Natural compounds for oxidative stress and neuroprotection in schizophrenia: composition, mechanisms, and therapeutic potential.

OBJECTIVE: An imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms is believed to be a critical factor in the development of schizophrenia (SCZ) like neurological illnesses. Understanding the roles of ROS in the development of SCZ and the potential activity of natural antioxidants against SCZ could lead to more effective therapeutic options for the prevention and treatment of the illness. METHODS: SCZ is a mental disorder characterised by progressive impairments in working memory, attention, and executive functioning. In present investigation, we summarized the experimental findings for understanding the role of oxidative stress (OS) in the development of SCZ and the potential neuroprotective effects of natural antioxidants in the treatment of SCZ. RESULTS: Current study supports the use of the mentioned antioxidant natural compounds as a potential therapeutic candidates for the treatment of OS mediated neurodegeneration in SCZ. DISCUSSION: Elevated levels of harmful ROS and reduced antioxidant defense mechanisms are indicative of increased oxidative stress (OS), which is associated with SCZ. Previous research has shown that individuals with SCZ, including non-medicated, medicated, first-episode, and chronic patients, exhibit decreased levels of total antioxidants and GSH. Additionally, they have reduced antioxidant enzyme levels such as catalase (CAT), glutathione (GPx), and, superoxide dismutase (SOD) and lower serum levels of brain-derived neurotrophic factor (BDNF) in their brain tissue. The mentioned natural antioxidants may assist in reducing oxidative damage in individuals with SCZ and increasing BDNF expression in the brain, potentially improving cognitive function and learning ability.

The discerning influence of dynamic contrast-enhanced MRI in anticipating molecular subtypes of breast cancer through the artistry of artificial intelligence - a narrative review.

Radio genomics is an exciting new area that uses diagnostic imaging to discover genetic features of diseases. In this review, we carefully examined existing literature to evaluate the role of artificial intelligence (AI) and machine learning (ML) on dynamic contrastenhanced MRI (DCE-MRI) data to distinguish molecular subtypes of breast cancer (BC). Implications to noninvasive assessment of molecular subtype include reduction in procedure risks, tailored treatment approaches, ability to examine entire lesion, follow-up of tumour biology in response to treatment and evaluation of treatment resistance and failure secondary to tumour heterogeneity. Recent studies leverage radiomics and AI on DCE-MRI data for reliable, non-invasive breast cancer subtype classification. This review recognizes the potential of AI to predict the molecular subtypes of breast cancer non-invasively.

Tawakkul Mediates Between Personality Traits, Depression, and Anxiety in Pakistani Muslim Adults.

Tawakkul in Islam is defined as the belief in the sufficiency of Allah (God) that invokes patience and efforts to achieve goals while accepting the outcomes unconditionally. The present research intended to investigate the mediating role of tawakkul between personality traits and mental health (anxiety and depression) in a purposive sample of (N = 350) Muslim adults. Urdu versions of three instruments, namely the Tawakkul Scale (Gondal, et al., 2021), Depression, Anxiety Stress Scale of (DASS 21; Aslam, 2018), and Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI; Chishti & Kamal, 2002), were used to measure the variables. Path analysis revealed that extraversion had no association with tawakkul and anxiety, but it was inversely related to depression. Neuroticism was inversely related to tawakkul and positively related to both depression and anxiety, and these relationships were partially mediated by a low degree of tawakkul. Implications of the study and recommendations for future research are discussed.

Development and Validation of Apeiroanxiety Scale in the Context of the Afterlife for Pakistani Muslim Adults.

Apeiroanxiety is a fear of infinity. Some people may experience anxiety or discomfort when contemplating the vastness or endless nature of certain concepts, such as time or space. Addressing any form of anxiety is important as it can impact an individual's daily functioning, wellbeing, and quality of life. The current study is aimed at developing a reliable and valid measure of apeiroanxiety in the context of the afterlife for the Pakistani Muslim population. The research had three studies: Query Study I generated an item pool of 18 items based on a literature review, semi-structured interviews, and expert opinion. This item pool was administered to a convenient sample of Pakistani Muslim participants (n = 1277). As a result of exploratory factor analysis, a uni-dimensional factor solution with five items was yielded (α = 0.90). Confirmatory factor analysis confirmed the obtained uni-dimensional factor solution in study II of the research with an excellent model fit. In study III, the convergent and discriminant validity of the scale was established on a separate independent sample (n = 485). Results yielded evidence of convergent validity as negative afterlife belief and rumination had a positive correlation with apeiroanxiety. The discriminant validity was established by a non-significant relationship between positive afterlife belief and apeiroanxiety. Moreover, the limitations, suggestions, and implications of the study are discussed.

