Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin ...system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of albuminuria has been under-investigated in patients with type 2 diabetes mellitus. Patients with type 2 diabetes and regular outpatient visits were recruited from the Puli Branch of the Taichung Veterans General Hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the albuminuria incidence. Univariable and multivariable Cox regression analysis were employed to explore the relation between uric acid and incident albuminuria. Uric acid cutoffs for incident albuminuria were determined with the receiver operator characteristic curve. We included 247 qualified subjects (mean age: 64.78 years old standard deviation = 11.29 years; 138 55.87% men). During a 4.5-year follow-up duration, 20 subjects with incident albuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident albuminuria (adjusted hazard ratio = 2.39; 95% confidence interval: 1.53-3.75; P < .001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident albuminuria. Serum uric acid was associated with incident albuminuria among patients with type 2 diabetes.
A hallmark of Alzheimer’s disease (AD) pathogenesis is the accumulation of extracellular plaques mainly composed of amyloid-β (Aβ) derived from amyloid precursor protein (APP) cleavage. Recent ...reports suggest that transport of APP in vesicles with huntingtin-associated protein-1 (HAP1) negatively regulates Aβ production. In neurons, HAP1 forms a stable complex with Abelson helper integration site-1 (AHI1), in which mutations cause neurodevelopmental and psychiatric disorders. HAP1 and AHI1 interact with tropomyosin receptor kinases (Trks), which are also associated with APP and mediate neurotrophic signaling. In this study, we hypothesize that AHI1 participates in APP trafficking and processing to rescue AD pathology. Indeed, AHI1 was significantly reduced in mouse neuroblastoma N2a cells expressing human Swedish and Indiana APP (designed as AD model cells) and in 3xTg-AD mouse brain. The AD model cells as well as
Ahi1-
knockdown cells expressing wild-type APP-695 exhibited a significant reduction in viability. In addition, the AD model cells were reduced in neurite outgrowth. APP C-terminal fragment-β (CTFβ) and Aβ42 were increased in the AD cell lysates and the culture media, respectively. To investigate the mechanism how AHI1 alters APP activities, we overexpressed human AHI1 in the AD model cells. The results showed that AHI1 interacted with APP physically in mouse brain and transfected N2a cells despite APP genotypes. AHI1 expression facilitated intracellular translocation of APP and inhibited APP amyloidogenic process to reduce the level of APP-CTFβ in the total lysates of AD model cells as well as Aβ in the culture media. Consequently, AHI1–APP interactions enhanced neurotrophic signaling through Erk activation and led to restored cell survival and differentiation.
Abstract
Background
Human life expectancy has increased rapidly in recent decades. Regular exercise can promote health, but the effect of exercise on mortality is not yet well understood.
Objective
...To investigate the association of exercise with mortality in the older people.
Methods
We used data from annual health check-ups of the older citizens of Taipei in 2006. Participants were interviewed by trained nurses using a structured questionnaire to collect data on demographics and lifestyle behaviours. Overnight fasting blood was collected for measuring blood glucose, liver and renal function and lipid profiles. Exercise frequency was categorised into no exercise, 1–2 times in a week and more than 3–5 times in a week. All-cause mortality was ascertained from the National Registration of Death. All participants were followed up until death or December 312012, whichever came first. Kaplan–Meier curves and Cox proportional hazard analysis were used to investigate the association between exercise and all-cause mortality.
Results
In total, 42,047 older people were analysed; 22,838 (54.32%) were male and with a mean (SD) age of 74.58 (6.32) years. Kaplan–Meier curves of all-cause mortality stratified by exercise frequency demonstrated significant findings (Log-rank P < 0.01). Multivariate Cox regression analysis showed that older people with higher exercise levels had a significantly decreased risk of mortality (moderate exercise HR = 0.74, 95% CI: 0.68–0.81, high exercise HR = 0.65, 95% CI: 0.59–0.70) after adjusting for potential confounders, with a significant trend (P for trend<0.01).
Conclusions
Older people with increased exercise levels had a significantly decreased risk of all-cause mortality.
To investigate the clinical features of Kikuchi-Fujimoto disease (KFD) in children, and place an emphasis on the therapeutic effects of hydroxychloroquine as monotherapy.
We retrospectively reviewed ...the medical records of all children diagnosed with KFD during the period January 1992 to September 2016 at a tertiary medical center in Taiwan.
