Air pollution and survival in patients with malignant mesothelioma and asbestos-related lung cancer: a follow-up study of 1591 patients in South Korea.

BACKGROUND: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer. METHODS: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 µm, and fine particulate matter with a diameter < 2.5 µm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality. RESULTS: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30). CONCLUSION: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival.

Exposure to biocides and its association with atopic dermatitis among children and adolescents: A population-based cross-sectional study in South Korea.

BACKGROUND: Biocides have emerged as a contributor to the rising cases of atopic dermatitis among children and adolescents. Previous animal studies suggested that phenols, parabens, and pyrethroid insecticides present in these products might play a role in atopic dermatitis. However, there's limited epidemiological evidence confirming the individual or combined effects of exposure to these chemicals on atopic dermatitis in young populations. This study aimed to investigate the association between phenol, paraben, and pyrethroid metabolite levels in urine and atopic dermatitis among Korean children and adolescents METHODS: We analyzed 556 preschool children (3-5 years), 701 schoolchildren (6-11 years), and 731 adolescents (12-17 years) enrolled in the 4th Korean National Environmental Health Survey (KoNEHS) (2018-2020). We used logistic regression and Bayesian kernel machine regression to evaluate the association between atopic dermatitis and individual or mixed exposure to urinary triclosan (TCS), parabens (methylparaben, ethylparaben, propylparaben, and butylparaben), and 3-phenoxybenzoic acid (3-PBA) levels. RESULTS: Urinary TCS levels were positively associated with atopic dermatitis in schoolchildren. When stratified by sex, male schoolchildren exhibited an increasing prevalence of atopic dermatitis as their urinary TCS and 3-PBA levels increased. The combined effect of biocide mixtures on atopic dermatitis was also significantly increased in male schoolchildren, with TCS as the main contributor. CONCLUSIONS: These study findings suggest that biocides at levels found in Korean children and adolescents affect atopic dermatitis.

Balanced crystalloids (RInger's lactate) versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department (BRISK-ED): a pilot randomised controlled trial.

BACKGROUND: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA. METHODS: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation. RESULTS: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up. CONCLUSIONS: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED. TRIAL REGISTRATION NUMBER: NCT04926740.

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 .

Health risks of pest control and disinfection workers after the COVID-19 outbreak in South Korea.

The exposure patterns of pest control and disinfection workers have changed after the coronavirus disease 2019 (COVID-19) outbreak, but the health risks of chemical exposure have not been assessed. We identified these workers' chemical exposure patterns and risks before and after the COVID-19 outbreak. We used data conducted between 2018 (pre-pandemic) and 2021 (post-pandemic) from three-year cross-sectional surveys on pest control and disinfection workers. Inhalation and dermal exposure concentrations were estimated using equations based on a biocidal product risk assessment model from the Korean National Institute of Environmental Research. The non-carcinogenic and carcinogenic risks of chemicals were calculated using the United States Environmental Protection Agency risk assessment model. We found that the annual work frequency (50th percentile) of foggers using disinfectants increased the most among all the work types, from 140 uses/year to 176 uses/year after the COVID-19 outbreak. Moreover, all chemicals' non-carcinogenic and carcinogenic risks increased regardless of exposure routes. In the worst scenario (95th percentile), the margin of exposure for citric acid, benzethonium chloride, benzyl-C12-16-alkyldimethyl chlorides, and sodium chlorite of inhalation exposure, and isopropyl alcohol and benzyl-C12-16-alkyldimethyl chlorides of dermal exposure were acceptable (>100) before the COVID-19 outbreak but became unacceptable (<100) after the COVID-19 outbreak. Carcinogenic risks of dichlorvos from inhalation and dermal exposure were above acceptable levels (>10-6) before and after the COVID-19 outbreak but comparatively high after the COVID-19 outbreak. Additionally, significantly more workers experienced health symptoms after the COVID-19 outbreak (p<0.05), with the most common being muscle lethargy (31%), skin/face stinging (28.7%), and breath shortness/neck pain (24.1%).

Astrocytic FoxO1 in the hypothalamus regulates metabolic homeostasis by coordinating neuropeptide Y neuron activity.