Race/Ethnicity and Birthplace as Risk Factors for Gastric Intestinal Metaplasia in a Multiethnic United States Population.

INTRODUCTION: Several US subgroups have increased risk of gastric cancer and gastric intestinal metaplasia (GIM) and may benefit from targeted screening. We evaluated demographic and clinical risk factors for GIM and examined the interaction between race/ethnicity and birthplace on GIM risk. METHODS: We identified patients who had undergone esophagogastroduodenoscopy with gastric biopsy from 3/2006-11/2016 using the pathology database at a safety net hospital in Houston, Texas. Cases had GIM on ≥1 gastric biopsy histopathology, whereas controls lacked GIM on any biopsy. We estimated odds ratios and 95% confidence intervals (CI) for associations with GIM risk using logistic regression and developed a risk prediction model of GIM risk. We additionally examined for associations using a composite variable combining race/ethnicity and birthplace. RESULTS: Among 267 cases with GIM and 1,842 controls, older age (vs <40 years: 40-60 years adjusted odds ratios (adjORs) 2.02; 95% CI 1.17-3.29; >60 years adjOR 4.58; 95% CI 2.61-8.03), Black race (vs non-Hispanic White: adjOR 2.17; 95% CI 1.31-3.62), Asian race (adjOR 2.83; 95% CI 1.27-6.29), and current smoking status (adjOR 2.04; 95% CI 1.39-3.00) were independently associated with increased GIM risk. Although non-US-born Hispanics had higher risk of GIM (vs non-Hispanic White: adjOR 2.10; 95% CI 1.28-3.45), we found no elevated risk for US-born Hispanics (adjOR 1.13; 95% CI 0.57-2.23). The risk prediction model had area under the receiver operating characteristic of 0.673 (95% CI 0.636-0.710) for discriminating GIM. DISCUSSION: We found that Hispanics born outside the United States were at increased risk of GIM, whereas Hispanics born in the United States were not, independent of Helicobacter pylori infection. Birthplace may be more informative than race/ethnicity when determining GIM risk among US populations.

Staging exocrine pancreatic dysfunction.

Digestive capacity of the gastrointestinal tract, largely but not wholly, depends on exocrine pancreatic function to achieve near complete digestion and absorption of ingested food. Coefficient of fat absorption (CFA), the proportion of ingested fat absorbed (normal >93%), reflects digestive capacity. Exocrine pancreatic insufficiency (EPI) is the state of insufficient digestive capacity (CFA <93%) caused by severe loss of pancreatic exocrine function despite variable compensation by upregulation of extra-pancreatic lipolysis. Fecal elastase 1 (FE1) level is the most widely used, though imperfect, non-invasive test of pancreatic enzyme output. Decline in pancreas enzyme output, or pancreatic exocrine dysfunction (EPD), has a variable correlation with measurable decline in CFA. EPI results in steatorrhea, weight loss and nutrient deficiency, which are mitigated by pancreatic enzyme replacement therapy (PERT). We propose a staging system for EPD, based on measurement of fecal elastase (FE1) and, if necessary, CFA and serum fat-soluble vitamin levels. In Stage I (Mild) EPD, FE1 is 100-200 mcg/gm; if steatorrhea is present, non-pancreatic causes are likely. In Stage II (Moderate) EPD), FE1 is < 100 mcg/gm without clinical and/or laboratory evidence of steatorrhea. In Stage III, there are marked reductions in FE1 and CFA, but vitamin levels remain normal (Severe EPD or EPI without nutritional deficiency). In Stage IV all parameters are abnormal (Severe EPD or EPI with nutritional deficiency). EPD stages I and II are pancreas sufficient and PERT may not be the best or first approach in management of early-stage disease; it needs further study to determine clinical utility. The term EPI refers strictly to EPD Stages III and IV which should be treated with PERT, with Stage IV requiring micronutrient supplementation as well.

