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One-year anti-osteoporosis medication therapy and muscle mass changes in community-dwelling osteoporotic women
No full text[[abstract]]Objective: Anti-osteoporosis medications (AOMs) offer proven benefits for bone health, yet their impact on muscle health is still under investigation. This study aims to investigate the impact of one of the AOMs, zoledronate, on muscle mass in osteoporotic women in rural communities. Methods: This study was a subanalysis from the HOPE trail, a randomized controlled trial conducted in a rural community, aims to prevent disability through community-based integrated care intervention. In the present study, women aged 50 years and older diagnosed with osteoporosis were included. Those with a history of aAOM treatment were excluded. AOM used in this study was zoledronate. Participants were divided into two groups: a AOM treatment group (n = 136) and a control group (n = 134). Participants’ appendicular skeletal muscle (ASM), handgrip strength (HS), the Short Physical Performance Battery (SPPB) assessment, and the Mini Nutritional Assessment (MNA) were measured at o, and 12 months. Results: Participants had a mean age of 74.95 ± 7.42 in the AOM group, and 77.04 ± 8.64 in the control group. There were no significant differences in ASM, handgrip strength, SPPB score and the MNA score between treatment group and control group at baseline. Substantial enhancements in the physical condition were observed in both groups during the treatment period. At 12 months, the control group significantly improved in ASM (1.46 ± 3.77, p < 0.001) and HS (3.55 ± 8.51, p < 0.001), while the AOM group showed significant improvement in ASM (0.81 ± 4.33, p = 0.036) and handgrip strength 2.76 ± 8.48, p < 0.001). However, there were no statistically significant differences in the mean change between the treatment group and the control group in ASM (0.81 vs. 1.46, p = 0.296), handgrip strength (2.76 vs. 3.55, p = 0.059), SPPS score (0.42 vs. 1.08, p = 0.302), and MNA score (− 0.24 vs. − 0.35, p = 0.406), respectively. Conclusion: In conclusion, community-dwelling osteoporotic women treated with AOM did not exhibit statistically significant differences in changes in ASM, handgrip strength, SPPS score, and MNA score in the first year
Transplantation of exosomes derived from human wharton's jelly mesenchymal stromal cells enhances functional improvement in stroke rats
No full text[[abstract]]Cerebral ischemic stroke is a major cerebrovascular disease and the leading cause of adult disability. We and others previously demonstrated that transplantation of human Wharton's jelly mesenchymal stromal cells (WJ-MSCs) attenuated neuronal damage and promoted functional improvement in stroke animals. This study aimed to investigate the protective effects of human WJ-MSC exosome (Exo) transplant in cellular and rat models of cerebral stroke. Administration of Exo significantly antagonized glutamate-mediated neuronal loss and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-X nick end labeling (TUNEL) in rat primary cortical neuronal cultures. Adult male rats underwent a 60-min middle cerebral artery occlusion (MCAo); Exo or vehicle was injected through the tail vein 5-10 min after the MCAo. Two days later, the rats underwent a series of behavioral tests. Stroke rats receiving Exo developed a significant improvement in locomotor function and forelimb strength while reductions in body asymmetry and Bederson's neurological score. After the behavioral test, brain tissues were harvested for histological and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. Animals receiving Exo had less infarction volume, measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Transplantation of Exo increased the expression of protective neurotrophic factors (BMP7, GDNF) and anti-apoptotic factors (Bcl2, Bcl-xL) in the ischemic brain. These findings suggest that early post-treatment with WJ-MSC Exo, given non-invasively through the vein, improved functional recovery and reduced brain damage in the stroke brain
Association of ambient particulate matter (PM<sub>2.5</sub>) with reduced sex ratio at birth after the implementation of a rapid transit system in Taipei, Taiwan
No full text[[abstract]]Sex ratio at birth (SRB) is a simple, noninvasive way to monitor the reproductive health of a population. Apparently only a few studies have assessed the relationship between ambient air pollution and SRBs. The studies that investigated this relationship have yielded inconsistent results. Ambient air pollution levels, including particulate matter (PM2.5) levels, have decreased in Taipei city after a mass rapid transit (MRT) system commenced operations in 1996. The aim of this study was to determine whether the changes in levels of PM2.5 after the implementation of the MRT system in Taipei may have influenced the concurrent alterations noted in the SRB. In order to assess this potential association, annual numbers of male and female births were obtained from Taiwan's Department of Household Registration, Ministry of Interior Affairs from 1992 to 2023. Mean yearly SRBs were calculated for 4 time periods, 1992-1995, 1996-2004, 2005-2015, and 2016-2023. Linear logistic regression was employed to evaluate the variation in officially reported PM2.5 levels during those periods and alterations in the ratios. The ratios for time periods 1 to 4 were 52.61%, 52.22%, 51.78%, and 51.67%, respectively. Compared to Period 1 (pre-MRT), the odds ratios for Periods 2, 3, and 4 were 0.98 (0.97-0.99), 0.97 (0.96-0.98), and 0.96 (0.95-0.98), respectively. The trend toward the decreased SRB was found to be gradual but significant