The forkhead box transcription factor O1 (FoxO1) is expressed ubiquitously throughout the central nervous system, including in astrocytes, the most prevalent glial cell type in the brain. While the role of FoxO1 in hypothalamic neurons in controlling food intake and energy balance is well-established, the contribution of astrocytic FoxO1 in regulating energy homeostasis has not yet been determined. In the current study, we demonstrate the essential role of hypothalamic astrocytic FoxO1 in maintaining normal neuronal activity in the hypothalamus and whole-body glucose metabolism. Inhibition of FoxO1 function in hypothalamic astrocytes shifts the cellular metabolism from glycolysis to oxidative phosphorylation, enhancing astrocyte ATP production and release meanwhile decreasing astrocytic export of lactate. As a result, specific deletion of astrocytic FoxO1, particularly in the hypothalamus, causes a hyperactivation of hypothalamic neuropeptide Y neurons, which leads to an increase in acute feeding and impaired glucose regulation and ultimately results in diet-induced obesity and systemic glucose dyshomeostasis.

Exposure to volatile organic compounds and polycyclic aromatic hydrocarbons is associated with the risk of non-alcoholic fatty liver disease in Korean adolescents: Korea National Environmental Health Survey (KoNEHS) 2015-2017.

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent liver diseases among adolescents. Several animal studies have suggested that volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) increase NAFLD risk. However, few epidemiological studies have confirmed the association between VOCs, PAHs and NAFLD in the general adolescent population. Therefore, we analyzed 798 adolescents from the Korean National Environmental Health Survey (KoNEHS), 2015-2017, to examine the associations of urinary metabolites of VOCs and PAHs with serum alanine aminotransferase (ALT) activity and NAFLD prevalence. We performed linear regression, logistic regression, and Bayesian kernel machine regression (BKMR) to evaluate the association of urinary VOCs and PAHs metabolites with ALT levels and NAFLD prevalence. After adjusting for all covariates, urinary benzylmercapturic acid and 2-hydroxyfluorene levels were found to increase ALT activity and NAFLD prevalence. Additionally, the BKMR analyses showed a significantly positive overall effect on ALT activity and NAFLD prevalence with urinary concentrations of VOCs and PAHs metabolites, with 2-hydroxyfluorene as the biggest contributor. Our study suggests that exposure to low-level VOCs and PAHs may have a detrimental effect on NAFLD risk in adolescents. Given the increasing prevalence of NAFLD in adolescents, future cohort studies are confirmed to comprehend the effect of these chemicals on NAFLD risk.

Occupational exposure to VOCs and carbonyl compounds in beauty salons and health risks associated with it in South Korea.

Long-term exposure to volatile organic compounds (VOCs) and carbonyl compounds in beauty products may adversely impact the health of beauty salon technicians. Previous studies have focused on assessing indoor air concentrations of chemicals, such as benzene and toluene, and not on personal exposure concentrations. This study measured the indoor and personal exposure concentrations of VOCs and carbonyl compounds in fifty-three beauty salons in Korea. Non-carcinogenic and carcinogenic risks and sensitivity were analyzed using the Monte Carlo simulation technique. The indoor and personal exposure concentrations of acetone were 82.24 µg/m3 and 104.97 µg/m3, respectively, the highest among all measured chemicals. Beauty salon technicians who experienced adverse health effects had significantly higher concentrations of acetone, benzaldehyde, and toluene than those who did not experience adverse health effects (p-value < 0.05). The average hazard quotients of formaldehyde and acetaldehyde were higher than the acceptable risk level (1), and the average cancer risks of formaldehyde exceeded the acceptable risk level (10-6). Wearing personal protective equipment was the most efficient risk reduction strategy for reducing the non-cancer risks of acetaldehyde and formaldehyde and the carcinogenic risks of formaldehyde. The results of this study can be used as a basis for reducing exposure to VOCs and carbonyl compounds among salon technicians.

Distribution-Free Approach to the Design and Analysis of Randomized Stroke Trials With the Modified Rankin Scale.

