High-intensity interval training vs. yoga in improving binge eating and physical fitness in inactive young females.

Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (- 20.25%, p = 0.006, ηp2 = 0.408), fat mass (FM, - 3.13%, p = 0.033, ηp2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, ηp2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, - 1.78%, p = 0.006, ηp2 = 0.433), FM (- 3.94%, p = 0.033, ηp2 = 0.285), and BMI (- 1.80%, p = 0.006, ηp2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, ηp2 = 0.088; YG: 11.90%, p = 0.009, ηp2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, ηp2 = 0.03) and CG (11.91%, p = 0.022, ηp2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness.

Excision of large median and ulnar nerve schwannomas: a case series.

OBJECTIVE: Schwannomas are benign, slow-growing tumors originating from Schwann cells in peripheral nerves, commonly affecting the median and ulnar nerves in the forearm and wrist. Surgical excision is the gold standard treatment. This study presents our treatment strategies and outcomes for large-sized ulnar and median nerve schwannomas at the forearm and wrist level. METHODS: From 2012 to 2023, we enrolled 15 patients with schwannomas over 2 cm in size in the median or ulnar nerve at the forearm and wrist. The study included 12 patients with median nerve schwannomas (mean age: 61 years) and 3 with ulnar nerve schwannomas (mean age: 68 years), with a mean follow-up of 26.9 months. RESULTS: After surgery, all patients with median nerve schwannomas experienced mild, transient numbness affecting fewer than two digits, resolving within six months without motor deficits. Ulnar nerve schwannoma excision caused mild numbness in two patients, also resolving within six months, but all three developed ulnar claw hand deformity, which persisted but improved at the last follow-up. Despite this, patients were satisfied with the surgery due to relief from severe tingling pain. CONCLUSIONS: Schwannomas of the median, ulnar, and other peripheral nerves should be removed by carefully dissecting the connecting nerve fascicles to avoid injury to healthy ones. Sensory deficits may occur but are unlikely to significantly impact quality of life. However, in motor-dominant nerves like the ulnar nerve, there is a risk of significant motor deficits that could affect hand function, though not completely. Therefore, thorough preoperative discussion and consideration of interfascicular nerve grafting are essential.

Chemical modulation of Akt signaling enhances spinal cord regeneration in zebrafish.

Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients.

Prevalence and Factors Associated With Occupational Noise-Induced Hearing Loss Among Palm Oil Mill Workers in Selangor, Malaysia.

Introduction Occupational noise-induced hearing loss (NIHL) continues to be a significant public health issue globally, with Malaysia being no exception. In Malaysia, the majority of NIHL cases are reported from the manufacturing sector, with Selangor among the states with the highest number of confirmed cases. This study aimed to assess the prevalence of and factors associated with occupational NIHL among palm oil mill workers in Selangor, Malaysia. Methods A cross-sectional study was conducted to analyze the data from the data collection form, noise risk assessment reports, and audiometric test results done between 2021 and 2022 with a comparable baseline audiometric test. Results A total of 143 participants from three palm oil mills joined this study. The prevalence of NIHL was 42.7% (n = 61). Following the logistic regression model, NIHL was significantly associated with a duration of employment of 10 years and above, a history of occupational noise exposure at the previous workplace, and the use of personal hearing protectors at the current workplace with an adjusted OR of 2.41 (95% CI (1.14, 5.07)), 5.89 (95% CI (2.38, 14.53)), and 0.36 (95% CI (0.16, 0.83)), respectively. Conclusion The prevalence of NIHL among the study participants was high, and the associated factors are modifiable factors that can be prevented with a comprehensive hearing conservation program in the palm oil mills.

Comparative study of CTA/CTV and MRTA for preoperative simulation of microvascular decompression in neurovascular compression syndromes.

Neurovascular compression syndrome (NVCS), characterized by cranial nerve compression due to adjacent blood vessels at the root entry zone, frequently presents as trigeminal neuralgia (TN), hemifacial spasm (HFS), or glossopharyngeal neuralgia (GN). Despite its prevalence in NVCS assessment, Magnetic Resonance Tomographic Angiography (MRTA)'s limited sensitivity to small vessels and veins poses challenges. This study aims to refine vessel localization and surgical planning for NVCS patients using a novel 3D multimodal fusion imaging (MFI) technique incorporating computed tomography angiography and venography (CTA/CTV). A retrospective analysis was conducted on 76 patients who underwent MVD surgery and were diagnosed with single-site primary TN, HFS, or GN. Imaging was obtained from MRTA and CTA/CTV sequences, followed by image processing and 3D-MFI using FastSurfer and 3DSlicer. The CTA/CTV-3D-MFI showed higher sensitivity than MRTA-3D-MFI in predicting responsible vessels (98.6% vs. 94.6%) and NVC severity (98.6% vs. 90.8%). Kappa coefficients revealed strong agreement with MRTA-3D-MFI (0.855 for vessels, 0.835 for NVC severity) and excellent agreement with CTA/CTV-3D-MFI (0.951 for vessels, 0.952 for NVC). Resident neurosurgeons significantly preferred CTA/CTV-3D-MFI due to its better correlation with surgical reality, clearer depiction of surgical anatomy, and optimized visualization of approaches (p < 0.001). Implementing CTA/CTV-3D-MFI significantly enhanced diagnostic accuracy and surgical planning for NVCS, outperforming MRTA-3D-MFI in identifying responsible vessels and assessing NVC severity. This innovative imaging modality can potentially improve outcomes by guiding safer and more targeted surgeries, particularly in cases where MRTA may not adequately visualize crucial neurovascular structures.

Pay-for-performance in Taiwan: A systematic review and meta-analysis of the empirical literature.

OBJECTIVES: This study aimed to assess the impact of pay-for-performance (P4P) programmes on healthcare in Taiwan. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: A systematic literature search was performed using the PubMed, Medline, Embase, Cochrane review, Scopus, Web of Science and PsycINFO databases up to July 2023. Meta-analysis of the available outcomes was conducted using a random-effects model. RESULTS: The search yielded 85 studies, of which 58 investigated the programme for diabetes mellitus (DM), eight looked at the programme for chronic kidney disease (CKD), and the remaining studies examined programmes for breast cancer, tuberculosis, schizophrenia and chronic obstructive pulmonary disease. The DM P4P programme was a cost-effective strategy associated with reduced hospitalisation and subsequent complications. The CKD P4P was associated with a lower risk of dialysis initiation. The P4P programme also improved outcomes in breast cancer, cure rates in tuberculosis, reduced admissions for schizophrenia and reduced acute exacerbation in chronic obstructive pulmonary disease. The meta-analysis revealed that the P4P programme for DM (odds ratio [OR] = 0.59; 95% confidence interval [CI] = 0.48-0.73) and CKD (OR = 0.73; 95% CI = 0.67-0.81) significantly reduced mortality risk. However, participation rate in the DM P4P programme was only 19% in 2014. CONCLUSIONS: P4P programmes in Taiwan improve quality of care. However, participation was voluntary and the participation rate was very low, raising the concern of selective enrolment of participants (i.e. 'cherry-picking' behaviour) by physicians. Future programme reforms should focus on well-designed features with the aim of reducing healthcare disparities.

The impact of tumor resection on survival and functional outcomes for patients with primary central nervous system lymphoma.

PURPOSE: The role of tumor resection remains undetermined in treating primary central nervous system lymphomas (PCNSLs). This study aimed to clarify the impact of tumor resection on survival and functional outcomes, and to identify subgroups benefiting from resection. METHODS: We retrospectively reviewed records from 2010 to 2021 for PCNSL diagnosed at Chang Gung Memorial Hospital, Linkou. Patients were categorized by extent of resection: gross total resection (GTR), partial resection (PR), and biopsy. Univariate and multivariate analyses were performed to identify prognostic factors for survival and functional outcomes. Subgroup analysis was conducted to characterize patients who benefit from tumor resection. RESULTS: Of 88 patients, 12 had GTR, 25 had PR, and 51 received biopsy. GTR correlated with longer progression free survival (PFS) (HR 0.25, p=0.039), remaining significant in multivariate analysis (adjusted HR 0.09, p=0.004). In solitary PCNSLs, GTR also independently predicted longer PFS (adjusted HR 0.13, p= 0.023). Patients with dominant tumors measuring ≥ 3 cm trended towards improved overall survival (OS) with cytoreductive surgery versus biopsy (median survival 38.6 months vs 22.3 months, p=0.083). Age ≥ 60 years (adjusted OR 16.9, p = 0.008) and preoperative Karnofsky Performance Scale ≤ 70 (adjusted OR 4.97, p = 0.049) predicted poorer functional outcomes, while radiation therapy (adjusted OR 0.10, p = 0.033) was protective. CONCLUSIONS: GTR significantly improved PFS in treating PCNSLs, particularly in solitary cases. For patients with dominant tumors measuring ≥ 3 cm, cytoreductive surgery may improve OS. Neither cytoreductive surgery nor GTR correlated with poor functional outcomes.

