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Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection. Mice lacking IL-1β (IL-1β -/-) failed to recruit neutrophils to the gut during infection, which reduced tissue damage and prevented depletion of short-chain fatty acid (SCFA)-producing commensals. Changes in epithelial cell metabolism that typically support pathogen expansion, such as switching energy production from fatty acid oxidation to fermentation, were absent in infected IL-1β -/- mice which inhibited Salmonella expansion. Additionally, we found that IL-1β induces expression of complement anaphylatoxins and suppresses the complement-inactivator carboxypeptidase N (CPN1). Disrupting this process via IL-1β loss prevented mortality in Salmonella-infected IL-1β -/- mice. Finally, we found that IL-1β expression correlates with expression of the complement receptor in patients suffering from sepsis, but not uninfected patients and healthy individuals. Thus, Salmonella exploits IL-1β signaling to outcompete commensal microbes and establish gut colonization. Moreover, our findings identify the intersection of IL-1β signaling and the complement system as key host factors involved in controlling mortality during invasive Salmonellosis.

Background: We aimed to compare the analgesic effect and quality of recovery of transmuscular quadratus lumborum block (QLB) and erector spinae plane block (ESPB) in the presence of multimodal analgesia following Caesarean section. Methods: This randomised controlled trial included full-term pregnant women who underwent elective Caesarean section under spinal anaesthesia without intrathecal morphine. The included women were randomised to receive either bilateral QLB (n = 51) or bilateral thoracic ESPB (n = 51), in addition to the control group (n = 51) who did not receive any block. All participants received regular paracetamol (1 g/6h) and diclofenac (50 mg/8 h). Intravenous morphine was used as a rescue analgesic. The primary outcome was time to first morphine requirement. Secondary outcomes included total postoperative morphine consumption and total Obstetric Quality of Recovery-11 (ObsQoR-11) score. Results: We analysed 51, 50 and 48 patients in the QLB, ESPB and control groups, respectively. The time to first morphine requirement in both QLB and ESPB groups was longer than that in the control group (median [quartiles] time: 6 [6,12] h, 6 [6,6] h and 4 [3,4] h, respectively; p -value <0.001), without significant differences between the two former groups. The total morphine consumption in both QLB and ESPB groups was lower than that in the control group (median [quartiles]:0 [0,5] mg, 0 [0,5] mg and 25 [25,30] mg, respectively; p -value <0.001), without significant differences between the two former groups. The QLB and ESPB groups had comparable ObsQoR-11 score, and both groups' scores were higher than the control group. Conclusion: In patients undergoing elective Caesarean section under spinal anaesthesia without intrathecal morphine, both QLB and ESPB provided superior analgesia and quality of recovery compared to the standard care, without significant difference between the two blocks. [ABSTRACT FROM AUTHOR]

The selective drug delivery of asthma treatment is more challenging. Mullet fish contain several types of medically essential substances, such as collagen, which can be an effective and straightforward method of drug delivery. The present study aimed at extracting collagen from mullet fish scales and forming collagen nanoparticles using ethanol (non-solvent for collagen) to provide a desolvation process and loading of theophylline with the nanoprecipitation method collagen nanoparticles in the presence of glutaraldehyde as a crosslinker. The cytotoxicity effect of theophylline loaded with collagen nanoparticles compared to collagen nanoparticles and free theophylline was evaluated using MTT assay on NHSF cell line at the first dose of 3 mM theophylline with double fold serial dilutions. Our research demonstrated the efficacy of theophylline loading in collagen nanoparticles, and we were assured of the result by energy dispersive Xray mapping (EDX) and optical microscopy. The order of increase in cytotoxicity was collagen nanoparticles < theophylline loaded with collagen nanoparticles < theophylline for all concentrations. These findings imply that collagen nanoparticles are an effective and safe method to use as a drug delivery system. [ABSTRACT FROM AUTHOR]