Identifying the presence of atrial fibrillation during sinus rhythm using a dual-input mixed neural network with ECG coloring technology
No full text[[abstract]]BackgroundUndetected atrial fibrillation (AF) poses a significant risk of stroke and cardiovascular mortality. However, diagnosing AF in real-time can be challenging as the arrhythmia is often not captured instantly. To address this issue, a deep-learning model was developed to diagnose AF even during periods of arrhythmia-free windows.MethodsThe proposed method introduces a novel approach that integrates clinical data and electrocardiograms (ECGs) using a colorization technique. This technique recolors ECG images based on patients' demographic information while preserving their original characteristics and incorporating color correlations from statistical data features. Our primary objective is to enhance atrial fibrillation (AF) detection by fusing ECG images with demographic data for colorization. To ensure the reliability of our dataset for training, validation, and testing, we rigorously maintained separation to prevent cross-contamination among these sets. We designed a Dual-input Mixed Neural Network (DMNN) that effectively handles different types of inputs, including demographic and image data, leveraging their mixed characteristics to optimize prediction performance. Unlike previous approaches, this method introduces demographic data through color transformation within ECG images, enriching the diversity of features for improved learning outcomes.ResultsThe proposed approach yielded promising results on the independent test set, achieving an impressive AUC of 83.4%. This outperformed the AUC of 75.8% obtained when using only the original signal values as input for the CNN. The evaluation of performance improvement revealed significant enhancements, including a 7.6% increase in AUC, an 11.3% boost in accuracy, a 9.4% improvement in sensitivity, an 11.6% enhancement in specificity, and a substantial 25.1% increase in the F1 score. Notably, AI diagnosis of AF was associated with future cardiovascular mortality. For clinical application, over a median follow-up of 71.6 +/- 29.1 months, high-risk AI-predicted AF patients exhibited significantly higher cardiovascular mortality (AF vs. non-AF; 47 [18.7%] vs. 34 [4.8%]) and all-cause mortality (176 [52.9%] vs. 216 [26.3%]) compared to non-AF patients. In the low-risk group, AI-predicted AF patients showed slightly elevated cardiovascular (7 [0.7%] vs. 1 [0.3%]) and all-cause mortality (103 [9.0%] vs. 26 [6.4%]) than AI-predicted non-AF patients during six-year follow-up. These findings underscore the potential clinical utility of the AI model in predicting AF-related outcomes.ConclusionsThis study introduces an ECG colorization approach to enhance atrial fibrillation (AF) detection using deep learning and demographic data, improving performance compared to ECG-only methods. This method is effective in identifying high-risk and low-risk populations, providing valuable features for future AF research and clinical applications, as well as benefiting ECG-based classification studies
Simultaneous method of volatile organic compounds’ metabolites in human urine samples using a novel in-syringe based fast urinary metaboites extraction (FaUMEx) technique coupled with UHPLC-MS/ MS analysis
No full text[[abstract]]Assessing the impact of human exposure to environmental toxicants is often crucial to biomonitoring the exposed dose. In this work, we report a novel fast urinary metabolites extraction (FaUMEx) technique coupled with UHPLC-MS/MS analysis for the highly sensitive and simultaneous biomonitoring of the five major urinary metabolites (thiodiglycolic acid, s-phenylmercapturic acid, t,t-muconic acid, mandelic acid, and phenyl glyoxylic acid) of common volatile organic compounds’ (VOCs) exposure (vinyl chloride, benzene, styrene, and ethylbenzene) in human. FaUMEx technique comprises of two-steps, liquid-liquid microextraction was performed first in an extraction syringe using 1 mL of methanol (pH 3) as an extraction solvent and then, the extractant was passed through a clean-up syringe (pre-packedwith various sorbents including 500 mg anhydrous MgSO4, 50 mg C18, and 50 mg SiO2) to obtain the high order of matrice clean-up and preconcentration efficiency. The developed method displayed excellent linearity, and the correlation coefficients were >0.998 for all the target metabolites with detection and quantification limits of 0.02-0.24 ng/ mL and 0.05-0.72 ng/ mL, respectively. Furthermore, the matrix effects were < ±5%, and inter and intra-day precision were <9%. Moreover, the presented method was applied and validated to real sample analysis for biomonitoring of VOC’s exposure levels. The results showed that the developed FaUMEx-UHPLC-MS/MS method is fast, simple, low-cost, low-solvent consumption, high sensitivity with good accuracy and precision for five targeted urinary VOCs’ metabolites. Therefore, the presented dual-syringe mode FaUMEx strategy with UHPLC-MS/MS technique can be applied to biomonitoring of various urinary metabolites to assess human exposure to environmental toxicants
