed mandibular repair. Judicious, guided fluid management, adequate nutrition, and prompt weaning off the ventilator allowed early discharge of the patient from the hospital. The minimal weakness present in his left lower limb at the time of discharge had improved by the time of follow-up. This report shows the utility of early and rapid anti-snake venom in envenomated victims with coagulopathy. The role of cryoprecipitate, tranexamic acid, and viscoelastometric testing needs further exploration in specific hematotoxic snakebites.

Survey of Emergency and Essential Surgical, Obstetric and Anaesthetic Services Available in Bangladeshi Government Health Facilities.

OBJECTIVE: Evaluate the capacity of government-run hospitals in Bangladesh to provide emergency and essential surgical, obstetric and anaesthetic services. METHODS: Cross-sectional survey of 240 Bangladeshi Government healthcare facilities using the World Health Organisation Situational Analysis Tool to Assess Emergency and Essential Surgical Care (SAT). This tool evaluates the ability of a healthcare facility to provide basic surgical, obstetric and anaesthetic care based on 108 queries that detail the infrastructure and population demographics, human resources, surgical interventions and reason for referral, and available surgical equipment and supplies. For this survey, the Bangladeshi Ministry of Health sent the SAT to sub-district, district/general and teaching hospitals throughout the country in April 2013. RESULTS: Responses were received from 240 healthcare facilities (49.5% response rate): 218 sub-district and 22 district/general hospitals. At the sub-district level, caesarean section was offered by 55% of facilities, laparotomy by 7% and open fracture repair by 8%. At the district/general hospital level, 95% offered caesarean section, 86% offered laparotomy and 77% offered open fracture treatment. Availability of anaesthesia services, general equipment and supplies reflected this trend, where district/general hospitals were better equipped than sub-district hospitals, though equipment and infrastructure shortages persist. CONCLUSION: There has been overall impressive progress by the Bangladeshi Government in providing essential surgical services. Areas for improvement remain across all key areas, including infrastructure, human resources, surgical interventions offered and available equipment. Investment in surgical services offers a cost-effective opportunity to continue to improve the health of the Bangladeshi population and move the country towards universal healthcare coverage.

Antimicrobial drug use in food-producing animals and associated human health risks: what, and how strong, is the evidence?

BACKGROUND: Antimicrobial resistance is a public health threat. Because antimicrobial consumption in food-producing animals contributes to the problem, policies restricting the inappropriate or unnecessary agricultural use of antimicrobial drugs are important. However, this link between agricultural antibiotic use and antibiotic resistance has remained contested by some, with potentially disruptive effects on efforts to move towards the judicious or prudent use of these drugs. MAIN TEXT: The goal of this review is to systematically evaluate the types of evidence available for each step in the causal pathway from antimicrobial use on farms to human public health risk, and to evaluate the strength of evidence within a 'Grades of Recommendations Assessment, Development and Evaluation'(GRADE) framework. The review clearly demonstrates that there is compelling scientific evidence available to support each step in the causal pathway, from antimicrobial use on farms to a public health burden caused by infections with resistant pathogens. Importantly, the pathogen, antimicrobial drug and treatment regimen, and general setting (e.g., feed type) can have significant impacts on how quickly resistance emerges or spreads, for how long resistance may persist after antimicrobial exposures cease, and what public health impacts may be associated with antimicrobial use on farms. Therefore an exact quantification of the public health burden attributable to antimicrobial drug use in animal agriculture compared to other sources remains challenging. CONCLUSIONS: Even though more research is needed to close existing data gaps, obtain a better understanding of how antimicrobial drugs are actually used on farms or feedlots, and quantify the risk associated with antimicrobial use in animal agriculture, these findings reinforce the need to act now and restrict antibiotic use in animal agriculture to those instances necessary to ensure the health and well-being of the animals.

MicroRNAs: Clinical Relevance in Colorectal Cancer.