COVID-19 Hospitalization Outcomes for Long-Term Care Facility Residents With Dementia: Mediation by Pre-existing Health Conditions.

Background: This study explores COVID-19 emergency admission and length of hospital stay hospitalization outcomes for Long-Term Care Facility (LTCF) residents with dementia. Methods: Utilizing a cross-sectional case control design, we employed logistic regression to analyze Texas Inpatient Public Use Data File (PUDF) for 1,413 dementia patients and 1,674 non-dementia patients (>60 years) to predict emergency admission and length of hospital stay with mediation by pre-existing conditions. Results: LTCF residents with dementia have a higher likelihood of COVID-19 emergency admission and shorter hospital stays. Adjusting for confounders of demographics, health insurance, and lifestyle, dementia diagnosis remained significantly associated with emergency admission and shorter hospital stays with preexisting conditions. Conclusion: Findings underscore the heightened risk for adverse COVID-19 hospitalization care disparities with dementia. Targeted health support programs for LTCF residents with dementia should aim to improve their COVID19 hospitalization outcomes, treating pre-existing health conditions and reducing their risk for excess mortality.

Whole-Exome Sequencing and Experimental Validation Unveil the Roles of TMEM229A Q200del Mutation in Lung Adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. METHODS: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. RESULTS: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK and p-AKT (Ser473), and the reduced protein level of p-ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. CONCLUSION: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

Polarization-Switchable Electrochemistry of 2D Layered Bi2O2Se Bifunctional Microreactors by Ferroelectric Modulation.

Ferroelectric catalysts are known for altering surface catalytic activities by changing the direction of their electric polarizations. This study demonstrates polarization-switchable electrochemistry using layered bismuth oxyselenide (L-Bi2O2Se) bifunctional microreactors through ferroelectric modulation. A selective-area ionic liquid gating is developed with precise control over the spatial distribution of the dipole orientation of L-Bi2O2Se. On-chip microreactors with upward polarization favor the oxygen evolution reaction, whereas those with downward polarization prefer the hydrogen evolution reaction. The microscopic origin behind polarization-switchable electrochemistry primarily stems from enhanced surface adsorption and reduced energy barriers for reactions, as examined by nanoscale scanning electrochemical cell microscopy. Integrating a pair of L-Bi2O2Se microreactors consisting of upward or downward polarizations demonstrates overall water splitting in a full-cell configuration based on a bifunctional catalyst. The ability to modulate surface polarizations on a single catalyst via ferroelectric polarization switching offers a pathway for designing catalysts for water splitting.

Revisiting the Policy Implications of Medical Tourism in the Post-COVID-19 Pandemic From a Malaysian Perspective: A Qualitative Study.

Background Malaysia has been one of the most prominent destination countries for medical tourism. The industry received significant government support to create a conducive environment for its growth, such as the provision of an investment tax allowance for the facilities participating in medical tourism and the establishment of the Malaysia Healthcare Travel Council (MHTC) to coordinate collaboration between various industry stakeholders to promote medical tourism activities at the international level and facilitate inbound medical tourists. The establishment of the MHTC facilitates collaboration between various industry stakeholders. In addition to facilitating medical tourism activities, MHTC is also involved in analysing relevant data, including but not limited to the socio-demography of medical tourists, the trend of their healthcare service utilisation, revenue generated, and market intelligence to promote the industry's growth. The council serves as a medium to facilitate the collaboration of stakeholders such as the hospitals participating in medical tourism, the Association of Private Hospitals Malaysia, the Malaysian Society for Quality in Health, and various government agencies, including the Ministry of Health and the Department of Immigration, Malaysia. We explore the policy-related implications of medical tourism and its relationship with the Malaysian national healthcare system. Methodology We revisited Pocock and Phua's conceptual framework of policy implications for medical tourism to explore its relevance after more than a decade of intensive government support and the aftermath of the COVID-19 pandemic. We employed a qualitative case study design using semi-structured, in-depth interviews with stakeholders from the Ministry of Health Malaysia, the private health sector, professional bodies, academics, and health-related civil society organisations. Results Our study found that many issues identified in the original framework remain relevant after over a decade. However, we also identified additional implications, such as the role of insurance portability in encouraging the growth of international hospital accreditation and the issue of equitable access to healthcare within the context of the current Malaysian healthcare system in the aftermath of COVID-19. Conclusion Due to its vulnerability, there is a need to develop a strategic collaboration that includes incorporating medical tourism activities into a broader framework, such as promoting aged care within the retirement destinations package for expatriates, which could ensure its sustainability instead of relying solely on medical tourism activities. In the meantime, policy implications arising from the industry remain relevant and should be addressed through a comprehensive structural reform of the national healthcare system involving stakeholders from the public and private health sectors.

Cardiovascular disease incidence and its predictors among school teachers in Peninsular Malaysia: a prospective cohort study.

Cardiovascular disease (CVD) caused substantial morbidity among occupationally active populations. However, data regarding the longitudinal burden of CVD were limited, particularly among school teachers. The objectives of our study were to estimate the incidence rate of CVD and determine its predictors among school teachers in Peninsular Malaysia through a prospective cohort study. We followed 14,046 eligible school teachers recruited between 2013 and 2014 until 31st December 2021. We accessed three computerised, country-level registries to determine incident CVD cases during the study period from 2013 to 2021. Baseline sociodemographic, lifestyle, work-related and clinical characteristics were recorded. Cox proportional hazard regression models with adjusted hazard ratio and 95% confidence interval were reported. With a median follow-up of 7.71 yr, we observed 209 incident CVD cases (or 195.7 CVD cases per 100,000 person-years). Male gender, age ≥40 yr old, Indian or others ethnicity (as compared to Chinese), family history of CVD, laboratory-confirmed diabetes mellitus, self-reported hypertension, high low-density lipoprotein cholesterol and high triglyceride were predictors for incident CVD among school teachers. Neither work-related nor lifestyle factors were significantly associated with incident CVD. Screening at-risk teachers for diabetes mellitus, hypertension or dyslipidemia is recommended to delay the onset or progression of CVD.

Manipulating Ferroelectric Polarization and Spin Polarization of 2D CuInP2S6 Crystals for Photocatalytic CO2 Reduction.

Manipulating electronic polarizations such as ferroelectric or spin polarizations has recently emerged as an effective strategy for enhancing the efficiency of photocatalytic reactions. This study demonstrates the control of electronic polarizations modulated by ferroelectric and magnetic approaches within a two-dimensional (2D) layered crystal of copper indium thiophosphate (CuInP2S6) to boost the photocatalytic reduction of CO2. We investigate the substantial influence of ferroelectric polarization on the photocatalytic CO2 reduction efficiency, utilizing the ferroelectric-paraelectric phase transition and polarization alignment through electrical poling. Additionally, we explore enhancing the CO2 reduction efficiency by harnessing spin electrons through the synergistic introduction of sulfur vacancies and applying a magnetic field. Several advanced characterization techniques, including piezoresponse force microscopy, ultrafast pump-probe spectroscopy, in situ X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier transformed spectroscopy, are performed to unveil the underlying mechanism of the enhanced photocatalytic CO2 reduction. These findings pave the way for manipulating electronic polarizations regulated through ferroelectric or magnetic modulations in 2D layered materials to advance the efficiency of photocatalytic CO2 reduction.

Dtx2 Deficiency Induces Ependymo-Radial Glial Cell Proliferation and Improves Spinal Cord Motor Function Recovery.

Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DELTEX proteins (DTXs) regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.

Generating complex vectorial optical fields via surface lattice resonances.

Vectorial optical fields (VOFs) with extra degrees of freedom hold promise for many photonic applications. However, current methods to generate VOFs are either bulky in size or exhibit limited functionalities. Here, we demonstrate a tunable VOF generator by exciting plasmonic surface lattice resonances (SLRs) with axial symmetry. By meticulously arranging bilayer circular arrays with opposite handedness, we achieve a high Q-factor of 103 via just a few particles despite the general belief that too small array size suppresses the SLRs. This work presents tunable complex VOFs with distinct inhomogeneous spatial polarization distributions, which may enable various applications in integrated and polarization optics.