Aldehyde dehydrogenases as drug targets for cancer: SAR and structural biology aspects for inhibitor design
No full text[[abstract]]Aldehydes are organic compounds containing a carbonyl group found exogenously or produced by normal metabolic processes and their accumulation can lead to toxicity if not cleared. Aldehyde dehydrogenases (ALDHs) are NAD(P)+-dependent enzymes that catalyze the oxidation of such aldehydes and prevent their accumulation. Along with this primary detoxification function, the known 19 human isoforms of ALDHs, which act on different substrates, are also involved in various physiological and developmental processes. Functional alterations of ALDHs via mutations or expression levels cause various disease conditions, including many different cancer types like lung, ovarian, etc. These properties make this family of enzymes an ideal therapeutic and prognostic target for drug development. However, sequence similarities between the ALDH isoforms force the need to design inhibitors for a specific isoform using the differences in the substrate-binding sites of each protein. This has resulted in developing isoform-specific inhibitors, especially for ALDH1A1, ALDH2, and ALDH3A1, which are implicated in various cancers. In this review, we briefly outline the functional roles of the different isoforms of the ALDH family members, their role in cancer and discuss the various selective inhibitors that have been developed for the ALDH1A1 and ALDH3A1 enzymes, along with a detailed examination of the respective structure–activity relationship (SAR) studies available. From the available SAR and structural biology data, insights into the functional groups and interactions necessary to develop selective inhibitors for ALDH1A1 and ALDH3A1 are highlighted, which can act as a guide for developing more potent and selective inhibitors of ALDH isoforms
Telemedicine facilitates medical care for hospitalized patients in quarantine
No full text[[abstract]]Background/purpose: Telemedicine is an innovative medical care system that facilitates visual communication between patients and healthcare workers (HCWs), mainly in a community-based setting. We investigated the clinical effectiveness of in-patient telemedicine care for patients in quarantine for the Coronavirus disease 2019 (COVID-19). Methods: We conducted a prospective study to include patients with mild-to-moderate severity of COVID-19 and their primary-care HCWs. Patients were stratified into the “telemedicine” group and the “standard-care” group. The telemedicine group received additional telemedicine communications and wearable devices for vital signs monitoring during hospitalization. The primary endpoint was the usability of the telemedicine system assessed by the modified telehealth usability questionnaire (TUQ) on a 7-point ordinal Likert scale. The secondary endpoints were the outcomes of COVID-19. Results: Overall, we included 30 and 48 patients in the respective standard-care group and telemedicine group. In addition, 31 primary care residents and 56 nurses were included in the HCW groups. For all participants, the modified TUQ responses in the categories of usefulness (6.2), ease of use (6.1), effectiveness (6.0), and satisfaction (6.1) were significantly greater than 5 (somewhat agree), except for the reliability sectors (5.3). The telemedicine group liked the telemedicine system significantly more than the HCWs. The doctors scored significantly higher than the nurses in the categories of effectiveness and satisfaction of the telemedicine systems. The outcomes of COVID-19 were comparable between the telemedicine and the standard-care group. Conclusions: Our study demonstrated the clinical effectiveness and satisfaction of the telemedicine for the care of quarantined COVID-19 patients during hospitalization
単離抗体,医薬組成物,単離抗体結合体,ダイマー化阻害方法,シグナル伝達阻害方法,管新生阻害方法,治療方法,および断片検出方法
No full text[[abstract]]An isolated antibody, comprising heavy chain complementary determining regions CDR1, CDR2, and CDR3 from a heavy chain variable region sequence having SEQ ID NO: 1 or 3; light chain complementary determining regions CDR1, CDR2, and CDR3 from a light chain variable region sequence having SEQ ID NO: 2 or 4; wherein the antibody binds specifically to both vascular endothelial growth factor receptor-2 (VEGFR2) and vascular endothelial growth factor receptor-3 (VEGFR3)
Aminothiazole compounds as protein kinase inhibitors
No full text[[abstract]]Aminothiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds:Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds
Aminothiazole compounds as protein kinase inhibitors
No full text[[abstract]]Aminothiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds. Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds