The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells.

Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT, we discovered that the gut-colonizing protist Tritrichomonas (T.) arnold promotes oral tolerance and protects against reovirus- and murine norovirus-mediated LOT, independent of the microbiota. Protection was not attributable to antiviral host responses or T. arnold-mediated innate type 2 immunity. Mechanistically, T. arnold directly restrained the proinflammatory program in dietary antigen-presenting DCs, subsequently limiting Th1 and promoting regulatory T cell responses. Finally, analysis of fecal microbiomes showed that T. arnold-related Parabasalid strains are underrepresented in human CeD patients. Altogether, these findings will motivate further exploration of oral-tolerance-promoting protists in CeD and other immune-mediated food sensitivities.

Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.

New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. Here we show that SARS-CoV-2 lineages have distinct evolutionary spaces (a probabilistic definition of the sequence states that can be occupied by expanding virus subpopulations). This space can be accurately inferred from the patterns of amino acid variability at the whole-protein level. Robust networks of co-variable sites identify the highest-likelihood mutations in new VOC sublineages and predict remarkably well the emergence of subvariants with resistance mutations to COVID-19 therapeutics. Our studies reveal the contribution of low frequency variant patterns at heterologous sites across the protein to accurate prediction of the changes at each position of interest.

Labour market integration among young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) at working age.

METHODS: Multiple Swedish nationwide registers were used to identify 8045 individuals, aged 20-29, with an incident diagnosis of ADHD 2006-2011. Labour market integration was conceptualized according to the core-peripheral model as a continuum from a strong (core) to a weak (peripheral) connection to the labour market. Sequence analyses categorized clusters of labour market integration, from 1 year before to 5 years after their ADHD diagnosis for individuals diagnosed with ADHD and a matched control group without ADHD. Multinomial logistic regression computed odds ratios (ORs) with 95% confidence intervals (CIs) between sociodemographic factors and comorbid disorders and the identified clusters. RESULTS: About one-fourth of the young adults diagnosed with ADHD belonged to clusters characterized by a transition to a mainly peripheral labour market position, which was approximately four-times higher compared to controls without ADHD. Foremost, those living in small cities/villages (OR 1.9; CI 1.5-2.2), those having comorbid autism-spectrum disorder (OR 13.7; CI 6.8-27.5) or schizophrenia/psychoses (OR 7.8; CI 3.8-15.9) were associated with a transition towards a peripheral labour market position throughout the study period. Those with a high educational level (OR 0.1; CI 0.1-0.1), and men (OR 0.7; CI 0.6-0.8) were less likely to have a peripheral labour market position. CONCLUSIONS: Young adults diagnosed with ADHD are four-times more likely to be in the peripheral labour market position compared to those without ADHD. To increase labour market participation, special attention is warranted to those with low educational level, those living outside big cities and those with comorbid mental disorders.

Effects of glucagon-like peptide-1 receptor agonists on endoscopy outcomes: A systematic review & meta-analysis.

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known to cause delayed gastric emptying, however the effect on clinical outcomes during upper endoscopy/colonoscopy remains unclear. We conducted a meta-analysis to reconcile the data. METHODS: Online databases were searched for studies evaluating GLP-1RAs vs control group (no GLP-1RAs) in patients undergoing endoscopy. The outcomes of interest were rate of retained gastric contents (RGC), aborted procedures, aspiration events and subjective bowel preparation quality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS: A total of 23 studies with 77,271 patients (4,449 in the GLP-1 RA arm and 72,703 in the control arm) were included. The mean age ranged from 47.6 to 72 years and 58.4% were females. As compared to the control group, the GLP-1 RA group had higher odds of RGC (OR 15.39, 95% CI 4.65-50.99, p < 0.01) and aborted procedures (OR 13.86, 95% CI 4.42-43.43, p < 0.01). No significant differences were observed between the two groups in terms of aspiration events (OR 21.06, 95% CI 0.13-3379.01, p=0.24) and subjective bowel preparation quality (OR 0.94, 95% CI 0.67-1.31, p=0.83). CONCLUSION: While statistical significance was reached in terms of visible RGC and early termination of endoscopies in patients on GLP-1RAs, these events were overall rare. GLP-1RAs do not appear to pose significant risk, as the odds of developing aspiration were comparable in the two groups.

Unraveling the gut microbiota's role in Rheumatoid arthritis: dietary pathways to modulation and therapeutic potential.

Rheumatoid arthritis (RA) is a significant global health issue. Recent research highlights the gut microbiota's critical role in RA's development, noting how dietary factors can alter these microbial communities. This has led to an increased focus on how the gut microbiota (GM) influences RA and the potential for dietary ingredients to offer anti-RA benefits by modifying GM. This review presents a concise examination of the GM associated with RA, identifying specific microbial taxa at various levels that are implicated in the disease. It delves into dietary components known for their anti-RA properties through GM modulation and their mechanisms. Findings from numerous studies, including both animal and human research, show significant differences in the GM composition between individuals with early and established RA. Certain microbes like Tenericutes, Synergistetes, and Proteobacteria have been linked to RA progression, whereas Bacteroidetes and some strains of Lactobacillus are shown to have protective effects against RA. Dietary elements such as fibers, polysaccharides, resistant starch, and peptides have been identified as influential in combating RA. These components work by altering the GM's metabolites and impacting immune cells related to the GM. This review suggests the potential for developing functional foods aimed at treating RA by targeting GM.

Prevalence of Sleep CALM nocturia factors in a male veteran population.

INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

Prevalence of asthma among children and adolescents in WHO's Eastern Mediterranean Region: a meta-analysis of over 0.5 million participants.

OBJECTIVE: This study aims to evaluate the epidemiology of asthma among children and adolescents in the Eastern Mediterranean Region. METHODS: Exhaustive searches were conducted across databases, including PubMed, Scopus, Web of Knowledge Core Collection, Embase, and Google Scholar. The selection criteria included studies reporting asthma prevalence in individuals aged 0 to 19 years, using validated questionnaires. Data were extracted and synthesized using the DerSimonian and Laird random effects model. RESULTS: The overall prevalence of asthma in Eastern Mediterranean Regional Office (EMRO) countries, among the 514,468 children and adolescents included in this meta-analysis, was 10.61%, synthesized from 95 studies. Among the countries studied, Qatar exhibited the highest prevalence at 16.69%, followed by Saudi Arabia at 16.57%, Iraq at 16.22%, Oman at 15.20%, and Afghanistan at 14.90%. Adolescents showed a slightly higher prevalence of asthma at 10.10% compared to children at 9.70%. Boys exhibited a higher prevalence at 11.48% compared to girls at 9.75%. Urban areas demonstrated a higher prevalence at 11.27% than rural areas at 8.29%. CONCLUSION: Efforts to reduce asthma prevalence in Arab countries and address underdiagnosis in African nations within the EMRO are crucial. Targeted interventions should focus on addressing environmental triggers and improving access to healthcare. Enhanced diagnostic capabilities and healthcare infrastructure are necessary in African countries. Collaborative action is essential to alleviate the asthma burden and promote respiratory health across the EMRO region.

Trusted Information Sources About the COVID-19 Vaccine Vary in Underserved Communities.

The COVID-19 pandemic was one of the deadliest global public health events. In the United States, over 1.1 million individuals have died, and now COVID-19 is the third leading cause of death (CDC, 2023). Vaccine uptake has stalled among different demographics. Vaccine hesitancy, a delay in accepting or refusing vaccines, poses a significant challenge regardless of the availability of safe and effective COVID-19 vaccines. This study aimed to identify disparate COVID-19 vaccine uptake among individuals in Western New York. The primary objective was to identify the factors contributing to lower rates of COVID-19 vaccination within this population.Data were collected from 585 adults recruited from 20 Niagara and Erie Counties sites using a self-administered survey on vaccine hesitancy, vaccination status, and COVID-19-related characteristics. The survey included the adult Vaccine Hesitancy Scale (aVHS) and acquired information on demographic characteristics and COVID-19 impact, knowledge, and information sources. Data were analyzed using descriptive statistics, a chi-squared test, a Wilcoxon rank-sum test, and a logistic regression model.Findings suggest that unvaccinated participants (n = 35) were concerned about vaccine side effects (48.6%). For vaccinated/unboosted participants (n = 52), they (40.0%) reported clinical concerns. After adjusting for gender and age, healthcare provider guidance and family guidance remained significant predictors of vaccination status, while clinical research studies were significant predictors of booster status. Findings from this study suggest public health interventions that target vaccine education and facilitate well-informed decisions about COVID-19 vaccines lead to less vaccine hesitancy.

Factors associated with children's cognitive, language, and motor development in deprived urban settings in Bangladesh.

BACKGROUND: Children's development is multifactorial. Although there have been several studies exploring the association of children's development with maternal, child, and environmental factors, we are unaware of any study that assessed those factors in children whose mothers were enrolled in a social safety net programme in low- and middle-income countries. This study aimed to identify the factors associated with disadvantaged children's cognitive, language, and motor development at age 6-16 months in deprived settings of urban Bangladesh and to identify relative importance of these factors of children's development. We also explored if there were any gender differences in child development. METHODS: This cross-sectional study was conducted in a deprived setting of urban Bangladesh. Bayley III was used for assessing children's cognitive, language, and motor development. Multivariable linear regression model was used to find the factors associated with children's development, and dominance analysis was used to explore the relative importance of the factors. RESULTS: Out of the total 599 mother-child dyads, 303 (50.58%) were girls. The factors associated with children's development were length-for-age Z-score (cognitive: B = 1.21 [95% CI = 0.31, 2.11], P = 0.008; language: 1.67 [0.79, 2.55] P < 0.001; motor: 2.15 [1.01, 3.29] P < 0.001) and home environment (cognitive: 0.58 [0.27, 0.89] P < 0.001; language: 0.59 [0.27, 0.92], P < 0.001; motor: 0.44 [0.09, 0.79] P = 0.013). Girls had higher cognitive (1.90 [0.17, 3.6], P = 0.031) and language (2.53 [0.55, 4.51], P = 0.013) development compared with boys. Families with a higher number of under five children within the households had lower language (-1.57 [-2.78, -0.36], P = 0.011) development. Violence against the mother and the families' food security status were not associated with the children's development. Children's length-for-age Z-score (27%) and home stimulation environment (23%) were the most important factors of cognitive development. CONCLUSION: Children's nutritional status and home environment are important factors for disadvantaged children's development in deprived urban settings of Bangladesh. Both early child development-focussed parenting and nutrition interventions should be considered when designing child development programmes in urban settings in low- and middle-income countries.

Removal of N-Nitrosodiphenylamine from contaminated water: A novel modeling framework using metaheuristic-based ensemble models.

Investigating the complex interactions among physicochemical variables that influence the adsorptive removal of pollutants is a challenge for conventional one-variable-at-a-time (OVAT) batch methods. The adoption of machine learning-based chemometric prediction models is expected to be more accurate than the conventional method. This study proposed a novel modeling framework for predicting and optimizing the adsorptive removal of N-Nitrosodiphenylamine (NDPhA). Initially, models were trained by using OVAT data, with their hyperparameters subsequently fine-tuned through Bayesian optimization. In the second phase, the particle swarm optimization (PSO) technique was adopted to identify optimal parameters, specifically time, concentration, temperature, pH, and dose, to ensure the highest removal. The adopted analytical method enhances both prediction accuracy and removal efficiency. Utilizing OVAT data for NDPhA removal, the XGBoost regressor significantly outperformed other models. With a correlation coefficient of 0.9667 in the testing dataset, the XGBoost model exhibited its accuracy, emphasized by its low mean squared errors of 28.45 and mean absolute errors of 0.0982. Feature importance analysis consistently identified time and concentration as the most critical factors across all models.

