Hybrid dysgenesis is a sterility syndrome resulting from the mobilization of certain transposable elements in the Drosophila germline. Particularly extreme is the hybrid dysgenesis syndrome caused by P-element DNA transposons, in which dysgenic female ovaries often contain few or no germline cells. Those offspring that are produced from dysgenic germlines exhibit high rates of de novo mutation and recombination, implicating transposition-associated DNA damage as the cause of germline loss. However, how this loss occurs, in terms of the particular cellular response that is triggered (cell cycle arrest, senescence, or cell death) remains poorly understood. We demonstrate that two components of the DNA damage response, Checkpoint kinase 2 and its downstream target p53, determine the frequency of ovarian atrophy that is associated with P-element hybrid dysgenesis. We further show that p53 is strongly induced in the germline stem cells (GSCs) of dysgenic females, and is required for their maintenance. Our observations support the critical role for p53 in conferring tolerance of transposable element activity in stem cells.

The sternoclavicular joint (SCJ) is anatomically and clinically significant considering its proximity to important neuro-vascular structures like the subclavian vessels and the phrenic nerve. Infections of this joint masquerade multiple disorders, delay diagnosis and spread to the bone and deep tissues. There is no standardized workup and treatment protocol for sternoclavicular joint infections (SCJI) as defined in literature. Here, we review the existing literature to understand the current knowledge of the diagnosis and treatment of SCJI. We searched English publications in PubMed and included clinical trials, case reports, case series, retrospective cohort studies, literature and systematic reviews after excluding non-infectious etiology of SCJ pathologies. There are many risk factors for SCJI, such as immunocompromised status, intravenous drug use, trauma and arthropathies. But a large percentage of patients with disease have none of these risk factors. SCJIs can present with fever, joint swelling, immobility, and rarely with vocal cord palsy or dysphagia. While Staphylococcus aureus causes over 50% of SCJI cases, other pathogens such as Pseudomonas and Mycobacterium are frequently seen. When diagnosed early, the infection can be medically managed with antibiotics or joint aspirations. Most cases of SCJI, however, are diagnosed after extensive spread to soft tissue and bones requiring en-bloc resection with or without a muscle flap. Complications of undertreatment can range from simple abscess formation to mediastinitis, even sepsis. SCJIs are rare but serious infections prompting early detection and interventions. Most cases of SCJI treated adequately show complete resolution in months while retaining maximum functionality. Key features of proper healing include aggressive physiotherapy to prevent adhesive shoulder capsulitis and decreased range of motion.

Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.

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Background Changes in the esophageal microbiome correlate with esophageal disease, but the effects of proton pump inhibitor (PPI) drugs are incompletely characterized. Our objective was to identify the effects of PPI use on the microbial community of the esophagus. Methods Mucosal biopsies of the distal esophagus were analyzed using a customized esophageal microbiome qPCR panel array (EMB). Patient demographics, use of PPIs, duration of use and dose were recorded. Results Fifty-eight patients were included. Mean age was 60.5 years. Ninety percent (52/58) of patients were on PPIs. Mean dose was 42.7 mg. Mean duration of use was 2.5 years. The use of PPIs led to a significant difference in absolute levels of only one organism, Actinomyces, in the entire array (p < 0.01). Among patients who used proton pump inhibitors, there was no significant association between dose and absolute levels of any organism. Similarly, there was no association between duration of use and absolute levels of any organism. Conclusions PPI use does not seem to cause significant changes in the distal esophageal microbial community. Future studies with larger sample sizes and esophageal pH testing should be performed to determine the level of acidity and its relationship to the microbial community.

