Glycemic status, insulin resistance, and mortality from lung cancer among individuals with and without diabetes.

BACKGROUND: The effects of glycemic status and insulin resistance on lung cancer remain unclear. We investigated the associations between both glycemic status and insulin resistance, and lung cancer mortality, in a young and middle-aged population with and without diabetes. METHODS: This cohort study involved individuals who participated in routine health examinations. Lung cancer mortality was identified using national death records. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% CIs for lung cancer mortality risk. RESULTS: Among 666,888 individuals (mean age 39.9 ± 10.9 years) followed for 8.3 years (interquartile range, 4.6-12.7), 602 lung cancer deaths occurred. Among individuals without diabetes, the multivariable-adjusted HRs (95% CI) for lung cancer mortality comparing hemoglobin A1c categories (5.7-5.9, 6.0-6.4, and ≥ 6.5% or 39-41, 42-46, and ≥ 48 mmol/mol, respectively) with the reference (< 5.7% or < 39 mmol/mol) were 1.39 (1.13-1.71), 1.72 (1.33-2.20), and 2.22 (1.56-3.17), respectively. Lung cancer mortality was associated with fasting blood glucose categories in a dose-response manner (P for trend = 0.001) and with previously diagnosed diabetes. Insulin resistance (HOMA-IR ≥ 2.5) in individuals without diabetes was also associated with lung cancer mortality (multivariable-adjusted HR, 1.41; 95% CI, 1.13-1.75). These associations remained after adjusting for changing status in glucose, hemoglobin A1c, insulin resistance, smoking status, and other confounders during follow-up as time-varying covariates. CONCLUSIONS: Glycemic status within both diabetes and prediabetes ranges and insulin resistance were independently associated with an increased risk of lung cancer mortality.

Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Disparities in cancer incidence by sexual orientation.

INTRODUCTION: Cancer risk factors are more common among sexual minority populations (e.g., lesbian, bisexual) than their heterosexual peers, yet little is known about cancer incidence across sexual orientation groups. METHODS: The 1989-2017 data from the Nurses' Health Study II, a longitudinal cohort of female nurses across the United States, were analyzed (N = 101,543). Sexual orientation-related cancer disparities were quantified by comparing any cancer incidence among four sexual minority groups based on self-disclosure-(1) heterosexual with past same-sex attractions/partners/identity; (2) mostly heterosexual; (3) bisexual; and (4) lesbian women-to completely heterosexual women using age-adjusted incidence rate ratios (aIRR) calculated by the Mantel-Haenszel method. Additionally, subanalyses at 21 cancer disease sites (e.g., breast, colon/rectum) were conducted. RESULTS: For all-cancer analyses, there were no statistically significant differences in cancer incidence at the 5% type I error cutoff among sexual minority groups when compared to completely heterosexual women; the aIRR was 1.17 (95% CI,0.99-1.38) among lesbian women and 0.80 (0.58-1.10) among bisexual women. For the site-specific analyses, incidences at multiple sites were significantly higher among lesbian women compared to completely heterosexual women: thyroid cancer (aIRR, 1.87 [1.03-3.41]), basal cell carcinoma (aIRR, 1.85 [1.09-3.14]), and non-Hodgkin lymphoma (aIRR, 2.13 [1.10-4.12]). CONCLUSION: Lesbian women may be disproportionately burdened by cancer relative to their heterosexual peers. Sexual minority populations must be explicitly included in cancer prevention efforts. Comprehensive and standardized sexual orientation data must be systematically collected so nuanced sexual orientation-related cancer disparities can be accurately assessed for both common and rare cancers.

The Role of α-Enolase on the Production of Interleukin (IL)-32 in Con A-Mediated Inflammation and Rheumatoid Arthritis (RA).

Interleukin (IL)-32 is produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. IL-32 induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1ß, IL-6, and IL-8, and IL-32 expression is highly increased in rheumatoid arthritis (RA) patients. Enolase-1 (ENO1) is a glycolytic enzyme and the stimulation of ENO1 induces high levels of pro-inflammatory cytokines in concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and macrophages in RA patients. In addition, there are many reports that anti-ENO1 antibody is correlated with the disease progression of RA. It implies that ENO1 could regulate IL-32 production during inflammation related to the pathogenesis of RA. Therefore, we investigated the role of ENO1 in IL-32 production using Con A-activated PBMCs and RA PBMCs. IL-32 expression is increased by ENO1 stimulation using real-time PCR and ELISA. In addition, we confirmed that IL-32 production was decreased in Con A-activated PBMCs and RA PBMCs pre-treated with NF-κB or p38 MAPK pathway inhibitors. Taken together, these results suggest that ENO1 plays an important role in inflammation through the induction of IL-32 production by the activation of the NF-κB and p38 MAPK pathways.