Racial and Ethnic Inequities in Use of Preventive Services Among Privately Insured Adults With a Pediatric-Onset Disability.

PURPOSE: Cerebral palsy (CP) and spina bifida (SB) are pediatric-onset disabilities. Adults living with CP/SB are in a greater need of preventive care than the general population due to their increased risk for chronic diseases. Our objective was to compare White/Black and White/Hispanic inequities in the use of preventive services. METHODS: Using 2007-2017 private claims data, we identified a total of 11,635 adults with CP/BS. Of these, 8,935 were White, 1,457 Black, and 1,243 Hispanic. We matched health-related variables (age, sex, comorbid conditions) between White adults and those in each minority subpopulation. Generalized estimating equations were used and all models were adjusted for age, sex, comorbidities, income, education, and US Census divisions. Outcomes of interest were: (1) any office visit; (2) any physical/occupational therapy; (3) wellness visit; (4) bone density screening; (5) cholesterol screening; and (6) diabetes screening. RESULTS: The rate of recommended services for all subpopulations of adults with CP/SB was low. Compared with White adults, Hispanic adults had lower odds of wellness visits (odds ratio [OR] = 0.71, 95% CI, 0.53-0.96) but higher odds of diabetes screening (OR = 1.48, 95% CI, 1.13-1.93). Compared with White adults, Black adults had lower odds of wellness visits (OR = 0.50, 95% CI, 0.24-1.00) and bone density screening (OR = 0.54, 95% CI, 0.31-0.95). CONCLUSIONS: Preventive service use among adults with CP/SB was low. Large White-minority disparities in wellness visits were observed. Interventions to address physical accessibility, adoption of telehealth, and increased clinician education may mitigate these disparities, particularly if initiatives target minority populations.

Preventative Services Use and Risk Reduction for Potentially Preventative Hospitalizations Among People With Traumatic Spinal Cord Injury.

OBJECTIVE: To examine the risk of potentially preventable hospitalizations (PPHs) for adults (18 years or older) with traumatic spinal cord injury (TSCI) to identify the most common types of preventable hospitalizations and their associative risk factors. DESIGN: Cohort study. SETTING: Using 2007-2017 U.S. claims data from the Optum Clinformatics Data Mart, we identified adults (18 years or older) with diagnosis of TSCI (n=5380). Adults without TSCI diagnosis were included as controls (n=1,074,729). Using age and sex, we matched individuals with and without TSCI (n=5173) with propensity scores to address potential selection bias. Generalized linear regression was applied to examine the risk of TSCI on PPHs. Models were adjusted for age; sex; race and ethnicity; Elixhauser comorbidity count; any cardiometabolic, psychological, and musculoskeletal chronic conditions; U.S. Census Division; socioeconomic variables; and use of certain preventative care services. Adjusted odds ratios were compared within a 4-year follow-up period. PARTICIPANTS: Adults with and without TSCI (N=5,173). INTERVENTION: Not applicable. MAIN OUTCOMES MEASURES: Any PPH and specific PPHs RESULTS: Adults with TSCI had higher risk for any PPH (odds ratio [OR], 1.67; 95% CI,1.20-2.32), as well as PPHs because of urinary tract infection (UTI) (OR, 3.78; 95% CI, 2.47-5.79), hypertension (OR, 3.77; 95% CI, 1.54-9.21), diabetes long-term complications (OR, 2.54; 95% CI, 1.34-4.80), and pneumonia (OR, 1.71; 95% CI. 1.21-2.41). Annual wellness visit was associated with reduced PPH risk compared with cases and controls without annual wellness visit (OR, 0.57; 95% CI, 0.46-0.71) and among people with TSCI (OR, 0.69; 95% CI, 0.55-0.86) compared with cases without annual wellness visit. CONCLUSIONS: Adults with TSCI are at a heightened risk for PPH. They are also more susceptible to certain PPHs such as UTIs, pneumonia, and heart failure. Encouraging the use of preventative or health-promoting services, especially for respiratory and urinary outcomes, may reduce PPHs among adults with TSCI.

