Characteristics of intestinal metaplasia in the gastric cardia

OBJECTIVE: Intestinal metaplasia of the gastroesophageal junction is frequently grouped together with Barrett's esophagus. The area of the gastroesophageal junction is comprised of the distal esophagus and the gastric cardia. The aim of the present study was to assess whether intestinal metaplasia in the distal esophagus and gastric cardia represent two different entities with a different set of risk factors. METHODS: Patients presenting for elective upper endoscopy were enrolled into a prospective study. The presence of gastritis and intestinal metaplasia was evaluated in gastric biopsies taken from the antrum, corpus, and cardia. Barrett's esophagus was defined by the presence of any length of columnar mucosa above the gastroesophageal junction. RESULTS: Of 302 patients, 50 patients had intestinal metaplasia of the gastric cardia, 73 Barrett's esophagus, and 116 erosive esophagitis. Men were more prone than women to develop Barrett's esophagus or erosive esophagitis. Both conditions were also more common among whites than nonwhites. Smoking was particularly common among patients with Barrett's esophagus. Patients with cardiac intestinal metaplasia did not share these demographic characteristics. The prevalence of daily reflux symptoms, erosive esophagitis, and Barrett's esophagus was similar among patients both with and without cardiac intestinal metaplasia. However, atrophy and intestinal metaplasia of the gastric antrum and corpus were found more frequently among patients with than without cardiac intestinal metaplasia. CONCLUSIONS: Intestinal metaplasia of the gastric cardia is different from Barrett's esophagus. Although cardiac intestinal metaplasia is closely associated with signs of gastritis in other parts of the stomach, gastroesophageal reflux disease does not seem to be a risk factor. A diagnosis of Barrett's esophagus should not be made based on the presence of intestinal metaplasia within the cardiac portion of the gastroesophageal junction.     

Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use

Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our in vitro results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate.     

mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity

The epithelial Na⁺ channel (ENaC) is essential for Na⁺ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na⁺ and K⁺ transport in WT and Sgk1^–/– mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na⁺ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K⁺ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na⁺ homeostasis through SGK1-dependent modulation of ENaC activity.     

Death-associated protein kinase 1 promotes growth of p53-mutant cancers

Estrogen receptor–negative (ER-negative) breast cancers are extremely aggressive and associated with poor prognosis. In particular, effective treatment strategies are limited for patients diagnosed with triple receptor–negative breast cancer (TNBC), which also carries the worst prognosis of all forms of breast cancer; therefore, extensive studies have focused on the identification of molecularly targeted therapies for this tumor subtype. Here, we sought to identify molecular targets that are capable of suppressing tumorigenesis in TNBCs. Specifically, we found that death-associated protein kinase 1 (DAPK1) is essential for growth of p53-mutant cancers, which account for over 80% of TNBCs. Depletion or inhibition of DAPK1 suppressed growth of p53-mutant but not p53-WT breast cancer cells. Moreover, DAPK1 inhibition limited growth of other p53-mutant cancers, including pancreatic and ovarian cancers. DAPK1 mediated the disruption of the TSC1/TSC2 complex, resulting in activation of the mTOR pathway. Our studies demonstrated that high DAPK1 expression causes increased cancer cell growth and enhanced signaling through the mTOR/S6K pathway; evaluation of multiple breast cancer patient data sets revealed that high DAPK1 expression associates with worse outcomes in individuals with p53-mutant cancers. Together, our data support targeting DAPK1 as a potential therapeutic strategy for p53-mutant cancers.     

Isolation and Antibiogram of Clostridium tetani from Clinically Diagnosed Tetanus Patients

Clostridium tetani, the etiologic agent of tetanus, produces a toxin that causes spastic paralysis in humans and other vertebrates. This study was aimed for isolation, identification, and determination of antimicrobial susceptibility of C. tetani from clinically diagnosed tetanus patients. Isolation was done from deep-punctured tissues of the foot and arm injuries of 80 clinically diagnosed tetanus patients from the Pakistan Institute of Medical Sciences hospital. We successfully screened out five C. tetani isolates out of 80 samples based on the strain-specific characteristics confirmed through biochemical testing and toxin production. A disc diffusion method was used for antimicrobial susceptibilities and C. tetani isolates showed susceptibility to cefoperazone, chloramphenicol, metronidazole, penicillin G, and tetracycline, but were found to be resistant to erythromycin and ofloxacin. During animal testing, all the infected mice developed symptoms of tetanus. The results showed that identification of C. tetani is possible using biochemical and molecular tools and that the strains of C. tetani isolated had not developed resistance against the antibiotics most often used for the treatment of tetanus.     

Staged versus one-step approach for multivessel percutaneous coronary interventions

Background Percutaneous coronary interventions (PCIs) in patients with multivessel coronary artery disease (CAD) may be staged or performed in a single session. No data exist about the relative safety and efficacy of these 2 strategies. Our aim was to compare short-term and long-term outcomes of patients with multivessel CAD who underwent PCI in 1 versus 2 sessions. Methods and Results The study included 264 consecutive patients who underwent treatment in our center during 1997 and 1998. PCI was conducted in a single session in 129 patients and was staged in 135 patients. The mean interval between the sessions in the staged group was 45.6 ± 22.3 days. The rates of major adverse cardiac events (MACEs) during in-hospital stay did not differ significantly between the staged (combined for both stages) and nonstaged groups (2.2% vs 4.6%; P = .28). A trend for lower event rates at 30-day (2.9% vs 6.9%; P = .13) and 1-year follow-up (26.1 vs 35.9; P = .08) favored the staged arm. Diameter stenosis ≥50% was found in 17% of patients in the staged group in the second session and was successfully retreated in most of them. No MACE occurred between the sessions. Multivariate analysis identified staging of the procedure as a single independent predictor of MACE at 1-year follow-up (P = .05). Conclusion Our results suggest that a practical staging strategy within 4 to 8 weeks is safe and allows for identification and treatment of potential excessive proliferative response in the previously intervened lesions during the second procedure. (Am Heart J 2002;143:1017-26.)     

Psychological distress,job satisfaction,and work engagement among Palestinian teachers: a cross-sectional study

Background

Work engagement is a positive, fulfilling affective and motivational state of work-related wellbeing and a protective factor for workers' mental health. The aim of the present study was to examine the association between psychological distress (conceptualised as the target variable), job satisfaction, and work engagement in contexts of low-intensity warfare and political violence. According to the salutogenic perspective, the relationship between job satisfaction and psychological distress is influenced by the level of work engagement.

Association between preeclampsia and prostasin polymorphism in Pakistani females

Objectives:To investigate the relationship between a prostasin gene variations and the development of preeclampsia in a Pakistani female population.Methods:This was a case-control study carried out at University of Karachi, Karachi, Pakistan between May 2018 and 2019. A single nucleotide polymorphism (SNP) at rs12597511 locus was examined with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses in 76 preeclamptic and 74 normotensive expecting mothers.Results:We observed significantly increased risk of preeclampsia associated with the CC genotype of rs12597511 polymorphism as compared to TT (p<0.001, OR=8.08, 95% CI:1.28-31.19) and TT/TC (p<0.001, OR=14.66 and 95% CI: 3.31-65.07) genotypes carriers. Calculation of the allelic distribution revealed a higher frequency of the T allele (82%) among controls; however, the C allele was more prevalent in the preeclamptic group (36%) significantly.Conclusion:The significantly higher C allele frequency in the prostasin gene at the rs12597511 locus in the preeclamptic group indicates that the distribution of the C allele of the prostasin gene is a potential risk factor contributing to the development of preeclampsia.