Colorectal cancer is one of the most common cancer diagnoses and causes of mortality worldwide. MicroRNAs are a class of small, non-coding regulatory RNAs that have shown strong associations with colorectal cancer. Through the repression of target messenger RNAs, microRNAs modulate many cellular pathways, such as those involved in cell proliferation, apoptosis, and differentiation. The utilization of microRNAs has shown significant promise in the diagnosis and prognosis of colorectal cancer, owing to their unique expression profile associations with cancer types and malignancies. Moreover, microRNA therapeutics with mimics or antagonists show great promise in preclinical studies, which encourages further development of their clinical use for colorectal cancer patients. The unique ability of microRNAs to affect multiple downstream pathways represents a novel approach for cancer therapy. Although still early in its development, we believe that microRNAs can be used in the near future as biomarkers and therapeutic targets for colorectal cancer.

Impact of Gluten-Free and Casein-Free Diet on Behavioural Outcomes and Quality of Life of Autistic Children and Adolescents: A Scoping Review.

BACKGROUND: Gluten- and casein-containing foods could aggravate the symptoms of children and adolescents with autism spectrum disorder (ASD), and subsequently impact their quality of life. However, there is a mixed opinion among researchers concerning the impact of alternative diet on reducing ASD symptoms. OBJECTIVE: This scoping review aimed at examining the impact of the "gluten-free, casein-free" (GFCF) diet on health outcomes and the quality of life among autistic children and adolescents. METHODS: A scoping review of the literature was performed following the Joanna Briggs Institute (JBI) guidelines. Four databases, including EbscoHost, Medline, CINAHL, and ProQuest, were used to obtain subject-specific studies relevant to the research question and published between July 2013 and March 2024. A comprehensive search using keywords such as "autism spectrum disorder", "gluten-free diet", and "casein-free diet" was conducted to obtain articles related to the research focus area. Only full-text, peer-reviewed, written in English articles were selected. Data extraction and data analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension to Scoping Review (PRISMA-ScR) protocol. RESULTS: From the initial 586 studies, a total of 27 articles were included in the final analysis of the review. The thematic analysis included "GFCF diet and improvement of the core autistic symptoms", "the gut-brain link", "dietary interventions and autism", "possible side effects due to the GCFC diet", and "inconclusive studies and mixed opinions". A majority of the studies showed a positive effect of the GFCF diet on a variety of autistic symptoms, including positive changes in cognitive skills, behaviour, and gastrointestinal symptoms, while some showed conflicting evidence. CONCLUSIONS: The currently available evidence on the impact of the "GFCF" diet on the quality of life of autistic children and adolescents may warrant potentially effective interventions for alleviating symptoms of autism spectrum disorders. However, this scoping review highlights the need for more research to provide more reliable evidence on the health outcomes and quality of life of ASD sufferers to guide practice.

Collapsing Glomerulopathy in a Patient with Tuberculosis and Poncet's Disease.

A 39-year-old woman presented with inflammatory polyarthritis, low-grade fever, progressive pedal edema, and frothy urination of three weeks duration. She had nephrotic range proteinuria and elevated creatinine. Kidney biopsy showed collapse of capillary tuft in the glomeruli and proliferation, hyperplasia, and hypertrophy of the overlying podocytes suggestive of collapsing glomerulopathy. Histology of the cervical lymph node showed necrotizing granulomatous inflammation suggestive of tuberculosis. With all other possible causes of polyarthritis ruled out, a diagnosis of Poncet's disease-a form of polyarthritis observed in patients suffering from an active form of extrapulmonary tuberculosis (TB)-was considered. Association between TB lymphadenitis and collapsing glomerulopathy (CG) is very rare, and the patient had partial remission of the disease after being started on anti-tuberculosis therapy (ATT) along with steroids.

Clinical Significance of Myositis-Specific and Myositis-Associated Antibody Profiles in Dermatomyositis.

