Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.

Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.

The Methylcitrate Cycle and Its Crosstalk with the Glyoxylate Cycle and Tricarboxylic Acid Cycle in Pathogenic Fungi.

In fungi, the methylcitrate cycle converts cytotoxic propionyl-coenzyme A (CoA) to pyruvate, which enters gluconeogenesis. The glyoxylate cycle converts acetyl-CoA to succinate, which enters gluconeogenesis. The tricarboxylic acid cycle is a central carbon metabolic pathway that connects the methylcitrate cycle, the glyoxylate cycle, and other metabolisms for lipids, carbohydrates, and amino acids. Fungal citrate synthase and 2-methylcitrate synthase as well as isocitrate lyase and 2-methylisocitrate lyase, each evolved from a common ancestral protein. Impairment of the methylcitrate cycle leads to the accumulation of toxic intermediates such as propionyl-CoA, 2-methylcitrate, and 2-methylisocitrate in fungal cells, which in turn inhibits the activity of many enzymes such as dehydrogenases and remodels cellular carbon metabolic processes. The methylcitrate cycle and the glyoxylate cycle synergistically regulate carbon source utilization as well as fungal growth, development, and pathogenic process in pathogenic fungi.

Median Arcuate Ligament Syndrome: Comparing the Safety of Open and Laparoscopic Management in a Large Cohort.

BACKGROUND: Open surgery has been the traditional approach for Median Arcuate Ligament Syndrome (MALS) management. However, there has been a recent rise in laparoscopic management for MALS. In this study we used a large-scale database to compare perioperative complications between open and laparoscopic approaches for MALS. METHODS: Using the National Inpatient Sampling database, we identified all patients surgically treated for MALS between 2008 and 2018 through conventional open and laparoscopic approaches. International Classification of Diseases (ICD)-9 and ICD-10 codes were used to identify patients and their specific surgical interventions. Statistical analyses were conducted to compare the perioperative complications between the 2 MALS surgical approaches, as well as and length of hospital stays and total charges. The complications include postoperative bleeding, accidental operative laceration/puncture, surgical wound infection, ileus, hemothorax/pneumothorax, and cardiac and respiratory complications. RESULTS: A total of 630 patients were identified: 487 (77.3%) patients underwent open surgery while 143 (22.7%) patients underwent laparoscopic decompression. The majority of the study population consisted of female patients (74.8%) with a mean age of 40.6 ± 19 years. Patients who underwent laparoscopic decompression had significantly less all-cause perioperative complications compared to their open surgery counterparts (0.7% vs. 9.9%; P = 0.001). Additionally, prolonged hospitalization was noted in the open group compared to the laparoscopic 1 (5.8 days vs. 3.5; P < 0.001, respectively) with a significantly higher mean of total hospital charges ($70,095.8 vs. 56,113.5; P = 0.016). CONCLUSIONS: Laparoscopic management of MALS has significantly less perioperative complications than open surgical decompression with shorter hospitalization and lower total charges. Given that, laparoscopic technique could be a safe option in treating select MALS patients.

Calculus anuria: a urological emergency with an excellent outcome.

Calculus anuria is a catastrophic condition with dire consequences if not treated promptly. The purpose of this study was to identify factors which influence the short-term outcome of patients with calculus anuria. A retrospective analysis was conducted from January 2016 to December 2021, in children up to the age of 18 years, who presented with calculus anuria and required emergency decompression at Sindh Institute of Urology and Transplantation, Pakistan. One hundred and twenty-five children were included. Majority were born to consanguineous parents and a few of them had positive family history of stone disease. Severe illness was found in 25 (20%) patients and among them 8 (32%) required hemodialysis. Decompression by double J stenting is the preferred intervention in our institute and was done in 106 (85%) children, followed by percutaneous nephrostomy tube in 10 (8%) successfully. A small number of patients, 9 (7%) required both procedures to relieve their obstruction. A significant number of patients, about 115 (92%), attained normal renal functions after intervention. No pertinent factors were identified, relating to incomplete renal recovery in nine (7%) of the patients who unfortunately progressed to chronic kidney disease.