Bacterial contamination of surgical gloves during clean orthopedic surgery.

This study examines the presence of bacterial contamination on surgical gloves and suggests appropriate measures for an aseptic surgical environment. To prevent glove contamination during surgery, surgeons and assistants should change gloves periodically, and scrub nurses should be careful when opening packages and handing over implants.

Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

Progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Early outcomes of single-port robotic left lateral sectionectomy in patients with hepatic tumor.

Purpose: Laparoscopic left lateral sectionectomy (L-LLS) stands as a cornerstone procedure in hepatobiliary minimal surgery, frequently employed for various benign and malignant liver lesions. This study aimed to analyze the peri- and postoperative surgical outcomes of single-port robotic left lateral sectionectomy (SPR-LLS) vs. those of L-LLS in patients with hepatic tumors. Methods: From January 2020 through June 2023, 12 patients underwent SPR-LLS. During the same period, 30 L-LLS procedures were performed. In total, 12 patients in the robotic group and 24 patients in the laparoscopic group were matched. Results: When the SPR-LLS and L-LLS groups were compared, the operation time was longer in the SPR-LLS group with less blood loss and shorter hospital stay. Postoperative complications were observed in 3 patients in the L-LLS group (12.5%) and 1 patient in the SPR-LLS group (8.3%). Conclusion: SPR-LLS using the da Vinci SP system was comparable to laparoscopic LLS in terms of surgical outcomes. SPR-LLS was associated with lower blood loss and less postoperative length of stay compared to L-LLS. These findings suggest that left lateral sectionectomy is technically feasible and safe with the da Vinci SP system in select patients.

Training efficacy of robotic duct-to-mucosa pancreaticojejunostomy simulation using silicone models for surgical fellows.

Purpose: In the era of minimally invasive surgery (MIS), robotic pancreatoduodenectomy (PD) is actively performed, and clinical fellows need to thoroughly prepare for MIS-PD during the training process. Although pancreaticojejunostomy (PJ) is a difficult anastomosis that requires repeated practice, there are obstacles preventing its practice that concerns patient safety and limited time in the actual operating room. This study evaluated the efficacy of simulation-based training of robotic duct-to-mucosa PJ using pancreatic and intestinal silicone models using a scoring system. Methods: Three pancreatobiliary clinical fellows who had never performed a real robotic PJ participated in this study. Each trainee, who was well acquainted with master's video created by a senor surgeon, performed the robotic PJ procedures 9 times, and 3 independent pancreatobiliary surgeons assessed the videos and analyzed the scores using a blind method. Results: The mean robotic PJ times for the 3 trainees were 42.8 and 29.1 minutes for the first and 9th videos, respectively. The mean score was 13.8 (range, 6-17) for the first video and 17.7 (range, 15-19) for the 9th video. When comparing earlier and later attempts, the PJ time decreased significantly (2,201.67 seconds vs. 2,045.50 seconds, P = 0.007), whereas test scores increased significantly (total score 14.22 vs. 16.89, P = 0.011). Conclusion: This robotic education system will help pancreatobiliary trainees overcome the learning curves efficiently and quickly without raising ethical concerns associated with animal models or direct practice with human subjects. This will be of practical assistance to trainees preparing for MIS-PD.

Effects of 625 nm light-emitting diode irradiation on preventing ER stress-induced apoptosis via GSK-3ß phosphorylation in MC3T3-E1.

Prolonged endoplasmic reticulum (ER) stress contributes to cell apoptosis and interferes with bone homeostasis. Although photobiomodulation (PBM) might be used for ER stress-induced diseases, the role of PBM in relieving cell apoptosis remains unknown. During ER stress, glycogen synthase kinase-3ß (GSK-3ß) is critical; however, its functions in PBM remain uncertain. Thus, this study aimed to investigate the role of GSK-3ß in 625 nm light-emitting diode irradiation (LEDI) relieving tunicamycin (TM)-induced apoptosis. Based on the results, pre-625 nm LEDI (Pre-IR) phosphorylated GSK-3ß via ROS production. Compared with the TM group, Pre-IR + TM group reduced the phosphorylation of the α-subunit of eukaryotic translation initiation factor 2 (eIF-2α) and B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax)/Bcl-2 ratio through regulating GSK-3ß. Furthermore, a similar tendency was observed between Pre-IR + TM and Pre-LiCl+TM groups in preventing TM-induced early and late apoptosis. In summary, this study suggests that the Pre-IR treatment in TM-induced ER stress is beneficial for preventing cell apoptosis via GSK-3ß phosphorylation.