Background: Myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) are clinically useful biomarkers that point to the diagnosis, clinical manifestations, and prognosis of dermatomyositis (DM). Materials and Methods: To estimate the prevalence of MSA as well as MAA and analyze possible clinical correlations of these autoantibodies in patients diagnosed with DM, we conducted a cross-sectional study of 30 patients who were diagnosed with DM. Results: MSA were positive in 19 patients (63%) in which Mi 2 was positive in 8 (27%) patients, and this was the most frequently found MSA. A total of 11 (36.7%) patients showed positive MAA. AntiPM/Scl 75 and anti-Ro 52 were positive in 5 (16.7%) patients each and these were the most commonly found MAA. Anti-La was absent in all our patients. There were 8 (27%) patients in whom both MSA and MAA were positive. Either MSA and/or MAA were positive in 22 (73%) patients. On a bivariate analysis, the patients who were positive for anti-PM/Scl 75 showed a significant difference in manifesting cutaneous ulcers (P value 0.023). It was also found that anti-SAE-positive patients showed a significant difference with malignancy (P value 0.014). Anti-Ro 52-positive patients were less likely to have symmetrical proximal muscle weakness (P value 0.006). Conclusions: All patients who were anti-MDA 5 positive had myositis and none of the anti-MDA 5-positive patients had rapidly progressive interstitial lung disease (RPILD). More than one MSA in the same patient was noted in three patients.

Real-World Effectiveness of COVID-19 Vaccine and Identification of SARS-CoV-2 Variants among People Living with HIV on Highly Active Antiretroviral Therapy in Central Kerala of India-An Ambi-Directional Cohort Study.

BACKGROUND: Vaccine effectiveness for first-generation coronavirus disease (COVID-19) vaccines among People Living with HIV (PLHIV) in India remains unexplored. This study entails the estimation of the real-world effectiveness of COVID-19 vaccines (AZD1222/Covishield, BBV152/Covaxin) among PLHIV and the identification of variants of SARS-CoV-2 among those infected with COVID-19. METHODS: An ambi-directional cohort study was conducted among 925 PLHIV above 18 years of age in two districts of central Kerala, India, from February 2022 to March 2023. Selected PLHIV were recruited as Participant Liaison Officers (PLOs) for the follow-up on the study participants. At enrolment, basic details, baseline CD4 count, and a Nasopharyngeal (NP) swab for RT-PCR were collected. In the follow-up phase, NP swabs were collected from subjects with COVID-19 symptoms. Positive subjects had a CD4 count and genomic sequencing performed. RESULTS: The mean age of the participants was 46.93 ± 11.00 years. The majority, 819 (93.6%), of participants had received at least one dose of any vaccine, while 56 (6.4%) were unvaccinated. A total of 649 (79.24%) participants were vaccinated with Covishield and 169 (20.63%) with Covaxin. In the vaccinated group, 158 (19.3%) reported COVID-19 infection. Vaccine Effectiveness (VE) for one dose of any vaccine was 43.2% (95% CI: 11.8-64.5), p = 0.015. The effectiveness of full vaccination with Covishied was 63.8% (95% CI: 39.3-79.2), p < 0.001, and Covaxin was 73.4% (95% CI: 44.3-87.3). VE was highest, at 60.7% (95% CI: 23.6-81.3), when the two doses of the vaccine were given at an interval of less than 6 weeks. Participants with a baseline CD4 count > 350 had greater protection from COVID-19, at 53.4% (95% CI: 19.6-75.3) p = 0.004. The incident cases were sub-variants of Omicron (BA.2, BA.2.38, BA.2.10). CONCLUSIONS: Full vaccination with Covishield and Covaxin was effective against COVID-19 infection among PLHIV on treatment; albeit, that of Covaxin was higher. A gap of 4 to 6 weeks between the two doses of COVID-19 vaccine was found to have higher VE among PLHIV.