Structure-Guided Design of an Anti-dengue Antibody Directed to a Non-immunodominant Epitope.

Dengue is the most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral responses may not be accessible by conventional B cell panning methods. To demonstrate an alternative strategy to generating a therapeutic antibody, we employed a non-immunodominant, but functionally relevant, epitope in domain III of the E protein, and engineered by structure-guided methods an antibody directed to it. The resulting antibody, Ab513, exhibits high-affinity binding to, and broadly neutralizes, multiple genotypes within all four serotypes. To assess therapeutic relevance of Ab513, activity against important human clinical features of dengue was investigated. Ab513 mitigates thrombocytopenia in a humanized mouse model, resolves vascular leakage, reduces viremia to nearly undetectable levels, and protects mice in a maternal transfer model of lethal antibody-mediated enhancement. The results demonstrate that Ab513 may reduce the public health burden from dengue.

Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

The Ethyl Acetate Extract of Caulerpa microphysa Promotes Collagen Homeostasis and Inhibits Inflammation in the Skin.

Inflammation and collagen-degrading enzymes' overexpression promote collagen decomposition, which affects the structural integrity of the extracellular matrix. The polysaccharide and peptide extracts of the green alga Caulerpa microphysa (C. microphysa) have been proven to have anti-inflammatory, wound healing, and antioxidant effects in vivo and in vitro. However, the biological properties of the non-water-soluble components of C. microphysa are still unknown. In the present study, we demonstrated the higher effective anti-inflammatory functions of C. microphysa ethyl acetate (EA) extract than water extract up to 16-30% in LPS-induced HaCaT cells, including reducing the production of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Furthermore, the excellent collagen homeostasis effects from C. microphysa were proven by suppressing the matrix metalloproteinase-1 (MMP-1) secretion, enhancing type 1 procollagen and collagen expressions dose-dependently in WS1 cells. Moreover, using UHPLC-QTOF-MS analysis, four terpenoids, siphonaxanthin, caulerpenyne, caulerpal A, and caulerpal B, were identified and may be involved in the superior collagen homeostasis and anti-inflammatory effects of the C. microphysa EA extract.

Mice lacking MBNL1 and MBNL2 exhibit sudden cardiac death and molecular signatures recapitulating myotonic dystrophy.

Myotonic dystrophy (DM) is caused by expansions of C(C)TG repeats in the non-coding regions of the DMPK and CNBP genes, and DM patients often suffer from sudden cardiac death due to lethal conduction block or arrhythmia. Specific molecular changes that underlie DM cardiac pathology have been linked to repeat-associated depletion of Muscleblind-like (MBNL) 1 and 2 proteins and upregulation of CUGBP, Elav-like family member 1 (CELF1). Hypothesis solely targeting MBNL1 or CELF1 pathways that could address all the consequences of repeat expansion in heart remained inconclusive, particularly when the direct cause of mortality and results of transcriptome analyses remained undetermined in Mbnl compound knockout (KO) mice with cardiac phenotypes. Here, we develop Myh6-Cre double KO (DKO) (Mbnl1-/-; Mbnl2cond/cond; Myh6-Cre+/-) mice to eliminate Mbnl1/2 in cardiomyocytes and observe spontaneous lethal cardiac events under no anesthesia. RNA sequencing recapitulates DM heart spliceopathy and shows gene expression changes that were previously undescribed in DM heart studies. Notably, immunoblotting reveals a nearly 6-fold increase of Calsequestrin 1 and 50% reduction of epidermal growth factor proteins. Our findings demonstrate that complete ablation of MBNL1/2 in cardiomyocytes is essential for generating sudden death due to lethal cardiac rhythms and reveal potential mechanisms for DM heart pathogenesis.

Investigating the Mechanisms Underlying U46619-Induced Contraction on Porcine Lower Esophageal Sphincter.

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619, were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. SIGNIFICANCE STATEMENT: This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles.