40 patients were histopathologically confirmed as KFD, and the mean age of the patients was 13.9 ± 3.1 years. The male to female ratio was 1:1. The lymph node involvements were often cervical (95%) with features of unilateral predisposition (75%), polyadenopathy (84.4%) and tenderness (56.3%). Fever, cough, rhinorrhea, and tonsillitis were other common presentations. Laboratory findings included leukopenia (56.5%), monocytosis (63.6%), with positive results of EB-VCA IgG (88.9%), EB-VCA IgM (22.2%), EBEA IgG (22.2%) and EBNA IgG (88.9%). The univariate analyses of prolonged fever with lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology were disclosed as statistically significant (P < 0.05). Corticosteroids and hydroxychloroquine were administered in 15.6% of patients respectively, along with symptomatic treatments for the rest. Recurrence occurred in 13.0% of patients without corticosteroids or hydroxychloroquine treatment. There were neither recurrences nor relevant major adverse effects in all the five KFD cases treated with hydroxychloroquine.
KFD should be suspected in children with febrile cervical lymphadenopathy, especially when concomitant with leukopenia and monocytosis. Lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology are reliable predictors for prolonged fever. Hydroxychloroquine may be an alternative choice to corticosteroids for its favorable effects and safety.
There are very few programs that identify patients with coronavirus disease 2019 (COVID-19) who need palliative care. This cohort study presents a model to use a validated palliative care screening ...tool (PCST) to systematically identify hospitalized patients with COVID-19 in need of palliative care. In this prospective study, we consecutively recruited patients with COVID-19 admitted to Taipei City Hospital between 1 January and 30 July 2021. Patients' palliative care needs were determined by using the PCST. Advance care planning (ACP) and advance directives (AD) were systemically provided for all patients with a PCST score ≥ 4. Of 897 patients, 6.1% had a PCST score ≥ 4. During the follow-up period, 106 patients died: 75 (8.9%) with a PCST score < 4 and 31 (56.4%) with a PCST score ≥ 4. The incidence of mortality was 2.08 and 0.58/100 person-days in patients with PCST scores ≥ 4 and <4, respectively. After controlling for other covariates, a PCST score ≥ 4 was associated with a higher risk of mortality in patients with COVID-19 (adjusted HR = 2.08; 95% CI: 1.22-3.54;
< 0.001). During hospitalization, 55 patients completed an ACP discussion with their physicians, which led to 15 of them completing the AD. Since hospitalized patients with COVID-19 had a high mortality rate, it is imperative to implement a comprehensive palliative care program to early identify patients needing palliative care and promotion of AD and ACP.
Neuroblastoma (NB) is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. In this ...study, we aimed to investigate novel MYCN-related genes and assess how they affect NB cell behavior. The different gene expression found in 10 MYCN amplification NB tumors and 10 tumors with normal MYCN copy number were analyzed using tissue oligonucleotide microarrays. Ingenuity Pathway Analysis was subsequently performed to identify the potential genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, was found to be inversely correlated with MYCN expression in NB tissues. This correlation was confirmed in a further 14 human NB samples. Moreover, AHR expression in NB tumors was found to correlate highly with histological grade of differentiation. In vitro studies revealed that AHR overexpression in NB cells induced spontaneous cell differentiation. In addition, it was found that ectopic expression of AHR suppressed MYCN promoter activity resulting in downregulation of MYCN expression. The suppression effect of AHR on the transcription of MYCN was compensated for by E2F1 overexpression, indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore, AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings suggest that AHR is one of the upstream regulators of MYCN. Through the modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect NB differentiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
people with weakened immunity because of age or co-morbidities comprised the fastest growing portion of tuberculosis (TB). Higher mortality before or during TB treatment was observed. In spite of the ...increasing longevity worldwide, surveys focussing specifically on elderly TB are scarce.
to identify prognostic factors of mortality before and during TB treatment among the elderly.
we provided a retrospective cohort study of patients aged 65 and above with pulmonary TB in an Asian city with ageing population. A total of 2,546 patients were enrolled, including 743 (29.2%) cases aged 85 or beyond. Study subjects were categorised by treatment outcomes: treatment success, death prior to TB treatment or death during TB treatment. Demographics and laboratory findings were compared between the three groups.
after controlling for potential confounders, advanced age was the leading determinant of mortality. Adjusted odds ratios (AORs) of death during treatment were 1.79 (aged 75-84) and 3.43 (aged 85 and above) while comparing with patients aged 65-74. AORs of death prior to treatment were 2.95 and 5.66. Other prognostic factors included malignancy, end-stage renal disease receiving dialysis, need of intensive or long-term care, result of sputum acid-fast bacilli examination, findings of pleural effusion on chest X-ray and educational level.
this research manifested significant determinants of mortality in elderly patients prior to or during TB treatment. High awareness, timely intervention and close monitoring of treatment are recommended to older TB patients, especially with the properties mentioned in this study.
BACKGROUND:Although the HIV can cause myocardial inflammation, the association of HIV infection with subsequent development of heart failure (HF) has not been extensively studied. This nationwide ...cohort study aimed to determine the risk of incident HF in people living with HIV/AIDS (PLWHA).
METHODS:We identified PLWHA using the Taiwan Centers for Disease Control and Prevention HIV Surveillance System. An age- and sex-matched control group without HIV infection was selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed up until December 2014 and were observed for a new diagnosis of HF. A time-dependent Cox proportional hazards model was used to determine the association of HIV and highly active antiretroviral therapy with incident HF, with death as a competing risk event.
RESULTS:Of the 120,765 patients (24,153 PLWHA and 96,612 matched controls), 641 (0.53%) had incident HF during a mean follow-up period of 5.84 years, including 192 (0.79%) PLWHA and 449 (0.46%) controls. Time to diagnosis of incident HF was significantly shorter in PLWHA than in those without HIV infection (P < 0.001, the log-rank test). After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident HF (adjusted hazard ratio, 1.52; 95% confidence interval1.27 to 1.82). As the duration of highly active antiretroviral therapy increased, the risk of HF decreased (P = 0.014).
CONCLUSIONS:HIV infection was an independent risk factor for incident HF. Clinicians need to be aware of the higher risk of HF in PLWHA.
To examine whether changes in metabolic syndrome (MetS) status over time are associated with risk of all-cause and cardiovascular disease related (CVD) mortality.
This prospective cohort study ...consisted of 544,749 individuals who participated in a self-funded comprehensive health surveillance program offered by Taiwan MJ Health Management Institution between 1998 and 2016. We included 236,216 adults who had at least two repeated MetS measures 5.9 (4.6) years apart and were followed up for mortality over 18.8 (5.2) years. Participants were classified according to the change in their MetS status as follows: MetS-free at both time points (n = 173,116), MetS-developed (n = 22,607), MetS-recovered (n = 13,616), and MetS-persistent (n = 26,877). Multivariable Cox proportional hazards model was used to determine the association between change in MetS status and risk of all-cause and CVD mortality.
Over the 4,436,842 person-years follow-up period, 14,226 participants died, including 2671 (19%) of CVD-related causes. The crude CVD mortality rate per 1000 person-years in the study groups were MetS-free, 0.32; MetS-developed, 0.75; MetS-recovered, 1.22; and MetS-persistent, 2.00 (P < 0.001). Compared to the persistent MetS group, participants in the MetS-recovered group had a lower risk of all-cause (adjusted hazard ratio aHR, 0.87; 95%CI, 0.82–0.92) and CVD mortality (aHR, 0.81; 95% confidence interval CI, 0.71–0.93). Development of MetS increased the risk for all-cause (aHR, 1.11; 95%CI, 1.05–1.17) and CVD mortality (aHR, 1.22; 95%CI, 1.07–1.39), compared to the MetS-free group.
Recovery from MetS was significantly associated with a lower risk of all-cause and CVD mortality, whereas development of MetS was associated with increased risk.
Vaccination is the most important preventive measure to protect people from coronavirus disease 2019 (COVID-19). Governments worldwide have prioritized their vaccination policy against COVID-19. ...However, there is a lack of relevant research on Taiwanese attitudes and considerations toward COVID-19 vaccination. This study aimed to investigate the cognition, preventive behaviors, and attitudes toward COVID-19 vaccines that influence people’s willingness to get vaccinated in Taiwan.
From October 1 to 31, 2021, a computer-assisted telephone interview system was used to randomly select Taiwanese people to investigate their COVID-19 preventive behaviors, knowledge, and willingness to be vaccinated.
We included 2,000 participants of whom 96.45% showed vaccination willingness. The overall mean age and knowledge scores were 48.6 years and 5.78, respectively. All of the participants chose to wear masks, and 80% chose to be vaccinated to prevent COVID-19. Compared with the non-willing vaccination participants, those with younger ages, higher incomes, and higher knowledge scores regarding masks and vaccination were more likely to be vaccinated. Furthermore, apprehensions about vaccine side effects and negative news about COVID-19 vaccines were the major reasons for vaccination hesitancy.
To improve people’s willingness to get vaccinated, the government should strive to deliver correct knowledge and refute inappropriate negative information about COVID-19 vaccination. Moreover, recommendation by physicians was an important factor for older individuals to decide on receiving the COVID-19 vaccine, and policies could be implemented from this aspect.
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