Risk factors for pancreatic cancer: case-control study

OBJECTIVES: Although cigarette smoking is the most well-established environmental risk factor for pancreatic cancer, the interaction between smoking and other risk factors has not been assessed. We evaluated the independent effects of multiple risk factors for pancreatic cancer and determined whether the magnitude of cigarette smoking was modified by other risk factors in men and women. METHODS: We conducted a hospital-based case-control study involving 808 patients with pathologically diagnosed pancreatic cancer and 808 healthy frequency-matched controls. Information on risk factors was collected by personal interview, and unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method. RESULTS: Cigarette smoking, family history of pancreatic cancer, heavy alcohol consumption (>60 mL ethanol/day), diabetes mellitus, and history of pancreatitis were significant risk factors for pancreatic cancer. We found synergistic interactions between cigarette smoking and family history of pancreatic cancer (AOR 12.8, 95% confidence interval [CI] 1.6-108.9) and diabetes mellitus (AOR 9.3, 95% CI 2.0-44.1) in women, according to an additive model. Approximately 23%, 9%, 3%, and 5% of pancreatic cancer cases in this study were related to cigarette smoking, diabetes mellitus, heavy alcohol consumption, and family history of pancreatic cancer, respectively. CONCLUSIONS: The significant synergy between these risk factors suggests a common pathway for carcinogenesis of the pancreas. Determining the underlying mechanisms for such synergies may lead to the development of pancreatic cancer prevention strategies for high-risk individuals.     

Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone

Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (five females, six males) aged 35-75 years (mean age 54.1 +/- 11.4) suffering from nonorganic insomnia (F 51.0) related to a depressive episode (F 32) or recurrent depressive disorder (F 33). as compared with 11 age- and sex-matched normal controls (five females, six males) aged 36-75 years (mean age 53.0 +/- 13.5). PSG demonstrated decreased sleep efficiency, total sleep time (TST), total sleep period (TSP) and sleep stage S2, as well as increased wakefulness during TSP, early morning awakening, sleep latency to S1, S2, S3 and sleep stage S1 in depressed patients. Subjective sleep quality and the total score of the Self-Assessment of Sleep and Awakening Quality Scale (SSA) were deteriorated as were morning and evening well being, drive, mood and fine motor activity right. Evening and morning blood pressure, the O2 desaturation index and periodic leg movement (PLM) index were increased. In a subsequent acute, placebo-controlled cross-over design study, the acute effects of 100 mg of trazodone, a serotonin reuptake inhibitor with a sedative action due to 5-HT2 and alpha1 receptor blockade, were investigated in the patients. As compared with placebo, trazodone induced an increase in sleep efficiency (primary target variable), TST, TSP and SWS (S3 + S4), as well as a decrease in wakefulness during the TSP, early morning awakening and S2. There was no change in rapid eye movement (REM) sleep with the exception of an increase in the REM duration in minutes. Trazodone also caused an improvement in subjective sleep quality, affectivity, numerical memory and somatic complaints. All respiratory variables remained within normal limits. Critical flicker frequency and moming diastolic blood pressure were decreased. The present study demonstrated that depression induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg of trazodone, thus suggesting a key-lock principle in the treatment of depression.     

Measuring stigma associated with hepatitis B virus infection in Sierra Leone: Validation of an abridged Berger HIV stigma scale

Stigma associated with hepatitis B virus (HBV) is common in endemic countries; however; instruments are lacking to accurately measure HBV-related stigma. We therefore aimed to develop and validate a concise instrument for measuring perceived HBV-related stigma in Sierra Leone. We enrolled 220 people living with HBV (PWHB) aged ≥18 years from August to November 2022. The initial Likert-scale instrument entailed 12 items adapted from Berger's HIV Stigma Scale. We included four additional items adapted from the USAID indicators for enacted stigma. The proposed scale's psychometric properties were assessed. After item reduction, the final HBV Stigma Scale consisted of 10 items and had good internal consistency (overall Cronbach's α = 0.74), discriminant, and construct validity. Exploratory factor analysis produced a three-dimensional structure accounting for 59.3% of variance: personalized stigma driven by public attitudes (six items), negative self-image (two items), and disclosure concerns (two items). Overall, 72.8% of respondents reported perceived HBV-related stigma (mean score 29.11 ± 4.14) and a similar proportion (73.6%) reported at least one instance of enacted stigma. In assessing criterion-related validity, perceived HBV-related stigma correlated strongly with enacted stigma (r = 0.556) and inversely with having family/friends with HBV (r = −0.059). The 10-item HBV Stigma Scale demonstrated good internal consistency and validity and is suitable for screening for HBV-related stigma in Sierra Leone. The psychometric properties of the scale can be optimized with item additions/modifications and confirmatory factor analysis. The scale may help in combating stigma as a barrier to achieving HBV global elimination goals.     

The role of glucagon-like peptide-1 receptor agonists in metabolic dysfunction-associated steatohepatitis

Despite its considerable and growing burden, there are currently no Food and Drug Administration-approved treatments for metabolic dysfunction-associated steatotic liver disease or its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) and other agents are in various phases of clinical development for use in MASH; an ideal therapy should reduce liver fat content, improve chronic liver disease, help mitigate metabolic comorbidities and decrease all-cause mortality. Because of interconnected disease mechanisms, metabolic dysfunction-associated steatotic liver disease/MASH often coexists with type 2 diabetes (T2D), obesity and cardiovascular disease. Various GLP-1RAs are Food and Drug Administration-approved for use in T2D, and two, liraglutide and semaglutide, are approved for overweight and obesity. GLP-1RAs decrease glucose levels and body weight and improve cardiovascular outcomes in people with T2D who are at high risk of cardiovascular disease. In addition, GLP-1RAs have been reported to reduce liver fat content and liver enzymes, reduce oxidative stress and improve hepatic de novo lipogenesis and the histopathology of MASH. Weight loss may contribute to these effects; however, the exact mechanisms are unknown. Adverse events that are commonly associated with GLP-1RAs include vomiting, nausea and diarrhoea. There is a lack of evidence from meta-analyses regarding the increased risk of acute pancreatitis and various forms of cancer with GLP-1RAs. Large-scale, phase 3 trials, which will provide definitive data on GLP-1RAs and other potential therapies in MASH, are ongoing. Given the spectrum of modalities under investigation, it is hoped that these trials will support the identification of pharmacotherapies that provide clinical benefit for patients with MASH.     

Pomegranate protective effect on experimental ischemia/reperfusion retinal injury in rats (histological and biochemical study)

Oxidative stress is one mechanism involved in the pathogenesis of ischemia/reperfusion (/R) retinal injury. The histological, biochemical, and functional changes associated with pomegranate (PMG) treatment prior to retinal I/R were analyzed using 40 adult male albino rats. Rats were divided into four groups: Groups I and II (sham operated and received saline or PMG, respectively); Groups III and IV (I/R rat models with prior administration of saline or 250 mg/kg/day PMG, respectively). Electroretinogram (ERG) results were recorded and eye specimens were taken and processed for light and electron microscopic examinations and for assessment of oxidative status in retinal homogenate. I/R lead to degenerative changes in retinal layers with a significant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2) immunoreactivity in concomitant with significant oxidant–antioxidant disturbance and decreased a- and b-wave amplitude in the ERG. These alterations were ameliorated with prior PMG treatment. In conclusion, PMG treatment, as an antioxidant, attenuated retinal structural and functional I/R injury through activation of Nrf2 which could be a base for future therapy designs.