BACKGROUND: Many methods have been suggested for analyzing the modified Rankin Scale (mRS). However, there lacks a unified approach to analysis and sample size determination that properly uses the ordinal nature of the data. We propose a simple method for CI estimation and corresponding sample size determination. METHODS: We quantify treatment effect by the win probability (WinP) that a randomly selected patient in the treatment group has an equal or a better mRS score than a patient in the control group. Thus, a win probability of 0.5 means no effect, likened to a draw in competitive sports. We estimate the win probability and its SE based on the ranks of mRS scores, where tied scores are handled by average ranks. Corresponding methods for hypothesis testing, CI estimation, and sample size determination are derived. The methods are evaluated with a simulation study based on real data from 10 randomized stroke trials that used mRS as the outcome measure. RESULTS: Simulation results demonstrated that the methods performed very well in terms of CI coverage, tail errors, and assurance to achieving the prespecified precision. Because the methods are very simple, we implemented them in an Excel spreadsheet, requiring only user inputs on frequencies of mRS scores in 2 comparison groups. CONCLUSIONS: Sound statistical methods are important for the success of randomized stroke trials. The proposed methods and associated spreadsheet should prove useful for stroke researchers in the planning and analysis of randomized trials. Meta-analysis has also been made easy for trials with ordinal scores.

Enhancing biosynthesis of 2'-Fucosyllactose in Escherichia coli through engineering lactose operon for lactose transport and α -1,2-Fucosyltransferase for solubility.

2'-Fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and one of the most actively studied human milk oligosaccharides (HMOs). When 2'-FL is produced through biological production using a microorganism, like Escherichia coli, d-lactose is often externally fed as an acceptor substrate for fucosyltransferase (FT). When d-glucose is used as a carbon source for the cell growth and d-lactose is transported by lactose permease (LacY) in lac operon, d-lactose transport is under the control of catabolite repression (CR), limiting the supply of d-lactose for FT reaction in the cell, hence decreasing the production of 2'-FL. In this study, a remarkable increase of 2'-FL production was achieved by relieving the CR from the lac operon of the host E. coli BL21 and introducing adequate site-specific mutations into α-1,2-FT (FutC) for enhancement of catalytic activity and solubility. For the host engineering, the native lac promoter (Plac ) was substituted for tac promoter (Ptac ), so that the lac operon could be turned on, but not subjected to CR by high d-glucose concentration. Next, for protein engineering of FutC, family multiple sequence analysis for conserved amino acid sequences and protein-ligand substrate docking analysis led us to find several mutation sites, which could increase the solubility of FutC and its activity. As a result, a combination of four mutation sites (F40S/Q150H/C151R/Q239S) was identified as the best candidate, and the quadruple mutant of FutC enhanced 2'-FL titer by 2.4-fold. When the above-mentioned E. coli mutant host transformed with the quadruple mutant of futC was subjected to fed-batch culture, 40 g l-1 of 2'-FL titer was achieved with the productivity of 0.55 g l-1 h-1 and the specific 2'-FL yield of 1.0 g g-1 dry cell weight.

Family physician virtual care during COVID-19 in London-Middlesex, Ontario, Canada: a mixed methods exploration.

Context: On March 14, 2020, the Ontario, Canada health insurance plan approved COVID-19 physician virtual billing codes; family physicians (FPs) rapidly adopted a new model of care. Virtual care may remain post-pandemic; however, its future should be informed by evidence that considers access and continuity. Objective: 1) to determine FP virtual visit volumes and patient characteristics and 2) to explore FPs' perspectives on virtual visit adoption and implementation. Study Design: Mixed methods: Secondary analysis of health administrative (HA) data and semi-structured qualitative interviews with FPs. Setting or Dataset: London and Middlesex County, Ontario, Canada. HA data through ICES, Ontario entity holding data. Population studied: FPs and their patients. Outcome Measures: Volumes of FP in-person and virtual visits during early pandemic; characteristics of patients receiving care; FPs' perspectives on adopting and delivering virtual care. Results: Overall visit volume dropped by 36% during first wave, recovered to pre-pandemic levels by October 2020. Sharp in-person visit drop of 73% and virtual visit uptake from 0.08% of total visits to 57% within two weeks of March 2020. FPs described this initial drop in volume as patients not seeking care and practices lacking PPE. The move to virtual care was largely to telephone visits. Patient characteristics compared to pre-pandemic, the proportion seeking care were older (46 vs 50 years), more vulnerable (38% vs 41%), and more multimorbidity (33% vs 41%). This was consistent with FP reports that healthier patients stayed away, routine care deferred, sicker patients needed to be seen. FPs believed most vulnerable patients had access to care but cautioned highly vulnerable such as those homeless did not have cell phone access or a safe place to receive calls. Rural FPs reported access issues because of lack of high-speed internet. FPs attributed success of virtual care to the continuity in relationships they had with patients that were established in person pre-pandemic. Conclusions: FPs moved rapidly to virtual care. FP offices remained open despite PPE concerns but overall volumes dropped initially. Vulnerable and sicker patients received care but FPs expressed concern for highly vulnerable and rural residents. FPs believed they could offer patient-centred care over the phone but indicated the importance of maintaining in-person care to build relationships.