Evaluation and Classification of Supraorbital Nerve Emerging Patterns.

BACKGROUND: Numerous significant variations in the supraorbital nerve (SON) pass through the notches and foramina. During endoscopic forehead lifting, the passage and the location of the nerve against the frontal bone render it susceptible to injury, resulting in diminished or absent sensation in the corresponding location. We attempted to obtain accurate knowledge of the SON emergence routes. METHODS: Data of patients who underwent an endoscopic forehead lift in a plastic surgery clinic between November 2015 and August 2021 were retrospectively analyzed. Deep and superficial branch pathways of SONs were identified and compared according to side and gender. We also classified the nerve patterns into six types. RESULTS: Altogether, 942 patients (1884 SON cases) were evaluated. Out of the patients, 86 patients were male, and 856 were female. The overall mean age was 48.6 (± 13.1) years. In the deep branches, 49% came from the notch, and 51% came from the foramen. In the superficial branches, 67% came from the notch, and 33% of superficial branches came from the foramen. Unlike the deep branch, superficial branches from the notch were significant. Deep and superficial branches of male patients were much more notched than those of female patients. Branches emerged together in 56% and separately in 44% of the cases. CONCLUSION: The absolute number of SON notches was higher than that of SON foramina. This study with the largest number of SON cases will help surgeons understand the variation and course of SON. LEVEL OF EVIDENCE IV: This journal requires that authors 38 assign a level of evidence to each article. For a full 39 description of these Evidence-Based Medicine ratings, 40 please refer to the Table of Contents or the online 41 Instructions to Authors www.springer.com/00266 .

Anatomical Relationship between the Inferior Temporal Septum and the Temporal Branch of the Facial Nerve for Clinical Applications.

BACKGROUND: The inferior temporal septum (ITS) is a fibrous adhesion between the superficial temporal fascia and the superficial layer of the deep temporal fascia. This study identified detailed the anatomical relationship between the ITS and the temporal branch of the facial nerve (TBFN) for facial nerve preservation during temple interventions. METHODS: Among 33 Korean cadavers, 43 sides of TBFNs in temporal regions were dissected after identifying the ITS between the superficial temporal fascia and superficial layer of the deep temporal fascia through blunt dissection. The topography of the ITS and TBFN were investigated with reference to several facial landmarks. Regional relationships with the ITS and TBFN within the temporal fascial layers were histologically defined from five specimens. RESULTS: At the level of the inferior orbital margin by the tragion, the mean distances from the lateral canthus to the anterior and posterior branches of the TBFN were 5 and 6.2 cm, respectively. At the lateral canthus level, the mean distance from the lateral canthus to the posterior branch of the TBFN was similar to that to the ITS, at 5.5 cm. At the superior orbital margin level, the posterior branch of the TBFN ran cranial to the ITS adjacent to the frontotemporal region. The TBFN ran through the subsuperficial temporal fascia layer and the nerve fibers located cranially, and within the ITS meshwork in the upper temporal compartment. CONCLUSION: The area of caution during superficial temporal fascia interventions related to the TBFN was clearly identified in the upper temporal compartment, which is known to lack important structures.

Physical Activity Promotion in North Carolina: a Reassessment of Public Park and Recreation Directors.

Regular physical activity is widely considered by public health and parks and recreation professionals as a key determinant of individual and community health and well-being. Prior research has shown that building sustainable health partnerships with community organizations can help parks and recreation departments meet many US health challenges. This descriptive study examined the perceptions of North Carolina public parks and recreation directors regarding physical activity and health partnership practices in their communities. The study was also a 15-year follow-up to a study and examined whether park and recreation director perceptions of health partnerships had changed given the many social, economic, and health events that have occurred since the original survey. Directors from two hundred seventy-five North Carolina city and county parks and recreation departments were surveyed in the Spring of 2022 to determine 1) directors' effort allocation in promoting physical activity toward vulnerable populations, 2) challenges associated with promoting community physical activity, and 3) differences in effort allocation, future priorities, and partnership among varying director and departmental demographics. Results were compared to findings from a 2007 study of NC perceptions of health partnerships, upon which the present study was based. One hundred twenty-three completed questionnaires were returned, resulting in a response rate of 45%. Directors in 2022 allocated similarly higher levels of effort toward older adults, families, and people with low income as did directors in 2007, while youth and adults with disabilities and people with chronic health conditions received lower allocations of effort from directors in 2022. Barriers such as lack of staff knowledge on how to promote physical activity, lack of citizen and political support, and lack of knowledge of under-represented groups' physical activity preferences were less pronounced in 2022 compared to 2007. Several distinct differences were revealed between female and male directors' rankings of effort and future priorities, as well as their perceptions of physical activity opportunities for women and people with disabilities. Partnerships with county health departments are being reported more in counties with the highest health disparities compared to more healthy counties, indicating that partnerships are being targeted and implemented in areas where resources are most needed. This study represents a meaningful extension of research conducted prior to the 2008 Great Recession and COVID-19 pandemic and provides recommendations for public parks and recreation departments to consider promoting physical activity and building community resilience in the face of future economic and health challenges.