A novel interpretable machine learning and metaheuristic-based protocol to predict and optimize ciprofloxacin antibiotic adsorption with nano-adsorbent.

The existence of antibiotics in water sources poses substantial hazards to both the environment and public health. To effectively monitor and combat this problem, accurate predictive models are essential. This research focused on employing machine learning (ML) techniques to construct some models for analyzing the adsorption capacity of ciprofloxacin (CIP) antibiotic from contaminated water. The robustness of ten machine learning algorithms was evaluated using performance metrics such as the Coefficient of determination (R2), Mean Square Error (MSE), Median Absolute Error (MedAE), Mean Absolute Error (MAE), Correlation coefficient (R), Nash-Sutcliffe Efficiency (NSE), Kling-Gupta Efficiency (KGE), and Root Mean Square Error (RMSE). The hyperparameters of the ML models were fine-tuned using the Bayesian optimization algorithm. The optimized models were comprehensively evaluated using feature importance analysis to quantify the relative significance of operational variables accurately. After a thorough assessment and comparison of various machine learning models, it was evident that the HistGradientBoosting (HGB) model outperformed others in terms of CIP adsorption performance. This was supported by their low MAE value of 0.1865 and high R2 value of 0.9999. The modeling projected the highest antibiotic adsorption (99.28%) under optimized conditions, including 10 mg/L of CIP, 357 mg/L of CuWO4@TiO2 adsorbent, a contact time of 60 min at room temperature, and near neutral pH (7.5). The combination of advanced ML algorithms and nano adsorbents has great potential for addressing the problem of antibiotic pollution in water sources.

Nursing students' stressors and coping strategies during their first clinical training: a qualitative study in the United Arab Emirates.

BACKGROUND: Understanding the stressors and coping strategies of nursing students in their first clinical training is important for improving student performance, helping students develop a professional identity and problem-solving skills, and improving the clinical teaching aspects of the curriculum in nursing programmes. While previous research have examined nurses' sources of stress and coping styles in the Arab region, there is limited understanding of these stressors and coping strategies of nursing students within the UAE context thereby, highlighting the novelty and significance of the study. METHODS: A qualitative study was conducted using semi-structured interviews. Overall 30 students who were undergoing their first clinical placement in Year 2 at the University of Sharjah between May and June 2022 were recruited. All interviews were recorded and transcribed verbatim and analyzed for themes. RESULTS: During their first clinical training, nursing students are exposed to stress from different sources, including the clinical environment, unfriendly clinical tutors, feelings of disconnection, multiple expectations of clinical staff and patients, and gaps between the curriculum of theory classes and labatories skills and students' clinical experiences. We extracted three main themes that described students' stress and use of coping strategies during clinical training: (1) managing expectations; (2) theory-practice gap; and (3) learning to cope. Learning to cope, included two subthemes: positive coping strategies and negative coping strategies. CONCLUSIONS: This qualitative study sheds light from the students viewpoint about the intricate interplay between managing expectations, theory practice gap and learning to cope. Therefore, it is imperative for nursing faculty, clinical agencies and curriculum planners to ensure maximum learning in the clinical by recognizing the significance of the stressors encountered and help students develop positive coping strategies to manage the clinical stressors encountered. Further research is required look at the perspective of clinical stressors from clinical tutors who supervise students during their first clinical practicum.

Deep learning for biological age estimation.

Modern machine learning techniques (such as deep learning) offer immense opportunities in the field of human biological aging research. Aging is a complex process, experienced by all living organisms. While traditional machine learning and data mining approaches are still popular in aging research, they typically need feature engineering or feature extraction for robust performance. Explicit feature engineering represents a major challenge, as it requires significant domain knowledge. The latest advances in deep learning provide a paradigm shift in eliciting meaningful knowledge from complex data without performing explicit feature engineering. In this article, we review the recent literature on applying deep learning in biological age estimation. We consider the current data modalities that have been used to study aging and the deep learning architectures that have been applied. We identify four broad classes of measures to quantify the performance of algorithms for biological age estimation and based on these evaluate the current approaches. The paper concludes with a brief discussion on possible future directions in biological aging research using deep learning. This study has significant potentials for improving our understanding of the health status of individuals, for instance, based on their physical activities, blood samples and body shapes. Thus, the results of the study could have implications in different health care settings, from palliative care to public health.