RNA therapeutics has advanced into the third milestone in pharmaceutical drug development, following chemical and protein therapeutics. RNA itself can serve as therapeutics, carriers, regulators, or substrates in drug development. Due to RNA's motile, dynamic, and deformable properties, RNA nanoparticles have demonstrated spontaneous targeting and accumulation in cancer vasculature and fast excretion through the kidney glomerulus to urine to prevent possible interactions with healthy organs. Furthermore, the negatively charged phosphate backbone of RNA results in general repulsion from negatively charged lipid cell membranes for further avoidance of vital organs. Thus, RNA nanoparticles can spontaneously enrich tumor vasculature and efficiently enter tumor cells via specific targeting, while those not entering the tumor tissue will clear from the body quickly. These favorable parameters have led to the expectation that RNA has low or little toxicity. RNA nanoparticles have been well characterized for their anticancer efficacy; however, little detail on RNA nanoparticle pathology and safety is known. Here, we report the in vitro and in vivo assessment of the pathology and safety aspects of different RNA nanoparticles including RNA three-way junction (3WJ) harboring 2'-F modified pyrimidine, folic acid, and Survivin siRNA, as well as the RNA four-way junction (4WJ) harboring 2'-F modified pyrimidine and 24 copies of SN38. Both animal models and patient serum were investigated. In vitro studies include hemolysis, platelet aggregation, complement activation, plasma coagulation, and interferon induction. In vivo studies include hematoxylin and eosin (H&E) staining, hematological and biochemical analysis as the serum profiling, and animal organ weight study. No significant toxicity, side effect, or immune responses were detected during the extensive safety evaluations of RNA nanoparticles. These results further complement previous cancer inhibition studies and demonstrate RNA nanoparticles as an effective and safe drug delivery vehicle for future clinical translations.

Determining the Association Between Insurance Type and Myofascial Release in Large Ventral Hernias.

INTRODUCTION: Abdominal wall reconstruction (AWR) utilizes advanced myofascial releases to perform complex ventral hernia repair (VHR). The relationship between the performance of AWR and disparities in insurance type is unknown. METHODS: The Abdominal Core Health Quality Collaborative was queried for adults who had undergone an elective VHR between 2013 and 2020 with a hernia size ≥10 cm. Patients with missing insurance data were excluded. Comparison groups were divided by insurance type: favorable (private, Medicare, Veteran's Administration, Tricare) or unfavorable (Medicaid and self-pay). Propensity score matching compared the cumulative incidence of AWR between the favorable and unfavorable insurance comparison groups. RESULTS: In total, 26,447 subjects met inclusion criteria. The majority (89%, n = 23,617) had favorable insurance, while (11%, n = 2830) had unfavorable insurance. After propensity score matching, 2821 patients with unfavorable insurance were matched to 7875 patients with favorable insurance. The rate of AWR with external oblique release or transversus abdominis release was significantly higher (23%, n = 655) among the unfavorable insurance group compared to those with favorable insurance (21%, n = 1651; P = 0.013). CONCLUSIONS: This study provides evidence that patients with unfavorable insurance may undergo AWR with external oblique or transversus abdominis release at a greater rate than similar patients with favorable insurance. Understanding the mechanisms contributing to this difference and evaluating the financial implications of these trends represent important directions for future research in elective VHR.

Robotic approach for retromuscular ventral hernia repair may be associated with improved wound morbidity in high-risk patients: a propensity score analysis.

BACKGROUND: Retromuscular sublay (RMS) technique for repair of ventral hernias has gained popularity due to lower risk of recurrence and wound complications. Robotic approaches to RMS have been shown to decrease hospital stay; however, previous studies have failed to show a significant reduction in wound morbidity. Utilizing the Abdominal Core Health Quality Collaborative (ACHQC) database, this study sought to determine the effect of robotic approach on wound morbidity, while specifically focusing on a high-risk population. METHODS: A retrospective review of elective robotic and open RMS repairs in the ACHQC database was performed. Patients deemed to be high-risk for wound complications were included: adult patients with BMI greater than 35 and who were either current smokers or diabetics. A propensity score match was then done to balance covariates between the two groups. Main outcomes of concern were surgical site occurrences (SSO), surgical site infections (SSI), and surgical site occurrence requiring procedural intervention (SSOPI) at 30-day follow-up. RESULTS: A total of 917 patients met inclusion criteria. After propensity score matching, 211 patients matched for each approach. There was no difference in overall SSO (18% for Open vs 23% for Robotic, p = 0.23). Open repair was associated with higher rates of SSI (4% vs 1%, p = 0.032) and SSOPI (9% SSOPI vs 3%, p < 0. 015). As seen in previous studies, there was a higher rate of seroma associated with Robotic RMS repair (87% vs 48%, p < 0.001) in patients that developed an SSO. CONCLUSIONS: In this analysis, a robotic approach was associated with decreased rates of SSI and SSOPI in obese patients who were either current smokers or diabetics. In effort to reduce wound morbidity and the associated physical and economic costs, robotic approach for retromuscular ventral hernia repair should be considered in this patient population.

dbAMP 2.0: updated resource for antimicrobial peptides with an enhanced scanning method for genomic and proteomic data.