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease: A Novel Analysis of the VITAL Trial Using Win Ratio and Hierarchical Composite Outcomes.

This study aimed to investigate whether n-3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n-3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults (n = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n-3 fatty acids to placebo. The primary result was a nonsignificant benefit of this supplementation for the prioritized primary CVD outcome (reciprocal win ratio [95% confidence interval]: 0.90 [0.78-1.04]), similar to the 0.92 (0.80-1.06) hazard ratio in our original time-to-first event analysis without outcome prioritization. Its benefits came from reducing MI (0.71 [0.57-0.88]) but not stroke (1.01 [0.80 to 1.28]) components. For the primary CVD outcome, participants with low fish consumption at baseline benefited (0.79 [0.65-0.96]) more than those with high consumption (1.05 [0.85-1.30]). These results are consistent with, but slightly stronger than, those without outcome prioritization.

Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL).

Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention.Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 × 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011-March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9.Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 [0.25 to 1.53]; omega-3s vs placebo: 1.08 [0.46 to 2.71]). There were no significant differences in PHQ-9 score change comparing either supplement with placebo.Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited.Trial Registration: ClinicalTrials.gov identifier: NCT01696435.

A Retrospective Multicenter Study of the Clinicopathological Characteristics and Prognosis of Young Adult Patients with Colorectal Cancer: Effects of Chemotherapy on Prognosis.

BACKGROUND: The objective of this study was to evaluate clinicopathologic features of young patients with colorectal cancer (CRC) and to compare their prognosis with those of older patients Methods: We retrospectively reviewed the medical records of patients who underwent surgery for stage 0-III CRC at four university-affiliated hospitals between January 2011 and December 2020. The patients were divided into two groups, the young adult group (≤45 years) and the older group (>45 years). RESULTS: Of 1992 patients, 93 (4.6%) were young adults and 1899 (95.3%) were older patients. Young patients showed more symptoms (p = 0.014) and more poorly or undifferentiated adenocarcinoma (p = 0.047) than older patients. The young adult patients were more likely to receive adjuvant chemotherapy (p < 0.001) and multidrug agents (p = 0.029), and less likely to cease chemotherapy (p = 0.037). The five-year RFS (recurrence-free survival) rate was better in the young adults than in the older patients (p = 0.009). In the multivariable analysis, young age was a significant prognostic factor for better RFS (p = 0.015). CONCLUSIONS: Young patients with CRC had more symptoms, aggressive histological features than older patients. They received more multidrug agents and discontinued chemotherapy less often, resulting in better prognosis.

625 nm Light Irradiation Prevented MC3T3-E1 Cells from Accumulation of Misfolded Proteins via ROS and ATP Production.

Osteoblasts must acquire a considerable capacity for folding unfolded and misfolded proteins (MPs) to produce large amounts of extracellular matrix proteins and maintain bone homeostasis. MP accumulation contributes to cellular apoptosis and bone disorders. Photobiomodulation therapy has been used to treat bone diseases, but the effects of decreasing MPs with photobiomodulation remain unclear. In this study, we explored the efficacy of 625 nm light-emitting diode irradiation (LEDI) to reduce MPs in tunicamycin (TM) induced-MC3T3-E1 cells. Binding immunoglobulin protein (BiP), an adenosine triphosphate (ATP)-dependent chaperone, is used to evaluate the capacity of folding MPs. The results revealed that pretreatment with 625 nm LEDI (Pre-IR) induced reactive oxygen species (ROS) production, leading to the increased chaperone BiP through the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1s (XBP-1s) pathway, and then restoration of collagen type I (COL-I) and osteopontin (OPN) expression relieving cell apoptosis. Furthermore, the translocation of BiP into the endoplasmic reticulum (ER) lumen might be followed by a high level of ATP production. Taken together, these results suggest that Pre-IR could be beneficial to prevent MP accumulation through ROS and ATP in TM-induced MC3T3-E1cells.

Adherence to Healthy Lifestyle Prior to Infection and Risk of Post-COVID-19 Condition.

Importance: Few modifiable risk factors for post-COVID-19 condition (PCC) have been identified. Objective: To investigate the association between healthy lifestyle factors prior to SARS-CoV-2 infection and risk of PCC. Design, Setting, and Participants: In this prospective cohort study, 32 249 women in the Nurses' Health Study II cohort reported preinfection lifestyle habits in 2015 and 2017. Healthy lifestyle factors included healthy body mass index (BMI, 18.5-24.9; calculated as weight in kilograms divided by height in meters squared), never smoking, at least 150 minutes per week of moderate to vigorous physical activity, moderate alcohol intake (5 to 15 g/d), high diet quality (upper 40% of Alternate Healthy Eating Index-2010 score), and adequate sleep (7 to 9 h/d). Main Outcomes and Measures: SARS-CoV-2 infection (confirmed by test) and PCC (at least 4 weeks of symptoms) were self-reported on 7 periodic surveys administered from April 2020 to November 2021. Among participants with SARS-CoV-2 infection, the relative risk (RR) of PCC in association with the number of healthy lifestyle factors (0 to 6) was estimated using Poisson regression and adjusting for demographic factors and comorbidities. Results: A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years (SD, 4.6; range, 55-75); 97.4% (n = 1929) were White; and 42.8% (n = 848) were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk (RR, 0.51; 95% CI, 0.33-0.78) of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC (BMI, 18.5-24.9 vs others, RR, 0.85; 95% CI, 0.73-1.00, P = .046; sleep, 7-9 h/d vs others, RR, 0.83; 95% CI, 0.72-0.95, P = .008). If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors (population attributable risk percentage, 36.0%; 95% CI, 14.1%-52.7%). Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment. Conclusions and Relevance: In this prospective cohort study, pre-infection healthy lifestyle was associated with a substantially lower risk of PCC. Future research should investigate whether lifestyle interventions may reduce risk of developing PCC or mitigate symptoms among individuals with PCC or possibly other postinfection syndromes.

Genetic Associations Between Smoking- and Glaucoma-Related Traits.

Purpose: The purpose of this study was to describe the genetic relationship between smoking and glaucoma. Methods: We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants. Results: We identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (-0.18 mm Hg per SD, 95% confidence interval [CI] = -0.30 to -0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (-0.09 mm Hg per SD, 95% CI = -0.17 to -0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13). Conclusions: MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma. Translational Relevance: Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.

Beneficial Effects of Fermentation of Red Chili Pepper Using Lactococcus lactis subs. Cremoris RPG-HL-0136 in High-Fat Diet-Induced Obese Mice.

Red chili pepper is a beneficial natural spicy food that has antiobesity and antitype II diabetes effects, but it is not conducive to in-depth research as a dietary strategy to treat obesity. This study aims to investigate the beneficial effects of red chili pepper, fermented with a novel Lactococcus lactis subs. cremoris RPG-HL-0136. LC-MS/MS analysis is conducted to detect the content of capsaicin and dihydrocapsaicin, and no significant difference is observed between the nonfermented red chili pepper (NFP) (W/W) and the prepared L. lactis subs. cremoris RPG-HL-0136-fermented chili mixture (LFP). After establishing a high-fat diet-induced obese type II diabetic mouse model, the effects on weight gain, weight loss of liver and testicular fat, total cholesterol, triglyceride, fasting glucose, insulin, and homeostatic model assessment for insulin resistance in LFP were evaluated to be better than those in NFP following 10 weeks of interventions. All animal experiments were approved by the Institutional Animal Care and Use Committee of Xinxiang medical university. NFP and LFP could increase the expression of transient receptor potential vanilloid subfamily 1, peroxisome proliferator-activated receptor-alpha and caspase-2 in the high-fat mice. Compared with unfermented red chili pepper, the fermented red chili pepper complex significantly reduced LPS, tumor necrosis factor-alpha, and interleukin-6 in serum (P < .05). Intake of LFP significantly increased the expression of claudin-1 and occludin in the colon of the high-fat mice (P < .05), and there was no damage to the stomach and colon. This study provides scientific evidence that red chili pepper, fermented with L. lactis subs. cremoris RPG-HL-0136, may be beneficial for future treatment of obesity and accompanying diabetes. (IACUC.No.XYLL-20200019).