The activating immune ligands, MICA/B, act as a "kill me" signal through the NKG2D receptor expressed on natural killer (NK) cells. Recently, the oncogenic miR-20a was found to mediate immune escape through repressing MICA/B levels in breast cancer (BC) cells. However, targeting miR-20a-MICA/B using natural compounds has rarely been investigated. Our group has successfully isolated 3'-O-acetylvitexin that showed cytotoxic effects against colon cancer cells but has never been evaluated in BC. Our aim is to investigate the effects of 3'-O-acetylvitexin on BC cell lines and to further elucidate its molecular mechanism of action.The results showed that 3'-O-acetylvitex depicted a more pronounced dose-dependent repression of TNBC cellular viability, colonogenicity and migration capacity than Vitexin. 3'-O-acetylvitexin treatment resulted in a marked dose-dependent repression of miR-20a with a concomitant dose-dependent increase in MICA/B expression. In conclusion, 3'-O-acetylvitexin might act as a promising therapeutic agent for TNBC patients. [ABSTRACT FROM AUTHOR]

Current mortality prediction models and scoring systems for intensive care unit patients are generally usable only after at least 24 or 48 h of admission, as some parameters are unclear at admission. However, some of the most relevant measurements are available shortly following admission. It is hypothesized that outcome prediction may be made using information available in the earliest phase of intensive care unit admission. This study aims to investigate how early hospital mortality can be predicted for intensive care unit patients. We conducted a thorough time-series analysis on the performance of different data mining methods during the first 48 h of intensive care unit admission. The results showed that the discrimination power of the machine-learning classification methods after 6 h of admission outperformed the main scoring systems used in intensive care medicine (Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score and Sequential Organ Failure Assessment) after 48 h of admission. [ABSTRACT FROM AUTHOR]

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.

Introduction: Overcrowding in the emergency departments (ED) is linked to adverse clinical outcomes, a negative impact on patient safety, patient satisfaction, and physician efficiency. We aimed to design a medical admission prediction scoring system based on readily available clinical data during ED presentation., Methods: In this retrospective cross-sectional study, data on ED presentations and medical admissions were extracted from the Emergency and Internal Medicine departments of a tertiary care facility in Qatar. Primary outcome was medical admission., Results: Of 320299 ED presentations, 218772 were males (68.3%). A total of 11847 (3.7%) medical admissions occurred. Most patients were Asians (53.7%), followed by Arabs (38.7%). Patients who got admitted were older than those who did not (p <0.001). Admitted patients were predominantly males (56.8%), had a higher number of comorbid conditions and a higher frequency of recent discharge (within the last 30 days) (p <0.001). Age > 60 years, female gender, discharge within the last 30 days, and worse vital signs at presentations were independently associated with higher odds of admission (p<0.001). These factors generated the scoring system with a cut-off of >17, area under the curve (AUC) 0.831 (95% CI 0.827-0.836), and a predictive accuracy of 83.3% (95% CI 83.2-83.4). The model had a sensitivity of 69.1% (95% CI 68.2-69.9), specificity was 83.9% (95% CI 83.7-84.0), positive predictive value (PPV) 14.2% (95% CI 13.8-14.4), negative predictive value (NPV) 98.6% (95% CI 98.5-98.7) and positive likelihood ratio (LR+) 4.28% (95% CI 4.27-4.28)., Conclusion: Medical admission prediction scoring system can be reliably applied to the regional population to predict medical admissions and may have better generalizability to other parts of the world owing to the diverse patient population in Qatar., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zahid 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.)

Telomere maintenance protects the cell against genome instability and senescence. Accelerated telomere attrition is a characteristic of premature aging syndromes including Dyskeratosis congenita (DC). Mutations in hRTEL1 are associated with a severe form of DC called Hoyeraal-Hreidarsson syndrome (HHS). HHS patients carry short telomeres and HHS cells display telomere damage. Here we investigated how hRTEL1 contributes to telomere maintenance in human primary as well as tumor cells. Transient depletion of hRTEL1 resulted in rapid telomere shortening only in the context of telomerase-positive cells with very long telomeres and high levels of telomerase. The effect of hRTEL1 on telomere length is telomerase dependent without impacting telomerase biogenesis or targeting of the enzyme to telomeres. Instead, RTEL1 depletion led to a decrease in both G-overhang content and POT1 association with telomeres with limited telomere uncapping. Strikingly, overexpression of POT1 restored telomere length but not the overhang, demonstrating that G-overhang loss is the primary defect caused by RTEL1 depletion. We propose that hRTEL1 contributes to the maintenance of long telomeres by preserving long G-overhangs, thereby facilitating POT1 binding and elongation by telomerase.