High-throughput discovery of MHC class I- and II-restricted T cell epitopes using synthetic cellular circuits.

Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity.

CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus.

Development of type 2 diabetes mellitus (T2DM) is associated with low-grade chronic type 2 inflammation and disturbance of glucose homeostasis. Group 2 innate lymphoid cells (ILC2s) play a critical role in maintaining adipose homeostasis via the production of type 2 cytokines. Here, we demonstrate that CB2, a G-protein-coupled receptor (GPCR) and member of the endocannabinoid system, is expressed on both visceral adipose tissue (VAT)-derived murine and human ILC2s. Moreover, we utilize a combination of ex vivo and in vivo approaches to explore the functional and therapeutic impacts of CB2 engagement on VAT ILC2s in a T2DM model. Our results show that CB2 stimulation of ILC2s protects against insulin-resistance onset, ameliorates glucose tolerance, and reverses established insulin resistance. Our mechanistic studies reveal that the therapeutic effects of CB2 are mediated through activation of the AKT, ERK1/2, and CREB pathways on ILC2s. The results reveal that the CB2 agonist can serve as a candidate for the prevention and treatment of T2DM.

Volumetric Analysis: Effect on Diagnosis and Management of Indeterminate Solid Pulmonary Nodules in Routine Clinical Practice.

OBJECTIVE: To evaluate the effect of volumetric analysis on the diagnosis and management of indeterminate solid pulmonary nodules in routine clinical practice. METHODS: This was a retrospective study with 107 computed tomography (CT) cases of solid pulmonary nodules (range, 6-15 mm), 57 pathology-proven malignancies (lung cancer, n = 34; metastasis, n = 23), and 50 benign nodules. Nodules were evaluated on a total of 309 CT scans (average number of CTs/nodule, 2.9 [range, 2-7]). CT scans were from multiple institutions with variable technique. Nine radiologists (attendings, n = 3; fellows, n = 3; residents, n = 3) were asked their level of suspicion for malignancy (low/moderate or high) and management recommendation (no follow-up, CT follow-up, or care escalation) for baseline and follow-up studies first without and then with volumetric analysis data. Effect of volumetry on diagnosis and management was assessed by generalized linear and logistic regression models. RESULTS: Volumetric analysis improved sensitivity (P = 0.009) and allowed earlier recognition (P < 0.05) of malignant nodules. Attending radiologists showed higher sensitivity in recognition of malignant nodules (P = 0.03) and recommendation of care escalation (P < 0.001) compared with trainees. Volumetric analysis altered management of high suspicion nodules only in the fellow group (P = 0.008). κ Statistics for suspicion for malignancy and recommended management were fair to substantial (0.38-0.66) and fair to moderate (0.33-0.50). Volumetric analysis improved interobserver variability for identification of nodule malignancy from 0.52 to 0.66 (P = 0.004) only on the second follow-up study. CONCLUSIONS: Volumetric analysis of indeterminate solid pulmonary nodules in routine clinical practice can result in improved sensitivity and earlier identification of malignant nodules. The effect of volumetric analysis on management recommendations is variable and influenced by reader experience.

Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response.

Background: Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications. Methods: A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases. Results: A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies. Conclusion: Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.

The effect of climate changes on incidence of benign paroxysmal positional vertigo; a systematic review with meta-analysis of 16144 patients.

BACKGROUND: There were controversial findings in terms of the association between the incidence of Benign Paroxysmal Positional Vertigo (BPPV) and climate changes, so the current systematic review plus meta-analysis is designed to discover this possible relationship. METHODS: Web of science, PubMed, Scopus, Google Scholar, Embase, and Cochrane library were systematically searched up to August 2023. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Problem/Population, Intervention, Comparison, and Outcome (PICO) guidelines were used. Two authors independently reviewed the eligible articles and assessed the quality of them. RESULTS: In total, 15 studies including 16144 patients met the inclusion criteria. Ten studies reported the relation of BPPV to monthly mean temperature, 7 to monthly average humidity, 4 to monthly average rainfall, 6 to monthly sunlight time, and 2 to average solar radiation. The incidence of BPPV was associated significantly with atmospheric pressure (P: 0.003) and rainfall (P: 0.017). However, there was not any statistically significant correlation between incidence of BPPV and humidity, sunlight time, temperature, and solar radiation level (P > 0.05). CONCLUSIONS: The incidence of BPPV was higher in cold months of a year in both northern hemisphere and southern hemisphere countries. Although it can be because of negative correlation with temperature, the current meta-analysis did not find any statistically significant negative correlation with temperature. In addition, the incidence of BPPV was associated significantly with atmospheric pressure (positive correlation) and rainfall (negative correlation).

Efficacy of plasma rich in growth factors for healing chronic skin ulcers: a systematic review of randomized controlled trials with meta-analysis.

BACKGROUND: Chronic skin ulceration is a serious pathological condition for which the adjuvant use of platelet-rich plasma (PRP) has been indicated. However, evidence for the use of PRP in patients with chronic skin ulcers remains insufficient due to a large heterogeneity in experimental designs, PRP composition, and preparation protocols. OBJECTIVE: To assess previously published reports of the clinical effect of plasma rich in growth factors (PRGF) on chronic skin wounds. METHODS: A comprehensive search of the PubMed, Cochrane Library, and Scopus databases was performed to identify randomized controlled trials (RCTs) assessing the effect of PRGF on chronic ulcer healing, with no limitation regarding publication date (up to September 1, 2022). Percentage area reduction and probability of complete healing in chronic ulcers, pain reduction, infection risk, and cost savings were analyzed. A meta-analysis was performed, and the overall evidence was qualified using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: A total of 113 studies were identified. After full-text screening, 5 RCTs met the inclusion criteria. The meta-analysis showed a significant effect of PRGF on both wound area reduction (mean difference, 56.90% [95% CI, 52.28-61.51], I² = 0%; P = .56) and on the probability of complete healing (RR, 7.07 [95% CI, 1.84-27.16], I² = 0%; P = .53) in chronic ulcers. The overall risk of bias rating was "some concerns," whereas the certainty of evidence was high for both outcomes. A qualitative analysis suggested that PRGF did not increase infection risk and was able to reduce wound pain. CONCLUSION: The use of PRGF significantly enhances wound area reduction and also the probability of complete healing in chronic ulcers. More studies are needed to assess the effect of PRGF on pain and infection, as well as its cost-effectiveness.

Metabolomic Profiles in Jamaican Children With and Without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, metabolic perturbations associated with ASD, which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls in order to identify specific metabolites that may serve as biomarkers for the disorder. We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica, an age and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and missing data imputation, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. The amino acid sarcosine exhibited a significant association with ASD. These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

Ipsilateral Foot Drop and Erectile Dysfunction After the Use of a Traction Table in Intramedullary Femur Fixation: A Case Report and Review of the Literature.

This report presents a case of ipsilateral foot drop and erectile dysfunction following the use of a traction table during intramedullary femur fixation. The patient, a 39-year-old male, underwent surgery for a femur fracture using an intramedullary nail and was positioned on a traction table during the procedure. Post-operatively, he developed foot drop and erectile dysfunction. Neurological examination revealed peroneal nerve injury as the likely cause of the foot drop. The erectile dysfunction was attributed to pudendal nerve injury. Various treatment options were considered, including physical therapy for foot drop and phosphodiesterase inhibitors for erectile dysfunction. In conclusion, this case underscores the importance of recognizing and addressing potential complications associated with traction table use in orthopedic procedures, particularly concerning neurological sequelae and sexual dysfunction.

Epidemiologic Features and Risk Factors for Crimean-Congo Hemorrhagic Fever in Dhi Qar Province, Iraq.

BACKGROUND: Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Iraq, where recurrent epidemics have been constantly observed during the last five years. The present study aimed to determine the factors associated with Crimean-Congo hemorrhagic fever (CCHF) cases in Dhi Qar province during the year 2022. METHODS: A test-negative case-control design was used to analyze 621 CCHF patients, of which 162 were confirmed and 459 were suspected cases. To identify the confirmed and suspected cases, reverse transcriptase polymerase chain reaction (RT-PCR) was used. Suspected patients whose PCR test results were negative were selected as the control group. Data on potential risk factors for CCHF were collected as existing data for previous years for the same geographical locations in Dhi Qar province. Logistic regression analyses were used to determine the correlation between probable risk factors and confirmed CCHF cases. RESULTS: The incidence rate of CCHF was 6.8% per 100,000 people. The total number of deaths was 48 for patients with a case fatality rate of 7.7%. The patients' ages ranged from one year to 65 years, with an overall mean ± SD of 36.08 ± 18.29 years. A total of 98.2% of the patients were between 15 and 65 years of age; 58% of the reported patients were male, and the male-to-female ratio was 1.4:1. Additionally, contact with raw meat, animal contact, and tick bite had the highest percentages for CCHF positivity cases. CONCLUSIONS: Male gender, high-risk jobs like housewives, health staff, shepherds, butchers, animal dealers, slaughterhouse workers, veterinary staff, and farmers, tick bites, and contact with raw meat were statistically significant predictors for increasing CCHF incidence in Dhi Qar province during the year 2022.

Outcomes Among Racial and Ethnic Minority Patients With Advanced Cancers in Phase 1 Trials: A Meta-Analysis.

Importance: Patients from racial and ethnic minority groups (eg, Asian, Hispanic, and non-Hispanic Black patients) have low representation in clinical trials, especially in phase 1 trials in cancer. These trials represent valuable options for patients with advanced cancer who experience disease progression with standard therapy. Objective: To determine whether the benefit of enrollment to phase 1 cancer trials extends to Asian, Hispanic, and non-Hispanic Black patients as much as it does for non-Hispanic White patients. Data Sources: Patient records at a single institution from January 1999 to December 2016 were reviewed. Treatment-related responses, toxic effects, and deaths were recorded. Study Selection: All phase 1 studies were included. Data Extraction and Synthesis: Data underwent independent extraction by multiple observers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The primary outcome was overall survival (OS), assessed using univariate and multivariable time-to-event analyses. Results: A total of 738 patients (median [range], 60 [22-93] years; 467 [63.3] female) including 197 Hispanic patients (26.7%), 238 non-Hispanic Black patients (32.2%), and 282 non-Hispanic White patients (38.2%), were enrolled in 64 phase 1 trials, including 33 cytotoxic trials (51.5%), 21 biologic trials (32.8%), and 10 combined therapy trials (15.6%). The primary cancer diagnoses were colorectal (187 patients [25.3%]), ovarian (141 patients [19.1%]), lung (58 patients [7.9%]), uterine (49 patients [6.6%]), and breast (41 patients [5.6%]). Patients underwent a median (range) of 3 (0-13) therapies prior to trial enrollment. Among 558 patients evaluated for response, the clinical benefit rate (ie, stable disease plus response rates) was 49.1%, and the overall response rate was 6.5%. Grade 3 or 4 nonhematological toxic effects were observed in 27.8% (95% CI, 24.6%-31.3%) of patients and grade 3 or 4 hematological toxic effects were observed in 19.7% (95% CI, 17.0%-22.8%) of patients. The treatment-related mortality rate was 0.9% (95% CI, 0.4%-1.9%). Median OS was 9.6 (95% CI, 8.2-11.0) months among Hispanic patients, 8.3 (95% CI, 6.7-10.4) months among non-Hispanic Black patients, and 9.8 (95% CI, 8.5-11.4) months among non-Hispanic White patients (P = .13). In a multivariable analysis, age older than 60 years, Eastern Cooperative Oncology Group performance status score of 2 or greater, more than 2 metastatic sites, lactate dehydrogenase grade 1 or 2, grade 2 or greater low albumin, grade 1 or greater total bilirubin, and grade 2 or greater anemia were associated with worse prognosis, whereas leukocytosis greater than grade 1 was associated with better OS. Conclusions and Relevance: In this meta-analysis assessing outcomes in phase 1 cancer trials among patients from racial and ethnic minority groups, Hispanic and non-Hispanic Black patients had benefits similar to those of non-Hispanic White patients.

Comparative Study on the Chemical Composition and Biological Activities of the Essential Oils of Lavandula angustifolia and Lavandula x intermedia Cultivated in Lebanon.

The phytochemical profile of essential oils is influenced by genetic and paragenetic factors. In this research, we studied the essential oils of Lavandula angustifolia and Lavandula x intermedia cultivated in Lebanon. The latter is a cross hybrid between Lavandula angustifolia and Lavandula latifolia and is also known as lavandin and Lavandula hybrida. Specifically, the chemical composition and biological activities (antibacterial, antioxidant, anticancer, and hemolytic) of the essential oils were assessed. GC-MS results showed marked differences in the chemical compositions of the oils. For example, linalool was more abundant in L. x intermedia (44.15%) than in L. angustifolia (32%), while an opposite trend was observed for the percentages of 1,8-cineole (8.6% in L. angustifolia and 4.0% in L. x intermedia). FTIR analysis confirmed the richness of both oils in monoterpenes and sesquiterpenes. In terms of antioxidant activity, L. angustifolia essential oil demonstrated significantly better activity (IC50= 5.24 ± 1.20 mg/mL) compared to L. x intermedia oil in the DPPH radical scavenging assay. MTT cell viability assays revealed that L. angustifolia essential oil was a slightly more potent antiproliferative agent than L. x intermedia oil on human colorectal (HCT-116) and human breast (MCF-7) cancer cells. The antibacterial activity of the essential oils was tested against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Serratia marcescens. Both oils showed good antibacterial activities with MIC values of 0.174 and 0.169 mg/mL for L. angustifolia and L. x intermedia oils, respectively. MBC determinations revealed that the antibacterial activity was bactericidal against all bacteria, except Staphylococcus aureus. Furthermore, both essential oils did not exhibit notable hemolytic activity on red blood cells. Overall, Lebanese L. angustifolia and L. x intermedia essential oils have promising industrial and medicinal values.

Medicare billing and utilization trends in vascular surgery.

OBJECTIVE: Within the past decade, Medicare Part B reimbursements for various surgical procedures have been declining, whereas health care expenses continue to increase. As a result, hospitals may increase service charges to offset losses in revenue, which may disproportionately affect underinsured patients. Our analysis aimed to characterize Medicare billing and utilization trends across common vascular surgical procedures. METHODS: The 2017 to 2021 Medicare Physician and Other Practitioners by Provider and Service dataset was queried for Current Procedural Terminology (CPT) codes for common vascular surgery procedures. The average charges, reimbursements, charge-to-reimbursement ratios, and service counts were calculated for the most common interventions performed by vascular surgeons. Data was stratified by care setting, facility (inpatient and outpatient hospital) vs non-facility locations. All monetary values were adjusted to the 2021 United States dollars to account for inflation. RESULTS: For facility settings, the mean charge billed to Medicare Part B increased from $3708 to $3952 (6.6%) from 2017 to 2021, with the average charge-to-reimbursement ratio increasing from 7.2 to 8.6. There were 17 of the 19 facility procedures that had a decline in reimbursements, decreasing from an average of $558 to $499 (-10.4%). Stab phlebectomy had the largest individual decrease in facility reimbursement (-53.5%), followed by above-knee amputation (-11.3%) and below-knee amputation (-11.0%). Both non-facility charges (-10.8%) and reimbursements (-12.2%) declined over the study period. Procedural utilization remained stable from 2017 to 2019. Tibial and femoral-popliteal atherectomy had increases of 45.9% and 33.7%, respectively, in overall procedural utilization when performed in non-facility settings from 2017 to 2019. CONCLUSIONS: Our analysis of vascular surgery procedures billed to Medicare Part B from 2017 to 2021 demonstrates an increase in charges, a decline in reimbursements, and a resultant increase in charge-to-reimbursement ratios for facility care settings. In contrast, non-facility charges have decreased in the face of declining reimbursements. These markups in submitted charges in facility locations may serve as an additional barrier to accessing care for patients who are underinsured.

Phylogenetic group distribution and antibiotic resistance of Escherichia coli isolates in aquatic environments of a highly populated area.

Background: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae including Escherichia coli (E. coli), are recognized as a global public health threat due to their multidrug-resistant (MDR) phenotypes and their rapid dissemination in aquatic environments. Nevertheless, studies investigating the prevalence and antimicrobial resistance (AMR) profile of ESBL-producing E. coli in Lebanese surface water are limited. Objective: This study aimed to assess the physicochemical properties and microbial contamination load and to determine the distribution of AMR patterns of ESBL-producing E. coli in surface water samples from different sites in the North Governorate of Lebanon. Methods: Water samples were collected from 25 major sites in North Lebanon. These samples were analyzed for the presence of total coliforms, E. coli, and fecal enterococci. Phenotypic and genetic characterizations were then performed for E. coli isolates to determine their resistance patterns and phylogenetic groups. Results: Fifty-six samples out of 100 samples were positive for ESBL-producing E. coli, mostly harboring blaCTX-M (40/56, 71%) including blaCTX-M-15 (33/40, 82%), blaTEM gene (36/56, 64%), blaSHV (20/56, 36%), and blaOXA (16/56, 29%) including blaOXA-48 gene (11/16, 69%). Most ESBL-producing E. coli isolates belonged to the extra-intestinal pathogenic phylogroup B2 (40/56, 71.4%) while 10/56 (17.9%) belonged to the commensal phylogroup A. Conclusion: Our results highlight the need to implement effective water monitoring strategies to control transmission of ESBL-producing E. coli in surface water and thus reduce the burden on human and animal health.

MXene-Based Flexible Electrodes for Electrophysiological Monitoring.

The advancement of flexible electrodes triggered research on wearables and health monitoring applications. Metal-based bioelectrodes encounter low mechanical strength and skin discomfort at the electrode-skin interface. Thus, recent research has focused on the development of flexible surface electrodes with low electrochemical resistance and high conductivity. This study investigated the development of a novel, flexible, surface electrode based on a MXene/polydimethylsiloxane (PDMS)/glycerol composite. MXenes offer the benefit of featuring highly conductive transition metals with metallic properties, including a group of carbides, nitrides, and carbonitrides, while PDMS exhibits inherent biostability, flexibility, and biocompatibility. Among the various MXene-based electrode compositions prepared in this work, those composed of 15% and 20% MXene content were further evaluated for their potential in electrophysiological sensing applications. The samples underwent a range of characterization techniques, including electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), as well as mechanical and bio-signal sensing from the skin. The experimental findings indicated that the compositions demonstrated favorable bulk impedances of 280 and 111 Ω, along with conductivities of 0.462 and 1.533 mS/cm, respectively. Additionally, they displayed promising electrochemical stability, featuring charge storage densities of 0.665 mC/cm2 and 1.99 mC/cm2, respectively. By conducting mechanical tests, Young's moduli were determined to be 2.61 MPa and 2.18 MPa, respectively. The composite samples exhibited elongation of 139% and 144%, respectively. Thus, MXene-based bioelectrodes show promising potential for flexible and wearable electronics and bio-signal sensing applications.

24 Factorial Design Formulation Optimization and In vitro Characterization of Desloratadine Nanosuspension Prepared Using Antisolvent Precipitation.

INTRODUCTION: Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics properties. METHOD: This study investigated the impact of polymer, surfactant types, and concentration on the particle size, zeta potential, and dissolution efficiency of nanosuspensions formulated through the solvent antisolvent precipitation method. To optimize the delivery of Desloratadine nanosuspension, we used Minitab software and a 4-factor, 2-level full factorial design. Physicochemical properties and drug release studies were conducted to evaluate the suggested nanosuspension formulations. The optimization goals included minimizing particle size and zeta potential while maximizing dissolution efficiencies. RESULT: The selected optimal nanosuspension demonstrated favourable values, including a particle size of 478.63 ± 15.67 nm, a zeta potential of -36.24 ± 3.21 mV, and dissolution efficiencies in double distilled water and buffer of 90.29 ± 3.75 % and 93.70 ± 3.67 %, respectively. The optimized formulation was subjected to additional analysis using X-ray powder diffraction (XPRD), scanning and transmission electron microscopy (SEM and TEM), and Fourier-transform infrared spectroscopy (FTIR). CONCLUSION: The optimized nanosuspension formulation also underwent further studies under optimal lyophilization conditions, revealing the effectiveness of mannitol as a cryoprotectant at a concentration of 8%.

Awareness and Interest in Rhinoplasty and Its Postoperative Complications Among Females in the Northern Border Region, Saudi Arabia.

BACKGROUND: Rhinoplasty is a popular cosmetic surgical procedure that aims to reshape the nose, enhance its appearance, and improve nasal function. This study investigated the awareness, attitudes, and interest in rhinoplasty among females in the Northern Border Region of Saudi Arabia, as well as their knowledge of potential postoperative complications. METHODS: An online survey was used to perform a cross-sectional study. Female participants aged between 18 and 45 years, living in the Northern Border Region of Saudi Arabia, were selected. The questionnaire consisted of three main sections: personal information, attitude toward rhinoplasty, and complications of rhinoplasty. RESULTS: 905 females participated in our study. The majority (87.8%, n=795) had heard about rhinoplasty before, and 54.9% (n=497) knew someone who had undergone the surgery. Social media was the most common source of information about rhinoplasty (67.2%, n=608). A significant proportion of participants (72.4%, n=655) believed that their nose appearance sometimes or always limited their social and professional activities. However, only 16.7% (n=151) expressed a desire to change or improve their nose appearance through surgery. The educational status of the participant (*p*=0.027) and their father (*p*=0.011) were significantly associated with interest in rhinoplasty. Satisfaction with nose appearance, breathing, and family and friends' opinions about the participant's nose were also significantly associated with interest in rhinoplasty (*p*<0.001 for all). The majority of participants (88.4%, n=800) were aware of at least one complication, with the most recognized complications being breath disorders (74.6%, n=675), headache (70.6%, n=639), and mismatch of their new noses with the rest of their faces (69.8%, n=632). Age (*p*=0.008), city of residence (*p*<0.001), and satisfaction of family and friends with the participant's nose (*p*=0.019) were significantly associated with complication awareness. CONCLUSION: This study found that women in Saudi Arabia's Northern Border Region had a high level of awareness and interest in rhinoplasty, despite concerns regarding the safety, availability of educational resources, and ethical considerations in promoting the procedure. The findings highlight the need for accurate and comprehensive information about rhinoplasty and its potential complications to be readily available to the public, particularly through targeted educational interventions and responsible advertising regulations.

A geospatial analysis of local intermediate snail host distributions provides insight into schistosomiasis risk within under-sampled areas of southern Lake Malawi.

BACKGROUND: Along the southern shoreline of Lake Malawi, the incidence of schistosomiasis is increasing with snails of the genera Bulinus and Biomphalaria transmitting urogenital and intestinal schistosomiasis, respectively. Since the underlying distribution of snails is partially known, often being focal, developing pragmatic spatial models that interpolate snail information across under-sampled regions is required to understand and assess current and future risk of schistosomiasis. METHODS: A secondary geospatial analysis of recently collected malacological and environmental survey data was undertaken. Using a Bayesian Poisson latent Gaussian process model, abundance data were fitted for Bulinus and Biomphalaria. Interpolating the abundance of snails along the shoreline (given their relative distance along the shoreline) was achieved by smoothing, using extracted environmental rainfall, land surface temperature (LST), evapotranspiration, normalised difference vegetation index (NDVI) and soil type covariate data for all predicted locations. Our adopted model used a combination of two-dimensional (2D) and one dimensional (1D) mapping. RESULTS: A significant association between normalised difference vegetation index (NDVI) and abundance of Bulinus spp. was detected (log risk ratio - 0.83, 95% CrI - 1.57, - 0.09). A qualitatively similar association was found between NDVI and Biomphalaria sp. but was not statistically significant (log risk ratio - 1.42, 95% CrI - 3.09, 0.10). Analyses of all other environmental data were considered non-significant. CONCLUSIONS: The spatial range in which interpolation of snail distributions is possible appears < 10km owing to fine-scale biotic and abiotic heterogeneities. The forthcoming challenge is to refine geospatial sampling frameworks with future opportunities to map schistosomiasis within actual or predicted snail distributions. In so doing, this would better reveal local environmental transmission possibilities.

Initial versus Staged Thyroidectomy for Differentiated Thyroid Cancer: A Retrospective Multi-Dimensional Cohort Analysis of Effectiveness and Safety.

The optimal surgical approach for differentiated thyroid cancer remains controversial, with debate regarding the comparative risks of upfront total thyroidectomy versus staged completion thyroidectomy following the initial lobectomy. This study aimed to assess the complication rates associated with these two strategies and identify the optimal timing for completion thyroidectomy using a multi-dimensional analysis of four cohorts: an institutional series (n = 148), the National Surgical Quality Improvement Program (NSQIP) database (n = 39,992), the TriNetX repository (n > 30,000), and a pooled literature review (10 studies, n = 6015). Institutional data revealed higher overall complication rates with total thyroidectomy (18.3%) compared to completion thyroidectomy (6.8%), primarily due to increased temporary hypocalcemia (10% vs. 0%, p = 0.004). The NSQIP analysis demonstrated that total thyroidectomy was associated with a 72% increased risk of transient hypocalcemia (p < 0.001) and a 25% increased risk of permanent hypocalcemia (p < 0.001). TriNetX data confirmed these findings and identified obesity and concurrent neck dissection as risk factors for complications. A meta-analysis showed that total thyroidectomy increased the rates of transient (RR = 1.63) and permanent (RR = 1.23) hypocalcemia (p < 0.001). Institutional and TriNetX data suggested that performing completion thyroidectomy between 1 and 6 months after the initial lobectomy minimized permanent complication rates compared to delays beyond 6 months. In conclusion, for differentiated thyroid cancer, total thyroidectomy is associated with higher risks of transient and permanent hypocalcemia compared to staged completion thyroidectomy. However, performing completion thyroidectomy within 1-6 months of the initial lobectomy may mitigate the risk of permanent complications. These findings can inform personalized surgical decision-making for patients with differentiated thyroid cancer.

Understanding the Quality of Life Among Patients With Cancer in Saudi Arabia: Insights From a Cross-Sectional Study.

INTRODUCTION: Cancer patients' quality of life (QoL) significantly influences treatment response and mortality rates. Understanding QoL domains among patients with cancer and what affects it can help create interventions that improve QoL and ease patients' experience. This study measures the OoL among patients with cancer and influencing factors. METHODS: A prospective cross-sectional questionnaire-based study included cancer patients aged >18 currently receiving treatment. The questionnaire collected social and economic data, followed by the validated Arabic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Means and standard deviations for described numeric variables and frequencies and percentages described categorical variables. Analysis of variance, F-tests, and P-values were reported. RESULTS: Among 182 cancer patients, 60% were female. Younger patients exhibited higher QoL in physical and role functioning (P = .016 and .03) and experienced more significant financial impact (P = .0144). Females reported more adverse effects from cancer symptoms, including fatigue, nausea, vomiting, and pain (36.7% vs 25.5%, P = .005; 20.6% vs 11.5%, P = .0186; 34.7% vs 25.1%, P = .0281). Single patients had superior QoL in physical functioning compared to others (P = .0127). Patients traveling long distances were more likely to face adverse financial consequences (P = .007). Asthmatic patients exhibited lower QoL in physical, role, and cognitive functioning (72.3 vs 37.8, P = .0147; 76.4 vs 22.2, P = .0024; 84.7 vs 44.4, P = .0038) and reported increased dyspnea and appetite loss (16 vs 55.6 and 26.1 vs 66.7, both P < .05). CONCLUSION: Factors influencing QoL in Saudi cancer patients include age, marital status, gender, hospital distance, and chronic conditions. Thus emphasizing the necessity for personalized care strategies to enhance outcomes and alleviate the overall burden of cancer care.

The cochlear dose and the age at radiotherapy predict severe hearing loss after passive scattering proton therapy and cisplatin in children with medulloblastoma.

BACKGROUND: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin. METHODS: We identified patients aged 3-21 years who were treated at our centers between 2007-2022. Audiograms were graded using the International Society of Pediatric Oncology-Boston scale. Time to grade 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Seventy-nine patients were treated with PSPT at a median age of 7.5 years (range:3.1-21.1). The mean cochlear dose (Dmc) (±S.D.) was 31.5±8.5 Gy, and the cumulative cisplatin dose was 295±50 mg/m2. Fifty-nine patients (75%) received amifostine. Patients completed a median of 9 audiograms (range:4-22) with a median audiogram follow-up of 49 months (range:6-177). Twenty-seven patients (34%) had grade 3-4 HL. In adjusted Cox models, only higher Dmc (HR=1.12, 95% CI:1.06-1.18) was associated with grade 3-4 HL. The predicted 3-year incidence of grade 3-4 HL was 40.0% (95% CI: 21.3-66.3) and 66.7% (95% CI: 35.4-93.7) for children with Dmc ≥36 Gy and age at radiotherapy ≥7 and <7 years, respectively (p=0.042). It was 8.9% (95% CI: 2.3-31.6) and 15.6% (95% CI: 5.3-41.1) for children with Dmc <36 Gy and age at radiotherapy ≥7 and <7 years, respectively (p=0.78). CONCLUSIONS: Children <7 years at radiotherapy with a Dmc ≥36 Gy are at higher risk for HL.