Peripheral artery disease and extracorporeal membrane oxygenation: Examining a high-risk cohort over time.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a resource-intensive approach for the management of refractory cardiogenic shock. Within this population exists a substantial cohort of patients with peripheral artery disease (PAD), which independently increases the risk of complications and all-cause mortality. We studied 10-year national trends of the impact of PAD among VA-ECMO recipients to better understand the prevalence of PAD and implications on outcomes in this vulnerable population. METHODS: This 10-year retrospective, propensity score-matched study identified all adult patients (≥18) who underwent VA-ECMO between 2009 and 2018, from a large US database (National Inpatient Sample). Patients with an ICD diagnosis of PAD were identified. The primary endpoints of in-hospital mortality, bleeding complications and major limb loss (above- or below-knee amputation) were compared between patients with PAD to those without. RESULTS: A total of 6768 patients were identified, of which 342 (5.3%) had PAD. The median age at admission was significantly higher in PAD patients [64 years vs. 55 years; p < .01], as was male gender [71% vs. 64%; p < .01]. Patients with PAD had higher rates of smoking (38.9% vs. 23.3%), hypertension (71.1% vs. 50%), diabetes (37.4% vs. 27.0%), chronic kidney disease (30.1% vs. 18.0%), coronary artery disease (76.0% vs. 35.0%) and dyslipidemia (76.0% vs. 35.0); all p < .01. After propensity-matching 2:1 for comorbidities, PAD patients were found to have significantly greater overall complications, including in-hospital mortality, bleeding, surgical wound infections, pseudoaneurysms, and major adverse limb events [71.9% vs. 63.9%; p < .01]. Subgroup analysis revealed greater in-hospital mortality [62.2% vs. 55.3%; p < .05], major amputations [4.1% vs. 0.3%; p < .01] and blood transfusions [32.2% vs. 26.2%; p < .05] in PAD patients. Over 2014-2018, the non-PAD group demonstrated statistically discernable trends in a 51.1% decrease in overall complications and a 28.1% increase in survival to discharge (all p < .01). Over the same time period the PAD cohort experienced a modest, nonsignificant, decrease in complications [7.0%, p = .40] and a decrease in those surviving to discharge [47.1% vs. 40.5%, p = .91]. CONCLUSION: Patients with PAD on VA-ECMO are sicker at baseline and experience significantly greater major amputations and higher in-hospital mortality. They have not benefitted from the considerable decrease in complication rates and increase in survival to discharge over time as compared to their non-PAD counterparts. These findings demonstrate the substantial frailty of the PAD population within an already high-risk cohort, and highlight the need for better procedural approaches and innovative technologies.

Variance in management of extracorporeal membrane oxygenation-associated fibrin sheaths at a single institution.

Objective: Extracorporeal membrane oxygenation (ECMO) support for patients with cardiac or respiratory failure has been increasingly used by advanced critical care practitioners. The thromboembolic complications of ECMO have been extensively discussed and researched; however, research and discussion on the development, risks, and management of cannulae-associated fibrin sheaths are lacking. Methods: Institutional review board approval was not required. We have presented three cases detailing the identification and individualized management of ECMO-associated fibrin sheaths at our institution. The three patients provided written informed consent for the report of their case details and imaging studies. Results: Of our three patients with ECMO-associated fibrin sheaths, two were managed successfully with anticoagulation alone. One could not receive anticoagulation therapy and underwent inferior vena cava filter placement. Conclusions: Fibrin sheath formation around indwelling ECMO cannulae is an unresearched complication of ECMO cannulation. We would recommend an individualized approach to the management of these fibrin sheaths and have provided three examples of successful management.

Comparison of academic productivity and funding support between United States and international medical graduate vascular surgeons.

