Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.

Vertebrate genomes are partitioned into chromatin domains or topologically associating domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at domain boundaries correlates with better insulation; however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant INK4a/ARF and MYC TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer-promoter interactions, and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters, we show that active TAD enhancers, but not promoters, induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.

Understanding the role of frailty in local and systemic complications and healthcare resource utilization in acute pancreatitis: Findings from a national cohort.

BACKGROUND: Acute pancreatitis (AP) is a significant gastrointestinal cause of hospitalization with increasing incidence. Risk stratification is crucial for determining AP outcomes, but the association between frailty and AP outcomes is poorly understood. Moreover, age disparities in severity indices for AP complicate risk assessment. This study investigates frailty's impact on local and systemic complications in AP, readmission rates, and healthcare resource utilization. METHODS: Using the National Readmission Database from 2016 to 2019, we identified adult AP patients and assessed frailty using the Frailty Risk Score. Our analysis included local and systemic complications, resource utilization, readmission rates, procedures performed, and hospitalization outcomes. Multivariate regression was employed, and statistical significance was set at P < 0.05 using Stata version 14.2. RESULTS: Among 1,134,738 AP patients, 6.94 % (78,750) were classified as frail, with a mean age of 63.42 years and 49.71 % being female. Frail patients experienced higher rates of local complications (e.g., pseudocyst, acute pancreatic necrosis, walled-off necrosis) and systemic complications (e.g., pleural effusion, acute respiratory distress syndrome, sepsis, abdominal compartment syndrome) compared to non-frail patients. Frailty was associated with increased readmission rates and served as an independent predictor of readmission. Frail patients had higher inpatient mortality (7.11 % vs. 1.60 %), longer hospital stays, and greater hospitalization costs. CONCLUSION: Frailty in AP patients is linked to elevated rates of local and systemic complications, increased mortality, and higher healthcare costs. Assessing frailty is crucial in AP management as it provides a valuable tool for risk stratification and identifying high-risk patients, thereby improving overall outcomes.

Incidence, implications and predictors of abdominal compartment syndrome in acute pancreatitis: A nationwide analysis.

BACKGROUND: Acute pancreatitis (AP) often presents with varying severity, with a small fraction evolving into severe AP, and is associated with high mortality. Complications such as intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are intricately associated with AP. OBJECTIVE: To assess the clinical implications and predictors of ACS in AP patients. METHODS: We conducted a retrospective study using the National Inpatient Sample (NIS) database on adult AP patients, further stratified by the presence of concurrent ACS. The data extraction included demographics, underlying comorbidities, and clinical outcomes. Multivariate linear and logistic regression analyses were performed using STATA (v.14.2). RESULTS: Of the 1,099,175 adult AP patients, only 1,090 (0.001%) exhibited ACS. AP patients with ACS had elevated inpatient mortality and all major complications, including septic shock, acute respiratory distress syndrome (ARDS), requirement for total parenteral nutrition (TPN), and intensive care unit (ICU) admission (P < 0.01). These patients also exhibited increased odds of requiring pancreatic drainage and necrosectomy (P < 0.01). Predictor analysis identified blood transfusion, obesity (BMI ≥30), and admission to large teaching hospitals as factors associated with the development of ACS in AP patients. Conversely, age, female gender, biliary etiology of AP, and smoking were found less frequently in patients with ACS. CONCLUSION: Our study highlights the significant morbidity, mortality, and healthcare resource utilization associated with the concurrence of ACS in AP patients. We identified potential factors associated with ACS in AP patients. Significantly worse outcomes in ACS necessitate the need for early diagnosis, meticulous monitoring, and targeted therapeutic interventions for AP patients at risk of developing ACS.

Nonvariceal upper gastrointestinal bleeding in COVID-19 patients: insights from the National Inpatient Sample.