2The study investigated the spectrum of antibiotic resistance and the associated genes for 3 aminoglycoside, macrolide and ESBL class of antibiotics using clinical isolates. A total of 430 4 preserved bacterial strains (Acinetobacter baumannii, n= 20; Pseudomonas aeruginosa, n= 26; 5 Klebsiella pneumoniae, n= 42; E.coli, n= 85; Staphylococcus aureus, n= 84; Salmonella Typhi, 6 n= 82; Enterococcus spp., n= 27; Streptococcus pneumoniae, n= 36 and CNS, n= 28) were 7 examined. The strains were isolated from patients admitted to various tertiary hospitals of Dhaka 8 city between 2015 and 2019 with either acute respiratory infections, wound infections, typhoid 9 fever or diarrhea. The isolates were reconfirmed by appropriate microbiological and biochemical 10 methods. Antimicrobial susceptibility tests were done using Kirby-Bauer disk diffusion approach. 11PCR amplification using resistance gene-specific primers for aminoglycoside, macrolide and 12 ESBL class of antibiotics was done and the amplified products were confirmed by Sanger 13 sequencing. Of the total isolates, 53% came out as MDR with 96.6% of E. coli and 90% of 14 Staphylococcus aureus. There was a year-wise gradual increase of MDR isolates from 2015-2018 15 and by 2019 the increase in MDR isolates became almost 2-fold compared to 2015. Among the 16 five ESBL genes investigated, CTXM-1 came out as the most prevalent (63%) followed by NDM-17 1 (22%) and E. coli isolates were the predominant reservoir of these genes. ErmB (55%) was the 18 most frequently detected macrolide resistance gene, whereas aac(6)-Ib (35.44%) was the most 19 prevalent aminoglycoside resistance gene and these genes were most prevalent in E. coli and P. 20 aeruginosa isolates, respectively. CTXM-1 and ErmB (16.66%) were the most frequent partners 21 of coexistence followed by CTXM-1 and aac(3)-II.22 24 Antimicrobial resistance (AMR) is becoming a very challenging problem worldwide. Solving the 25 AMR problem should be the priority of global efforts. Nosocomial infections have been 26 recognized as the hub for thriving multidrug resistant (MDR) pathogens. It is estimated that around 27 8.7% of the hospitalized patients worldwide develop nosocomial infections which is the leading 28 cause of surgical failure, transplant rejection, treatment failure, increased costs and even deaths 29 [1]. Numerous reports suggest that absolute numbers of infections due to resistant microbes are 30 increasing globally [2-4]. It is conservatively estimated that at least 2 million illnesses and 23,000 31 deaths had been caused by antibiotic resistant organisms per year in the USA [5]. The present trend 32 predicts that infections by resistant bacterial pathogens may cause up to 10 million deaths/year -33 more than any other causes -by 2050 and like the most global issues, the problem is inequitably 34 distributed, with approximately 90% of the predicted deaths are estimated to happen in Asia and 35 Africa [6]. Additionally, treatment of the patients infected with resistant pathogens is associated 36 with...

1 2Hybrid dysgenesis is a sterility syndrome resulting from the mobilization of certain 3 transposable elements in the Drosophila germline. Particularly extreme is the hybrid 4 dysgenesis syndrome caused by P-element DNA transposons, in which dysgenic 5 female ovaries often contain few or no germline cells. Those offspring that are 6 produced from dysgenic germlines exhibit high rates of de novo mutation and 7 recombination, implicating transposition-associated DNA damage as the cause of 8 germline loss. However, how this loss occurs, in terms of the particular cellular 9 response that is triggered (cell cycle arrest, senescence, or cell death) remains 10poorly understood. We demonstrate that two components of the DNA damage 11 response, Checkpoint kinase 2 and its downstream target p53, are determine the 12 frequency of ovarian atrophy that is associated with P-element hybrid dysgenesis. 13We further show that p53 is strongly induced in the germline stem cells (GSCs) of 14 dysgenic females, and is required for their maintenance. Our observations support 15 the critical role for p53 in conferring tolerance of transposable element activity in 16 stem cells.

Introduction: Diabetes mellitus (DM) is considered one of the largest emerging threats to health and bacterial infections are more frequent in diabetic patients causing sepsis. Several indicators have been proposed as new diagnostic tests to assess sepsis in hospitalized patients. Aim: This study aims was to compare the efficacy of Procalcitonin (PCT) and high sensitive C-reactive protein (hs-CRP) in the diagnosis of sepsis in diabetic patients. Methods: In this cross-sectional study total of 60 age and sex-matched diabetic patients above 18 years were randomly chosen with at least 2 SIRS (Systemic inflammatory response syndrome) criteria from the indoor department of BIRDEM General Hospital. Basic hematological, biochemical, microbiological laboratory data were recorded from laboratory reports. Sepsis and its different stages were determined according to American College of Chest Physicians (ACCP) guidelines. The PCT was measured by sandwich enzyme immunoassay (Bio-Vendor, Germany) and the hs-CRP level was measured using an immune-turbidimetric assay (Beckman, Carlsbad, CA 92010, USA). Results: The patient’s mean age was 51.90±9.89 years where male 51.2% and female 48.8% and 50-60 years age group was the most common 40%. 38 (63.33%) patients were bacteriological culture-positive and 22 (36.67%) patients were bacteriological culture-negative where the most common organism was Klebsiella (28.95%). Statistically, a significant difference was found in PCT values in the bacteriological culture positive and negative group (p<0.05), but there was no significant difference found in hs-CRP values (p>0.05). There was an increasing trend of serum PCT with the developing stages of sepsis. Receiver operating characteristic curve shows the area under the curve for PCT was 0.785 (95% CI; 0.654-0.915), sensitivity 89.47%, specificity 50%, PPV 75.55% and NPV 73.33% with the best cut-off value >753pg/ml which support PCT as a superior and reliable marker of sepsis. Conclusion: Our results suggest that serum PCT is a more reliable diagnostic marker of sepsis than other traditional markers like hs-CRP. Combinatorial use of these biomarkers will help in early diagnosis and also greatly improve outcomes. Bangladesh Crit Care J March 2022; 10 (1): 38-42