Evaluation of in vitro dissolution profiles of modified-release metoprolol succinate tablets crushed using mortar and pestle technique.

PURPOSE: Clinical practice guidelines advise against crushing modified-release dosage forms. Metoprolol succinate modified-release (MS-MR) tablets are commonly crushed in clinical practice to facilitate administration to patients with swallowing difficulties or using feeding tubes. To date, the effect of this practice remains unexplored. The in vitro effects of crushing commercially available MS-MR tablets were explored using a holistic approach. METHODS: Dissolution profiles of crushed versus whole MS-MR tablets were compared. Tablets were crushed to powder state using pragmatic method mimicking hospital practices. For standardization purposes, the same operator, duration (60 seconds), hand, and mortar-pestle apparatus were used. Dissolution studies were conducted per U.S. Pharmacopeia at pH 1.2, pH 4.5, and pH 6.8 with USP apparatus 2 (paddle) at rotation speed of 50 rpm at 37±0.5 °C in 500 mL dissolution media. Samples were withdrawn at predetermined time points. Percent drug dissolved was measured by validated UV-vis Spectrophotometry. Comprehensive analysis of the dissolution data was conducted using model-independent, model-dependent, and ANOVA-based approaches (SPSS v.23 at α=0.05). Similarity (f2) and difference (f1) factors were calculated to compare the dissolution profiles between crushed (CT) and whole tablets (WT). Goodness of fit (GOF) analysis examined the compliance between in vitro dissolution behaviors and several drug release models. Model selection was based on GOF plots, Akaike criteria and adjusted coefficient of determination (R2adj). Imaging and particle size distribution analysis were conducted to examine associated surface and morphologic changes. RESULTS: The dissolution profiles were not similar at pH 4.5 (f2=45.43, f1=18.97) and pH 6.8 (f2=31.47, f1=32.94). CT best fitted with Higuchi (pH 1.2: R2adj=0.9990), Weibull (pH 4.5: R2adj=0.9884), and Korsmeyer-Peppas (pH 6.8: R2adj=0.9719). Contrastingly, WT best fitted with Hopfenberg (pH 1.2: R2adj=0.9986), logistic (pH 4.5: R2adj=0.9839) and first-order (pH 6.8: R2adj=0.9979) models. A significant difference in the dissolution profiles was found between CT and WT using multivariate analysis of variance per time points and between the tablet forms (p=0.004). This was confirmed by unparalleled dissolution profiles. Crushing resulted in variations in particle size and surface morphological changes to the micropellets. CONCLUSION: Crushing practices change the dissolution profile of MS-MR tablets by deforming the surface morphology of embedded micropellets. Amounts of drug dissolved between CT and WT were not the same at the compared time points across gastrointestinal pH ranges. This suggests potential clinical impact on plasma-concentration profiles of critically ill patients using feeding tube.

Lupus Nephritis Biomarkers: A Critical Review.

Lupus nephritis (LN), a major complication in individuals diagnosed with systemic lupus erythematosus, substantially increases morbidity and mortality. Despite marked improvements in the survival of patients with severe LN over the past 50 years, complete clinical remission after immunosuppressive therapy is achieved in only half of the patients. Therefore, timely detection of LN is vital for initiating prompt therapeutic interventions and improving patient outcomes. Biomarkers have emerged as valuable tools for LN detection and monitoring; however, the complex role of these biomarkers in LN pathogenesis remains unclear. Renal biopsy remains the gold standard for the identification of the histological phenotypes of LN and guides disease management. However, the molecular pathophysiology of specific renal lesions remains poorly understood. In this review, we provide a critical, up-to-date overview of the latest developments in the field of LN biomarkers.

Complex Chromosomal Rearrangement Involving Chromosomes 10 and 11, Accompanied by Two Adjacent 11p14.1p13 and 11p13p12 Deletions, Identified in a Patient with WAGR Syndrome.