Glucogallin Attenuates RAW 264.7 Cells from Arsenic Trioxide Induced Toxicity via the NF-Ò¡B/NLRP3 Pathway.

Chronic arsenic (As) poisoning is mostly due to subsoil water contaminated with As and its salts. Exposure to As has been found to cause an elevation in reactive oxygen species (ROS), leading to the damage of DNA and proteins, and it also causes immunotoxicity. Treatment regimens are primarily based on chelation therapy and amino acid and vitamin supplementations. Recent studies have established that natural products display effective and progressive relief from arsenicosis without any side effects. ß-glucogallin (BGG), a gallo-tannin natural product, is reported to possess anti-oxidant and anti-inflammatory properties. In the present study, we aim to observe the protective role of BGG against As-induced cytotoxicity, apoptosis, mitochondrial dysfunction, and the underlying mechanisms in RAW 264.7 macrophage cells. We found that BGG alleviates As-induced ROS, apoptosis, and mitochondrial dysfunction in RAW 264.7 macrophage cells. Thus, BGG can be used therapeutically to prevent As-induced toxicity.

Covid-19 association with anterior uveitis (post-covid acute anterior uveitis).

The Covid-19 outbreak in Wuhan on 31st December 2019 soon became a pandemic. Ocular manifestations in post covid patients have been widely reported. Anterior uveitis is a common form of intraocular inflammation observed on a daily basis by Ophthalmologists. Diagnosis of AAU is relatively simple but identification of its etiology is difficult, specifically with Covid-19. Post Covid-19 AAU is not reported in Pakistan yet. The patient in the given case is investigated thoroughly, no possible cause of AAU is identified. The patient was managed for uveitis.

Prescription patterns of pancreatic enzyme replacement therapy for patients with pancreatic cancer in the United States.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) is frequently seen in patients with pancreatic cancer (PDAC) and is thought to contribute to nutritional complications. While EPI can be pharmacologically temporized with pancreatic enzyme replacement therapy (PERT), there is lack of clear evidence informing its use in PDAC. Here we aim to survey pancreatic surgeons regarding their utilization of PERT in the management of EPI for PDAC. METHODS: An online survey was distributed to the members of The Americas Hepato-Pancreato-Biliary Association (AHPBA) and The Pancreas Club. RESULTS: 86.5% (180/208) of surgeons prescribe PERT for at least some resectable/borderline resectable PDAC cases. Only a minority of surgeons order investigations to confirm EPI before starting PERT (28.1%) or test for adequacy of therapy (28.3%). Few surgeons believe that PERT has an effect on overall survival (19.7%) or disease-free survival (6.25%) in PDAC. CONCLUSION: PERT is widely prescribed in patients with resectable/borderline resectable PDAC, but investigations establishing EPI and assessing PERT adequacy are underutilized. A substantial proportion of surgeons are unclear as to the effect of PERT on survival outcomes in PDAC. These data call for prospective studies to establish guidelines for optimal use of PERT and its effects on survival outcomes in PDAC.

Association between temperature exposure and cognition: a cross-sectional analysis of 20,687 aging adults in the United States.

BACKGROUND: Older adults are particularly vulnerable to the adverse health effects of extreme temperature-related events. A growing body of literature highlights the importance of the natural environment, including air pollution and sunlight, on cognitive health. However, the relationship between exposure to outdoor temperatures and cognitive functioning, and whether there exists any differences across climate region, remains largely unexplored. We address this gap by examining the temperature-cognition association, and whether there exists any variation across climate regions in a national cohort of aging adults. METHODS: In this cross-sectional study, we obtained data on temperature exposure based on geocoded residential location of participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. For each participant, this information was linked to their cognitive scores from Word List Learning and Recall tests to assess cognitive functioning. We used distributed lag non-linear models (dlnm) to model temperature effects over 2 days. Multivariable linear regression was used to compute temperature-cognitive functioning associations, adjusted for important covariates. Region-specific ("Dry", "Mediterranean/oceanic", "Tropical" and "Continental") associations were examined by including an interaction term between climate region and temperature. RESULTS: Amongst 20,687 individuals (mean age = 67.8; standard deviation = 9.2), exposure to region-specific extreme cold temperatures in the "dry" region (e.g., Arizona) over 2 days was associated with lower cognitive scores (Mean Difference [MD]: -0.76, 95% Confidence Interval [CI]: - 1.45, - 0.07). Associations remained significant for cumulative effects of temperature over 2 days. Extremely cold exposure in the "Mediterranean/oceanic" region (e.g., California) over 2 days was also associated with significantly lower cognitive performance (MD: -0.25, 95% CI: - 0.47, - 0.04). No significant associations were observed for exposure to hot temperatures. Cognitive performance was slightly higher in late summer and fall compared to early summer. CONCLUSION: We noted adverse cognitive associations with cold temperatures in traditionally warmer regions of the country and improved cognition in summer and early fall seasons. While we did not observe very large significant associations, this study deepens understanding of the impact of climate change on the cognitive health of aging adults and can inform clinical care and public health preparedness plans.