BACKGROUND: This retrospective study, conducted using the U.S. National Inpatient Sample (NIS), examines the outcomes and management of nonvariceal upper gastrointestinal bleeding (NVUGIB) in COVID-19 patients and identifies predictive factors to enhance patient prognosis. METHODS: We analyzed the 2020 U.S. NIS data involving adult patients (≥18 years) admitted with NVUGIB and categorized them based on the presence of COVID-19. Primary and secondary outcomes, NVUGIB-related procedures, and predictive factors were evaluated. RESULTS: Of 184,885 adult patients admitted with NVUGIB, 1.6% (2990) had COVID-19. Patients with NVUGIB and COVID-19 showed higher inpatient mortality, acute kidney injury, need for intensive care, and resource utilization metrics. Notably, there was a lower rate of early esophagogastroduodenoscopy (EGD). Multivariate logistic regression revealed conditions like peptic ulcer disease, mechanical ventilation, and alcohol abuse as significant positive predictors for NVUGIB in COVID-19 patients, whereas female gender and smoking were negative predictors. CONCLUSION: Our findings suggest that COVID-19 significantly increases the risk of mortality and complications in NVUGIB patients. The observed decrease in early EGD interventions, potentially contributing to higher mortality rates, calls for a review of treatment strategies. Further multicenter, prospective studies are needed to validate these results and improve patient care strategies.

Analyzing the utility of renal replacement therapy to manage hepatorenal syndrome in alcoholic hepatitis without liver transplantation: a nationwide analysis.

BACKGROUND: Hepatorenal syndrome (HRS) frequently complicates alcoholic hepatitis (AH) and portends poor survival in this population. Published literature indicates mixed benefits from renal replacement therapy (RRT) for HRS refractory to medical management. Therefore, we sought to assess the utilization of RRT in AH and clinical outcomes at a national level. METHODS: Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified adult patients with AH with a coexisting diagnosis of HRS from the National Readmission Database 2016 through 2019. Mortality, morbidity, and resource utilization were compared. We compared proportions using the Fisher exact test and computed adjusted P-values based on multivariate regression analysis. Analyses were performed using Stata, version 14.2, considering a two-sided P < 0.05 as statistically significant. RESULTS: A total of 73 203 patients with AH were included in the analysis (mean age 46.2 years). A total of 3620 individuals had HRS diagnosis (5%), of which 14.7% (n: 532) underwent RRT. HRS patients receiving RRT had a higher mortality rate than those who did not (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI]: 1.3-2.6, P: 0.01), along with higher resource utilization. Only those patients with HRS who underwent liver transplantation (LT) experienced a mortality reduction (24.4% for those not receiving RRTs and 36.5% for those receiving RRT). CONCLUSIONS: RRT is associated with higher mortality and morbidity when offered to patients with AH and HRS, who do not undergo LT. Therefore, our results suggest careful selection of AH patients when deciding to initiate RRT for HRS.

Comparative Efficacy and Safety of Different Stent Types for Pancreatic Fluid Collections: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND AIMS: Drainage of pancreatic fluid collections (PFCs) is required in select cases including infected or symptomatic collections. In this network meta-analysis, we have compared lumen-apposing metal stents (LAMS), fully covered self-expandable metal stents (FCSEMS), and double-pigtail stents (DPS) to identify the most useful stent type in the management of PFCs. METHODS: We reviewed several databases to identify studies that compared DPS or FCSEMS with LAMS and the ones which compared DPS with FCSEMS for the treatment of PFCs. Our outcomes of interest were clinical success, adverse events, technical success, recurrence of PFCs, and procedure duration. Random effects model and frequentist approach were used for statistical analysis. RESULTS: We included 28 studies with 2974 patients. Rate of clinical success was significantly lower with DPS compared to LAMS, OR (95% CI): 0.43 (0.32, 0.59). Rate of recurrence was higher with DPS compared to LAMS, OR (95% CI): 2.06 (1.19, 3.57). We found no significant difference in rate of adverse events between groups. Rate of technical success was higher for FCSEMS compared to LAMS. Procedure duration was significantly shorter for LAMS compared to DPS and FCSEMS. Based on frequentist approach, LAMS was found to be superior to DPS and FCSEMS in achieving higher clinical success, lower rate of adverse events and recurrence, and shorter procedure time. CONCLUSIONS: This network meta-analysis demonstrates the superiority of LAMS over DPS and FCSEMS in the management of PFCs in achieving a higher clinical success, shorter procedure time, and lower rate of recurrence. Some of the analyses are not adequately powered to make firm conclusions, and future large multicenter RCTs are required to further evaluate this issue.