OBJECTIVE: The demand for vascular surgeons in the United States stands to far exceed the current supply. International medical graduates (IMGs) are not only vital to meeting the country's growing health care needs, but also help to advance clinical research and medical education in the field of vascular surgery. Nearly 17% of practicing vascular surgeons in the United States are IMGs, yet little is known about their relative contributions to academic vascular surgery. Our study aims to compare the academic profiles and funding support for IMG vascular surgeons to that of their US medical graduate (USMG) counterparts. METHODS: A cross-sectional study was performed on all IMG and USMG academic vascular surgeons practicing in US-based hospitals with vascular surgery residency and/or fellowship programs. In addition to the baseline surgeon characteristics, academic profiles and research output were also collected. Furthermore, the National Institutes of Health (NIH) research reporting tool and open payments database were queried for any funding/payments to surgeons in both groups. Matching for year of vascular surgery training program graduation was performed where appropriate. RESULTS: A total of 908 academic vascular surgeons were included; 759 (83.6%) were USMGs and 149 (16.4%) were IMGs. The median year of graduation was comparable between the two groups, but USMGs had a significantly higher proportion of female surgeons (23.6% vs 10.7%; P = .0003). There were no significant differences in the academic profiles and leadership positions between the two groups. Although research productivity is similar between the two groups, IMG surgeons were more likely to have first or senior-authorship papers (47.1% vs 37.5%; P < .001). Additionally, faculty departments chaired/cheifed by a USMG were less likely to be staffed with IMG vascular surgeons (1.6 surgeons vs 3.1 surgeons; P < .0001). Following grant analysis, USMG surgeons received more NIH R01 grants (5.7% vs 1.3%; P = .026). R01-funded surgeons had significantly greater research output by number of publications (121.0 vs 47.5), citations (3872 vs 938), H-index (32.0 vs 17.5), and average journal impact factor (>10: 86.7% vs 33.3%) (all P < .001). CONCLUSIONS: The efforts to further diversify vascular surgery are vital to better serving an increasingly diverse US population, amid growing disparities in health care. Although IMGs account for a minority of academic vascular surgeons, and contribute significantly to their published research, they had less NIH R01 funding, warranting further investigation.

The effects of major depression disorder on neurogenic thoracic outlet syndrome surgery outcomes.

OBJECTIVES: Thoracic outlet syndrome (TOS) is a group of disorders caused by impingement of the neurovascular structures at the thoracic outlet. Neurogenic TOS (nTOS), which is thought to be caused by a compression of the brachial plexus, accounts for more than 90% of the cases. Although treatment for nTOS is successful through physiotherapy and/or surgical decompression, little is known about the impact of psychosocial factors, namely, major depressive disorder (MDD), on postoperative outcomes such as non-routine discharge (NRD). Here, we assess whether MDD predicts the type of discharge following nTOS surgical intervention. METHODS: A retrospective analysis of the National Inpatient Sample database from the years 2005-2018 was performed. Using the International Classification of Diseases Clinical Modification, Ninth and Tenth revisions, patients who underwent a surgical intervention for nTOS were identified. Our primary outcome was to investigate the effects of MDD on nTOS patient disposition status after surgical management; secondary outcomes included analysis of total hospital charges and length of stay. NRD was defined as anything beyond discharge home without healthcare services. Univariate and multivariable logistic regression analyses were conducted to assess MDD and other potential independent predictors of NRD and prolonged hospital stay (> 2 days) following surgical intervention. RESULTS: A total of 6099 patients were identified: 596 (9.77%) patients with MDD and 5503 (90.23%) without MDD. On average, patients with MDD were older (39.6 ± 12.0 years vs. 36.0 ± 13.0 years; p < 0.001), female (80.7% vs. 63.5%; p < 0.001), white (89.6% vs. 85.6%; p = 0.030), and on Medicare (9.6% vs 5.2%; p < 0.001). Univariate and multivariable logistic regression models identified MDD as an independent risk factor associated with a higher risk of NRD (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.0-2.2). Additionally, chronic kidney disease (aOR, 2.60; 95% CI, 1.2-5.4), postoperative complications (aOR, 1.87; 95% CI, 1.2-2.9), and Medicare (aOR, 2.95; 95% CI, 1.9-4.7) were statistically significant predictors for higher risk of NRD. However, MDD was not associated with prolonged hospital stay (aOR, 1.00; 95% CI, 0.8-1.2) or higher median of total charges (MDD group: $27,867 vs. non-MDD group: $28,123; p = 0.799). CONCLUSION: Comorbid MDD was strongly associated with higher NRD rates following nTOS surgical intervention. MDD had no significant impact on length of hospital stay or total hospital charges. Additional prospective research is necessary in order to better evaluate the impact of MDD in patients with nTOS.

The Physiological Function and Potential Role of the Ubiquitous Na+/H+ Exchanger Isoform 8 (NHE8): An Overview Data.

The Na+/H+ exchanger transporters (NHE) play an important role in various biologic processes including Na+ absorption, intracellular pH homeostasis, cell volume regulation, proliferation, and apoptosis. The wide expression pattern and cellular localization of NHEs make these proteins pivotal players in virtually all human tissues and organs. In addition, recent studies suggest that NHEs may be one of the primeval transport protein forms in the history of life. Among the different isoforms, the most well-characterized NHEs are the Na+/H+ exchanger isoform 1 (NHE1) and Na+/H+ exchanger isoform 3 (NHE3). However, Na+/H+ exchanger isoform 8 (NHE8) has been receiving attention based on its recent discoveries in the gastrointestinal tract. In this review, we will discuss what is known about the physiological function and potential role of NHE8 in the main organ systems, including useful overviews that could inspire new studies on this multifaceted protein.

An acute gastroenteritis outbreak associated with a contaminated water supply system, Turkey, 2018.

Disruption of routine monitorization and chlorination of the water supply system during a week-long holiday led to a multi-organism gastroenteritis outbreak in a district with limited laboratory support. More than a 10-fold increase in patients with gastroenteritis was reported. Enteropathogenic Escherichia coli, Enteroaggregative E. coli, and norovirus were detected in human specimen samples. The main water tank and pipes were rusted; 13 out of the 19 water samples tested positive for total Coliform (1-920 colony-forming units (CFU)/100 ml) and E. coli (1-720 CFU/100 ml). Chlorine levels were below 0.2 ppm in seven of the nine samples. Information of 1,815 cases was obtained from the hospital records with a crude attack rate of 2.9%. Cases widespread in the district increased throughout the holiday, epidemic curve revealed a point-source outbreak. The case-control study revealed that consumption of drinking tap water and using it to clean vegetables/fruits were significantly associated with the illness. While drinking only bottled water had a protective effect against the illness. The culture technique showed that the water supply samples were positive for pathogenic bacteria. Upon decision in a multi-stakeholder meeting, the water tank was cleaned, and the Municipality initiated the renovation of the water supply system.

Transcarotid Transcatheter Aortic Valve Replacement With Simple "Flip-n-Flex" Technique.

Transcarotid transcatheter aortic valve replacement (TAVR) is increasingly accepted as a safe and efficacious alternative when transfemoral access is contraindicated. Technical and anatomic considerations unique to transcarotid access warrant several adaptations to the routine TAVR procedure. This report describes an approach to overcome these challenges and improve efficiency, including adoption of the "flip-n-flex" technique originally developed for right transaxillary TAVR. This technique has been used at Tufts Medical Center (Boston, MA) since 2019 in both left and right transcarotid TAVR approaches with success to ensure coaxial alignment of the transcatheter heart valve to the aortic root.

Knowledge, attitudes and practices towards deceased organ donation among parents of children with End Stage Kidney Disease.

OBJECTIVE: To assess the knowledge, attitudes, and practices (KAP) towards deceased organ donation (DOD) of the parents/ guardians of children with end stage kidney disease (ESKD). METHODS: This cross sectional survey was conducted between April and December 2020. A structured questionnaire was filled to assess the sociodemographic information, knowledge, attitude, and practice about DOD. RESULTS: A total of 130 participants with a mean age of 37±7 years were included in the study. Among all, 66 (50.8%) claimed that they had prior knowledge about DOD. However, on further questioning, no one knew who can be the deceased organ donor. Their responses about registration place and permission from religion were positive in 24(36.4%) and 31(47.0%) cases respectively. Regarding attitude, positive responses to willingness to get registered and discussing DOD in social circle were given by 37(56.1%) and 21 (31.8%) participants respectively. Only one participant was registered as donor. The remaining 64(49.2%) participants who had no prior knowledge were given relevant information and were interviewed after one week. Only 24(37.5%) showed willingness to get registered as donors and 06 (9.4%) participants discussed the topic of DOD in their social circle. CONCLUSIONS: The results showed that the knowledge, attitudes, and practices of people who are most desperate for transplantation of their children were poor and did not change significantly even after providing them relevant information.

Outcomes of Infrainguinal Bypass in Patients with Cannabis vs Opioid Use Disorder.

BACKGROUND: Marijuana and opioids are commonly used illicit drugs in the United States and their use continues to rise. Cannabis use disorder (CUD) and Opioid use disorder (OUD) are associated with adverse effects on public health and postoperative outcomes. However, their impact on vascular surgery, specifically infrainguinal bypass repair (IIB). is not well described in the literature. Therefore, our study aimed to assess perioperative outcomes in patients with CUD and OUD who underwent IIB. METHODS: A retrospective analysis of the National Inpatient Sample database for the years 2005 to 2018 was performed. Using the International Classification of Diseases Clinical Modification, Ninth and Tenth revisions, patients who were diagnosed with peripheral artery disease and underwent IIB repair.were identified. Our primary outcome was the comparison of rates of in-hospital complications between the groups, and the secondary outcomes included analysis of total hospital charges and length of stay. A 1:1 propensity score matching (PSM) CUD and OUD patients to their control groups without the disease was conducted using the nearest-neighbor method. The matching was based on select patient demographics and comorbidities included in our analyses. RESULTS: A total of 190,794 patients were identified: 972 patients with CUD and 682 patients with OUD. In the matched cohorts, patients with a diagnosis of CUD had a higher incidence of in-hospital cardiac complications (adjusted Odds Ratio [aOR], 1.76; 95% Confidence Interval [CI], 0.99-3.12) and acute kidney injury (AKI) (aOR, 1.51; CI, 1.09-2.08). Additionally, total hospital charges and mean length of stay were higher in the CUD group (P < 0.001). Those with OUD had a higher incidence of postoperative respiratory complications (aOR, 1.92; CI, 1.23-2.99), sepsis (aOR, 2.39; CI, 1.32-4.34), infection (aOR, 3.55; CI, 1.16-10.84), AKI (aOR, 2.11; CI,1.47-3.04), major amputations (aOR, 1.69; CI, 1.07-2.69), along with higher total charges and mean length of stay (P < 0.001). CONCLUSIONS: Both CUD and OUD have increased incidence of postoperative complications following IIB. The OUD group had generally worse outcomes compared to patients with CUD. Both were associated with a substantial increase in total hospital charges and length of hospital stay. A further prospective study is warranted to provide better insight on the effects of substance use disorders on the procedure's short- and long-term outcomes.

Prevalence of abdominal aortic aneurysms in patients with lung cancer.

OBJECTIVE: Concomitance of abdominal aortic aneurysm (AAA) and primary lung cancer (LC) is not uncommon due to several shared risk factors. To evaluate the incidence of this association, analysis of the National Inpatient Sample database was utilized. METHODS: A retrospective analysis of the National Inpatient Sample database between 2014 and 2018 for all patients diagnosed with primary LC was performed. The differences in the reported findings between the LC and control groups were assessed using the Pearson χ2, Fisher exact, Student t, and/or Mann-Whitney U tests where appropriate. Multivariable logistic regression analysis was conducted to determine independent predictors of the presence of documented AAA. RESULTS: A total of 158,904 patients were identified. Of these, 2430 patients (1.53%) were diagnosed with AAA and 156,474 (98.47%) without AAA. In the multivariable model, LC patients had higher odds of AAA compared with the general population (odds ratio, 1.43; 95% confidence interval, 1.35-1.51). In all age groups, female smokers had a higher rate of AAA compared with female nonsmokers (age <60 years, 0.13% vs 0.04%; 60-69 years, 0.77% vs 0.34%; 70-79 years, 1.65% vs 0.69%; and >80 years, 2.63% vs 1.31%; all P < .001). CONCLUSIONS: LC and AAA share similar risk factors, which may explain the higher AAA prevalence among patients with LC. Given the higher prevalence of AAA in smokers compared with nonsmokers across all age groups in both male and female patients with LC, further sex-based studies investigating the overall mortality and morbidity benefits of AAA screening among patients with LC are highly warranted. This consideration would potentially address the sex disparity in outcomes for AAA management.

Impact of Cardiac Cycle on Thoracic Aortic Geometry-Morphometric Analysis of Ecg Gated Computed Tomography.

BACKGROUND: Understanding morphological changes of ascending aorta, aortic arch and descending aorta with cardiac and respiratory motion is critical for planning of endovascular repair of thoracic aorta. The aim of this study was to determine the impact of the cardiac cycle on thoracic aortic geometry. METHODS: In this retrospective study, electrocardiogram-gated cardiac computed tomography from 116 patients who were evaluated for transcatheter aortic valve replacement were reviewed. A protocol for measurements of maximal diameters and lengths of the thoracic aorta and supra-aortic vessels was established. Measurements were made in multiplanar views perpendicular to the semiautomatically created centerline on both systolic and diastolic phases. RESULTS: Mean age was 77 ± 11 years of our study cohort. Mean systolic and diastolic diameter were 31.6 ± 0.42 and 30.1 ± 4.4 mm at the sinotubular junction (STJ), 35.6 ± 4.8 and 34.8 ± 4.7 mm in the ascending aorta, 29.1 ± 3.3 and 28.5 ± 3.3 mm in the aortic arch (distal left common carotid artery), and 26.7 ± 5.4 and 25.8 ± 5.4 mm in the descending aorta. Mean diameter change was 1.5 ± 0.9 mm at the STJ, 0.8 ± 0.9 mm in the ascending aorta, 0.6 ± 0.8 mm in the aortic arch, and 0.9 ± 1.2 mm in the descending aorta. Mean arterial strain was 5.0 ± 3.2% at the level of the STJ, 2.4 ± 2.7% in the ascending aorta, 2.0 ± 2.9% in the aortic arch, and 3.9 ± 5.7% in the descending aorta. CONCLUSIONS: Our results demonstrated that small but significant circumferential and longitudinal strain was present at every aortic level. These findings may have implications for endovascular thoracic aortic repair and may provide reference values for future comparison.

Patient Satisfaction with Health Care Services; An Application of Physician's Behavior as a Moderator.

Patient satisfaction is a measure of the extent to which a patient is content with the health care they received from their health care provider. Patient satisfaction is one of the most important factors to determine the success of a health care facility. The purpose of this study was to determine patient satisfaction with healthcare services and encompass the physician's behavior as moderation between patient satisfaction and healthcare services. The study seeks to measure the health care services, like a laboratory and diagnostic care, preventive healthcare and prenatal care, to patient satisfaction in the public health sectors of Pakistan. A descriptive survey research design was used for this study. The target population was patients from the out-patient department (OPD) of three public hospitals from Pakistan. By using the convenient sampling technique, 290 sample participants were selected from the target population. The reliability scales were tallied by using Cronbach's Alpha. The findings of the study are gleaned by using regression to explore patient satisfaction with the health care services, and whether or not the physician's behavior moderates the link of patient satisfaction and healthcare services. SPSS Hayes process was used for the moderation effect of the physician's behavior. The main results of the regression analysis validate that health care services, such as laboratory and diagnostic care, preventive healthcare, and prenatal care, have a significant and positive effect on patient satisfaction. Specifically, the study suggests that the physician's behavior significantly moderates the effect of health care services on the satisfaction of patients. The overall opinions about the satisfaction level of patients for the availability of health services in the hospitals were good. The degree of satisfaction was satisfactory with respect to laboratory and diagnostic care, preventive healthcare, and prenatal care services. Based on the outcomes, the study confirms that the proposed hypotheses are statistically significant. Furthermore, the directions for future research of the study are offered.

Zinc ameliorates intestinal barrier dysfunctions in shigellosis by reinstating claudin-2 and -4 on the membranes.

Whether zinc (Zn2+) regulates barrier functions by modulating tight-junction (TJ) proteins when pathogens such as Shigella alter epithelial permeability is still unresolved. We investigated the potential benefits of Zn2+ in restoring impaired barrier function in vivo in Shigella-infected mouse tissue and in vitro in T84 cell monolayers. Basolateral Shigella infection triggered a time-dependent decrease in transepithelial resistance followed by an increase in paracellular permeability of FITC-labeled dextran and altered ion selectivity. This led to ion and water loss into the intestinal lumen. Immunofluorescence studies revealed redistribution of claudin-2 and -4 to an intracellular location and accumulation of these proteins in the cytoplasm following infection. Zn2+ ameliorated this perturbed barrier by redistribution of claudin-2 and -4 back to the plasma membrane and by modulating the phosphorylation state of TJ proteins t hough extracellular signal-regulated kinase (ERK)1/2 dependency. Zn2+ prevents elevation of IL-6 and IL-8. Mice challenged with Shigella showed that oral Zn2+supplementation diminished diverse pathophysiological symptoms of shigellosis. Claudin-2 and -4 were susceptible to Shigella infection, resulting in altered barrier function and increased levels of IL-6 and IL-8. Zn2+ supplementation ameliorated this barrier dysfunction, and the inflammatory response involving ERK-mediated change of phosphorylation status for claudin-2 and -4. Thus, Zn2+ may have potential therapeutic value in inflammatory diarrhea and shigellosis. NEW & NOTEWORTHY Our study addresses whether Zn2+ could be an alternative strategy to reduce Shigella-induced inflammatory response and epithelial barrier dysfunction. We have defined a mechanism in terms of intracellular signaling pathways and tight-junction protein expression by Zn2+. Claudin-2 and -4 are susceptible to Shigella infection, whereas in the presence of Zn2+ they are resistant to infection-related barrier dysfunction involving ERK-mediated change of phosphorylation status of claudins.