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MiR-378a-5p/CPT1A-mediate fatty acid oxidation regulates tumor progression in Oral Cancer
No full text[[abstract]]Tumor progression requires a lot of energy. Energy-rich lipids are good energy fuel for tumor growth. In our OSCC tissue array, we identified several upregulated genes associated with FAO, including CPT1A. CPT1A is the rate-limiting enzyme in fatty acid metabolism. Blocking FAO by knockdown of CPT1A or etomoxir treatment could effectively inhibit the proliferation, invasion and migration of OSCCs, suggesting that CPT1A-mediated FAO plays an important role in oral carcinogenesis. Besides, overexpressed CPT1A promoted LDs degradation by lipolysis and lipophagy, and then releasing more free fatty acids for mitochondrial FAO to generate ATP. In contrast, knockdown of CPT1A resulted in the accumulation of LDs. We further found that CPT1A is a functional target of miR-378a-5p. MiR-378a-5p was not only significantly reduced in tumors but also strongly negatively correlated with CPT1A expression. Overexpressed miR-378a-5p can accumulate LDs and significantly inhibit the proliferation, invasion and migration of OSCC by inhibiting CPT1A. These results suggest that miR-378a-5p/CPT1A-mediated abnormal mitochondrial fatty acid metabolism may play an important role in oral cancer development
Synthesis, anticancer evaluation and structure-activity relationship of Taiwanin a derivatives
No full text[[abstract]]Taiwanin A, a natural naphthalide lignan isolated from the heartwoods of Taiwania cryptomerioides Hayata, has previously been reported to have cytotoxicity against human tumor cells. In this study, a series of taiwanin A derivatives were synthesized and evaluated for their structure-activity relationship. Among the eleven taiwanin A derivatives, four compounds showed higher in vitro cytotoxic activity than taiwanin A. The biological evaluation of the synthesized compounds illustrated that the introduction of an electron-donating group in aryl ring A contributed to the antiproliferative potency, while in aryl ring B, it attenuated the cytotoxic activity. Compound 20 demonstrated excellent anticancer activity with an IC50 value of 0.5 mu M against HONE-1 human carcinoma cell lines, indicating that it could be a promising lead compound for further drug development studies
Effects of osteoporosis treatment and multicomponent integrated care on intrinsic capacity and happiness among rural community-dwelling older adults: The Healthy Longevity and Ageing in Place (HOPE) randomised controlled trial
No full text[[abstract]]Background Monitoring and improving intrinsic capacity (IC) and well-being are essential for older adults to maintain functional abilities. However, evidence of effective interventions to improve IC and happiness is scarce. This study examined the effects of multicomponent interventions in the Healthy Longevity and Ageing in Place (HOPE) randomised controlled trial on IC and happiness among rural community-dwelling older adults.Methods This cluster randomised trial was conducted in rural communities in Taiwan (NCT05104034). Participants aged >= 50 were enrolled from September 2021 to April 2022 and randomly assigned by community level to one of three groups: multicomponent integrated care (MIC), osteoporosis care (OC) and usual care (UC). MIC included osteoporosis, sarcopenia and polypharmacy care, along with exercise and nutritional support. OC was a resource-conservative, focusing on osteoporosis screening and treatment alone. IC and happiness were measured at baseline and 12 months after follow-up. IC was assessed across cognition, locomotion, vitality, sensory and psychological domains per World Health Organization Integrated Care for Older People (ICOPE) guidelines. Happiness was measured using the 10-item Chinese Happiness Inventory. Generalised estimating equations were used to estimate the effect of the intervention.Results 567 residents were recruited from 30 congregate meal service centres. Mean IC score increased across all the groups, though the happiness score decreased. Compared to UC, the MIC group exhibited a significantly greater improvement in IC scores (adjusted estimate = 0.30, standard error (SE) = 0.11, P = .01), whereas OC did not show significant effects. Smaller reductions in happiness scores were observed in both the MIC (adjusted estimate = 1.46, SE = 0.48, P = .003) and OC groups (adjusted estimate = 0.95, SE = 0.48, P = .05).Conclusion MIC, including osteoporosis and pharmaceutical care, along with exercise and nutritional support, is an effective strategy to enhance IC and happiness compared to osteoporosis treatment alone and UC. This underscores the importance of comprehensive strategies for promoting healthy ageing in rural communities
Explore the role of inflammatory pathway of Tnfr1 in alcohol dependence and the potential to differentiate delirium tremens
No full text[[abstract]]Background: Inflammatory factor TNF-alpha has been implicated in the pathophysiology of alcohol withdrawal syndrome (AWS) and craving phenomenon in relation to alcohol dependence (AD) [1]. Its binding to TNF receptor 1 (TNFR1) has also been reported to be involved in the apoptosis pathway [2] and to lead to neuronal cell death. Delirium tremens (DT) is a serious subtype of AWS and associated with high mortality if inadequately treated. Little is known about the role of the soluble form TNFR1 (sTNFR1) in patients with AD and its relationship with DT. Aims & Objectives: This study aimed to compare sTNFR1 levels in patients with AD who experience DT during withdrawal to those without DT, in comparison to healthy controls. Method: A total of 224 patients with AD who were admitted for alcohol detoxification treatment and 117 non- AD controls were recruited. Blood levels of sTNFR1, and the inflammatory C-C motif chemokine ligand 11 (CCL11) were evaluated using enzyme-linked immunosorbent assay (ELISA). In patients with AD, we assessed various alcohol-related variables, including, Obsessive Compulsive Drinking Scale (OCDS) scores, Penn Alcohol Craving Score (PACS), Clinical Institute Withdrawal Assessment for Alcohol Scale, revised (CIWA-Ar) scores, and Alcohol Craving Questionnaire-Short Form-Revised total score (ACQ-SF-R). Results: The AD group exhibited lower body mass index (BMI) and fewer years of education, but had higher rates of cigarette smoking, as well as elevated plasma CCL11 [3] and sTNFR1 levels compared to age and sex- matched controls (Mann-Whitney U test, P<0.0001). Within the AD group, 11.2% (n = 25) experienced DT during their admission, referred to as the DT group. The DT group exhibited significantly higher levels of sTNFR1 (P<0.0001) compared to the non-DT group. In addition, the DT group was characterized by older age (P≦0.023), elevated plasma CCL11 levels (P=0.049), and more severe withdrawal symptoms, as indicated by CIWA-Ar scores (P≦0.0002). They also displayed greater craving, as reflected in OCDS total scores (P≦0.009), as well as PACS (P≦0.01) and ACQ-SF-R (P≦0.011) scores. Multiple linear regression analysis showed that sTNFR1 was significantly correlated with the occurrence of DT (partial r2=0.039, P=0.003), as well as OCDS total (partial r2=0.091, P≦0.0003) and plasma CCL11 levels (partial r2 =0.028, P≦0.008). Furthermore, the receiver operating characteristic (ROC) curve demonstrated that an sTNFR1 level of 1,050 pg/mL could effectively differentiate the DT group from the non-DT group (area under the ROC curve: 0.79; sensitivity: 96.0%, specificity: 56.3%, p <0.001). Discussion & Conclusion: These results indicate that AD patients with DT exhibited higher levels of inflammation, as evidenced by increased plasma levels of sTNFR1 and CCL-11. Furthermore, sTNFR1 may have the potential to discriminate those with development of DT. In conclusion, these findings suggest that sTNFR1 plays a role in the neurobiological mechanisms underlying AD and modifying the phenotype of DT
Investigation of gut microbiota composition alterations in depressive patients prescribed with vortioxetine
No full text[[abstract]]Background: Vortioxetine, a newer serotonergic antidepressant, has been used to treat adult depressive patients. It has been reported to enhance cognitive functions in patients. While the precise mechanism of action remains unknown, it’ s believed to share similarities with selective serotonin reuptake inhibitors (SSRIs). Since previous studies have indicated that SSRIs could alter gut microbial composition, and considering the correlation between depressive severity and cognitive function with gut microbiota through the gut-brain axis, we aimed to explore the disparities in gut microbial composition and cognitive function among patients treated with vortioxetine, SSRIs, and those without antidepressant treatment. Methods: We recruited 211 patients currently experiencing depressive symptoms from hospitals in northern Taiwan. We gather their demographic, dietary, and clinical characteristics through questionnaires and electrical medical records. The Continuous Performance Test AX version (CPT-AX) assessed patients' cognitive function. Fecal DNA was extracted from 271 patients and subjected to 16S rRNA V3V4 gene sequencing to obtain their gut microbial profiles. We categorized patients into three groups for microbial and taxa comparisons. Additionally, targeted taxa correlation networks and their associations with depressive symptom severity and cognitive function indices were computed. Results: While no significant differences in microbial diversity were observed among the groups, patients undergoing vortioxetine or SSRI treatments exhibited a decreasing trend. Compared to patients without antidepressant treatment, the vortioxetine group displayed reduced levels of four genera ( Ruminococcus, Turicibacter, Enterorhabdus, Lachnospira), and increased levels of four others ( Eggerthella, Gemella, Gordonibacter, Eubacterium). We also detected three decreased (Ruminococcus, Clostridia_UCG-014, Adlercreutzia) and one increased (Gemella) genera when comparing the vortioxetine and SSRIs groups. Notably, Eggerthella displayed a negative correlation with depression severity (r=- 0.44, p=0.04). Patients with antidepressant treatment had altered bacterial correlation compared to those without treatment. Patients taking vortioxetine exhibited slightly improved cognitive function and a more pronounced correlation trend between targeted taxa and cognitive function indices. Conclusion: Despite vortioxetine’ s partially distinct and still not fully understood mechanism in contrast to SSRIs, our study highlights its influence on gut microbial composition, particularly taxa associated with depression or SSRIs. These findings extend previous research, emphasizing the role of microbiota in the dynamics of SSRIs and novel non-SSRI medications. This underscores the crucial involvement of gut microbiota in antidepressant treatments. Given our study's preliminary and cross-sectional nature, further research is needed to deepen our understanding of more effective therapeutic interventions
Defining patient-reported outcomes in diabetes, obesity, cardiovascular disease, and chronic kidney disease for clinical practice guidelines - perspectives of the taskforce of the guideline workshop
No full text[[abstract]]Recent clinical practice guidelines for diabetes, obesity, cardiovascular disease (CVD) and chronic kidney disease (CKD) emphasise a holistic, person-centred approach to care. However, they do not include recommendations for the assessment of patient-reported outcomes (PROs), which would - dependent on the topic of guideline - be important for improving shared decision-making, patients' concordance with guideline recommendations, clinical outcomes and health-related quality of life (HRQoL). The Taskforce of the Guideline Workshop discussed PROs in diabetes, obesity, CVD and CKD as well as the relevance of their inclusion in clinical practice guidelines for the management of these conditions
Global epidemiology, seasonality and climatic drivers of the four human parainfluenza virus types
No full text[[abstract]]OBJECTIVES: Human parainfluenza viruses (hPIV) are a common cause of acute respiratory infections, especially in children under five years and the elderly. hPIV can be subclassified as types 1-4: these showed various seasonality patterns worldwide, and it is unclear how climatic factors might consistently explain their global epidemiology. METHODS: This study collected time-series incidence data from the literature and hPIV surveillance programs worldwide (47 locations). Wavelet analysis and circular statistics were used to detect the seasonality and the months of peak incidence for each hPIV type. Relationships between climatic drivers and incidence peaks were assessed using a generalized estimating equation. RESULTS: The average positive rate of hPIV among patients with respiratory symptoms was 5.6% and ranged between 0.69-3.48% for different types. In the northern temperate region, the median peak incidence months for hPIV1, hPIV2, and hPIV4 were from September to October, while for hPIV3, it was in late May. Seasonal peaks of hPIV3 were associated with higher monthly temperatures and lower diurnal temperatures range throughout the year; hPIV4 peaks appeared to correlate with lower monthly temperatures and higher precipitation throughout the year. Different hPIV types exhibit different patterns of global epidemiology and transmission. CONCLUSIONS: Climate drivers may play a role in hPIV transmission. More comprehensive and coherent surveillance of hPIV types would enable more in-depth analyses and inform the timing of preventive measures
Comparative analysis of surgical approaches in nonsyndromic multiple-suture synostosis: A systematic review and meta-analysis
No full text[[abstract]]OBJECTIVE: Nonsyndromic multiple-suture synostosis (MSS) is one of the rarest types of craniosynostosis. While both endoscopic and open surgical approaches have demonstrated efficacy for MSS patients, a comprehensive comparison of perioperative outcomes between the two approaches has yet to be fully explored. The aim of this systematic review and meta-analysis was to assess the available evidence among the two surgical approaches to better inform the management of complex craniosynostosis. METHODS: PubMed, Embase, and Scopus were searched for studies published from the first reports through February 2024 that reported surgical outcomes of either endoscopic or open surgery for nonsyndromic MSS. The main outcome was the reoperation rate, with secondary endpoints including transfusion rates, intraoperative complications, and overall complications, with a subgroup analysis conducted for patients with nonsyndromic bicoronal synostosis. RESULTS: Sixteen studies involving 310 patients were analyzed. Patients undergoing open surgery were older than those treated with endoscopy (mean age 10.39 vs 3.21 months). The pooled analysis showed a reoperation rate of 11% (95% CI 4%-23%, I2 = 25%) for endoscopic surgery compared with 22% (95% CI 14%-31%, I2 = 0) for open surgery (p = 0.11). Transfusion rates were 26% (95% CI 13%-45%, I2 = 50%) for endoscopic surgery and 50% (95% CI 22%-78%, I2 = 71%) for open surgery (p = 0.18). Intraoperative complications were similar: 17% (95% CI 7%-34%, I2 = 0%) for endoscopic vs 15% (95% CI 4%-42%, I2 = 76%) for open surgery (p = 0.85). Overall complication rates were 15% (95% CI 7%-31%, I2 = 45%) for endoscopic surgery and 20% (95% CI 9%-38%, I2 = 65%) for open surgery (p = 0.59). In the subgroup analysis of bicoronal synostosis, the reoperation rate was 10% (95% CI 4%-21%, I2 = 0%) for endoscopic surgery versus 16% (95% CI 7%-32%, I2 = 0%) for open surgery (p = 0.39). CONCLUSIONS: While both surgical approaches are reasonable options for nonsyndromic MSS, this meta-analysis suggests that endoscopic surgery could be associated with lower morbidity when compared with open surgery. Future studies with longer follow-up periods will be needed to validate these findings and contribute to the understanding of complex craniosynostosis management
[[alternative]]居家醫療病患使用遠距醫療與遠端監控之系統性文獻回顧：慢性病管理與住院風險
No full text[[abstract]]With the aging of the global population, home health care (HHC) has become a feasible alternative within health-care systems, particularly for patients with chronic diseases. However, the effectiveness of implementing remote patient monitoring (RPM) in HHC for reducing healthcare resource utilization among patients with chronic diseases remains unclear. This systematic review examined the effects of various RPM interventions on health-care resource utilization for HHC patients aged 50 years and older with chronic diseases. Keyword searches were conducted in PubMed, Scopus, and Embase for studies published from 1996 onwards on RPM interventions for HHC patients aged 50 years and above with chronic diseases. Following the removal of duplicate studies and a thorough literature screening process, eligible studies were included for analysis. A total 13 studies involving 4,528 patients, predominantly women, were analyzed. The durations of all RPM interventions were within 12 months. Most of the included studies focused on patients with heart failure and implemented HHC+RPM as a treatment. These interventions often incorporated multiple strategies to reduce hospitalizations and readmissions. RPM interventions significantly reduce readmission rates. Utilizing RPM models in combination with HHC interventions appears to be more effective than HHC alone in reducing hospitalizations and readmissions. (Taiwan J Public Health. 2024;43(6):527-536)
Streamlining whole genome sequencing for clinical diagnostics with ONT technology
No full text[[abstract]]Recent advances in whole-genome sequencing (WGS) have increased the accessibility of this tool, offering substantial potential for pathogen surveillance, outbreak response, and diagnostics. However, the routine clinical adoption of WGS is hindered by factors such as high costs, technical complexity, and the requirement for bioinformatics expertise for data analysis. To address these challenges, we propose RapidONT, a workflow designed for cost-effective and accessible WGS-based pathogen analysis. RapidONT employs a mechanical shearing–based DNA extraction protocol, followed by library construction by using a multiplexing Oxford nanopore technologies (ONT) rapid barcoding kit. Flye software is used for de novo assembly without manual intervention, followed by basic assembly polishing using Medaka and Homopolish. The polished assemblies are then analyzed using the user-friendly web-based platform Pathogenwatch, which facilitates species identification, molecular typing, and antimicrobial resistance (AMR) prediction, all while requiring minimal bioinformatics expertise. The efficacy of RapidONT was evaluated using nine clinically relevant pathogens, encompassing a total of 90 gram-positive and gram-negative bacterial strains. The workflow demonstrated high accuracy in critical tasks such as multilocus sequence typing (MLST) and AMR identification, using only ONT R9.4.1 flowcell data. Notably, limitations were observed with Salmonella spp. and Neisseria gonorrhoeae. Furthermore, RapidONT enabled the generation of genomic information for 48 bacterial isolates by using a single flow cell, significantly reducing sequencing costs. This approach eliminates the need for extensive experimentation in obtaining crucial genomic information. This workflow facilitates broader WGS implementation in clinical pathogen analysis and diagnostics