Dynamics of antibiotic resistance genes and the association with bacterial community during pig manure composting with chitin and glucosamine addition.

In modern ecological systems, the overuse and misuse of antibiotics have escalated the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), positioning them as emerging environmental contaminants. Notably, composting serves as a sustainable method to recycle agricultural waste into nutrient-rich fertilizer while potentially reducing ARGs and MGEs. This study conducted a 47-day composting experiment using pig manure and corn straw, supplemented with chitin and N-Acetyl-D-glucosamine, to explore the impact of these additives on the dynamics of ARGs and MGEs, and to unravel the interplay between these genetic elements and microbial communities in pig manure composting. Results showed that adding 5% chitin into composting significantly postponed thermophilic phase, yet enhanced the removal efficiency of total ARGs and MGEs by over 20% compared to the control. Additionally, the addition of N-Acetyl-D-glucosamine significantly increased the abundance of tetracycline-resistant and sulfonamide-resistant genes, as well as MGEs. High-throughput sequencing revealed that N-Acetyl-D-glucosamine enhanced bacterial α-diversity, providing diverse hosts for ARGs and MGEs. Resistance mechanisms, predominantly efflux pumps and antibiotic deactivation, played a pivotal role in shaping the resistome of composting process. Co-occurrence network analysis identified the key bacterial phyla Proteobacteria, Firmicutes, Gemmatimonadota, and Myxococcota in ARGs and MGEs transformation and dissemination. Redundancy analysis indicated that physicochemical factors, particularly the carbon-to-nitrogen ratio emerged as critical variables influencing ARGs and MGEs. The findings lay a foundation for the developing microbial regulation method to reduce the risks of ARGs in animal manure composts.

Features of bacterial and fungal communities in the rhizosphere of Gastrodia elata cultivated in greenhouse for early harvest.

Symbiotic microbes are essential for developing and growing Gastrodia elata, an achlorophyllous orchid of high medicinal value. Recently, the cultivation of G. elata in greenhouses has been adopted in Korea to produce mature tubers in a short time. However, no studies have been conducted on the microbial community structure of G. elata cultivated in greenhouse environments. Therefore, we analyzed the temporal features of bacterial and fungal communities in the rhizosphere of G. elata at the juvenile [JT; 2 months after sowing (MAS)], young (YT; 6 MAS), and mature (MT; 11 MAS) tuber stages using culture-dependent and high-throughput sequencing technology. The richness and diversity of the bacterial and fungal communities decreased with tuber growth of G. elata. The symbiotic fungi Mycena sp. and Armillaria sp. as well as tuber extract inhibited the growth of various soil-inhabiting fungal and bacterial strains, indicating that G. elata and its symbiotic fungi play important roles in the selection of rhizosphere microbes. Mortierella rishikesha was the most abundant fungal species in the rhizosphere. We also identified the microorganisms potentially beneficial for G. elata development during greenhouse cultivation. Tubers and symbiotic fungi actively exert selective pressure on rhizosphere microbes, influencing the diversity and abundance of bacterial and fungal communities as G. elata grows. This study is a first report on the temporal microbial community structure of G. elata cultivated in greenhouse. The results on the associated microbiome of G. elata will help understand their beneficial interactions with G. elata and contribute to improvement in cultivation.

Metabolomics analysis of advancing humification mechanism in secondary fermentation of composting by fungal bioaugmentation.

The aim of this study was to investigate the differential metabolites and core metabolic pathways caused by fungal bioaugmentation (pH regulation and Phanerochaete chrysosporium inoculation) in secondary fermentation of composting, as well as their roles in advancing humification mechanism. Metabolomics analyses showed that inoculation strengthened the expression of carbohydrate, amino acid, and aromatic metabolites, and pH regulation resulted in the up-regulation of the phosphotransferase system and its downstream carbohydrate metabolic pathways, inhibiting Toluene degradation and driving biosynthesis of aromatic amino acids via the Shikimate pathway. Partial least squares path model suggested that lignocellulose degradation, precursors especially amino acids and their metabolism process enhanced by the regulation of pH and Phanerochaete were the main direct factors for humic acid formation in composting. This finding helps to understand the regulating mechanism of fungal bioaugmentation to improve the maturity of agricultural waste composting.

Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography.

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination.

Midbrain dopaminergic degeneration differentially modulates primary motor cortex activity and motor behavior in hemi-parkinsonian rats.

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD.

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.

[Nursing Experience Caring for a Premature Infant With Bronchopulmonary Dysplasia].

A nursing experience supporting parents experiencing anxiety related to their 26+2 weeks preterm infant on continued ventilator assistance at home due to bronchopulmonary dysplasia is described in this article. Data were collected from March 21st to June 1st, 2021 via observation, interviews, clinical care, medical record reviews, and discharge preparation services. A holistic nursing assessment identified the main health issues as: gas exchange disorder, inefficient infant feeding patterns, and caregiver role stress. The parents were encouraged to participate in care activities, create individualized discharge plans, and view health education videos and caregiving skill demonstrations. Kangaroo care, comfortable positioning and soothing techniques were used to stabilize the emotions of the infant and to strengthen the parent-child bond. Psychological support was provided to alleviate parental anxiety and to enhance parenting ability and confidence. This experience supports the importance of tailoring clinical care to individual needs, adopting a family-centered approach, assessing family interactions, and making early preparations to obtain appropriate continuous care after discharge to ensure proper continuum of care.

Effects of Unilateral High Frequency Stimulation of the Subthalamic Nucleus on Risk-avoidant Behavior in a Partial 6-hydroxydopamine Model of Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. METHODS: This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. RESULTS: No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. CONCLUSIONS: These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.

Phosphate additives promote humic acid carbon and nitrogen skeleton formation by regulating precursors and composting bacterial communities.

This study aimed to compare the effect of different phosphate additives including superphosphate (CP) and MP [Mg(OH)2 + H3PO4] on nitrogen conversion, humus fractions formation and bacterial community in food waste compost. The results showed the ratio of humic acid nitrogen in total nitrogen (HA-N/TN) in CP increased by 49 %. Ammonium nitrogen accumulation was increased by 75 % (CP) and 44 % (MP). Spectroscopic techniques proved that phosphate addition facilitated the formation of complex structures in HA. CP enhanced the dominance of Saccharomonospora, while Thermobifida and Bacillus were improved in MP. Structural equation modeling and network analysis demonstrated that ammonium nitrogen can be converted to HA-N and has positive effects on bacterial composition, reducing sugars and amino acids, especially in CP with more clustered network and synergic bacterial interactions. Therefore, the addition of phosphate provides a new idea to regulate the retained nitrogen toward humification in composting.

Combined Plasma DHA-Containing Phosphatidylcholine PCaa C38:6 and Tetradecanoyl-Carnitine as an Early Biomarker for Assessing the Mortality Risk among Sarcopenic Patients.

The coming of the hyper-aged society in Taiwan prompts us to investigate the relationship between the metabolic status of sarcopenic patients and their most adverse outcome-death. We studied the association between any plasma metabolites and the risk for mortality among older Taiwanese sarcopenic patients. We applied a targeted metabolomic approach to study the plasma metabolites of adults aged ≥65 years, and identified the metabolic signature predictive of the mortality of sarcopenic patients who died within a 5.5-year follow-up period. Thirty-five sarcopenic patients who died within the follow-up period (Dead cohort) had shown a specific plasma metabolic signature, as compared with 54 patients who were alive (Alive cohort). Only 10 of 116 non-sarcopenic individuals died during the same period. After multivariable adjustment, we found that sex, hypertension, tetradecanoyl-carnitine (C14-carnitine), and docosahexaenoic acid (DHA)-containing phosphatidylcholine diacyl (PCaa) C38:6 and C40:6 were important risk factors for the mortality of sarcopenic patients. Low PCaa C38:6 levels and high C14-carnitine levels correlated with an increased mortality risk; this was even the same for those patients with hypertension (HTN). Our findings suggest that plasma PCaa C38:6 and acylcarnitine C14-carnitine, when combined, can be a better early biomarker for evaluating the mortality risk of sarcopenia patients.

Labdane-Type Diterpenoids from Streptomyces griseorubens and Their Antimicrobial and Cytotoxic Activities.

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1-3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC50) values ranging from 1.2 to 22.5 µM.

The contribution of microbial necromass to soil organic carbon and influencing factors along a variation of habitats in alpine ecosystems.

A growing consensus is reached that microbes contributes to regulating the formation and accumulation of soil organic carbon (SOC). Nevertheless, less is known about the role of soil microbes (necromass, biomass) in SOC accumulation in different habitat conditions in alpine ecosystems. To address this knowledge gap, the composition and distribution of amino sugars (ASs) and phospholipid fatty acids (PLFAs) as biomarkers of microbial necromass and biomass were investigated in forest, meadow and wetland soil profile (0-40 cm) of Mount Segrila, Tibet, China, as well the contribution of bacterial and fungal necromass to SOC. The results revealed that microbial necromass carbon contributed 45.15 %, 72.51 % and 78.08 % on average to SOC in 0-40 cm forest, meadow and wetland soils, respectively, and decreased with microbial biomass. Fungal necromass contributed more to SOC in these habitats than bacterial necromass. Microbial necromass increased with microbial biomass and both of them decreased with soil depth in all habitats. The necromass accumulation coefficient was significantly correlated with microbial necromass and biomass, affected by habitat and soil moisture. Structural equation model indicated that soil abiotic factors indirectly mediated the accumulation of SOC through microbial necromass and biomass. This study revealed that different habitats and soil depths control considerably soil physicochemical properties and microbial community, finally influencing SOC accumulation in alpine ecosystems, which emphasized the influence of abiotic factors on microbial necromass and biomass for SOC accumulation in alpine ecosystems.

Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 µM (ascorbic acid, EC50 = 7.81 µM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 µM, respectively (acarbose, IC50 = 301.93 µM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 µM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 µM.

Lobe-specific lymph node sampling is associated with lower risk of cancer recurrence.

Objective: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients. Methods: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data from operative and pathology reports for patients with clinical stage I NSCLC (2006-2016). For simplicity in comparison, we included patients who had right upper lobe (RUL) or left upper lobe (LUL) tumors. Based on modified European Society of Thoracic Surgeons guidelines, lobe-specific sampling was defined for RUL tumors (stations 2, 4, 7, and 10 or 11) and LUL tumors (stations 5 or 6, 7, and 10 or 11). Our primary outcome was the risk of cancer recurrence, as assessed by Fine and Gray competing risks modeling. Secondary outcomes included overall survival (OS) and pathologic upstaging. Analyses were adjusted for relevant patient, disease, and treatment variables. Results: Our study included 3534 patients with RUL tumors and 2667 patients with LUL tumors. Of these, 277 patients (7.8%) with RUL tumors and 621 patients (23.2%) with LUL tumors met lobe-specific assessment criteria. Comparatively, 34.7% of patients met the criteria for count-based assessment, and 25.8% met the criteria for station-based sampling (ie, any 3 N2 stations and 1 N1 station). Adherence to lobe-specific assessment was associated with lower cumulative incidence of recurrence (adjusted hazard ratio [aHR], 0.83; 95% confidence interval [CI], 0.70-0.98) and a higher likelihood of pathologic upstaging (aHR, 1.49; 95% CI, 1.20-1.86). Lobe-specific assessment was not associated with OS. Conclusions: Adherence to intraoperative LN sampling guidelines is low. Lobe-specific assessment is associated with superior outcomes in early-stage NSCLC. Quality metrics that assess adherence to intraoperative LN sampling, such as the CoC Operative Standards manual, also should consider lobe-specific criteria.

The Association of Agent Orange Exposure with the progression of monoclonal gammopathy of undetermined significance to multiple myeloma: a population-based study of Vietnam War Era Veterans.

Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association in a nationwide study of US Veterans. A natural language processing algorithm was used to confirm MGUS and progression to MM. We included Veterans who were diagnosed with MGUS from 10/1/1999 to 12/31/2021 and served during the Vietnam War Era from 1/9/1962 to 5/7/1975. AO exposure was stratified according to three TCDD exposure levels: high (1/9/1962-11/30/1965), medium (12/1/1965-12/31/1970), or low (1/1/1971-5/7/1975). The association between AO exposure and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. The analytic cohort included 10,847 Veterans with MGUS, of whom 26.3% had AO exposure and 7.4% progressed to MM over a median follow-up of 5.2 years. In multivariable analysis, high exposure was associated with an increased progression rate (multivariable-adjusted hazard ratio 1.48; 95% confidence interval 1.02-2.16), compared to Veterans with no exposure. This information is critical to inform progression risk in patients diagnosed with MGUS and prior AO exposure. It is also applicable to MGUS patients with occupational TCDD exposure from herbicides and pesticides.

Racial differences in treatment and survival among older patients with multiple myeloma.

BACKGROUND: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non-Hispanic African American (NHAA) and non-Hispanic White (NHW) patients are well-established, it is unclear whether they have persisted after the introduction of novel agents. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs). RESULTS: Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment during the first year, respectively. Discrepancy in the proportion of patients receiving treatment between the two groups increased from 2.9% in 2007 to 2009 to 6.9% in 2014-2017. After controlling for relevant factors, patients who received treatment within the first year had lower mortality than those who did not (HR = 0.90, 95% confidence interval [CI]: 0.86-0.94). NHAA patients had a lower probability to receive treatments during the first year than NHW patients (HR = 0.91, 95% CI: 0.85-0.97) but had lower mortality (HR = 0.94, 95% CI: 0.88-1.00). The lower mortality was only observed among patients who received no treatment (HR = 0.84, 95% CI: 0.77-0.93); NHAA and NHW patients who received treatment had similar survival (p = 0.63). CONCLUSIONS: The increasing racial disparity in treatment utilization over time is concerning. Efforts are needed to eliminate the barriers of receiving treatment.

Association between alcohol consumption and sleep traits: observational and mendelian randomization studies in the UK biobank.

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

Hospitalizations Among Veterans Treated for Metastatic Prostate Cancer With Abiraterone or Enzalutamide.

BACKGROUND: Abiraterone and enzalutamide are second generation androgen receptor pathway inhibitors (ARPIs) used to treat advanced or metastatic prostate cancer. Without head-to-head comparative studies identifying 1 agent as preferred initial therapy, physician preferences guide initial ARPI choice. This study compares hospitalizations among patients treated initially with abiraterone versus enzalutamide. PATIENTS AND METHODS: United States veterans treated with abiraterone or enzalutamide between May 13, 2011 and December 31, 2019; then compared hospitalization rate during first treatment with ARPI in the Veterans Healthcare Administration. Baseline incidence rate of hospitalization was determined from data 1 year prior to ARPI. Incidence Rate Difference (IRD) was calculated using χ2 test and difference in IRD using Poisson Regression. RESULTS: 19,775 veterans were identified; 13,527 (68.4%) were initially treated with abiraterone and 6248 (31.6%) initially with enzalutamide. The enzalutamide cohort was older (75.8 vs. 74.5 years, P < .001) and had higher baseline comorbidities at ARPI initiation (4.4 vs. 4.0, P < .001). Patients were treated with enzalutamide longer than abiraterone (median 9.0 vs. 8.0 months, P < .001). Total hospitalizations increased from 465 per 1000 person-years in the year prior to treatment with abiraterone to 567 during treatment. Total hospitalizations increased from 417 per 1000 person-years in the year prior to treatment with enzalutamide to 430 during treatment. Total rate of hospitalization increased 22% for abiraterone compared to a 3% increase for enzalutamide in the 12 months after ARPI initiation (P < .0001). Abiraterone was associated with greater increase in rates of acute heart failure, atrial fibrillation, acute kidney injury, urinary tract infections, sepsis, and pneumonia. CONCLUSION: By comparing the rate of hospitalization before vs. during treatment, real world analyses identified a 22% versus 3% increase in hospitalizations with abiraterone compared to enzalutamide respectively, despite being used in a younger population with less comorbid disease. Abiraterone was also associated with higher risk of infections, a novel finding.

Exposure to Agent Orange is associated with increased recurrence after surgical treatment of stage I non-small cell lung cancer.

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.