Conservation and upgradation of indigenous Cholistani cattle breed of Pakistan: a pathway to sustainable livestock.

Pakistan is endowed with many established indigenous zebu Bos indicus type (humped) cattle breeds including Sahiwal, Red Sindhi, Bhagnari and Cholistani. Amongst these indigenous cattle breeds, Sahiwal and Red Sindhi have extensively been navigated and hence these two are acclaimed as internationally recognized breeds. However, research work on Cholistani cattle breed actually initiated in 2010 and has attained a steady pace. This breed was a new entrant in Livestock Census of Pakistan since 2006. Cholistani is a hardy, tick-resistant, adaptable cattle breed being reared under pastoral nomadism of the Cholistan desert, Pakistan. The present narrative review is the first of its kind intended to sum-up all the research work conducted about this indigenous cattle breed, and to put forth research gaps for this formerly neglected cattle breed. The review discusses the research work conducted on Cholistani cattle breed under five major research subjects/domains i.e. production attributes, theriogenology-related attributes, hematochemical attributes, disease, epidemiologic and therapeutic attributes, and genetic attributes. Future horizon for research avenues has also been given. It is the dire need of time that specific breed-oriented conservation and propagation programs may be initiated in the country so that sustained livestock and enhance socioeconomic profiling of rural communities may be attained.

Systematic Review With Meta-Analysis: Chronic Opioid Use Is Associated With Esophageal Dysmotility in Symptomatic Patients.

INTRODUCTION: We aimed to conduct a systematic review and meta-analysis to assess the impact of chronic opioid exposure on esophageal motility in patients undergoing manometric evaluation. METHODS: Multiple databases were searched through October 2022 for original studies comparing the manometric results of patients who have used chronic opioids (for >90 days) with those who do not. The primary outcomes were esophageal dysmotility disorders. Three high-resolution manometry parameters were conducted as secondary outcomes. A random-effects model was applied to calculate the odds ratio (OR) and means difference (MD) along with a 95% confidence interval (CI). RESULTS: Nine studies were included in this meta-analysis. Opioid use was associated with higher esophageal dysmotility disorders, including distal esophageal spasm (pooled OR 4.84, 95% CI 1.60-14.63, P = 0.005, I 2 = 96%), esophagogastric junction outflow obstruction (pooled OR 5.13, 95% CI 2.11-12.43, P = 0.0003, I 2 = 93%), and type III achalasia (pooled OR 4.15, 95% CI 2.15-8.03, P < 0.0001, I 2 = 64%). No significant differences were observed for hypercontractile esophagus, type I achalasia, or type II achalasia. The basal lower esophageal sphincter pressure (MD 3.02, 95% CI 1.55-4.50, P < 0.0001, I 2 = 90%), integrated relaxation pressure (MD 2.51, 95% CI 1.56-3.46, P < 0.00001, I 2 = 99%), and distal contractile integral (MD 640.29, 95% CI 469.56-811.03, P < 0.00001, I 2 = 91%) significantly differed between the opioid use and nonopioid use group. However, opioid use was associated with a lower risk of ineffective esophageal motility (pooled OR 0.68, 95% CI 0.49-0.95, P = 0.02, I 2 = 53%). DISCUSSION: Chronic opioid exposure is associated with an increased frequency esophageal dysmotility disorders. Our results revealed that opioid use is significantly associated with type III achalasia but not with type I and II achalasia. Therefore, opioid treatment should be taken into account as a potential underlying risk factor when diagnosing these major esophageal motor abnormalities.

Timing matters: An analysis of the relationship between red cell transfusion timing and hospitalization outcomes in sickle cell crisis patients using the National Inpatient Sample database.

Vaso-occlusive pain crisis is a debilitating complication of sickle cell disease (SCD) and it is the most common cause of hospitalization among these individuals. We studied the inpatient outcomes among patients admitted with sickle cell crisis based on the timing of red blood cell transfusion. In this retrospective study, we used the United States National Inpatient Sample (NIS) data for the year 2019, to identify adult patients hospitalized with the principal diagnosis of sickle cell crisis who received simple red blood cell transfusion during their hospitalization. Patients were divided into two groups. Those who received simple red cell transfusion within 24 hours of admission were classified as early transfusion. After adjusting for confounders, the mean adjusted length of stay for patients with early transfusion was significantly lower than those who received a late blood transfusion by 3.51 days (p-value < 0.001) along with a decrease in mean adjusted hospitalization charges and cost, by 25,487 and 4,505 United States Dollar (USD) respectively. The early red cell transfusion was also associated with a decrease in inpatient mortality, demonstrated by an adjusted odds ratio (aOR) of 0.19 (p-value 0.036), and a reduction in in-hospital sepsis, with an aOR of 0.28 (p-value < 0.001), however, no statistically significant difference was found between the two groups regarding acute respiratory failure requiring intubation, vasopressors requirement, acute kidney injury requiring dialysis and intensive care unit (ICU) admission. We recommend timely triage and reassessment to identify sickle cell crisis patients requiring blood transfusion. This intervention can notably affect the inpatient length of stay, resource utilization, and hospitalization outcomes.

Cold snare versus cold forceps polypectomy for endoscopic resection of diminutive polyps: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The practices for resection of diminutive colon polyps vary among endoscopists, and U.S. Multi-Society Task force guidelines recommend use of cold snare polypectomy (CSP) for this purpose. In this meta-analysis, we compared CSP and cold forceps polypectomy (CFP) for resection of diminutive polyps. METHODS: Several databases were reviewed to identify randomized controlled trials that compared CSP and CFP for resection of diminutive polyps. The study outcomes of interest were complete resection of all diminutive polyps, complete resection of polyps ≤3 mm in size, failure of tissue retrieval, and polypectomy time. For categorical variables, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated; for continuous variables, mean differences (MDs) with 95% CIs were calculated. Data were analyzed by using a random-effects model, and heterogeneity was assessed by using the I2 statistic. RESULTS: We included 9 studies with 1037 patients. Rate of complete resection of all diminutive polyps was significantly higher in the CSP group (OR, 1.68; 95% CI, 1.09-2.58). Subgroup analysis, including jumbo or large-capacity forceps, found no significant difference in complete resection between groups (OR, 1.43; 95% CI, .80-2.56). We found no significant between-groups in the rates of complete resection of polyps ≤3 mm in size (OR, .83; 95% CI, .30-2.31). Rate of failure of tissue retrieval was significantly higher in the CSP group (OR, 10.13; 95% CI, 2.29-44.74). No significant between-group difference was noted in polypectomy time. CONCLUSIONS: CFP using large-capacity or jumbo biopsy forceps is noninferior to CSP for complete resection of diminutive polyps.

Tip-in Versus Conventional Endoscopic Mucosal Resection for Colorectal Neoplasia: A Systematic Review and Meta-analysis.

BACKGROUND: Early-stage gastrointestinal neoplasms are frequently treated with conventional endoscopic mucosal resection (C-EMR). However, C-EMR frequently leads to incomplete resection of large colorectal lesions. Tip-in endoscopic mucosal resection (EMR), which was recently introduced for en bloc resection of colorectal neoplasms, minimizes slippage during the procedure. METHODS: We conducted a systematic review and meta-analysis of published studies that compared Tip-in EMR with conventional EMR. We searched several electronic databases and included studies that reported on the primary outcomes of en bloc resection rate and complete resection rate, as well as secondary outcomes such as procedure time and procedure-related complications (including perforation and delayed bleeding rate). We used a random effects model to calculate odds ratios (ORs) with 95% CIs for dichotomous data and weighted mean differences with 95% CIs for continuous data. We also conducted several sensitivity analyses to assess the robustness of our findings. RESULTS: A total of 11 studies involving 1244 lesions (684 in the Tip-in EMR group and 560 in C-EMR group) were included in the meta-analysis. Our meta-analysis showed that compared with conventional EMR, Tip-in EMR significantly increased the en bloc resection rate in patients with colorectal neoplasia (OR=3.61; 95% CI, 2.09-6.23; P <0.00001; I2 =0%) and had a higher complete resection rate (OR=2.49; 95% CI, 1.65-3.76; P <0.0001; I2 =0%). However, the procedure time and rates of procedure-related complications did not differ significantly between the 2 groups. CONCLUSIONS: Tip-in EMR outperformed C-EMR for both the en bloc and complete resection of colorectal lesions with similar rates of procedural complications.