Associated Factors of Patients' Survival in Out of Hospital Cardiac Arrest; a Cross-sectional Study.

Introduction: Chinese populations have an increasingly high prevalence of cardiac arrest. This study aimed to investigate the prehospital associated factors of survival to hospital admission and discharge among out-of-hospital cardiac arrest (OHCA) adult cases in Macao Special Administrative Region (SAR), China. Methods: Baseline characteristics as well as prehospital factors of OHCA patients were collected from publicly accessible medical records and Macao Fire Services Bureau, China. Demographic and other prehospital OHCA characteristics of patients who survived to hospital admission and discharge were analyzed using multivariate logistic regression analysis. Results: A total of 904 cases with a mean age of 74.2±17.3 (range: 18-106) years were included (78%>65 years, 62% male). Initial shockable cardiac rhythm was the strongest predictor for survival to both hospital admission (OR=3.57, 95% CI: 2.26-5.63; p<0.001) and discharge (OR=12.40, 95% CI: 5.70-26.96; p<0.001). Being male (OR=1.63, 95% CI:1.08-2.46; p =0.021) and the lower emergency medical service (EMS) response time (OR=1.62, 95% CI: 1.12-2.34; p =0.010) were also associated with a 2-fold association with survival to hospital admission. In addition, access to prehospital defibrillation (OR=4.25, 95% CI: 1.78-10.12; p <0.001) had a 4-fold association with survival to hospital discharge. None of these associations substantively increased with age. Conclusion: The major OHCA predictors of survival were initial shockable cardiac rhythm, being male, lower EMS response time, and access to prehospital defibrillation. These findings indicate a need for increased public awareness and more education.

Structure-Based High-Efficiency Homogeneous Antibody Platform by Endoglycosidase Sz Provides Insights into Its Transglycosylation Mechanism.

Monoclonal antibodies (mAbs) have gradually dominated the drug markets for various diseases. Improvement of the therapeutic activities of mAbs has become a critical issue in the pharmaceutical industry. A novel endo-ß-N-acetylglucosaminidase, EndoSz, from Streptococcus equisubsp. zooepidemicus Sz105 is discovered and applied to enhance the activities of mAbs. Our studies demonstrate that the mutant EndoSz-D234M possesses an excellent transglycosylation activity to generate diverse glycoconjugates on mAbs. We prove that EndoSz-D234M can be applied to various marketed therapeutic antibodies and those in development for antibody remodeling. The remodeled homogeneous antibodies (mAb-G2S2) produced by EndoSz-D234M increase the relative ADCC activities by 3-26-fold. We further report the high-resolution crystal structures of EndoSz-D234M in the apo-form at 2.15 Å and the complex form with a bound G2S2-oxazoline intermediate at 2.25 Å. A novel pH-jump method was utilized to obtain the complex structure with a high resolution. The detailed interactions of EndoSz-D234M and the carried G2S2-oxazoline are hence delineated. The oxazoline sits in a hole, named the oxa-hole, which stabilizes the G2S2-oxazoline in transit and catalyzes the further transglycosylation reaction while targeting Asn-GlcNAc (+1) of Fc. In the oxa-hole, the H-bonding network involved with oxazoline dominates the transglycosylation activity. A mobile loop2 (a.a. 152-159) of EndoSz-D234M reshapes the binding grooves for the accommodation of G2S2-oxazoline upon binding, at which Trp154 forms a hydrogen bond with Man (-2). The long loop4 (a.a. 236-248) followed by helix3 is capable of dominating the substrate selectivity of EndoSz-D234M. In addition, the stepwise transglycosylation behavior of EndoSz-D234M is elucidated. Based on the high-resolution structures of the apo-form and the bound form with G2S2-oxazoline as well as a systematic mutagenesis study of the relative transglycosylation activity, the transglycosylation mechanism of EndoSz-D234M is revealed.

Customizable BAC-based DNA markers for pulsed-field gel electrophoresis.

DNA markers are used as a size reference and sample loading control during gel electrophoresis. Most markers are designed for conventional gel electrophoresis to separate DNA smaller than 20 kb. For larger molecules, pulsed-field gel electrophoresis (PFGE) marker is required. Limited PFGE markers are available because large DNA are prone to nicking and degradation, causing smeary bands. Here, we developed a robust marker based on bacterial artificial chromosomes (BACs) with bands up to 184 kb. This marker could consistently confer intense and distinct bands for accurate gel analysis in molecular biology studies, laboratory validations or clinical diagnosis.

Arthroscopic debridement, synovectomy, and thermal shrinkage for basal joint arthritis.

BACKGROUND: Ligamentous laxity, cartilage wear, and diffuse synovitis are frequently seen in thumb basal joint arthritis. Although these degenerative changes may be mild for the majority, they have the potential to cause discomfort during movement and compromised hand function. This study assesses the long-term outcomes of arthroscopic debridement, synovectomy, and thermal shrinkage in managing early-stage basal joint arthritis. METHODS: We retrospectively reviewed patients with basal joint arthritis who underwent arthroscopic debridement, synovectomy, and thermal shrinkage between November 2010 and January 2021 by a single surgeon at our medical institute. We assessed functional outcomes, thumb range of motion, perioperative nonsteroidal anti-inflammatory drug (NSAID) use, return to work and satisfaction level. RESULTS: A total of 12 patients (13 hands), with a mean follow-up of 72 months, were included in this study. Significant improvements were observed in pain scores and functional outcomes, along with a reduction in postoperative NSAID use. Patients also reported a relatively quick return to work and a high satisfaction level. CONCLUSION: The study highlights the benefits of arthroscopic intervention, providing a minimally invasive approach with favorable long-term outcomes for patients with symptomatic basal joint arthritis.

Enabling the design of surgical instruments for under-resourced patients through metal additive manufacturing: ulnar shortening osteotomy as an example.

BACKGROUND: Ulnar shortening osteotomy (USO) has demonstrated good outcomes for patients with ulnar impaction syndrome. To minimize complications such as non-union, precise osteotomy and firm fixation are warranted. Despite various ulnar shortening systems have been developed, current technology does not meet all needs. A considerable portion of patients could not afford those designated USO systems. To tackle this challenge, our team reported successful results in standardized free-hand predrilled USO technique. However, it is still technical demanding and requires sufficient experience and confidence to excel. Therefore, our team designed an ulnar shortening system based on our free-hand technique principle, using metal additive manufacturing technology. The goal of this study is to describe the development process and report the performance of the system. METHODS: Utilizing metal additive manufacturing technology, our team developed an ulnar shortening system that requires minimal exposure, facilitates precise cutting, and allows for the easy placement of a 3.5 mm dynamic compression plate, available to patients at zero out-of-pocket cost. For performance testing, two surgeons with different levels of experience in ulnar shortening procedures were included: one fellow-trained hand and wrist surgeon and one senior resident. They performed ulnar shortening osteotomy (USO) using both the free-hand technique and the USO system-assisted technique on ulna sawbones, repeating each method three times. The recorded parameters included time-to-complete-osteotomy, total procedure time, chip diameter, shortening length, maximum residual gap, and deviation angle. RESULTS: For the hand and wrist fellow, with the USO system, the time-to-complete osteotomy was significantly reduced. (468.7 ± 63.6 to 260.0 ± 5 s, p < 0.05). Despite the preop goal was shortening 3 mm, the average shortening length was significantly larger in the free-hand group (5 ± 0.1; 3.2 ± 0.2 mm, p < 0.05). Both maximum residual gap and deviation angle reported no statistical difference between the two techniques for the hand surgeon. As for the senior resident, the maximum residual gap was significantly reduced, using the USO system (2.9 ± 0.8; 0.4 ± 0.4 mm, p = 0.02). Between two surgeons, significant larger maximum residual gap and deviation angle were noted on the senior resident doctor, in the free-hand technique group, but not in the USO system group. CONCLUSION: The developed USO system may serve as a valuable tool, aiding in reliable and precise cutting as well as fixation for patients undergoing ulnar shortening osteotomy with a 3.5 mm dynamic compression plate, even for less experienced surgeons. The entire process, from concept generation and sketching to creating the CAD file and final production, serves as a translatable reference for other surgical scenarios.