Culturally-adapted behavioral intervention to improve colorectal cancer screening uptake among foreign-born South Asians in New Jersey: the Desi Sehat trial.

Objectives: Colorectal cancer (CRC) is the third most common cancer among Americans of South Asian (SA) descent and is a significant public health concern in SA communities. Rates of screening compliance among foreign-born SAs are very low. The goal of this study was to report on the development, acceptability, and preliminary impact of a culturally-targeted 1:1 intervention delivered in English, Hindi, and Urdu, called Desi-Sehat.Design: Ninety-three foreign-born SAs between the ages of 50 and 75 were recruited using community-based organization methods. Participants completed a baseline survey, participated in a 1:1 session with a community health educator, and a follow-up survey was administered four months after the baseline.Results: The acceptance rate was moderate (52.8%). Attendance at the intervention session was high. More than half of the population did not complete the follow-up survey (58.7%). Participant evaluations of the intervention were high. Intent-to-treat analyses indicate a 30% four month follow-up CRC screening uptake. There were significant increases in knowledge and significant reductions in perceived barriers to screening, worry about CRC screening tests, and worry about CRC. Effect sizes for significant changes were in the medium to large range.Conclusions: Desi Sehat was a well-evaluated and participation in the session was high, participant knowledge significantly increased, and screening barriers, worry about CRC, and worry about CRC screening tests declined significantly. Future studies should focus on enhancing recruitment and retention and include a randomized control design.

Nonceliac Gluten and Wheat Sensitivity.

Non-celiac gluten and/or wheat sensitivity (NCGS) is thought to be an immune-mediated reaction to gluten or other components of wheat (eg, fructans or amylase trypsin inhibitors) with intestinal and extraintestinal symptoms which improve once gluten and/or wheat is eliminated from the diet and after a diagnosis of celiac disease and wheat allergy have been excluded with appropriate testing. However, there is a great deal of skepticism within the scientific community questioning the existence of NCGS as a distinct clinical disorder. There are no strict diagnostic criteria and a placebo-controlled rechallenge trial has been recommended for diagnosis. In research settings, a double-blind placebo-controlled rechallenge trial has been recommended for diagnosis. There are limited studies estimating the prevalence of NCGS using this study design. The existing studies have variable results likely due to the lack of a uniform diagnostic criterion, a great deal of dependence on the patient's perception of symptoms and a large nocebo effect in existing studies. In clinical practice, a single blind placebo-controlled rechallenge trial has been recommended for diagnosis. The pathogenesis of NCGS is unclear and there is no known biomarker or diagnostic histologic lesion for this condition. It is important to adopt a multidisciplinary team approach to patients with suspected NCGS with involvement of the primary care doctor, gastroenterologist, pathologist and nutritionist who may play an important role in diagnosis and treatment. There may especially be a role in elimination of food containing high quantity of both gluten and fructans. Furthermore, patients should be educated on the nutritional implications of consuming a long-term gluten-free diet.

Mind Wandering in a Multimodal Reading Setting: Behavior Analysis & Automatic Detection Using Eye-Tracking and an EDA Sensor.