Comprehensive insights into the regulatory mechanisms of lncRNA in alkaline-salt stress tolerance in rice.

BACKGROUND: Alkaline-salt is one of the abiotic stresses that slows plant growth and developmental processes and threatens crop yield. Long non-coding RNAs (lncRNAs) are endogenous RNA found in plants that engage in a variety of cellular functions and stress responses. METHOD: lncRNAs act as competing endogenous RNAs (ceRNA) and constitute a new set of gene control. The precise regulatory mechanism by which lncRNAs function as ceRNAs in response to alkaline-salt stress remains unclear. We identified alkaline-salt responsive lncRNAs using transcriptome-wide analysis of two varieties including alkaline-salt tolerant [WD20342 (WD)] and alkaline-salt sensitive [Caidao (CD)] rice cultivar under control and alkaline-salt stress treated [WD20342 (WDT, and Caidao (CDT)] conditions. RESULTS: Investigating the competitive relationships between mRNAs and lncRNAs, we next built a ceRNA network involving lncRNAs based on the ceRNA hypothesis. Expression profiles revealed that a total of 65, 34, and 1549 differentially expressed (DE) lncRNAs, miRNAs, and mRNAs were identified in alkaline-salt tolerant WD (Control) vs. WDT (Treated). Similarly, 75 DE-lncRNAs, 34 DE-miRNAs, and 1725 DE-mRNAs (including up-regulated and down-regulated) were identified in alkaline-salt sensitive CD (Control) vs. CDT (Treated), respectively. An alkaline-salt stress ceRNA network discovered 321 lncRNA-miRNA-mRNA triplets in CD and CDT, with 32 lncRNAs, 121 miRNAs, and 111 mRNAs. Likewise, 217 lncRNA-miRNA-mRNA triplets in WD and WDT revealed the NONOSAT000455-osa_miR5809b-LOC_Os11g01210 triplet with the highest degree as a hub node with the most significant positive correlation in alkaline-salt stress response. CONCLUSION: The results of our investigation indicate that osa-miR5809b is dysregulated and plays a part in regulating the defense response of rice against alkaline-salt stress. Our study highlights the regulatory functions of lncRNAs acting as ceRNAs in the mechanisms underlying alkaline-salt resistance in rice.

The comparative transcriptome analysis of two green super rice genotypes with varying tolerance to salt stress.

BACKGROUND: Salinity is one of the main abiotic factors that restrict plant growth, physiology, and crop productivity is salt stress. About 33% of the total irrigated land suffers from severe salinity because of intensive underground water extraction and irrigation with brackish water. Thus, it is important to understand the genetic mechanism and identify the novel genes involved in salt tolerance for the development of climate-resilient rice cultivars. METHODS AND RESULTS: In this study, two rice genotypes with varying tolerance to salt stress were used to investigate the differential expressed genes and molecular pathways to adapt under saline soil by comparative RNA sequencing at 42 days of the seedling stage. Salt-susceptible (S3) and -tolerant (S13) genotypes revealed 3982 and 3463 differentially expressed genes in S3 and S13 genotypes. The up-regulated genes in both genotypes were substantially enriched in different metabolic processes and binding activities. Biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and plant signal transduction mechanisms were highly enriched. Salt-susceptible and -tolerant genotypes shared the same salt adaptability mechanism with no significant quantitative differences at the transcriptome level. Moreover, bHLH, ERF, NAC, WRKY, and MYB transcription factors were substantially up-regulated under salt stress. 391 out of 1806 identified novel genes involved in signal transduction mechanisms. Expression profiling of six novel genes further validated the findings from RNA-seq data. CONCLUSION: These findings suggest that the differentially expressed genes and molecular mechanisms involved in salt stress adaptation are conserved in both salt-susceptible and salt-tolerant rice genotypes. Further molecular characterization of novel genes will help to understand the genetic mechanism underlying salt tolerance in rice.