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus. The diagnosis of WAGR syndrome was suspected. De novo complex chromosomal rearrangement with balanced translocation t(10,11)(p15;p13) and a pericentric inversion inv(11)(p13q12), accompanied by two adjacent 11p14.1p13 and 11p13p12 deletions, were identified. Deletions are raised through the complex molecular mechanism of two subsequent rearrangements affecting chromosomes 11 and 10. WAGR syndrome diagnosis was clinically and molecularly confirmed, highlighting the necessity of comprehensive genetic testing in patients with congenital aniridia and/or WAGR syndrome.

How to Use Janus Kinase Inhibitors in the Treatment of Rheumatoid Arthritis? A Clinical Assessment of Risks and Benefits.

PURPOSE OF REVIEW: To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA). RECENT FINDINGS: Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors. Suboptimal treatment of treatment-refractory RA patients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk. New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.

Increased development of T-bet+CD11c+ B cells predisposes to lupus in females: Analysis in BXD2 mouse and genetic crosses.

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet+CD11c+ IgD+ activated naive B cells (aNAV) was higher in females and was associated with increased T-bet+CD11c+ IgD- age-related B cells, Fas+GL7+ germinal center B cells, Cxcr5-Icos+ peripheral T-helper cells, and Cxcr5+Icos+ follicular T-helper cells. IFN-ß was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.

The Role of Automated External Defibrillator Use in the Out-of-Hospital Cardiac Arrest Survival Rate and Outcome: A Systematic Review.

Out-of-hospital cardiac arrest (OHCA) remains a significant cause of death. The chance of survival significantly increases when immediate defibrillation with an on-site automated external defibrillator (AED) is available. Our aim is to systematically evaluate the impact of public access defibrillators (PAD) on the outcomes of outpatient cardiac arrest. We conducted a systematic review of the data from global studies on the role of bystander and emergency medical service (EMS) interventions, primarily focusing on the usage of AEDs, during OHCA events. The results highlight the critical significance of PADs in improving survival outcomes in OHCA settings. The majority of OHCA incidents occurred in private residences, but public spaces such as schools and airports had better outcomes, likely due to AED accessibility and trained individuals. Placing AEDs in public areas, especially high-risk zones, can boost survival chances. Timely defibrillation, particularly by bystanders, correlated with better survival and neurological conditions. The review emphasizes the importance of widespread cardiopulmonary resuscitation (CPR) and AED training, strategic AED placement, and continuous monitoring of interventions and outcomes to enhance survival rates and neurological recovery after OHCAs. This systematic review showed that bystander interventions, including CPR and AED usage, significantly increased the survival rate. Overall, immediate response and accessibility to AEDs in public areas can significantly improve outcomes in OHCA events.

Analysis of Cervix Intraepithelial Neoplasia Prevalence in the Kurdistan Region, Iraq.

BACKGROUND:  Cervix intraepithelial neoplasia (CIN) refers to abnormal changes in the squamous cells of the cervix, with more significant changes known as high-grade squamous intraepithelial lesions (HSIL) occurring in grades II and III. AIM:  The study aimed to estimate the prevalence of cervical intraepithelial neoplasia and explore potential risk factors for HSIL among women living in the Kurdistan region, Iraq. MATERIALS AND METHODS:  The research encompassed a sample size of 1300 female participants whose Papanicolaou (pap) smears were taken in several hospitals located within the Kurdistan region. The objective of the study was to determine the prevalence of cervical infection among these women. This was a multi-centre study conducted from January 2021 to the end of December 2021 for the determination of pap smears and the relationship between CIN and cervical cancer. Only 120 (9.23%) of those 1300 participants suffered from cervical or vaginal problems. A pap smear, also known as a pap test, is a routine screening procedure used to detect abnormal cervical cells that may indicate cervical cancer or precancerous conditions. The procedure involves collecting a sample of cells from the cervix. RESULTS:  The most important details in this study are the age groups and percentages of women who have undergone a pap smear. There were four women who tested positive for cervical cancer, accounting for 3.33% of the 120 participants with cervical or vaginal problems. However, there were 116 (96.67%) women who tested negative. With regard to the distribution of inflammation rates among the participants with cervical or vaginal problems, there were 114 (95%) women who suffered inflammation, whereas there were six (5%) women without inflammation. In each age group, the numbers of women with and without cervical cancer, as well as the corresponding percentages, were considered. The data suggest that the incidence of cervical cancer tends to increase with age since higher percentages were observed in older age groups. The study highlights the importance of regular screenings and age-specific cervical cancer prevention and detection strategies to ensure early diagnosis and effective medical interventions. CONCLUSION:  The prevalence of cervical cancer cases was relatively low, with only 0.31% of the total participants diagnosed with cervical cancer. The majority, accounting for 99.69%, did not have cervical cancer. These results highlight the importance of pap smear screenings as a valuable tool for early detection and prevention of cervical cancer. They also highlight the importance of regular screenings, especially for younger women, to detect and treat cervical abnormalities at an early stage.

Explainable machine learning for the prediction and assessment of complex drought impacts.

Drought is a common and costly natural disaster with broad social, economic, and environmental impacts. Machine learning (ML) has been widely applied in scientific research because of its outstanding performance on predictive tasks. However, for practical applications like disaster monitoring and assessment, the cost of the models failure, especially false negative predictions, might significantly affect society. Stakeholders are not satisfied with or do not "trust" the predictions from a so-called black box. The explainability of ML models becomes progressively crucial in studying drought and its impacts. In this work, we propose an explainable ML pipeline using the XGBoost model and SHAP model based on a comprehensive database of drought impacts in the U.S. The XGBoost models significantly outperformed the baseline models in predicting the occurrence of multi-dimensional drought impacts derived from the text-based Drought Impact Reporter, attaining an average F2 score of 0.883 at the national level and 0.942 at the state level. The interpretation of the models at the state scale indicates that the Standardized Precipitation Index (SPI) and Standardized Temperature Index (STI) contribute significantly to predicting multi-dimensional drought impacts. The time scalar, importance, and relationships of the SPI and STI vary depending on the types of drought impacts and locations. The patterns between the SPI variables and drought impacts indicated by the SHAP values reveal an expected relationship in which negative SPI values positively contribute to complex drought impacts. The explainability based on the SPI variables improves the trustworthiness of the XGBoost models. Overall, this study reveals promising results in accurately predicting complex drought impacts and rendering the relationships between the impacts and indicators more interpretable. This study also reveals the potential of utilizing explainable ML for the general social good to help stakeholders better understand the multi-dimensional drought impacts at the regional level and motivate appropriate responses.

Seroprevalence of anti-Lassa Virus IgG antibodies in three districts of Sierra Leone: A cross-sectional, population-based study.

BACKGROUND: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown. This cross-sectional study aimed to establish a baseline point seroprevalence of IgG antibodies to LASV in three administrative districts of Sierra Leone and identify potential risk factors for seropositivity and LASV exposure. METHODOLOGY AND PRINCIPAL FINDINGS: Between 2015 and 2018, over 10,642 participants from Kenema, Tonkolili, and Port Loko Districts were enrolled in this cross-sectional study. Previous LASV and LF epidemiological studies support classification of these districts as "endemic," "emerging," and "non-endemic", respectively. Dried blood spot samples were tested for LASV antibodies by ELISA to determine the seropositivity of participants, indicating previous exposure to LASV. Surveys were administered to each participant to assess demographic and environmental factors associated with a higher risk of exposure to LASV. Overall seroprevalence for antibodies to LASV was 16.0%. In Kenema, Port Loko, and Tonkolili Districts, seroprevalences were 20.1%, 14.1%, and 10.6%, respectively. In a multivariate analysis, individuals were more likely to be LASV seropositive if they were living in Kenema District, regardless of sex, age, or occupation. Environmental factors contributed to an increased risk of LASV exposure, including poor housing construction and proximity to bushland, forested areas, and refuse. CONCLUSIONS AND SIGNIFICANCE: In this study we determine a baseline LASV seroprevalence in three districts which will inform future epidemiological, ecological, and clinical studies on LF and the LASV in Sierra Leone. The heterogeneity of the distribution of LASV and LF over both space, and time, can make the design of efficacy trials and intervention programs difficult. Having more studies on the prevalence of LASV and identifying potential hyper-endemic areas will greatly increase the awareness of LF and improve targeted control programs related to LASV.

Interrelation of T cell cytokines and autoantibodies in systemic lupus erythematosus: A cross-sectional study.

