Chromosomal and microsatellite instability in sporadic gastric cancer

BACKGROUND: Gastric cancer can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (MSI). It is hypothesized that these two pathways are not always independent and that some tumors show overlap between these two mechanisms. METHODS: A total of 98 sporadic gastric cancers were classified based on their MSI status, using microsatellite assay with BAT26. Evidence for CIN was investigated by identifying loss of heterozygosity (LOH) events on chromosome arms, 5q, 10p, 17p, 17q, and 18q, which are regions harboring tumor suppressor genes that are significant in gastric cancer development. RESULTS: Twelve tumors (12%) showed high-frequency MSI (MSI-H). Overall, 43 of the tumors (44%) had at least one LOH event, with most frequent chromosomal losses observed on 10p and 18q (30%, respectively), followed by 5q (21%), 17p (14%), and 17q (12%). Interestingly, overlap was observed between CIN and MSI pathways. Of 43 cancers with LOH events, four (9%) were also MSI-H. It was also found that 48% of cancers without MSI-H had no LOH events identified, comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability. CONCLUSION: These results suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways in sporadic gastric cancers.     

Chronic Alcohol Abuse Leads to Gastric Atrophy and Decreased Gastric Secretory Capacity: A Histological and Physiological Study

We performed morphological and physiological studies in 43 male patients with alcohol dependence (ALC) who had no other apparent lesions in the upper gastrointestinal tract except atrophic and erosive gastritis. A gastric secretory study in which tetragastrin was used as the stimulant revealed that acid and pepsin secretion was less in ALC patients than in hospital controls (p less than 0.001). Endoscopic biopsy specimens of gastric mucosa from ALC patients revealed that atrophy of the gastric mucosa advanced with age. A strong negative correlation was also found between the secretory capacity of the stomach and the degree of atrophy. Possibly, the interval between recurrent episodes of acute mucosal damage was too short to allow complete healing of mucosal lesions. Failure to regenerate denuded epithelium would result in a decrease in the gastric secretory area. Thus, chronic alcohol abuse seems to be an etiological factor in atrophic gastritis.     

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients

BackgroundThe information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes.MethodsIn this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed.ResultsForty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67–22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26–7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05–5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39–9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without.ConclusionsThe presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.     

Does moxifloxacin alter oxidant status in the cornea? An experimental study

Objective: In this experimental study, we investigated the possible effects of intracameral moxifloxacin on oxidative stress parameters and endothelial cell morphology in corneal tissue.

Methods: In total, 30 rats were randomly assigned to three groups of 10 rats: the sham group (Group 1, n?=?10); the control group (Group 2), where balanced salt solution (BSS) was administered at a dose of 0.01?cc (n?=?10); and the treatment group (Group 3), where moxifloxacin was administered at a dose of 0.05?mg/0.01?cc (n?=?10). Total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood samples were measured and the oxidative stress index (OSI) was calculated. Also, corneal tissue histopathology was evaluated with caspase-3 and caspase-8 staining. Apoptotic activity was also evaluated.

Results: In blood samples, TAS, TOS, and OSI levels were not statistically significantly different (all p?>?0.05). Compared with the sham and control groups, TOS and OSI levels in cornea tissue were significantly different in the moxifloxacin group (all p?p?>?0.05). Compared with the sham and control groups, apoptotic activity was higher in the moxifloxacin group, in both immunohistochemical staining for caspase-3 and caspase-8.

Conclusions: Intracameral moxifloxacin injection seems to be safe systemically, but it may have toxic effects on corneal tissues, as suggested by oxidative stress parameters and a histopathological evaluation.     

New era of pediatric ventricular assist devices: Let us go to school

As there is still a shortage of pediatric donor hearts, several techniques have been used to assist pediatric patients to survive until transplantation. VADs provide long‐term support and ability of mobilization for children before a suitable heart becomes available. Several devices such as paracorporeal pumps have been used for this purpose, with acceptable morbidity and mortality rates. However, discharge is not possible, as there is no mobile drive unit for these small‐sized pumps. The possible negative psychosocial impact of long‐term hospitalization, away from home and school, may cause some adjustment problems in the future. In this case series, three pediatric patients that underwent intracorporeal LVAD implantation and returned to school are presented to share clinical experience and also to attract attention to the potential social and psychiatric implications.     

Effectiveness of Cognitive Behavioral Therapy for Individuals with Autism Spectrum Disorders and Comorbid Obsessive-Compulsive Disorder: A Review of the Research

Autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD) are highly comorbid, precipitating an urgent need to identify evidence-based practices that might be used to address this comorbidity exclusively. The aim of this study was to conduct a review of intervention research and clinical reports to examine the use of cognitive behavioral therapy (CBT) with individuals who have comorbid ASD and OCD. Based on the pre-determined review inclusion criteria, 11 studies were included in the review: three randomized control trials (RCT), one case controlled study, two single subject experimental designs, and five case studies. These studies offer promising data on the use of CBT interventions for individuals with ASD and comorbid OCD as well as for individuals with OCD and comorbid ASD when standard CBT protocol is enhanced with modifications such as parental involvement, increased use of visuals, personalized treatment metaphors, self-monitoring, positive reinforcement, and use of clear language and instructions. Limitations and implications for future research and practice are discussed.