Mind wandering is a drift of attention away from the physical world and towards our thoughts and concerns. Mind wandering affects our cognitive state in ways that can foster creativity but hinder productivity. In the context of learning, mind wandering is primarily associated with lower performance. This study has two goals. First, we investigate the effects of text semantics and music on the frequency and type of mind wandering. Second, using eye-tracking and electrodermal features, we propose a novel technique for automatic, user-independent detection of mind wandering. We find that mind wandering was most frequent in texts for which readers had high expertise and that were combined with sad music. Furthermore, a significant increase in task-related thoughts was observed for texts for which readers had little prior knowledge. A Random Forest classification model yielded an F 1 -Score of 0.78 when using only electrodermal features to detect mind wandering, of 0.80 when using only eye-movement features, and of 0.83 when using both. Our findings pave the way for building applications which automatically detect events of mind wandering during reading.

Development of levosulpiride-loaded solid lipid nanoparticles and their in vitro and in vivo comparison with commercial product.

The aim of this study was to develop levosulpiride-loaded solid lipid nanoparticles (SLNs) with enhanced solubilisation and bioavailability. The levosulpiride loaded-SLNs were composed of levosulpiride, stearic acid, and tween 80 in their respective weight ratios of (1, 5, and 1.5 mg) dissolved in 1 ml distilled water. Physicochemical properties of the SLNs such as particle size, shape, crystallinity, and chemical interaction were evaluated. Further, the in vitro drug dissolution, pharmacokinetic and stability studies of the SLNs were performed. The SLNs were rounded shaped stable nanoparticles with average diameter of 200 nm. They demonstrate 1.5- and 3-fold better drug dissolution when compared with the commercial product and levosulpiride powder, respectively. The SLNs enhanced the bioavailability of levosulpiride 3 times and 7 times, respectively, when compared with the commercial product and levosulpiride powder. It can be concluded that SLNs are capable to improve the dissolution and bioavailability of levosulpiride, even more than the commercial product.

Eriodictyol can modulate cellular auxin gradients to efficiently promote in vitro cotton fibre development.

BACKGROUND: Flavonoids have essential roles in flower pigmentation, fibre development and disease resistance in cotton. Previous studies show that accumulation of naringenin in developing cotton fibres significantly affects fibre growth. This study focused on determining the effects of the flavonoids naringenin, dihydrokaempferol, dihydroquerectin and eriodictyol on fibre development in an in vitro system. RESULTS: 20 µM eriodictyol treatment produced a maximum fibre growth, in terms of fibre length and total fibre units. To gain insight into the associated transcriptional regulatory networks, RNA-seq analysis was performed on eriodictyol-treated elongated fibres, and computational analysis of differentially expressed genes revealed that carbohydrate metabolism and phytohormone signaling pathways were differentially modulated. Eriodictyol treatment also promoted the biosynthesis of quercetin and dihydroquerectin in ovules and elongating fibres through enhanced expression of genes encoding chalcone isomerase, chalcone synthase and flavanone 3-hydroxylase. In addition, auxin biosynthesis and signaling pathway genes were differentially expressed in eriodictyol-driven in vitro fibre elongation. In absence of auxin, eriodictyol predominantly enhanced fibre growth when the localized auxin gradient was disrupted by the auxin transport inhibitor, triiodobenzoic acid. CONCLUSION: Eriodictyol was found to significantly enhance fibre development through accumulating and maintaining the temporal auxin gradient in developing unicellular cotton fibres.

The Association Between Statin Use After Diagnosis and Mortality Risk in Patients With Esophageal Cancer: A Retrospective Cohort Study of United States Veterans.

OBJECTIVE: Statins may reduce mortality from esophageal cancer by both reducing incidence but also improving prognosis. However, prior studies of statin use and mortality have reported conflicting results. METHODS: We identified 7882 patients with esophageal adenocarcinoma (EAC) and 3868 with esophageal squamous cell carcinoma (ESCC) from the VA Central Cancer Registry diagnosed between 2002 and 2016. We identified prescriptions for statins that were filled before and after cancer diagnosis. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3 month lag (following patients from 3 months after cancer diagnosis) to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between date of cancer diagnosis and start of follow-up. RESULTS: Statin use after diagnosis was recorded in 27.4% of EAC and 17.1% of ESCC patients. In EAC patients, statin use after diagnosis was associated with a decreased risk of cancer specific (HR, 0.79; 95% CI 0.70-0.88) and all-cause mortality (HR, 0.80; 95% CI 0.74-0.86). Similarly, statin use after diagnosis of ESCC was associated with a decreased risk of cancer specific (HR, 0.77; 95% CI 0.63-0.92) and all-cause mortality (HR, 0.83; 95% CI 0.74-0.95). The inverse associations were attenuated towards the null with a 6-month lag. CONCLUSIONS: Post-diagnosis statin use was associated with reduced mortality in esophageal cancer patients; however, the effect may be partially due to reverse causality as patients with poor prognosis are unlikely to initiate statin therapy.

