Identifying and Characterizing Genetic Variants Associated with Colorectal Cancer

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Latrunculin B Modulates Electrophysiological Characteristics and Arrhythmogenesis in Pulmonary Veins Cardiomyocytes

ABSTRACT Atrial fibrillation (AF) is the most common sustained arrhythmia, and the pulmonary veins (PVs) play a critical role in triggering AF. Stretch causes structural remodeling, including cytoskeleton re-arrangement, which may play a role in the genesis of AF. Latrunculin B (Lat-B), an inhibitor of actin polymerization, is involved in calcium (Ca 2+ ) regulation. However, it is unclear whether Lat-B directly modulates the electrophysiological characteristics and Ca 2+ homeostasis of the PVs. Conventional microelectrodes, whole-cell patch-clamp, and Fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca 2+ within isolated rabbit PV preparations, or within isolated single PV cardiomyocytes, before and after the administration of Lat-B (100 nM). Langendorff-perfused rabbit hearts were exposed to acute and continuous atrial stretch, and studied PV electrical activity. Lat-B (100 nM) decreased the spontaneous electrical activity by 16 ± 4% in PV preparations. Lat-B (100 nM) decreased the late-sodium current, L-type Ca 2+ current, sodium-calcium exchanger current, and stretch-activated BKCa current, but did not affect the sodium current in PV cardiomyocytes. Lat-B reduced the transient outward potassium current and ultra-rapid delayed rectifier potassium current, but increased the delayed rectifier potassium current in isolated PV cardiomyocytes. In addition, A c c e p t e d M a n u s c r i p

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study

Objective: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. Methods: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. Results: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn’t increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P  = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P  = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P  < .0001), emotions (58.33 vs 15.48, P  < .0001), functioning (46.67 vs 13.33, P  < .0001) and composite (52.60 vs 14.06, P  < .0001). Conclusion: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs

Effects of Managing Cancer and Living Meaningfully on Cancer-Related Fatigue and Cytokine Levels in Gastrointestinal Cancer Patients

Objective: To evaluate the effects of managing cancer and living meaningfully (CALM), a psychological intervention with semi-structured interviews, on cancer-related fatigue (CRF), quality of life (QOL), and sleep quality in patients with gastrointestinal (GI) cancer, which may be accompanied by changes in cytokine levels. Methods: A total of 152 GI cancer patients with CRF were enrolled in the study during treatment. Patients were randomly assigned to CALM or usual care (UC) groups. Patients in the CALM group received 12 weeks of CALM plus usual care, and patients in the UC group received usual care plus usual health education. All study participants were evaluated at baseline and at 12 weeks using the Revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30, and the Pittsburgh Sleep Quality Index scale, while cytokine levels were measured. Results: At 12 weeks, the differences in total CRF, QOL, sleep quality, IL-6, IL-4, and TNF-α levels were statistically significant not only in the CALM group compared to patients in the UC group ( t  = −7.902, t  = 2.163, t  = −2.187, t  = 3.313, t  = −4.120, t  = −3.853, respectively; P  < .05), but also in the CALM group compared to baseline ( t  = 11.331, t  = −5.492, t  = 5.450, t  = −2.418, t  = 2.186, t  = 2.699, respectively; P  < .05). Additionally, the total CRF at 12 weeks was correlated with IL-4, IL-6, and TNF-α levels ( r  = −.30, r  = .31, r  = .32, respectively; P  < .001). Conclusions: CALM alleviated CRF and improved QOL and sleep quality in patients with GI cancer, and these improvements were accompanied by changes in IL-4, IL-6, and TNF-α levels

Neurologic Complications of Patients With COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis

OBJECTIVES:. In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality. DATA SOURCES:. We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022. STUDY SELECTION:. We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO. DATA EXTRACTION:. Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model. DATA SYNTHESIS:. Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8–15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1–3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34–40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46–3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO. CONCLUSIONS:. COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH

Global, regional, and national consumption of animal-source foods between 1990 and 2018: findings from the Global Dietary Database

International audienceBackground:Diet is a major modifiable risk factor for human health and overall consumption patterns affect planetary health. We aimed to quantify global, regional, and national consumption levels of animal-source foods (ASF) to inform intervention, surveillance, and policy priorities.Methods:Individual-level dietary surveys across 185 countries conducted between 1990 and 2018 were identified, obtained, standardised, and assessed among children and adults, jointly stratified by age, sex, education level, and rural versus urban residence. We included 499 discrete surveys (91·2% nationally or subnationally representative) with data for ASF (unprocessed red meat, processed meat, eggs, seafood, milk, cheese, and yoghurt), comprising 3·8 million individuals from 134 countries representing 95·2% of the world population in 2018. We used Bayesian hierarchical models to account for differences in survey methods and representativeness, time trends, and input data and modelling uncertainty, with five-fold cross-validation.Findings:In 2018, mean global intake per person of unprocessed red meat was 51 g/day (95% uncertainty interval [UI] 48–54; region-specific range 7–114 g/day); 17 countries (23·9% of the world's population) had mean intakes of at least one serving (100 g) per day. Global mean intake of processed meat was 17 g/day (95% UI 15–21 g/day; region-specific range 3–54 g/day); seafood, 28 g/day (27–30 g/day; 12–44 g/day); eggs, 21 g/day (18–24 g/day; 6–35 g/day); milk 88 g/day (84–93 g/day; 45–185 g/day); cheese, 8 g/day (8–10 g/day; 1–34 g/day); and yoghurt, 20 g/day (17–23 g/day; 7–84 g/day). Mean national intakes were at least one serving per day for processed meat (≥50 g/day) in countries representing 6·9% of the global population; for cheese (≥42 g/day) in 2·3%; for eggs (≥55 g/day) in 0·7%; for milk (≥245 g/day) in 0·3%; for seafood (≥100 g/day) in 0·8%; and for yoghurt (≥245 g/day) in less than 0·1%. Among the 25 most populous countries in 2018, total ASF intake was highest in Russia (5·8 servings per day), Germany (3·8 servings per day), and the UK (3·7 servings per day), and lowest in Tanzania (0·9 servings per day) and India (0·7 servings per day). Global and regional intakes of ASF were generally similar by sex. Compared with children, adults generally consumed more unprocessed red meat, seafood and cheese, and less milk; energy-adjusted intakes of other ASF were more similar. Globally, ASF intakes (servings per week) were higher among more-educated versus less-educated adults, with greatest global differences for milk (0·79), eggs (0·47), unprocessed red meat (0·42), cheese (0·28), seafood (0·28), yoghurt (0·22), and processed meat (0·21). This was also true for urban compared to rural areas, with largest global differences (servings per week) for unprocessed red meat (0·47), milk (0·38), and eggs (0·20). Between 1990 and 2018, global intakes (servings per week) increased for unprocessed red meat (1·20), eggs (1·18), milk (0·63), processed meat (0·50), seafood (0·44), and cheese (0·14).Interpretation:Our estimates of ASF consumption identify populations with both lower and higher than optimal intakes. These estimates can inform the targeting of intervention, surveillance, and policy priorities relevant to both human and planetary health