The last 18 months, or more, have seen a profound shift in our global experience, with many of us navigating a once-in-100-year pandemic. To date, COVID-19 remains a life-threatening pandemic with little to no targeted therapeutic recourse. The discovery of novel antiviral agents, such as vaccines and drugs, can provide therapeutic solutions to save human beings from severe infections; however, there is no specifically effective antiviral treatment confirmed for now. Thus, great attention has been paid to the use of natural or artificial antimicrobial peptides (AMPs) as these compounds are widely regarded as promising solutions for the treatment of harmful microorganisms. Given the biological significance of AMPs, it was obvious that there was a significant need for a single platform for identifying and engaging with AMP data. This led to the creation of the dbAMP platform that provides comprehensive information about AMPs and facilitates their investigation and analysis. To date, the dbAMP has accumulated 26 447 AMPs and 2262 antimicrobial proteins from 3044 organisms using both database integration and manual curation of >4579 articles. In addition, dbAMP facilitates the evaluation of AMP structures using I-TASSER for automated protein structure prediction and structure-based functional annotation, providing predictive structure information for clinical drug development. Next-generation sequencing (NGS) and third-generation sequencing have been applied to generate large-scale sequencing reads from various environments, enabling greatly improved analysis of genome structure. In this update, we launch an efficient online tool that can effectively identify AMPs from genome/metagenome and proteome data of all species in a short period. In conclusion, these improvements promote the dbAMP as one of the most abundant and comprehensively annotated resources for AMPs. The updated dbAMP is now freely accessible at http://awi.cuhk.edu.cn/dbAMP.

Applying narrative medicine to prepare empathetic healthcare providers in undergraduate pharmacy education in Singapore: a mixed methods study.

BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores.

BACKGROUND: This study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. METHODS: 341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. RESULTS: Upgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. CONCLUSIONS: Smaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

The Application of Rho Kinase Inhibitors in the Management of Glaucoma.

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.

p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients.

The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells' behavior and resistance to neoadjuvant and adjuvant therapy. Our study aimed to ascertain the relationship between the differential expression of p21 in rectal cancer and patient survival outcomes. Using tissue microarrays, 266 rectal cancer specimens were immunohistochemically stained for p21. The expression patterns were scored separately in cancer cells retrieved from the center and the periphery of the tumor; compared with clinicopathological data, tumor regression grade (TRG), disease-free, and overall survival. Negative p21 expression in tumor periphery cells was significantly associated with longer overall survival upon the univariate (p = 0.001) and multivariable analysis (p = 0.003, HR = 2.068). Negative p21 expression in tumor periphery cells was also associated with longer disease-free survival in the multivariable analysis (p = 0.040, HR = 1.769). Longer overall survival times also correlated with lower tumor grades (p= 0.011), the absence of vascular and perineural invasion (p = 0.001; p < 0.005), the absence of metastases (p < 0.005), and adjuvant treatment (p = 0.009). p21 expression is a potential predictive and prognostic biomarker for clinical outcomes in rectal cancer patients. Negative p21 expression in tumor periphery cells demonstrated significant association with longer overall survival and disease-free survival. Larger prospective studies are warranted to investigate the ability of p21 to identify rectal cancer patients who will benefit from neoadjuvant and adjuvant therapy.

Establishing psychometric properties of the older volunteer competency scale in the community.

AIM(S): To investigate the factorial structure, test-retest reliability, and internal consistency of the Older Volunteer Competency Scale and establish its psychometric properties. DESIGN: Cross-sectional survey. METHODS: A total of 1,000 older volunteers were recruited through random sampling and asked to complete the Older Volunteer Competency Scale. Subsequently, 100 participants were selected to participate in a second test to determine the scale's test-retest reliability. Factorial structure was assessed through exploratory factor analysis and confirmatory factor analysis, and internal consistency was assessed using Cronbach's α. RESULTS: Favorable exploratory and confirmatory factor analysis results were obtained. In addition, the three dimensions of the Older Volunteer Competency Scale, namely service awareness, service skills, and interpersonal interaction, had high internal consistency and test-retest reliability. CONCLUSION: The Older Volunteer Competency Scale is an effective and reliable research instrument for evaluating competency and needs among older volunteers.

What do women need to know about long-acting reversible contraception? Perspectives of women from culturally and linguistically diverse backgrounds.

AIM: To identify components of an online education intervention to improve preference for, and uptake of, long-acting reversible contraception in women from culturally and linguistically diverse backgrounds (CALD). ISSUE ADDRESSED: Women from culturally and linguistically diverse (CALD) backgrounds have greater rates of unintended pregnancies than those born locally and are less likely to use long-acting reversible contraceptives (LARCs), which are highly effective at reducing unintended pregnancy. Increasing the uptake of LARC in women from CALD backgrounds may reduce the burden of unintended pregnancy in this high-risk group. An online education intervention has been shown to be effective at increasing preference for and uptake of LARC in young women. We aimed to describe what women from CALD backgrounds thought were the potentially effective components of an online education intervention to increase preference for, and uptake of, long-acting reversible contraception. METHODS: This qualitative study involved semi-structured interviews with six Australian English-speaking women from each of Chinese, Indian, and Middle Eastern cultural backgrounds. Women were recruited through targeted Facebook advertising. Data were analysed using Braun and Clarke thematic analysis. RESULTS: A total of 18 participants were interviewed. We have demonstrated the importance of messages tailored to cultural values, translating the video, widening the target audience to both men and women and using specific social media platforms. For all women, the video needs to highlight the covertness of contraceptive methods, alongside stating cost and approach to access. For Indian women, the video needs to highlight the effect of LARC methods on the menstrual period for Indian women and include basic information on women's health. For Middle Eastern women the video should be explicit about LARC not equating to abortion and emphasise the low efficacy of natural contraceptive methods. For Chinese women, the video should address the misconception that hormones damage the body. Regarding delivery of the video, it should be translated and delivered by a female doctor from the same culture. For Chinese women, the video should include women from the same culture sharing anecdotes and use WeChat and Chinese schools as a platform for dissemination. For Middle Eastern and Indian women government websites should be used for dissemination. The video should be made available to all decision-makers in the reproductive planning process including male partners of Middle Eastern women, parents and peers of Chinese women, and for Indian women the male partner, family, and community leaders. CONCLUSIONS: There is a wide range of cultural adaptations that can be made to the online education videos about LARCs to improve uptake of LARCs and hence reduce the burden of unintended pregnancy in women from CALD grounds. SO WHAT?: Our findings will be used to modify an online education video about LARCs so that it is culturally appropriate for women from CALD backgrounds.

Inequality in Older Volunteering: Association Between Volunteer Competency and Demographic Profiles.

The present survey research investigated older people's volunteering competency relating to social inequality by exploring the latent ability profile and demographic correlates of 1,000 older volunteers in 73 community care centersin southern Taiwan. Older volunteers were classified into advanced (n = 509), basic (n = 214), and novice (n = 277) groups. Demographics examined included: individualistic characteristics (religious beliefs), resources (education; number of chronic diseases), andsocial factors (serving area and spoken language, volunteering duration, marital status, and gender). Apparent inequality issues were revealed. The advanced group was better educated, Mandarin-speaking, and in urban areas. while the novice group featured the opposite (lower education Taiwanese-speaking suburban areas).

Development and characterization of anti-galectin-9 antibodies that protect T cells from galectin-9-induced cell death.

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a ß-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two novel Gal-9-neutralizing antibodies that specifically react with the N-carbohydrate-recognition domain of human Gal-9 with high affinity. We also show using cell-based functional assays that these antibodies efficiently protected human T cells from Gal-9-induced cell death. Notably, in a T-cell/tumor cell coculture assay of cytotoxicity, these antibodies significantly promoted T cell-mediated killing of tumor cells. Taken together, our findings demonstrate potent inhibition of human Gal-9 by neutralizing antibodies, which may open new avenues for cancer immunotherapy.

Robotic vs. Open Approach for Older Adults Undergoing Retromuscular Ventral Hernia Repair.

OBJECTIVE: To describe 30-day outcomes including post-operative complications, readmissions, and quality of life score changes for older adults undergoing elective ventral hernia repair with retromuscular mesh placement and to compare rates of these outcomes for individuals undergoing robotic versus open approaches. SUMMARY OF BACKGROUND DATA: Over one third of patients presenting for elective ventral hernia repair are over the age of 65 and many have complex surgical histories that warrant intricate hernia repairs. Robotic ventral hernia repairs have gained increasing popularity in the US and in some studies have demonstrated decreased rates of postoperative complications, and less pain resulting in shorter hospital stays. However, the robotic approach has several downsides including prolonged operative times as well as the use of pneumo-peritoneum which may be risky in older patients. METHODS: We performed a retrospective review of prospectively collected data in a national hernia specific registry (the Abdominal Core Health Quality Collaborative) and identified patients over the age of 65 undergoing either an open or robotic retromuscular ventral hernia repair. After propensity score matching adjusting for demographic, clinical, and hernia related factors, logistic regression was used to compare 30-day complications, readmission, and quality of life (QoL) scores as captured by the HerQLes scale for patients undergoing each approach. RESULTS: Of 2128 patients who met inclusion criteria, 1695 (79.7%) underwent open ventral hernia repair while 433 (20.3%) underwent robotic repair. After propensity score matching, there were 350 robotic cases and 759 open cases for analysis. Patients undergoing robotic repairs demonstrated significantly shorter length of stays (1 vs 4 days, P < 0.01) and had equivalent odds of both 30-day post-operative complications (odds ratio [OR] 1.15 95% confidence interval 0.92-1.44) and readmission (OR 1.09 95% confidence interval 0.74-1.6) compared to the open approach. QoL scores were similar between groups at 30 days but were slightly better for robotic patients at 1 year (92 vs 84 P < 0.01). CONCLUSIONS: Robotic ventral hernia repair is an option for appropriately selected older patients undergoing retromuscular ventral hernia repair, demonstrating shorter hospital stays and equivalent rates of complications and readmissions in the post-operative period. However, more data is needed regarding QoL outcomes and long-term function, especially as it relates to recurrence rates, between the two approaches.

Long-term Clinical and Patient-Reported Outcomes After Transversus Abdominis Release With Permanent Synthetic Mesh: A Single Center Analysis of 1203 Patients.

OBJECTIVE: We aimed to report long-term clinical and patient-reported outcomes of transversus abdominis release (TAR) with permanent synthetic mesh performed in a high-volume abdominal wall reconstruction practice. SUMMARY BACKGROUND DATA: Despite increasing utilization of TAR in abdominal wall reconstruction, long-term clinical and patient-reported outcomes remain uncertain. METHODS: Prospectively collected registry data from the Cleveland Clinic Center for Abdominal Core Health were analyzed retrospectively. Patients undergoing elective, open VHR with TAR and permanent synthetic mesh implantation between August 2014 and March 2020 with 30-day clinical and ≥1 year clinical or patient-reported outcome follow-up were included. Outcomes included composite hernia recurrence, characterized by patient-reported bulges and recurrent hernias noted on physical exam or imaging, as well as hernia-specific quality of life and pain. RESULTS: A total of 1203 patients were included. Median age was 60 years [interquartile range (IQR): 52-67], median body mass index was 32 kg/m 2 (IQR: 28-36), median hernia width was 15 cm (IQR: 12-19), and 57% of hernias were recurrent. Fascial reapproximation was achieved in 92%. At a median follow-up of 2 years (IQR: 1-4), the overall composite hernia recurrence rate was 26%, with sensitivity analysis yielding best-case and worst-case estimates of 5% and 28%, respectively. Patients experienced improved hernia-specific quality of life and pain regardless of recurrence outcome; however, those who did not recur experienced more substantial improvement. CONCLUSIONS: TAR with permanent synthetic mesh remains a valuable, versatile technique; however, surgeon and patient expectations should be tempered regarding long-term durability. Despite a high rate of recurrence, patients experience measurable improvements in quality of life.