Factors associated with door-in to door-out delays among ST-segment elevation myocardial infarction (STEMI) patients transferred for primary percutaneous coronary intervention: a population-based cohort study in Ontario, Canada.

BACKGROUND: Compared to ST-segment elevation myocardial infarction (STEMI) patients who present at centres with catheterization facilities, those transferred for primary percutaneous coronary intervention (PCI) have substantially longer door-in to door-out (DIDO) times, where DIDO is defined as the time interval from arrival at a non-PCI hospital, to transfer to a PCI hospital. We aimed to identify potentially modifiable factors to improve DIDO times in Ontario, Canada and to assess the impact of DIDO times on 30-day mortality. METHODS: A population-based, retrospective cohort study of 966 STEMI patients transferred for primary PCI in Ontario in 2012 was conducted. Baseline factors were examined across timely DIDO status. Multivariate logistic regression was used to examine independent predictors of timely DIDO as well as the association between DIDO times and 30-day mortality. RESULTS: The median DIDO time was 55 min, with 20.1% of patients achieving the recommended DIDO benchmark of ≤30 min. Age (OR> 75 vs 18-55 0.30, 95% CI: 0.16-0.56), symptom-to-first medical contact (FMC) time (OR61-120mins vs < 60mins 0.60, 95% CI: 0.39-0.90; OR>120mins vs < 60mins 0.53, 95% CI:0.35-0.81) and emergency medical services transport with a pre-hospital electrocardiogram (ECG) (OREMS transport + ECG vs self-transport 2.63, 95% CI:1.59-4.35) were the strongest predictors of timely DIDO. Patients with timely ECG were more likely to have recommended DIDO times (33.0% vs 12.3%; P < 0.001). A significantly higher proportion of those who met the DIDO benchmark had timely FMC-to-balloon times (78.7% vs 27.4%; P < 0.001). Compared to patients with DIDO time ≤ 30 min, those with DIDO times > 90 min had significantly higher adjusted 30-day mortality rates (OR 2.82, 95% CI:1.10-7.19). CONCLUSIONS: While benchmark DIDO times were still rarely achieved in the province, we identified several potentially modifiable factors in the STEMI system that might be targeted to improve DIDO times. Our findings that patients who received a pre-hospital ECG were still being transferred to non-PCI capable centres suggest strategies addressing this gap may improve patient outcomes.

Antioxidant defense and oxidative damage vary widely among high-altitude residents.

OBJECTIVES: People living at high altitude experience unavoidable low oxygen levels (hypoxia). While acute hypoxia causes an increase in oxidative stress and damage despite higher antioxidant activity, the consequences of chronic hypoxia are poorly understood. The aim of the present study is to assess antioxidant activity and oxidative damage in high-altitude natives and upward migrants. METHODS: Individuals from two indigenous high-altitude populations (Amhara, n = 39), (Sherpa, n = 34), one multigenerational high-altitude population (Oromo, n = 42), one upward migrant population (Nepali, n = 12), and two low-altitude reference populations (Amhara, n = 29; Oromo, n = 18) provided plasma for measurement of superoxide dismutase (SOD) activity as a marker of antioxidant capacity, and urine for measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of DNA oxidative damage. RESULTS: High-altitude Amhara and Sherpa had the highest SOD activity, while highland Oromo and Nepalis had the lowest among high-altitude populations. High-altitude Amhara had the lowest DNA damage, Sherpa intermediate levels, and high-altitude Oromo had the highest. CONCLUSIONS: High-altitude residence alone does not associate with high antioxidant defenses; residence length appears to be influential. The single-generation upward migrant sample had the lowest defense and nearly the highest DNA damage. The two high-altitude resident samples with millennia of residence had higher defenses than the two with multiple or single generations of residence.