Conduction band structure of high-mobility organic semiconductors and partially dressed polaron formation.

The energy band structure provides crucial information on charge transport behaviour in organic semiconductors, such as effective mass, transfer integrals and electron-phonon coupling. Despite the discovery of the valence (the highest occupied molecular orbital (HOMO)) band structure in the 1990s, the conduction band (the lowest unoccupied molecular orbital (LUMO)) has not been experimentally observed. Here we employ angle-resolved low-energy inverse photoelectron spectroscopy to reveal the LUMO band structure of pentacene, a prototypical high-mobility organic semiconductor. The derived transfer integrals and bandwidths from the LUMO are substantially smaller than those predicted by density functional theory calculations. To reproduce this bandwidth reduction, we propose an improved (partially dressed) polaron model that accounts for the electron-intramolecular vibrational interaction with frequency-dependent coupling constants based on Debye relaxation. This model quantitatively reproduces not only the transfer integrals, but also the temperature-dependent HOMO and LUMO bandwidths, and the hole and electron mobilities. The present results demonstrate that electron mobility in high-mobility organic semiconductors is indeed limited by polaron formation.

Association of trauma, post-traumatic stress disorder and non-affective psychosis across the life course: a nationwide prospective cohort study.

BACKGROUND: We aimed to examine the temporal relationships between traumatic events (TE), post-traumatic stress disorder (PTSD) and non-affective psychotic disorders (NAPD). METHODS: A prospective cohort study of 1 965 214 individuals born in Sweden between 1971 and 1990 examining the independent effects of interpersonal and non-interpersonal TE on incidence of PTSD and NAPD using data from linked register data (Psychiatry-Sweden). Mediation analyses tested the hypothesis that PTSD lies on a causal pathway between interpersonal trauma and NAPD. RESULTS: Increasing doses of interpersonal and non-interpersonal TE were independently associated with increased risk of NAPD [linear-trend incidence rate ratios (IRR)adjusted = 2.17 [95% confidence interval (CI) 2.02-2.33] and IRRadjusted = 1.27 (95% CI 1.23-1.31), respectively]. These attenuated to a relatively small degree in 5-year time-lagged models. A similar pattern of results was observed for PTSD [linear-trend IRRadjusted = 3.43 (95% CI 3.21-3.66) and IRRadjusted = 1.45 (95% CI 1.39-1.50)]. PTSD was associated with increased risk of NAPD [IRRadjusted = 8.06 (95% CI 7.23-8.99)], which was substantially attenuated in 5-year time-lagged analyses [IRRadjusted = 4.62 (95% CI 3.65-5.87)]. There was little evidence that PTSD diagnosis mediated the relationship between interpersonal TE and NAPD [IRRadjusted = 0.92 (percentile CI 0.80-1.07)]. CONCLUSION: Despite the limitations to causal inference inherent in observational designs, the large effect-sizes observed between trauma, PTSD and NAPD in this study, consistent across sensitivity analyses, suggest that trauma may be a component cause of psychotic disorders. However, PTSD diagnosis might not be a good proxy for the likely complex psychological mechanisms mediating this association.

Labour market marginalisation in young adults diagnosed with attention-deficit hyperactivity disorder (ADHD): a population-based longitudinal cohort study in Sweden.

BACKGROUND: The objective of this population-based register study was (1) to investigate the association between young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) and subsequent labour market marginalisation (LMM) in two comparison groups, i.e. matched young adults from the general population without ADHD and unaffected siblings to persons with ADHD and (2) to assess the role of comorbid disorders. METHODS: This study included all young adults in Sweden, aged 19-29 years, with an incident diagnosis of ADHD 2006-2011 (n = 9718). Crude and multivariate sex-stratified hazard ratios (HRs) with 95% confidence intervals (CIs) were measured 5 years after the diagnosis of ADHD for the risk of disability pension, long-term sickness absence (SA) (>90 days), long-term unemployment (>180 days) and a combined measure of all three in young adults with ADHD compared to their siblings without ADHD and a matched comparison group. RESULTS: In the adjusted analyses young adults with ADHD had a 10-fold higher risk of disability pension (HR = 10.2; CI 9.3-11.2), a nearly three-fold higher risk of long-term SA (HR = 2.7; CI 2.5-2.8) and a 70% higher risk of long-term unemployment (HR = 1.7; CI 1.6-1.8) compared to the matched comparison group. The risk estimates were lower compared to siblings for disability pension (HR = 9.0; CI 6.6-12.3) and long-term SA (HR = 2.5; CI 2.1-3.1) but higher in the long-term unemployed (HR = 1.9; CI 1.6-2.1). Comorbid disorders explained about one-third of the association between ADHD and disability pension, but less regarding SA and long-term unemployment. CONCLUSIONS: Young adults with ADHD have a high risk for different measures of LMM and comorbidities explain only a small proportion of this relationship.

Personalizing approaches to the management of metastatic hormone sensitive prostate cancer: role of advanced imaging, genetics and therapeutics.

PURPOSE: To summarize contemporary and emerging strategies for the diagnosis and management of metastatic hormone sensitive prostate cancer (mHSPC), focusing on diagnostic testing and therapeutics. METHODS: Literature review using PUBMED-Medline databases as well as clinicaltrials.gov to include reported or ongoing clinical trials on treatment for mHSPC. We prioritized the findings from phase III randomized clinical trials, systematic reviews, meta-analyses and clinical practice guidelines. RESULTS: There have been significant changes to the diagnosis and staging evaluation of mHSPC with the integration of increasingly accurate positron emission tomography (PET) imaging tracers that exceed the performance of conventional computerized tomography (CT) and bone scan. Germline multigene testing is recommended for the evaluation of patients newly diagnosed with mHSPC given the prevalence of actionable alterations that may create candidacy for specific therapies. Although androgen deprivation therapy (ADT) remains the backbone of treatment for mHSPC, approaches to first-line treatment include the integration of multiple agents including androgen receptor synthesis inhibitors (ARSI; abiraterone) Androgen Receptor antagonists (enzalutamide, darolutamide, apalautamide), and docetaxel chemotherapy. The combination of ADT, ARSI, and docetaxel chemotherapy has recently been evaluated in a randomized trial and was associated with significantly improved overall survival including in patients with a high burden of disease. The role of local treatment to the prostate with radiation has been evaluated in randomized trials with additional studies underway evaluating the role of cytoreductive radical prostatectomy. CONCLUSION: The staging and initial management of patients with mHSPC has undergone significant advances in the last decade with advancements in the diagnosis, treatment and sequencing of therapies.

The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects.

PURPOSE OF REVIEW: This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives. RECENT FINDINGS: The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.

Management of Pathologic Node-Positive Prostate Cancer following Radical Prostatectomy.

PURPOSE OF REVIEW: Approximately 15% of prostate cancer patients have lymph node metastases at the time of radical prostatectomy (RP). However, there is no universally accepted standard of care for these men. The options for treatment in this subset of patients range from observation to a combination of adjuvant androgen deprivation therapy (aADT) and radiation therapy (RT). RECENT FINDINGS: A recent systematic review showed that there was no clear choice out of the options above to treat these patients. Studies have shown that patients treated with adjuvant radiation therapy have lower all-cause mortality when compared to patients treated with salvage radiation therapy. In this review, we summarize treatment options for pathologic node-positive (pN1) patients and discuss the urgent need for robust clinical trials that includes observation as the control group to help establish a standard of care for treating patients with node-positive prostate cancer after RP.

Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications ("Sleep C.A.L.M.") in the evaluation and management of nocturia: A simple approach to a complex diagnosis.

INTRODUCTION: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. METHODS: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management. RESULTS: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. CONCLUSION: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets.