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The international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan. Between June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART. We included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm3 in 2012 to 298 cells/mm3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04-1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04-1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33-2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04-2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14-13.65) and older age (AHR, 1.06; 95% CI, 1.03-1.10). While the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population.

Diabetes and obesity are globally prevalent metabolic disorders posing significant public health challenges. The effective management of these conditions requires integrated and personalized strategies. This study conducted a systematic literature review, identifying 335 relevant papers, with 129 core articles selected after screening for duplicates and irrelevant studies. The focus of the study is on the synergistic roles of functional foods, microbiotics, and nutrigenomics. Functional foods, including phytochemicals (e.g., polyphenols and dietary fibers), zoochemicals (e.g., essential fatty acids), and bioactive compounds from macrofungi, exhibit significant potential in enhancing insulin sensitivity, regulating lipid metabolism, reducing inflammatory responses, and improving antioxidant capacity. Additionally, the critical role of gut microbiota in metabolic health is highlighted, as its interaction with functional foods facilitates the modulation of metabolic pathways. Nutrigenomics, encompassing nutrigenetics and genomics, reveals how genetic variations (e.g., single-nucleotide polymorphisms (SNPs)) influence dietary responses and gene expression, forming a feedback loop between dietary habits, genetic variations, gut microbiota, and metabolic health. This review integrates functional foods, gut microbiota, and genetic insights to propose comprehensive and sustainable personalized nutrition interventions, offering novel perspectives for preventing and managing type 2 diabetes and obesity. Future clinical studies are warranted to validate the long-term efficacy and safety of these strategies.

Background/Objectives: Diabetic kidney disease (DKD) is a major complication of type 2 diabetes mellitus (T2DM), and recent research highlights that amino acid composition—rather than total protein intake alone—may influence DKD risk. This study aimed to evaluate the associations between dietary protein intake, specific amino acid profiles, and the risk of DKD among adults with T2DM. Methods: A total of 378 T2DM patients were enrolled in this cross-sectional study. Dietary intake was assessed via a 24 h recall and a validated semi-quantitative food frequency questionnaire. Nutrient analysis was based on the Taiwanese Food Composition Database. Participants were categorized into three protein intake groups: Group 1 (≤0.8 g/kg), Group 2 (0.9–1.2 g/kg), and Group 3 (≥1.3 g/kg). Cox proportional hazards models were used to evaluate the associations of crude protein, branched-chain amino acids to aromatic amino acids (BCAA/AAA) ratio, and ketogenic amino acid intake with DKD risk. Adjustments were made for age, sex, diabetes duration, and blood pressure. Results: While crude protein intake showed no significant association with DKD risk, higher intake of ketogenic amino acids (e.g., leucine and lysine) was consistently and significantly associated with reduced DKD risk (adjusted HR range = 0.698–0.716, p < 0.01). Our findings highlight the protective potential of ketogenic amino acids such as leucine and lysine, which were significantly associated with lower DKD risk. The BCAA/AAA ratio also showed a downward trend in DKD risk, though not statistically significant. Kaplan–Meier analysis revealed that moderate protein intake (0.9–1.2 g/kg) corresponded to the most favorable DKD-free survival. Conclusions: Our findings suggest that, beyond total protein quantity, the intake of ketogenic amino acids may play a protective role in DKD prevention. Moderate protein consumption combined with higher leucine and lysine intake appears beneficial. These results support incorporating amino acid profiling in dietary strategies for DKD risk reduction. Further longitudinal and interventional studies are recommended to validate these associations.

ObjectiveViral infection is an exogenous factor for Sjögren’s syndrome (SS). The relationship between herpes zoster infection and the ensuring risk of SS has remained unclear. This study investigated the association between a history of herpes zoster infection and the risk of SS through a nationwide population-based case–control study.DesignRetrospective case–control study.SettingGeneral population of Taiwan.Data source2003–2013 National Health Insurance Research Database of Taiwan.ParticipantsWe identified all patients with newly diagnosed SS between 1 January 2007 and 31 December 2012 without a history of rheumatoid arthritis or systemic lupus erythematosus as the SS group.ControlsWe randomly selected patients without SS between 1 January 2003 and 31 December 2012 and matched 1:5 with controls based on index year, age and sex.Main outcome measureConditional logistic regression analysis to examine the association between a history of herpes zoster and the risk of SS.ResultsThe study included 5751 patients with SS and 28 755 matched controls. The risk of SS was significantly associated with a history of herpes zoster (model A (adjusted for Charlson Comorbidity Index (CCI) (excluding connective tissue disease, CTD)): OR 1.89; 95% CI 1.71 to 2.08; model B (adjusted for comorbidities used to calculate CCI (excluding CTD)): OR 1.90; 95% CI 1.72 to 2.10), in particular if the interval from the last visit for herpes zoster infection to the index date was <3 months (model A: OR 3.09; 95% CI 2.20 to 4.34; model B: OR 3.13; 95% CI 2.20 to 4.45). Such associations remained robust using various definitions of herpes zoster.ConclusionThis nationwide, population-based, case–control study revealed a significant association between a history of herpes zoster and the risk of SS.

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan.

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin–creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781–0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688–0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823–0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.

The study aimed to describe the evolution of the seroprevalence of hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-positive patients included in two cohorts in Taiwan. We retrospectively collected the information on demographic and clinical characteristics of 4,025 and 3,856 HIV-positive Taiwanese, who were aged 18 years or older at designated hospitals around Taiwan in 2004-2007, when an outbreak of HIV infection was occurring, and 2012-2016, when the outbreak was controlled with the implementation of harm reduction program, respectively. Comparisons of HCV seropositivity were made among different age and risk groups for HIV transmission between these two cohorts. The overall HCV seroprevalence of the 2004-2007 cohort and 2012-2016 cohort was 43.4% (1,288/2,974) and 18.6% (707/3,793), respectively (P<0.001). The HCV seroprevalence among injecting drug users (IDUs), though decreasing, was constantly high across the two cohorts, 96.4% and 94.0% (P = 0.02), respectively, and all age groups. In contrast, the corresponding figures among men who have sex with men (MSM) and heterosexuals in the two cohorts were 5.9% vs. 3.5% (P = 0.002) and 9.4% vs. 10.9% (P = 0.59), respectively. Among sexually transmitted HIV-positive patients, HCV seropositivity was significantly correlated with age (adjusted odds ratio [aOR], per 1-year increase, 1.03; 95% confidence interval [CI], 1.02-1.05) and a rapid plasma reagin (RPR) titer ≥1:8 (aOR, 1.58; 95% CI, 1.03-2.43) in a multivariate analysis including age, gender, route for HIV transmission, baseline CD4 count and plasma HIV RNA load, the presence of hepatitis B surface antigen, and an RPR titer ≥1:8. Compared with heterosexuals, the aOR for HCV seropositivity among MSM was 0.47 (95% CI, 0.31-0.72). HCV seroprevalence among HIV-positive patients in Taiwan decreased with time, probably related to the inclusion of younger adults and more non-IDUs, and remained high among IDUs. HCV seropositivity was associated with age and an RPR titer ≥1:8 among patients who acquired HIV through sexual contact.

The study aimed to describe the seroprevalence of hepatitis A virus (HAV) in HIV-positive adult patients in Taiwan between 2012 and 2016 and to examine the evolution of HAV seroprevalence between 2004-2007 and 2012-2016. Clinical information and data of anti-HAV antibody results were collected from 2,860 antiretroviral-naïve HIV-positive Taiwanese aged 18 years or older who initiated combination antiretroviral therapy at 11 hospitals around Taiwan between 2012 and 2016 (2012-2016 cohort). A multivariate logistic regression model was applied to identify independent variables associated with HAV seropositivity. Comparisons of HAV seroprevalences and associated clinical characteristics were made between this 2012-2016 cohort and a previous cohort of 1580 HIV-positive patients in 2004-2007 (2004-2007 cohort). Of the 2,860 HIV-positive patients between 2012 and 2016, the overall HAV seropositivity rate was 21.2% (605/2860), which was independently associated with an older age (adjusted odds ratio [AOR], per 1-year increase, 1.13; 95% confidence interval [95% CI], 1.11-1.15) and co-infection with hepatitis B virus (AOR 1.44; 95% CI, 1.08-1.93). Residence in southern Taiwan (AOR 0.49; 95% CI, 0.34-0.72) was inversely associated with HAV seropositivity. The overall HAV seroprevalence in the 2012-2016 cohort was significantly lower than that in the 2004-2007 cohort (21.2% vs 60.9%, p<0.01). The decreases of HAV seropositivity rate were observed in nearly every age-matched group, which suggested the cohort effect on HAV seroepidemiology. However, among individuals aged 25 years or younger, the HAV seropositivity rate increased from 3.8% (2/52) in the 2004-2007 cohort to 8.5% (50/587) in the 2012-2016 cohort, with 95.4% (560/587) being MSM in this age group of the latter cohort. HAV seroprevalence has decreased with time among HIV-positive adults in Taiwan. The cohort effect has increased the number of young HIV-positive patients that are susceptible to HAV infection in a country without nationwide childhood vaccination program against HAV.

Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity. The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

Novel drugs targeting Wnt signaling are gradually being developed for hepatocellular carcinoma (HCC) treatment. In this study, we used a Wnt-responsive Super-TOPflash (STF) luciferase reporter assay to screen a new compound targeting Wnt signaling. 3-(5′-Hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) was identified as a small molecule inhibitor of the Wnt/β-catenin pathway. Our coimmunoprecipitation (co-IP) data showed that YC-1 did not affect the β-catenin/TCF interaction. Then, by mass spectrometry, we identified the ErbB3 receptor-binding protein 1 (EBP1) interaction with the β-catenin/TCF complex upon YC-1 treatment. EBP1 encodes two splice isoforms, p42 and p48. We further demonstrated that YC-1 enhances p42 isoform binding to the β-catenin/TCF complex and reduces the transcriptional activity of the complex. The suppression of colony formation by YC-1 was significantly reversed after knockdown of both isoforms (p48 and p42); however, the inhibition of colony formation was maintained when only EBP1 p48 was silenced. Taken together, these results suggest that YC-1 treatment results in a reduction in Wnt-regulated transcription through EBP1 p42 and leads to the inhibition of tumor cell proliferation. These data imply that YC-1 is a drug that antagonizes Wnt/β-catenin signaling in HCC.