T-helper cytokines interferon gamma (IFNÉ£), interleukin 17 (IL-17) and IL-10 impact systemic lupus erythematosus (SLE) directly and indirectly via modulation of autoAb production. We determined the separate and combined effects on clinical manifestations of SLE (N = 62). IFNÉ£, IL-17 but not IL-10 were significantly elevated in patients with SLE. IFNÉ£ positively correlated with anti-DNA and anti-SSA. IL-17 positively correlated with anti-SSA and was significantly higher in patients with discoid rash and class V LN. IL-10 did not correlate with circulating autoantibodies but was significantly elevated in patients with LN. Patients with LN had elevated plasma levels of anti-DNA and anti-Sm/ribonuclear protein (RNP). Anti-Sm/RNP levels were decreased in patients with acute mucocutaneous manifestations, including photosensitivity and/or malar rash. The study provides critical insights into pathological mechanisms of LN, which could help guide future diagnoses and therapies.

Relationship between Renal Function and Bone Mineral Density in Postmenopausal Women.

Renal insufficiency is a risk factor for osteoporosis and can increase risk of fracture. It may be a result of an age-related decline in renal function or chronic kidney disease. In patients with CKD, accurate diagnosis of osteoporosis or CKD-MBD is important for determining the most appropriate treatment. This was a cross sectional study was done at Institute of nuclear medicine and Allied Sciences, BSMMU, Dhaka from 1st January 2014 to 31st December 2014. Study population was total 69 postmenopausal women age over 50 years. Women with Bilateral hip replacement or bilateral hip pins or screws, metallic rods in spine, Carrying out BMD scan within the week after other radiological investigation using contrast media e.g. Barium meals or enema, IVPs were excluded from study. Clinical variables were- age (years), height (cm), weight (kg), BMI. Laboratory variables were- serum creatinine and BMD (Dexa). Estimated GFR was determined by using the serum Creatinine by MDRD formula. Renal function test and Bone mineral density (BMD) were done in all of these patients. Majority (43.4%) of the patients were in 6th decade. The mean weight was found 57.4±11.2kg. Majority 41(59.4%) patients belonged to T score at hip (-1 to -2.5) and their mean T score at hip was found (-1.1±1.1). Osteopenia and osteoporosis were found in 59.4% and 4.3% respectively according to BMD. High serum creatinine level was found in 10.1% cases. Renal function impairment was found in 79.6% of patient. Majority (50.7%) patients had mild decrease of eGFR (60-89 ml/min/1.73m²), There was Pearson's correlation (r=0.156; p=0.200) but not significant was found between age with T score at hip of the patients. Positive Pearson's correlation (r=0.112; p=0.361) was found but not significant between age and serum creatinine level. A significant negative Pearson's correlation (r= -0.274; p=0.023) was found between T score at hip and serum creatinine level of the patients. A significant negative Spearman correlation (r=-0.278; p=0.021) was found between BMD and serum creatinine of the patients. A significant positive Spearman correlation (r=0.580; p=0.001) was found between BMD and estimated GFR of the patients. This study was undertaken to evaluate the relationship between renal function and bone mineral density in postmenopausal women. Majority of the postmenopausal women were in 6th decade and most of them were overweight and obese. Renal function impairment was found in 79.6% of patient. Osteoporosis was found in 04.3% and 20.3% cases according to T score at hip and T score at lumber spine respectively. Significant negative Pearson's correlation was found between T score at hip and serum creatinine level of the patients. Significant negative Spearman correlation was found between BMD and serum creatinine of the patients. Significant positive Spearman correlation was found between BMD and estimated GFR of the patients.

Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection.

BACKGROUND: Microbiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated. OBJECTIVE: We sought to investigate whether pulmonary metabolite manipulation through lung-delivered administration of SCFAs can modulate antiviral immunity to RV infection. METHODS: We studied the effects of intranasal administration of the SCFAs acetate, butyrate, and propionate on basal expression of antiviral signatures, and of acetate in a mouse model of RV infection and in RV-infected lung epithelial cell lines. We additionally assessed the effects of acetate, butyrate, and propionate on RV infection in differentiated human primary bronchial epithelial cells. RESULTS: Intranasal acetate administration induced basal upregulation of IFN-ß, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-λ expression during RV infection and reduced lung virus loads at 8 hours postinfection. Acetate ameliorated virus-induced proinflammatory responses with attenuated pulmonary mucin and IL-6 expression observed at day 4 and 6 postinfection. This interferon-enhancing effect of acetate was confirmed in human bronchial and alveolar epithelial cell lines. In differentiated primary bronchial epithelial cells, butyrate treatment better modulated IFN-ß and IFN-λ gene expression during RV infection. CONCLUSIONS: SCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection.

Clustering Patients With Gout Based on Comorbidities and Biomarkers: A Cross-Sectional Study.

OBJECTIVE: This single-center clinical study identifies clusters of different phenotypes and pathophysiology subtypes of patients with gout and associated comorbidities. METHODS: Patients clinically diagnosed with gout were enrolled between January 2018 and December 2019. Hierarchical cluster analyses were performed using clinical data or biological markers, inflammatory markers, and oxidative stress pathway metabolites assayed from serum and plasma samples. Subgroup clusters were compared using ANOVA for continuous data and chi-square tests for categorical data. RESULTS: Hierarchical cluster analysis identified 3 clusters. Cluster 1 (C1; n = 24) comprised dyslipidemia, hypertension, and early-onset gout, without tophi. Cluster 2 (C2; n = 25) comprised hypertension, dyslipidemia, nephrolithiasis, and obesity. Cluster 3 (C3; n = 39) comprised multiple comorbidities and tophi. Post hoc comparisons of data obtained from samples of patients in C1, C2, and C3 revealed significant differences in the levels of oxidative stress and inflammation-related markers, including 3-nitrotyrosine, tumor necrosis factor, C-reactive protein, interleukin (IL) 1ß, IL-6, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Reclustering patients based on all markers as well as on the biological markers that significantly differed among the initial clusters identified similar clusters. CONCLUSION: Oxidative stress and inflammatory marker levels may affect the development and clinical manifestations (ie, clinical phenotypes) of gout. Measuring oxidative stress and levels of inflammatory cytokines is a potential adjunctive tool and biomarker for early identification and management of gout.

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae.

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

A study of HBV infection and its risk factors in pregnant women in Zakho city, Iraq.

BACKGROUND: Despite vaccine and antiviral treatment availability, hepatitis B virus (HBV) continues to circulate among pregnant women in Iraq. HBV spread is due to many factors. This study evaluated HBV prevalence among pregnant women and Syrian refugees residing in Zakho city, Iraq, and identified risk factors associated with infection. MATERIALS AND METHODS: Demographic data were collected from 2,054 pregnant women via a questionnaire assessing risk factors associated with HBV infection. Blood samples were collected for hepatitis B surface antigen (HBsAg) and were screened using an enzyme-linked immunosorbent assay. RESULTS: Tests revealed that 1.1% of pregnant women in Zakho and 11.3% of Syrian refugees (p = 0.001) were positive for HBsAg. The average age of HBsAg-positive patients was 31.4286 ± 6.6746 years (p = 0.002). Average rates of parity and abortion in HBV-infected subjects were 3.5 ± 2.6874 and 0.1785 ± 0.5479, respectively (p = 0.044 and 0.012, respectively). The following were identified as associated risk factors for HBV infection: nationality, (Zakho versus the city centre), tattoos, and polygamy (p = 0.001, 0.03, 0.007, and 0.001, respectively). No significant associations between HBV prevalence and blood transfusion, prior injection history, dental procedures, or surgical procedures were found. CONCLUSION: The prevalence of HBV infection among Syrian refugees was higher than that of indigenous participants. Several risk factors were significantly associated with HBV positivity, which may facilitate effective preventive program implementation and decrease mother-to-child transmission risk. This will likely reduce infant and childhood HBV chronicity, and mortality rates.

Simulation-based Assessment to Measure Proficiency in Mechanical Ventilation among Residents.

Background: Mechanical ventilation (MV) skills are essential for clinicians caring for critically ill patients, yet few training programs use structured curricula and appropriate assessments. Objective structured clinical exams (OSCEs) have been used to assess clinical competency in many areas, but there are no OSCE models focused on MV. Objective: To develop and validate a simulation-based assessment (SBA) with an OSCE structure to assess baseline MV competence among residents and identify knowledge gaps. Methods: We developed an SBA using a lung simulator and a mechanical ventilator, and an OSCE structure, with six clinical scenarios in MV. We included internal medicine residents at the beginning of their rotation in the respiratory intensive care unit (ICU) of a university-affiliated hospital. A subset of residents was also evaluated with a validated multiple-choice exam (MCE) at the beginning and at the end of the ICU rotation. Scores on both assessments were normalized to range from 0 to 10. We used Cronbach's α coefficient to assess reliability and Spearman correlation to estimate the correlation between the SBA and the MCE. Results: We included 80 residents, of whom 42 also completed the MCE examinations. The final version of the SBA had 32 items, and the Cronbach's α coefficient was 0.72 (95% confidence interval [CI], 0.64-0.81). The average SBA score was 6.2 ± 1.3, and performance was variable across items, with 80% correctly adjusting initial ventilatory settings and only 12% correctly identifying asynchrony. The MCE had 24 questions, and the average score was 7.6 ± 2.4 at the beginning of the rotation and 8.2 ± 2.3 at the end of the rotation (increase of 0.6 points; 95% CI, 0.30-0.90; P < 0.001). There was moderate correlation between the SBA and the MCE (rho = 0.41; P = 0.002). Conclusion: We developed and validated an objective structured assessment on MV using a pulmonary simulator and a mechanical ventilator addressing the main competencies in MV. The performance of residents in the SBA at the beginning of an ICU rotation was lower than the performance in MCE, highlighting the need for greater emphasis on practical skills in MV during residency.

The prevalence of Post-Ebola Syndrome hearing loss, Sierra Leone.

BACKGROUND: Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world's population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa. Following the 2014 West African Ebola Outbreak, disease survivors began to describe hearing loss as part of the constellation of symptoms known as Post-Ebola Syndrome. The goal of this study was to more fully characterize hearing loss among Ebola Virus Disease (EVD) survivors. METHODOLOGY AND PRINCIPAL FINDINGS: EVD survivors and their household contacts were recruited (n = 1,12) from Eastern Sierra Leone. Each individual completed a symptom questionnaire, physical exam, and a two-step audiometry process measuring both air and bone conduction thresholds. In comparison to contacts, EVD survivors were more likely to have complaints or abnormal findings affecting every organ system. A significantly greater percentage of EVD survivors were found to have hearing loss in comparison to contacts (23% vs. 9%, p < 0.001). Additionally, survivors were more likely to have bilateral hearing loss of a mixed etiology. Logistic regression revealed that the presence of any symptoms of middle or inner ear (p < 0.001), eye (p = 0.005), psychiatric (p = 0.019), and nervous system (p = 0.037) increased the odds of developing hearing loss. CONCLUSIONS AND SIGNIFICANCE: This study is the first to use an objective and standardized measurement to report hearing loss among EVD survivors in a clinically meaningful manner. In this study it was found that greater than 1/5th of EVD survivors develop hearing loss. The association between hearing impairment and symptoms affecting the eye and nervous system may indicate a similar mechanism of pathogenesis, which should be investigated further. Due to the quality of life and socioeconomic detriments associated with untreated hearing loss, a greater emphasis must be placed on understanding and mitigating hearing loss following survival to aid in economic recovery following infectious disease epidemics.

Awareness of Colorectal Cancer Risk Factors in Palestine: Where Do We Stand?

PURPOSE: To assess the public awareness level of colorectal cancer (CRC) risk factors in Palestine and identify factors associated with the good awareness level. MATERIALS AND METHODS: Adult Palestinians were recruited using convenience sampling from hospitals, primary health care centers, and public locations in 11 governorates. The recognition of 11 CRC risk factors was evaluated using a translated-into-Arabic version of the validated bowel cancer awareness measure. Participants were given one point for each correctly recognized risk factor. The awareness level was determined by the number of CRC risk factors recognized: poor (0-3), fair (4-7), and good awareness (8-11). RESULTS: A total of 4,877 participants, of 5,254 approached, completed the questionnaire (response rate = 92.3%). The final analysis included 4,623 questionnaires, 2,700 from the West Bank and Jerusalem (WBJ) and 1,923 from the Gaza Strip. Participants from the WBJ were older, gained higher monthly income, and had more chronic diseases than participants from the Gaza Strip. The most recognized modifiable CRC risk factor was not doing 30 minutes of moderate physical activity five times a week (n = 3,846, 83.2%), whereas the least recognized was having a diet low in fiber (n = 1,985, 42.9%). The most recognized nonmodifiable CRC risk factor was having a bowel disease (n = 3,320, 71.8%), whereas the least recognized was having diabetes (n = 1,581, 34.2%). Only 1,840 participants (39.8%) demonstrated good awareness of CRC risk factors. Participants from the Gaza Strip were more likely than participants from the WBJ to have good awareness (46.5.0% v 35.0%). Female sex, knowing someone with cancer, and completing postsecondary education were all associated with good awareness. CONCLUSION: Awareness of CRC risk factors was found to be low in Palestine. There is a substantial need to raise awareness of CRC risk factors through educational campaigns and programs.

Validation of Convolutional Neural Networks for Fast Determination of Whole-Body Metabolic Tumor Burden in Pediatric Lymphoma.

18F-FDG PET/CT quantification of whole-body tumor burden in lymphoma is not routinely performed because of the lack of fast methods. Although the semiautomatic method is fast, it is not fast enough to quantify tumor burden in daily clinical practice. Our purpose was to evaluate the performance of convolutional neural network (CNN) software in localizing neoplastic lesions in whole-body 18F-FDG PET/CT images of pediatric lymphoma patients. Methods: The retrospective image dataset, derived from the data pool of the International Atomic Energy Agency (coordinated research project E12017), included 102 baseline staging 18F-FDG PET/CT studies of pediatric lymphoma patients (mean age, 11 y). The images were quantified to determine the whole-body tumor burden (whole-body metabolic tumor volume [wbMTV] and whole-body total lesion glycolysis [wbTLG]) using semiautomatic software and CNN-based software. Both were displayed as semiautomatic wbMTV and wbTLG and as CNN wbMTV and wbTLG. The intraclass correlation coefficient (ICC) was applied to evaluate concordance between the CNN-based software and the semiautomatic software. Results: Twenty-six patients were excluded from the analysis because the software was unable to perform calculations for them. In the remaining 76 patients, CNN and semiautomatic wbMTV tumor burden metrics correlated strongly (ICC, 0.993; 95% CI, 0.989 - 0.996; P < 0.0001), as did CNN and semiautomatic wbTLG (ICC, 0.999; 95% CI, 0.998-0.999; P < 0.0001). However, the time spent calculating these metrics was significantly (<0.0001) less by CNN (mean, 19 s; range, 11-50 s) than by the semiautomatic method (mean, 21.6 min; range, 3.2-62.1 min), especially in patients with advanced disease. Conclusion: Determining whole-body tumor burden in pediatric lymphoma patients using CNN is fast and feasible in clinical practice.

Feature selection approaches for predictive modelling of cadmium sources and pollution levels in water springs.

The World Health Organization lists cadmium (Cd) as one of the top ten chemicals of public health concern. Cd is toxic at relatively low exposure levels and has acute and chronic effects on both health and the environment. In this study, we investigate a suite of data-driven methods that could assist decision-makers in estimating Cd levels in water springs, and in identifying polluting sources. Machine learning (ML) regression models were used to identify sources of contamination and predict Cd levels based on support vector machines and a variety of tree-based models, including Random Forests, M5Tree, CatBoost, and gradient boosting. Feature selection analysis revealed that heavy traffic and distance to a major power plant in the sampled area play a leading role in springs Cd contamination, together with precipitation levels and average of slopes of the closest waste dumps upstream to sampled springs. Our best performing ML model was the Adaboost regression tree using all the features (RMSE = 19.36, R^2 = 0.64). Our findings highlight the effectiveness of predictive data-driven modeling in addressing environmental challenges, particularly in high-risk areas with low resources.