Systematic review and meta-analysis of cold snare polypectomy and hot snare polypectomy for colorectal polyps.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) has become increasingly utilized to resect colorectal polyps, given its efficacy and safety. This study aims to compare CSP and hot snare polypectomy (HSP) for resecting small (< 10 mm) and large (10-20 mm) colorectal lesions. METHODS: Relevant publications were obtained from Cochrane Library, Embase, Google Scholar, PubMed, and Web of Science databases. The publication search was limited by English-language and human studies. Pooled mean difference and odds ratios (ORs) were calculated for outcomes of interest. RESULTS: Twenty-three studies were included in this meta-analysis. Pooled OR of delayed post-polypectomy bleeding (DPPB) in the CSP group versus the HSP group was 0.29 (P = 0.0001, I2  = 29%). Subgroup analysis according to lesion size showed a significant reduction in the DPPB rate in lesion sizes 10-20 mm (pooled OR 0.08, P = 0.003, I2  = 0%) and < 10 mm (pooled OR 0.35, P = 0.001, I2  = 27%). Pooled OR of major bleeding in the CSP group was 0.23 (P = 0.0004, I2  = 0%). Subgroup analysis by lesion size revealed a significant decrease in the rate of major bleeding in the CSP group for both lesion sizes 10-20 mm (pooled OR 0.11, P = 0.04) and < 10 mm (pooled OR 0.26, P = 0.003). Complete resection, en bloc resection, and recurrence rate were comparable in the two groups. CONCLUSIONS: Cold snare polypectomy was associated with a lower rate of DPPB and lower risk of major bleeding compared with HSP in both small and large polyps. CSP should be considered as the polypectomy technique of choice for colorectal polyps.

Role of rifaximin in the management of alcohol-associated hepatitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Alcohol-associated hepatitis (AAH) is an acute, inflammatory liver disease with severe short-term and long-term morbidity and mortality. AAH can lead to severe complications including hepatic failure, gastrointestinal bleeding, sepsis, and the development or decompensation of cirrhosis. Rifaximin is an antibiotic that reduces bacterial overgrowth and gut translocation, and it may have a role in decreasing systemic inflammation and infection in patients with AAH. Therefore, we conducted a systematic review and meta-analysis to evaluate the role of rifaximin in the management of AAH. METHODS: A comprehensive search strategy was used to identify studies that met our inclusion criteria in Embase, MEDLINE (PubMed), Cochrane Library, Web of Science Core Collection, and Google Scholar. Outcomes of interest included rates of infection, 90-day mortality, and overall mortality between the rifaximin versus non-rifaximin group. Open Meta Analyst software was used to compute the results. RESULTS: Three studies with a total of 162 patients were included in the final meta-analysis. Of the three studies, two were randomized control trials (RCTs), and one was a case-control study. There was a significantly lower rate of infection in the rifaximin group versus the non-rifaximin group (RR: 0.331, 95% CI: 0.159-0.689, I2  = 0%, P = 0.003). There was no significant difference in 90-day mortality in the rifaximin versus non-rifaximin group (RR: 0.743, 95% CI: 0.298-1.850, I2  = 24%, P = 0.523), nor was there a significant difference in overall mortality (RR: 0.624, 95% 95% CI: 0.299-1.3, I2  = 7.1%, P = 0.208). CONCLUSIONS: The use of rifaximin in AAH is associated with a lower rate of infection rate than the non-rifaximin group. Additional research is needed to determine whether this effect is more pronounced in patients concurrently being treated with prednisolone. Differences in 90-day or overall mortality did not reach statistical significance. Further studies, particularly large randomized controlled trials, are needed to establish the role of rifaximin in AAH, especially as an adjunct therapy with prednisolone.

Over-the-Scope Clips Versus Standard Endoscopic Treatment for First Line Therapy of Non-variceal Upper Gastrointestinal Bleeding: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Over-The-Scope Clips (OTSC) use have shown promising results for first line treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). We conducted this meta-analysis to compare outcomes in patients treated with OTSC versus standard endoscopic intervention for first line endoscopic treatment of NVUGIB. METHODS: We reviewed several databases from inception to December 9, 2022 to identify studies comparing OTSC and standard treatments as the first line treatment for NVUGIB. The outcomes assessed included re-bleeding, initial hemostasis, need for vascular embolization, mortality, need for repeat endoscopy, 30 day readmission rate, and need for surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random effect model. Heterogeneity was assessed by I2 statistic. RESULTS: We included 11 studies with 1608 patients (494 patients in OTSC group and 1114 patients in control group). OTSC use was associated with significantly lower risk of re-bleeding (RR, 0.58; 95% CI 0.41-0.82). We found no significant difference in rates of initial hemostasis (RR, 1.05; 95% CI 0.99- 1.11), vascular embolization rates (RR, 0.93; 95% CI 0.40- 2.13), need for repeat endoscopy (RR, 0.78; 95% CI 0.40-1.49), 30 day readmission rate (RR, 0.59; 95% CI 0.17-2.01), need for surgery (RR, 0.81; 95% CI 0.29-2.28) and morality (RR, 0.69; 95% CI 0.38-1.23). CONCLUSIONS: OTSC are associated with significantly lower risk of re-bleeding compared to standard endoscopic treatments when used as first line endoscopic therapy for NVUGIB.

Ligand dependent gene regulation by transient ERα clustered enhancers.

Unliganded Estrogen receptor alpha (ERα) has been implicated in ligand-dependent gene regulation. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, unliganded ERα-bound sites and affects transient but robust gene expression. However, the underlying mechanisms are not fully understood. Here we demonstrate that upon ligand stimulation, persistent sites interact extensively, via chromatin looping, with the proximal transiently ERα-bound sites, forming Ligand Dependent ERα Enhancer Cluster in 3D (LDEC). The E2-target genes are regulated by these clustered enhancers but not by the H3K27Ac super-enhancers. Further, CRISPR-based deletion of TFF1 persistent site disrupts the formation of its LDEC resulting in the loss of E2-dependent expression of TFF1 and its neighboring genes within the same TAD. The LDEC overlap with nuclear ERα condensates that coalesce in a ligand and persistent site dependent manner. Furthermore, formation of clustered enhancers, as well as condensates, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish, at TFF1 and NRIP1 locus, a direct link between ERα condensates, ERα enhancer clusters, and transient, but robust, gene expression in a ligand-dependent fashion.

Assessing total erythrocyte count as a potential attribute for estimating hemoglobin in Cholistani cattle.

The main objective of the study was to confirm whether a specific and constant interrelationship exists between total erythrocyte count (TEC) and hemoglobin (Hb) concentration in Cholistani cattle blood and to navigate the potential of TEC for estimating Hb level in Cholistani cattle (n = 264) grouped as per gender (males, n = 122; females, n = 142) and age (young, n = 140; adults, n = 124). The TEC and Hb (HbD) estimation was carried out through veterinary hematology analyzer. The Hb was also calculated as TEC × 3 and was termed as HbC. Linear regression was implied, and accordingly, scatterplots were drawn between TEC, HbD, HbC, and corrected Hb (CHB). The regression prediction equation hence attained was used to deduce corrected hemoglobin (CHb). A significant (P ≤ 0.05) difference was noticed between HbD and HbC. A non-significant (P ≥ 0.05) difference was noticed, however, between HbD and CHb. Tests of level of agreement indicated a higher Cronbach's alpha and intraclass correlation coefficient (0.682 for average measures) for HbD and CHb as compared to that for HbD and HbC (0.559 for average measures). A convention of Hb concentration as three times of TEC (× 3) is not valid for Cholistani cattle. A different pen-side hematological formula, i.e., Hb (g/dL) = 0.66(TEC) + 6.1, however, provides a better estimate of Hb from the TEC in cattle blood. Using hemocytometry for TEC in the field, all the stakeholders associated with veterinary research, academics, and practice may benefit from this formula in resource-poor countries.

Effect of exogenous taurine on growth, oxidative defense, and nickel (Ni) uptake in canola (Brassica napus L.) under Ni stress.

Nickel (Ni) contamination and its associated hazardous effects on human health and plant growth are ironclad. However, the potential remedial effects of taurine (TAU) on Ni-induced stress in plants remain obscure. Therefore, the present study was undertaken to examine the effect of TAU seed priming (100 and 150 mg L‒1) as an alleviative strategy to circumvent the phytotoxic effects of Ni (150 mg kg‒1) on two canola cultivars (Ni-tolerant cv. Shiralee and Ni-sensitive cv. Dunkeld). Our results manifested an apparent decline in growth, biomass, photosynthetic pigments, leaf relative water content, DPPH free radical scavenging activity, total soluble proteins, nitrate reductase activity, and nutrient acquisition (N, P, K, Ca) under Ni toxicity. Further, Ni toxicity led to a substantial increase in oxidative stress reflected as higher levels of superoxide radicals (O2•‒) and hydrogen peroxide (H2O2) alongside increased relative membrane permeability, lipoxygenase (LOX) activity, and Ni accumulation in leaves and roots. However, TAU protected canola plants from Ni-induced oxidative damage through the amplification of hydrogen sulfide (H2S) production that intensified the antioxidant system to avert O2•‒, H2O2, and malondialdehyde (MDA) production. Further, TAU-mediated increase in H2S levels maintained membrane integrity that might have improved ionomics and bettered plant growth under Ni toxicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01359-9.

Is acid suppression associated with the increased length of stay in diabetic ketoacidosis patients? A nationwide analysis.

BACKGROUND: Diabetic ketoacidosis (DKA) patients present with low serum bicarbonate ( HCO3-${\rm{HCO}}_{3}^{-} $ ), and an increase in its level to ≥15 mEq/L is considered one of the criteria for DKA resolution. Both proton pump inhibitors and histamine-2 receptor antagonists inhibit downstream functioning of H+ /K+ ATPase in the gastric parietal cells, which results in the decreased secretion of HCO3-${\rm{HCO}}_{3}^{-} $ into the bloodstream. OBJECTIVES: We aimed to introduce the hypothesis that DKA patients on acid-suppressive medications may have a delayed rise in serum HCO3-${\rm{HCO}}_{3}^{-} $ to >15 mEq/L that may cause increased hospital length of stay (LOS) and sought to compare the outcomes of such patients. For the sake of simplicity, conditions requiring acid suppression are grouped under the term peptic ulcer disease (PUD) in this study. METHODS: This is a retrospective study using Nationwide Inpatient Sample employing International Classification of Diseases (ICD-10) codes for adult patients with a primary diagnosis of DKA. Analyses were performed using STATA, proportions were compared using Fisher exact test, and continuous variables using Student's t-test. Confounding variables were adjusted using propensity matching, multivariate logistic, and linear regression analyses. RESULTS: DKA patients with PUD had higher adjusted LOS, intensive care unit admission, and total hospital costs. Mortality and morbidity indicators were similar in both groups. The variables found to be independent predictors of increased LOS were malnutrition, Clostridium difficile infection, pneumonia, Glasgow Coma Scale score of 3-8, and higher Charlson comorbidity score. CONCLUSION: We found that Clostridium difficile and pneumonia predicted longer LOS in DKA patients with concomitant PUD, hinting at the possible role of acid suppression in prolonging the LOS in such patients. However, further studies are needed to examine the effect of lesser HCO3-${\rm{HCO}}_{3}^{-} $ generation on LOS.