Practice Patterns and Challenges in Managing Inherited Retinal Diseases across Asia-Pacific: A Survey from the APIED Network.

PURPOSE: The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region. METHODS: The 62-item questionnaire was distributed electronically via email. The questions covered five domains: (1) structure of the IRD service and registry/database; (2) genotyping practices; (3) genetic counselling; (4) deep phenotyping practices; (5) low-vision rehabilitation services. RESULTS: The survey was completed by 36 of 45 centres in twelve countries and regions in APAC. Among these centres, 42% reported managing more than 1000 patients. Notably, 39% of centres lack an IRD database or registry, and 44% of centres have tested less than one-quarter of their IRD patients. The majority of centres (67%) do not have genetic counsellors. While there was consistency in the imaging-based investigations, there was marked heterogeneity for functional testing using electrophysiology and formal perimetry. Only 34% of centres confirmed the availability of access to low-vision assistive devices. CONCLUSIONS: This study reveals several critical gaps in managing IRDs in the APAC region. These include the lack of IRD database/registry in one-third of centres, a substantial proportion of patients remaining genetically undiagnosed, and limited availability of genetic counsellors. The findings also underscore a need to harmonise investigations for evaluating retinal function and identify areas for improvement in the provision of low-vision rehabilitation services.

Full-Waveform Inversion Imaging of Cortical Bone Using Phased Array Tomography.

Classic ultrasound bone imaging modalities usually demand either a prior knowledge or an advanced estimation on speed of sound (SoS), which not only renders to a burdensome imaging process but also supplies a limited resolution. To overcome these drawbacks, this article proposed a frequency-domain full-waveform inversion (FDFWI) modality using phased array tomography for high-accuracy cortical bone imaging. A transmission scenario of ultrasound wave in 2-D space was presented in the frequency domain to simulate the forward wavefield propagation. Iterations in the inversion process were performed by matching the simulation wavefield to the experimental one from low to high discrete frequency points. Moreover, the association between the maximum initial frequency and the initial SoS model was explored to prevent the occurrence of cycle-skipping phenomenon, which could lead to the outcomes being trapped in local minima. The feasibility and effectiveness of the proposed imaging scheme were testified by simulation, phantom, and ex-vivo studies, with mean relative errors of cortical part being 3.18%, 8.71%, and 9.36%, respectively. It is verified that the proposed FDFWI method is an effective way for parametric imaging of cortical bone without any prior knowledge of sound speed.

Facial reconstruction with thinned anterolateral thigh free flap.

Facial reconstruction is challenging for plastic surgeons, as it can be difficult to decide the best approach. One technique that has been widely used is the anterolateral thigh (ALT) flap due to its numerous benefits. However, its thickness can be a drawback, especially regarding facial reconstruction. The thinning technique is not a new novel, but how to apply it to the ALT flap to get the best result hasn't been reported yet. Our study involved 117 patients, and we used 73 thinned ALT flaps to determine the best method to increase the flap's safety. After thinning, we significantly reduced the flap's thickness from an average of 22.5 mm to 5.9 mm, making it more suitable for contouring purposes. We apply a thinned ALT flap for coverage, contouring, and recreating the facial 3D structure. The 12/45 flap has the chance to make the multiple-paddle ALT flap, which helps to reconstruct difficult positions even more flexibly. The key to successfully thinning the ALT flap is understanding the perforator's structure and pathway through the fascia. With the thinning technique, we have overcome the limitations of the flap's thickness, making it suitable for use in whole-body reconstruction. The ALT flap can overcome the restriction of its thickness and can be applied even more extensively in whole-body reconstruction.

Plasma glucosylceramide levels are regulated by ATP10D and are not involved in Parkinson's disease pathogenesis.