Small steps, strong shield: directly measured, moderate physical activity in 65 361 adults is associated with significant protective effects from severe COVID-19 outcomes.

OBJECTIVE: To determine the association between directly measured physical activity and hospitalisation, intensive care unit (ICU) admission, ventilation and mortality rates in patients with a confirmed diagnosis of COVID-19. METHODS: Directly measured physical activity data from 65 361 adult patients with a COVID-19 diagnosis from 19 March 2020 to 30 June 2021, were grouped by activity level: low (<60 min/week), moderate (60-149 min/week) and high activity (≥150 min/week). The association of physical activity levels and the risk of adverse outcomes was analysed using modified Poisson regression. We accounted for demographics and comorbidities including conditions known to influence COVID-19 outcomes, as well as patient complexity as measured by the Johns Hopkins Adjusted Clinical Group system. The regression approach was further validated with a Bayesian network model built off a directed acyclic graph. RESULTS: High physical activity was associated with lower rates of hospitalisation (risk ratio, RR 0.66, 95% CI 0.63 to 0.70), ICU admission (RR 0.59, 95% CI 0.52 to 0.66), ventilation (RR 0.55, 95% CI 0.47 to 0.64) and death (RR 0.58, 95% CI 0.50 to 0.68) due to COVID-19 than those who engaged in low physical activity. Moderate physical activity also was associated with lower rates of hospitalisation (RR 0.87, 95% CI 0.82 to 0.91), admission to ICU (RR 0.80, 95% CI 0.71 to 0.89), ventilation (RR 0.73, 95% CI 0.62 to 0.84) and death (RR 0.79, 95% CI 0.69 to 0.91). CONCLUSIONS: Adults with high and moderate physical activity levels had significantly better outcomes than those with low activity when contracting COVID-19. The apparent protective effects of regular physical activity extended to those with concomitant chronic medical conditions.

The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks.

KEY POINTS: The capillary module, consisting of parallel capillaries from arteriole to venule, is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres. Using intravital video microscopy of resting extensor digitorum longus muscle in rats, we demonstrated the capillary fascicle as a series of interconnected modules forming continuous columns that align naturally with the dimensions of the muscle fascicle. We observed structural heterogeneity for module topology, and functional heterogeneity in space and time for capillary-red blood cell (RBC) haemodynamics within a module and between modules. We found that module RBC haemodynamics were independent of module resistance, providing direct evidence for microvascular flow regulation at the level of the capillary module. The capillary fascicle is an updated paradigm for characterizing blood flow and RBC distribution in skeletal muscle capillary networks. ABSTRACT: Capillary networks are the fundamental site of oxygen exchange in the microcirculation. The capillary module (CM), consisting of parallel capillaries from terminal arteriole (TA) to post-capillary venule (PCV), is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres, requiring co-ordination from numerous modules. It has previously been recognized that TAs and PCVs interact with multiple CMs, creating interconnected networks. Using label-free intravital video microscopy of resting extensor digitorum longus muscle in rats, we found that these networks form continuous columns of linked CMs spanning thousands of microns, herein denoted as the capillary fascicle (CF); this structure aligns naturally with the dimensions of the muscle fascicle. We measured capillary-red blood cell (RBC) haemodynamics and module topology (n = 9 networks, 327 modules, 1491 capillary segments). The average module had length 481 µm, width 157 µm and 9.51 parallel capillaries. We observed structural heterogeneity for CM topology, and functional heterogeneity in space and time for capillary-RBC haemodynamics within a module and between modules. There was no correlation between capillary RBC velocity and lineal density. A passive inverse relationship between module length and haemodynamics was remarkably absent, providing direct evidence for microvascular flow regulation at the level of the CM. In summary, the CF is an updated paradigm for characterizing RBC distribution in skeletal muscle, and strengthens the theory of capillary networks as major contributors to the signal that regulates capillary perfusion.

Joint Effect of Alcohol Drinking and Environmental Cadmium Exposure on Hypertension in Korean Adults: Analysis of Data from the Korea National Health and Nutrition Examination Survey, 2008 to 2013.

BACKGROUND: Hypertension is a common disease found in 1.13 billion adults worldwide. Several animal studies have provided evidence of the joint effect of alcohol drinking and cadmium exposure on hypertension. However, no epidemiologic study has examined the association between these 2 risk factors and hypertension. Therefore, we examined the individual effects of alcohol drinking and cadmium and the joint effect of their coexposure on hypertension in the general population. METHODS: We analyzed data from 8,403 South Korean adults who had been randomly assigned to the Korea National Health and Nutrition Examination Survey from 2008 to 2013. Multiple linear and logistic regression analyses were conducted to estimate the association of alcohol drinking and blood cadmium concentration with blood pressure and the odds ratio (OR) for hypertension. RESULTS: The weighted prevalence of hypertension and high-risk drinking was 25.7 and 13.6%, respectively. The weighted geometric mean of blood cadmium levels was 0.94 µg/L (95% confidence interval [CI]: 0.93 to 0.96). After adjusting for demographic characteristics, anthropometric measurements, health-related behaviors, and dietary and disease variables, the OR for hypertension in the group with the high-risk alcohol drinking was 1.67 (95% CI: 1.34 to 2.06) compared with the group without high-risk alcohol drinking. When the highest and the lowest blood cadmium quartiles were compared, the OR for hypertension was 1.46 (95% CI: 1.15 to 1.86). The positive joint effect of high-risk drinking and blood cadmium levels was statistically significant for systolic blood pressure (SBP; p = 0.037) and diastolic blood pressure (DBP; p < 0.001). CONCLUSIONS: Our results show that heavy alcohol drinking had a joint effect with cadmium exposure to increase the risk of hypertension. Future efforts are needed to reduce alcohol drinking and environmental cadmium exposure to prevent hypertension in the general population.

FamEvent: An R Package for Generating and Modeling Time-to-Event Data in Family Designs.

FamEvent is a comprehensive R package for simulating and modelling age-at-disease onset in families carrying a rare gene mutation. The package can simulate complex family data for variable time-to-event outcomes under three common family study designs (population, high-risk clinic and multi-stage) with various levels of missing genetic information among family members. Residual familial correlation can be induced through the inclusion of a frailty term or a second gene. Disease-gene carrier probabilities are evaluated assuming Mendelian transmission or empirically from the data. When genetic information on the disease gene is missing, an Expectation-Maximization algorithm is employed to calculate the carrier probabilities. Penetrance model functions with ascertainment correction adapted to the sampling design provide age-specific cumulative disease risks by sex, mutation status, and other covariates for simulated data as well as real data analysis. Robust standard errors and 95% confidence intervals are available for these estimates. Plots of pedigrees and penetrance functions based on the fitted model provide graphical displays to evaluate and summarize the models.

Oral Commissure Lift: A Retrospective Analysis of Complication Rates and Overall Outcomes.

BACKGROUND: Downward-turning oral commissures and sagging mouth corners can present an unfavorable impression. We introduced a new oral commissure lift procedure and investigated its effectiveness and complication rates. METHODS: Patients who underwent oral commissure lift in the plastic surgery clinic between January 2010 and December 2017 were enrolled retrospectively. Pre-and postoperative photographs were evaluated to measure oral commissure angles and analyze surgical complications, including visible scarring, unnatural appearance, and asymmetry. Many patients underwent a oral commissure lift with a simultaneous facelift. To exclude potential bias, we compared angular changes between patients receiving both oral commissure lift and facelift, with those receiving only oral commissure lift. Moreover, oral commissure angles of patients only receiving facelift were also measured. Statistical significance was set at p < 0.05. RESULTS: Oral commissure lift was performed in 51 patients. The mean ages and follow-up periods were 46.7 ± 11.9 years, and 25.2 ± 22.9 months, respectively. The preoperative mean angles of the right and left oral commissures measured - 3.1 ± 4.0° and - 3.4 ± 3.7°, respectively, and postoperative mean angles measured 3.6 ± 3.2° and 3.3 ± 3.5°, respectively. Postoperative changes in oral commissure angles were statistically significant (p < 0.05). The low complication rate included undercorrection in one patient, asymmetry in one patient, and visible scarring in three patients. We found no statistically significant differences in the studies excluding bias. CONCLUSIONS: The new oral commissure lift procedure for correcting sagging oral commissures was simple, safe, and effective with a low complication rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Competing Endogenous RNA of Snail and Zeb1 UTR in Therapeutic Resistance of Colorectal Cancer.

The epithelial-mesenchymal transition (EMT) comprises an important biological mechanism not only for cancer progression but also in the therapeutic resistance of cancer cells. While the importance of the protein abundance of EMT-inducers, such as Snail (SNAI1) and Zeb1 (ZEB1), during EMT progression is clear, the reciprocal interactions between the untranslated regions (UTRs) of EMT-inducers via a competing endogenous RNA (ceRNA) network have received little attention. In this study, we found a synchronized transcript abundance of Snail and Zeb1 mediated by a non-coding RNA network in colorectal cancer (CRC). Importantly, the trans-regulatory ceRNA network in the UTRs of EMT inducers is mediated by competition between tumor suppressive miRNA-34 (miR-34) and miRNA-200 (miR-200). Furthermore, the ceRNA network consisting of the UTRs of EMT inducers and tumor suppressive miRs is functional in the EMT phenotype and therapeutic resistance of colon cancer. In The Cancer Genome Atlas (TCGA) samples, we also found genome-wide ceRNA gene sets regulated by miR-34a and miR-200 in colorectal cancer. These results indicate that the ceRNA networks regulated by the reciprocal interaction between EMT gene UTRs and tumor suppressive miRs are functional in CRC progression and therapeutic resistance.

Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients.

PURPOSE: Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer. METHODS: One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia. RESULTS: More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia. CONCLUSIONS: Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.

Industrial attributes of ß-glucanase produced by Bacillus sp. CSB55 and its potential application as bio-industrial catalyst.

The ß-glucanase produced from Bacillus sp. CSB55 not only depicts the potent industrial characteristics but also relates as bio-industrial catalyst supporting the spontaneous formation of the products, high hydrolytic efficiency, and feasibility of the enzymatic reaction. A homogeneous ß-glucanase (GluB55) was purified via various purification processes resulting in 11.69% yield and 14.24-fold purity. Biochemical characterization of the purified enzyme revealed the molecular mass of approximately 40 kDa, which was verified by zymography. The optimum activity of GluB55 was determined at pH 7.2 and 55 °C. GluB55 could highly hydrolyze carboxymethylcellulose and was stable over a wide range of pH, retaining more than 70% residual activity at pH 5.8-11.0 and carried 100% thermostability as high as 60 °C. In addition, it showed 68% residual activity at 70 °C. The N-terminal amino acid sequence of GluB55 was Ala-Asn-Pro-Glu-Leu-Val-Asn-X-Gln-Ala-X-X-Ala-X-Gln-Gly. The enzyme activity was stimulated by Co2+ (158.6%), Zn2+ (211.1%), Mn2+ (264.4%), and Ba2+ (211.4%). Enzyme kinetics showed Km and Vmax values of 0.022 mg mL-1 and 994.56 ± 3.72 U mg-1, respectively. Q10 was calculated to be 1.12. ∆H, ∆G, and ∆S were low revealing that the formation of the transition phase and conversion to the product is very well organized. The lower the free energy change (∆G), the more feasible is the reaction.

ß-Neoendorphin Enhances Wound Healing by Promoting Cell Migration in Keratinocyte.

The skin is the largest and a remarkably plastic organ that serves as a protective barrier against environmental stimuli and injuries throughout life. Skin injuries are serious health problems, and wound healing is a critical process to replace devitalized cellular and tissue structures. Although some endogenous opioids are known to be involved in the modulation of wound healing, it remains to be determined whether the ß-neoendorphin (ß-NEP), an endogenous opioid, has beneficial effects on wound repair in human keratinocyte. In this study, we found that ß-NEP accelerated wound repair through activation of mitogen-activated protein kinase (MAPK)/Erk1/2 signaling pathways in human keratinocytes. Moreover, the wound healing effect of ß-NEP is mainly through the acceleration of keratinocyte migration without affecting cell proliferation. Therefore, our studies reveal that ß-NEP plays an important role in the regulation of wound repair and suggest a therapeutic strategy to promote wound healing using ß-NEP.