GBA1 variants and decreased glucocerebrosidase (GCase) activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), one of GCase main substrates, are involved in PD pathogenesis. Using multiple genetic methods, we show that ATP10D, not GBA1, is the main regulator of plasma GlcCer levels, yet it is not involved in PD pathogenesis. Plasma GlcCer levels were associated with PD, but not in a causative manner, and are not predictive of disease status. These results argue against targeting GlcCer in GBA1-PD and underscore the need to explore alternative mechanisms and biomarkers for PD.

Pre-cluster symptoms in a Taiwanese cohort of cluster headache: symptom profiles and clinical predictions.

BACKGROUND: Pre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy. METHODS: We prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients' headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil. RESULTS: A total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7-9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3-4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4-5.1], p = 0.003). CONCLUSION: PCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications.

The risk factors determined by four machine learning methods for the change of difference of bone mineral density in post-menopausal women after three years follow-up.

The prevalence of osteoporosis has drastically increased recently. It is not only the most frequent but is also a major global public health problem due to its high morbidity. There are many risk factors associated with osteoporosis were identified. However, most studies have used the traditional multiple linear regression (MLR) to explore their relationships. Recently, machine learning (Mach-L) has become a new modality for data analysis because it enables machine to learn from past data or experiences without being explicitly programmed and could capture nonlinear relationships better. These methods have the potential to outperform conventional MLR in disease prediction. In the present study, we enrolled a Chinese post-menopause cohort followed up for 4 years. The difference of T-score (δ-T score) was the dependent variable. Information such as demographic, biochemistry and life styles were the independent variables. Our goals were: (1) Compare the prediction accuracy between Mach-L and traditional MLR for δ-T score. (2) Rank the importance of risk factors (independent variables) for prediction of δ T-score. Totally, there were 1698 postmenopausal women were enrolled from MJ Health Database. Four different Mach-L methods namely, Random forest (RF), eXtreme Gradient Boosting (XGBoost), Naïve Bayes (NB), and stochastic gradient boosting (SGB), to construct predictive models for predicting δ-BMD after four years follow-up. The dataset was then randomly divided into an 80% training dataset for model building and a 20% testing dataset for model testing. A 10-fold cross-validation technique for hyperparameter tuning was used. The model with the lowest root mean square error for the validation dataset was viewed as the best model for each ML method. The averaged metrics of the RF, SGB, NB, and XGBoost models were used to compare the model performance of the benchmark MLR model that used the same training and testing dataset as the Mach-L methods. We defined that the priority demonstrated in each model ranked 1 as the most critical risk factor and 22 as the last selected risk factor. For Pearson correlation, age, education, BMI, HDL-C, and TSH were positively and plasma calcium level, and baseline T-score were negatively correlated with δ-T score. All four Mach-L methods yielded lower prediction errors than the MLR method and were all convincing Mach-L models. From our results, it could be noted that education level is the most important factor for δ-T Score, followed by DBP, smoking, SBP, UA, age, and LDL-C. All four Mach-L outperformed traditional MLR. By using Mach-L, the most important six risk factors were selected which are, from the most important to the least: DBP, SBP, UA, education level, TG and sleeping hour. δ T score was positively related to SBP, education level, UA and TG and negatively related to DBP and sleeping hour in postmenopausal Chinese women.

The Mediation Roles of Coping Modalities on the Relationship Between Stress and Quality of Life Among Jordanian Nurses.

Nurses are at the frontline, dealing with people's most immense healthcare needs in stressful and demanding work environments. Consequently, it is essential to thoroughly examine how various coping mechanisms might affect the relationship between stress and quality of life (QOL). This study aimed to examine the mediation effect of both problem-focused coping (PFC) and emotion-focused coping (EFC) mechanisms on mitigating the effect of stress on the QOL among Jordanian nurses. A multisite cross-sectional descriptive correlational design was used in this study. An online survey was completed by 203 nurses using a convenience sampling technique between October 2023 and January 2024. The study included nurses working in different Jordanian healthcare sectors including governmental, private, and university-affiliated hospitals. Several measures were used to collect data, including questionnaires on sociodemographics, QOL, coping, and stress. Two models were hypothesized for this study. The two models were analyzed using Andrew Hayes Process Macro Model 4 for testing the mediation effects. Additionally, descriptive and correlational analyses were run prior to the main analysis. The results showed that coping significantly mediated the relationship between stress and QOL with variations between PFC and EFC. In conclusion, psychological distress symptoms were common among Jordanian nurses; psychological distress, coping, and QOL are correlating variables. Nurses' stress levels and coping modalities can predict QOL with a superior effect of PFC compared with EFC. Strategies should be put in place to improve effective coping to improve nurses' QOL. The results of this study have important implications for nursing education, practice, future research, and policy.

Comparison Between Powered and Manual Toothbrushes Effectiveness for Maintaining an Optimal Oral Health Status.

This integrative literature review evaluates the effectiveness of power toothbrushes (PTBs) compared to manual toothbrushes (MTBs) across various populations, focusing on plaque removal, gingival health, calculus reduction, and stain removal. PTBs equipped with advanced technologies such as oscillating-rotating and high-frequency sonic mechanisms have been examined for their potential to enhance oral hygiene. Special attention is given to vulnerable groups, including the elderly and individuals with intellectual disabilities, to assess how PTBs meet their specific oral health needs. A comprehensive literature search was conducted in databases including PubMed, Cochrane Library, Embase, and Google Scholar using keywords such as "power toothbrush", "electric toothbrush", "manual toothbrush", "plaque removal", "gingivitis", "calculus", "dental stains", "oral hygiene", "elderly", and "intellectual disabilities". Studies published between 2000 and 2024 were selected based on their relevance to the PTB and MTB comparison, with an emphasis on outcomes related to oral hygiene efficacy. As this review is narrative rather than systematic, it focuses on synthesizing existing knowledge without applying strict inclusion or exclusion criteria. The results indicate that PTBs generally outperform MTBs in reducing plaque, gingivitis, and stains, though the benefits for special populations are less pronounced but still significant. However, practical issues such as user experience and mechanical reliability of PTBs warrant further investigation. In conclusion, this review enhances the understanding of PTB effectiveness, guides consumer choices, and informs future technological advancements in dental care practices.

Comprehensive Exploration of Bromophenol Derivatives: Promising Antibacterial Agents against SA and MRSA.

The incidence of treatment failure due to multidrug-resistant pathogens elevated over the years; the rate is much higher than new antibiotic drug discovery. Therefore, bromophenol derivatives as potential antibacterial agents on Staphylococcus aureus and MRSA were explored in this research via integrating chemistry, microbiology, and pharmacology to address significant knowledge gaps pertaining to the antibacterial activity of bromophenols based on their functional groups. Surprisingly, a simple molecule, 3-bromo-2,6-dihydroxyacetophenone (2), exhibited good anti-S. aureus activity and even MRSA, a drug-resistant strain. In addition, compound 2 also inhibited a common resistant pathway of pathogens, biofilm formation of S. aureus and MRSA. Moreover, the therapeutic index of 2 is up to 598, which can be viewed as highly selective and having low toxicity to human HEK-293 cells. Although these compounds displayed less effectiveness for the Gram-negative bacterium, Pseudomonas aeruginosa, they still manifested some effects on the virulence properties of P. aeruginosa, such as biofilm formation, pyocyanin production, and swarming motility. In silico analyses of the structure-activity relationship as well as ADMET properties were discussed in the end. This study shed some light on the antibacterial activities of bromophenols.

Flexible SERS chips for rapid on-site detection of tricyclazole pesticide in agricultural products.

A flexible, ultrasensitive, and practical SERS chip is presented based on a paper/f-TiO2/Ag structure. The chip enhances the self-assembly of Ag nanoparticles on a cellulose fiber matrix, facilitated by smart functionalized TiO2 nanomaterials (f-TiO2). This design enables superior detection of the hazardous pesticide tricyclazole (TCZ) on crops using an advanced, simple, and efficient analytical method. Despite its straightforward fabrication process via a solvent immersion method, the intrinsic smart surface properties of the TiO2 bridging material - both hydrophilic and hydrophobic - enable the uniform and dense self-assembly of hydrophilic Ag nanoparticles (NPs) on the cellulose fiber paper substrate. This innovative design provides superior sensing efficiency for TCZ molecules with a detection limit reaching 2.1 × 10-9 M, a remarkable improvement compared to Paper/Ag substrates lacking f-TiO2 nanomaterials, which register at 10-5 M. This flexible SERS substrate also exhibits very high reliability as indicated by its excellent reproducibility and repeatability with relative standard deviations (RSD) of only 5.93% and 4.73%, respectively. Characterized by flexibility and a water-attractive yet non-soluble surface, the flexible Paper/f-TiO2/Ag chips offer the convenience of direct immersion into the analytical sample, facilitating seamless target molecule collection while circumventing interference signals. Termed the "dip and dry" technique, its advantages in field analysis are indisputable, boasting in situ deployment, simplicity, and high efficiency, while minimizing interference signals to negligible levels. Through the application of this advanced technique, we have successfully detected TCZ in two high-value crops, ST25 rice and dragon fruit, achieving excellent recovery values ranging from 90 to 128%. This underscores its immense potential in ensuring food quality and safety. As a proof of concept, flexible Paper/f-TiO2/Ag SERS chips, with a simple fabrication process, advanced analytical technique, and superior sensing efficiency, bring SERS one step closer to field applications beyond the laboratory.

Thalamocortical Dysconnectivity in Treatment-Resistant Depression.

Thalamocortical connectivity is associated with cognitive and affective processing. The role of thalamocortical connectivity in the pathomechanism of treatment-resistant depression (TRD) remains unclear. This study included 48 patients with TRD and 48 healthy individuals. We investigated thalamocortical connectivity by performing resting-state functional MRI with the bilateral thalamus as the seed. In addition, patients with TRD were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS). Compared with the healthy individuals, the patients with TRD exhibited increased functional connectivity (FC) of the thalamus with the insula and superior temporal cortex and reduced the FC of the thalamus with the anterior paracingulate cortex and cerebellum crus II. Our study may support the crucial role of thalamocortical dysconnectivity in the TRD pathomechanism. However, the small sample size may limit the statistical power. A future study with a large sample size of patients with TRD would be required to validate our findings.

Sickle Cell Disease and Lead Poisoning in New York City, 2005-2019.

OBJECTIVES: Previous analyses of New York City (NYC) health department's lead registry indicated that, among children with lead poisoning, an increased prevalence of sickle cell disease (SCD) exists. However, SCD is not considered a risk factor for lead poisoning. We assessed the association between SCD and childhood lead poisoning to determine if specific lead poisoning prevention efforts are needed for children with SCD. METHODS: We analyzed NYC's lead registry data for children with venous blood lead levels (BLLs) ≥15 mcg/dL during 2005 to 2019. t tests and χ2 tests were performed to compare demographic characteristics, BLLs, and lead exposure risks in non-Hispanic Black children with and without SCD. A t test was used to compare observed SCD prevalence among Black children with BLLs ≥15 mcg/dL with an estimated 0.43% SCD prevalence among Black NYC children. RESULTS: Among 1728 Black children with BLLs ≥15 mcg/dL identified, 37 (2.14%) had SCD. When comparing children with and without SCD, both mean age at peak BLL (62.8 versus 42.7 months; P = .003) and peak BLL (42.59 versus 23.06 mcg/dL; P = .008) were higher for children with SCD. Among risk factors for lead exposure, children with SCD had higher prevalence of pica. Observed SCD prevalence was 1.71% higher than estimated SCD prevalence among Black NYC children (P < .001). CONCLUSIONS: We found a potential association between SCD and childhood lead poisoning. Pica emerged as a potentially important risk factor. Our findings might have implications for lead poisoning prevention guidelines for children with SCD.

The role of pattern recognition receptors in the innate immune system of Chinese mitten crab (Eriocheir sinensis).

Eriocheir sinensis (Chinese mitten crab) is one of the main economic species in China, which has evolved an extremely sophisticated innate immune system to fend off disease invasions. However, bacterial and viral infections have caused significant financial losses for the E. sinensis aquaculture in recent years. Making well-informed judgments for the control microbial infections would require a thorough understanding and clarification of the intricate innate immune system of E. sinensis. Innate immunity is essential for the host's defense against invasive pathogens. Pattern recognition receptors (PRRs) initially recognize pathogen-associated molecular patterns (PAMPs) and trigger an innate immune response, causing the generation of inflammatory cytokine and promoting the clearance and control of pathogens. In E. sinensis, Toll/Toll-like receptors, lipopolysaccharide and ß-1,3-glucan binding proteins, C-type lectins, galactoside-binding lectins, L-type lectins, scavenger receptors, and down syndrome cell adhesion molecules have been identified to be PRRs that are involved in the recognition of bacteria, fungi, and viruses. In this review, we give a comprehensive overview of the literature regarding PRRs' roles in the immunological defenses of E. sinensis, with the aim of providing clues to the mechanisms of innate immunity.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma.

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways "BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation" and "AMAN pathway". In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Modified stapled hemorrhoidopexy for lower postoperative stenosis: A five-year experience.

BACKGROUND: Stapled hemorrhoidopexy (SH) is currently a widely accepted method for treating the prolapse of internal hemorrhoids. Postoperative anal stenosis is a critical complication of SH. A remedy for this involves the removal of the circumferential staples of the anastomosis, followed by the creation of a hand-sewn anastomosis. Numerous studies have reported modified SH procedures to improve outcomes. We hypothesized that our modified SH technique may help reduce complications of anal stenosis after SH. AIM: To compare outcomes of staple removal at the 3- and 9-o'clock positions during modified SH in patients with mixed hemorrhoids. METHODS: This was a single-center, retrospective, observational study. Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1, 2015, and January 1, 2020, were included. The operation time, blood loss, length of hospital stay, and incidence of minor or major complications were recorded. RESULTS: Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1, 2015 and January 1, 2020, were included. Operation time, blood loss, length of hospital stay, and incidence of minor or major complications were recorded. We investigated 187 patients (mean age, 50.9 years) who had undergone our modified SH and 313 patients (mean age, 53.0 years) who had undergone standard SH. In the modified SH group, 54% of patients had previously undergone surgical intervention for hemorrhoids, compared with the 40.3% of patients in the standard SH group. The modified SH group included five (2.7%) patients with anal stenosis, while 21 (6.7%) patients in the standard SH group had complications of anal stenosis. There was a significant relationship between the rate of postoperative anal stenosis and the modified SH: 0.251 (0.085-0.741) and 0.211 (0.069-0.641) in multiple regression analysis. The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH. CONCLUSION: The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.

Male Sex and Ageing are Independent Risk Factors for Sarcopenia Stage in Patients With Chronic Kidney Disease Not Yet on Dialysis.

BACKGROUND: The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD. METHODS: The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance. RESULTS: Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001). CONCLUSIONS: This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.

First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial.

BACKGROUND: Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients. METHODS: In this phase 3 EVEREST trial (ClinicalTrials.gov: NCT03653546), patients with EGFR-sensitizing mutations, advanced treatment-naive non-small cell lung cancer (NSCLC), and non-irradiated symptomatic or asymptomatic CNS metastases were randomized (1:1) to zorifertinib or first-generation EGFR-TKI (gefitinib or erlotinib; control). The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival (PFS) per RECIST1.1. FINDINGS: Overall, 439 patients were randomized (zorifertinib n = 220; control n = 219). Most patients had the EGFR L858R mutation (55%) or >3 CNS lesions (54%). Median PFS was significantly longer with zorifertinib versus control (9.6 versus 6.9 months; hazard ratio [HR], 0.719; 95% confidence interval [CI], 0.580-0.893; p = 0.0024). Zorifertinib significantly prolonged intracranial PFS versus control (BICR per modified RECIST1.1: HR, 0.467; 95% CI, 0.352-0.619; investigator per RANO-BM: HR, 0.627; 95% CI, 0.466-0.844). Overall survival (OS) was immature; the estimated median OS was 37.3 months with zorifertinib and 31.8 months with control (HR, 0.833; 95% CI, 0.524-1.283) in patients subsequently treated with third-generation EGFR-TKIs. Safety profiles were consistent with previously reported data for zorifertinib. CONCLUSIONS: Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC. FUNDING: This work was funded by Alpha Biopharma (Jiangsu) Co., Ltd., China.

Antimicrobial Susceptibility Profile of Methicillin-Resistant Staphylococcus Aureus Isolated from Clinical Samples at Bac Ninh Provincial General Hospital, Vietnam.

Purpose: Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) strain, can become resistant to all classes of clinically available antibiotics and causes skin infections and severe infections in the lungs, heart, and bloodstream. The study aimed to evaluate antimicrobial susceptibility patterns and MRSA exhibiting multidrug resistance obtained through a microbiological culture of clinical specimens at Bac Ninh Provincial General Hospital in Bac Ninh Province, Vietnam. Methods: We employed a cross-sectional analysis at Bac Ninh Provincial General Hospital in Vietnam. 15,232 clinical samples from inpatients were examined. S. aureus isolates were identified using established protocols and tested for MRSA and antibiotic susceptibility. Data was analyzed using R software, with statistical calculations to assess associations between variables. Results: Staphylococcus aureus was isolated from 417 samples (2.7%), with 77.2% being MRSA and 22.8% methicillin-susceptible Staphylococcus aureus (MSSA). Significant sources of MRSA were wounds (64.6%) and the surgical unit (50%) according to sample types and hospital wards, respectively. S. aureus showed high resistance rates, the highest being azithromycin (83.2%), and was fully susceptible to vancomycin. Among 294 multidrug-resistant (MDR) strains, the prevalence was 82.0% in MRSA and 18.0% in MSSA. Conclusion: The study highlights widespread antimicrobial resistance among MRSA isolates from a provincial hospital in Vietnam, emphasizing the urgent need for antibiotic surveillance, formulation of antibiotic policies, and preventive measures to tackle the increasing prevalence of multidrug-resistant MRSA.

Fabrication of In Situ-Cross-Linked N-Succinyl Chitosan/Oxidized Alginate Hydrogel-Loaded Ascorbic Acid and Biphasic Calcium Phosphate for Bone Tissue Engineering.

Bone tissue engineering is a promising technology being studied globally to become an effective and sustainable method to treat the problems of damaged or diseased bones. In this work, we developed an in situ cross-linking hydrogel system that combined N-succinyl chitosan (NSC) and oxidized alginate (OA) at varying mixing ratios through Schiff base cross-linking. The hydrogel system also contains biphasic calcium phosphate (BCP) and ascorbic acid (AA), which could enhance biological characteristics and accelerate bone repair. The hydrogels' properties were examined through physicochemical tests such as scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), pore size and porosity measurement, swelling ratio, degradation rate, AA release study, as well as cytocompatibility, including live/dead and cytotoxicity assays. The results revealed that the supplementation of AA and BCP components can affect the physico-mechanical properties of the hydrogel system. However, they exhibited noncytotoxic properties. Overall, the results demonstrated that the hydrogel composed of 3% (w/v) NSC and 3% (w/v) OA (NSC: OA volume ratio is 8:2) loaded with 40% (w/w) BCP and 0.3 mg/mL AA has the potential for bone regeneration.