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The Protective Effects of Influenza Vaccination in Elderly Patients with Breast Cancer in Taiwan: A Real-World Evidence-Based Study
No full text[[abstract]]In elderly patients with newly diagnosed breast cancer, clarity is lacking regarding the effects of influenza vaccines, particularly on clinical outcomes. This study conducted two nationwide, population-based, and propensity score-matched cohorts to estimate and compare the protective effects of influenza vaccine in elderly women and elderly patients with breast cancer. Data were derived from the National Health Insurance Research Database and Cancer Registry Database. Generalized estimating equations (GEEs) were used to compare outcomes between the vaccinated and unvaccinated cohorts. Adjusted odds ratios (aORs) were used to estimate the relative risks, and stratified analyses in the breast cancer cohort were performed to further evaluate elderly breast cancer patients undergoing a variety of adjuvant therapies. The GEE analysis showed that the aORs of death and hospitalization, including for influenza and pneumonia, respiratory diseases, respiratory failure, and heart disease, did not significantly decrease in vaccinated elderly patients with newly diagnosed breast cancer. Conversely, the aORs of all influenza-related clinical outcomes were significantly decreased in elderly women. No protective effects of influenza vaccination were found in the elderly patients with a newly diagnosed breast cancer. More studies focusing on identifying strategies to improve the real-world effectiveness of influenza vaccination to the immunocompromised are needed. Our clinical outcomes will be valuable for future public health policy establishment and shared decision making for influenza vaccine use in elderly patients with newly diagnosed breast cancer. According to our findings, regular influenza vaccine administration for elderly patients with newly diagnosed breast cancer may be reconsidered, with potential contraindications for vaccination. On the other hand, implementing the vaccination of close contacts of patients with breast cancer may be a more important strategy for enhancing protection of those fragile patients
Tyrosinase Inhibitors Derived from Chemical Constituents of Dianella ensifolia
No full text[[abstract]]Dianella ensifolia is a perennial herb with thickened rhizome and is widely distributed in tropical and subtropical regions of Asia, Australia, and the Pacific islands. This plant has the potential to be used as a source of herbal medicine. This study investigated further phytochemistry and tyrosinase inhibitory effect of some constituents isolated from D. ensifolia. Four new flavans, (2S)-4'-hydroxy-6,7-dimethoxyflavan (1), (2S)-3',4'-dihydroxy-7-methoxy-8-methylflavan (2), (2S)-2'-hydroxy-7-methoxyflavan (3), and (2S,1'S)-4-hydroxy-4-(7-methoxy-8-methylchroman-2-yl)-cyclohex-2-enone (4), together with 67 known compounds, including 10 flavans (5-14), 5 flavanones (15-19), 3 flavone (20-22), 5 chalcones (23-27), 3 chromones (28-30), 15 aromatics (31-45), 7 phenylpropanoids (46-52), one lignan (53), 7 steroids (54-60), one monoterpene (61), one diterpene (62), 4 triterpenes (63-66), a carotenoid (67), 2 alkaloids (68 and 69), and 2 fatty acids (70 and 71) were isolated from D. ensifolia. Their structures were elucidated on the basis of physical and spectroscopic data analyses. Moreover, compounds 1-4, 8, 10-15, 20, 21, and 41 were evaluated for their mushroom tyrosinase inhibitory effect. Compounds 11 and 14 strongly inhibited mushroom tyrosinase activity with IC50 values of 8.6 and 14.5 μM, respectively
Age and sex-specific associations of visit-to-visit variability of glycated hemoglobin A1c with all-cause mortality in patients with diabetes
No full text[[abstract]]Background: Visit-to-visit variability (VVV) of glycated hemoglobin (HbA1c) levels have been found to be associated with prognosis of diabetes. However, little is known about whether or to what extent sex and age may modify the effects of VVV.
Methods: To investigate age- and sex-specific rates of mortality from all causes and relative hazards of mortality in association with VVV of HbA1c levels, 47,145 patients with diabetes and prescription of any antidiabetic agents >6 months were identified from outpatient visits of a tertiary medical center in northern Taiwan during 2003-2018. VVV of HbA1c was measured by quartiles of standard deviation (SD), coefficient of variation (CV), and average real variability (ARV), respectively. The study subjects were linked to Taiwan's National Death Registry to identify all-cause mortality. The person-year approach with the Poisson assumption was used to assess the all-cause mortality rates, and Cox proportional hazard regression model was used to evaluate the relative hazards of all-cause mortality concerning various levels of VVV of HbA1c.
Results: The lowest all-cause mortality rate was found in either the first or second quartile of various measures for VVV of HbA1c, but the highest mortality rate was consistently observed in the fourth quartile of VVV, regardless of SD, CV, or ARV across ages and sexes. Increased hazards of overall all-cause mortality were noticed from the second to fourth quartile of VVV of HbA1c. In detailed age- and sex-stratified analyses, elevated risk of mortality was seen in the fourth quartile of those aged 69 years, increased risk of mortality was noticed in the third and fourth quartiles of any VVV of HbA1c irrespective of sex. In those aged 50-69 years, incremental increased hazards of mortality were consistently observed in the second to fourth quartiles of VVV of HbA1c.
Conclusion: HbA1c variability whether it was SD, CV, or ARV could strongly predict the risks of all-cause mortality. The extent of the relationship between VVV of HbA1c and all-cause mortality in different age groups was comparable between both sexes. Given the importance of long-term glucose fluctuation, the inclusion of HbA1c variability calculated from the standardized method should be considered by clinical guideline policymakers as part of the biochemical panel in daily diabetes management
Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia: A Systematic Review and Network Meta-analysis
No full text[[abstract]]Importance Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear.
Objective To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms.
Data Sources The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021.
Study Selection A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included.
Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model.
Main Outcomes and Measures The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms.
Results Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation,??2.19 [95% CI,??3.36 to ?1.02]; intermittent theta-burst stimulation, ?1.32 [95% CI,??1.88 to ?0.76]; anodal transcranial direct current stimulation, ?1.28 [95% CI,??2.55 to ?0.02]; high-frequency rTMS, ?0.43 [95% CI,??0.68 to ?0.18]; extreme high-frequency rTMS, ?0.45 [95% CI,??0.79 to ?0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups.
Conclusions and Relevance In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted
Editorial: Modulation of NMDA Receptors: From Bench Side to Clinical Applications in Psychiatry
No full text[[abstract]]Editorial on the Research Topic
Modulation of NMDA Receptors: From Bench Side to Clinical Applications in Psychiatry
N-methyl -D- aspartate receptors (NMDARs) have a complex role in the developing and mature brain. Disruptions in NMDAR signaling have been observed in different psychiatric disorders such as schizophrenia, depressive disorder, and Alzheimer's disease (AD) (1). The articles in this Research Topic further advance our knowledge on the complex role of NMDARs in normal and pathological conditions and explore the possibility of novel therapeutic uses of NMDAR modulators.
The NMDAR hypofunction hypothesis of schizophrenia (2) is the basis for the current use of NMDAR modulators in modeling of this disease in animals and as potential therapeutics.
In the review article, Pei et al. address the use of direct and indirect NMDAR glycine-site modulators, such as glycine, D-cycloserine, D-serine, glycine transporter 1 (GlyT1) inhibitors, and D-amino acid oxidase (DAAO) inhibitors in the treatment of clinical symptoms and cognitive impairments seen in schizophrenia. Reviewed preclinical and clinical studies suggest that indirect NMDAR glycine-site enhancers such as GlyT1 inhibitors (sarcosine) and DAAO inhibitors (sodium benzoate, TAK-831) seem to be more potent in clinical efficacy and with fewer side effects than direct NMDAR glycine-site agonists, including glycine, D-cycloserine, and D-serine.
Due to the fact that D-serine is one of the most frequently used NMDAR modulators and findings of its nephrotoxicity in rats, important is the review of Meftah et al. that summarizes current findings of the safety of D-serine treatment in different mammals, including humans. The toxicity of D-serine to endocrine, cardiovascular, gastrointestinal and extrapyramidal systems, with a special focus on the kidneys, is comprehensively discussed. The authors conclude that in humans D-serine appears to be safe at currently studied maximal doses and suggest that in future work even higher doses combined with DAAO inhibitors should be investigated.
The kynurenic acid (KYNA), an endogenous NMDA receptor antagonist, is elevated in the brain of patients with schizophrenia (3). Wright et al. utilized pre-natal exposure to kynurenine to model prenatal insult in rats and have found gender and circadian changes in the extracellular levels of glutamate, GABA and KYNA in rat hippocampi. The authors suggested that sex and time-dependent changes in hippocampal neuromodulation, elicited by prenatal KYNA elevation, may influence behavioral phenotypes, and have translational relevance to psychotic disorders.
Mallien et al. focused to identify the cellular substrates of psychosis induced by NMDAR hypofunction at post-adolescent stages. For these purposes, they have analyzed the effect of the inducible ablation of NMDARs in ErbB4 expressing cells, as neuregulin 1 and its receptor ErbB4 have been identified as schizophrenia-associated susceptibility factors that closely interact with NMDARs. They concluded that post-adolescent NMDAR deletion, even in a wider cell population than parvalbumin-positive interneurons, is not sufficient to generate behavioral changes that mimic psychiatric disorders.
With ketamine's demonstrated efficacy in the treatment of unipolar depression (4), there are emerging questions on the mechanism of actions underlying its observed fast clinical improvement and the potential role of NMDA transmission in bipolar depression. Yang et al. in their article highlight the importance of NMDAR transmission in the generation of mental representation during working memory. They further postulate that the very rapid, antidepressant effect of intranasal ketamine may involve the disruption of NMDAR-generated aversive mood states by the anterior and subgenual cingulate cortices, providing the opportunity for the return of top-down regulation by higher prefrontal cortex areas.
The effects of a single intravenous infusion of ketamine hydrochloride on magnetoencephalographic recordings in drug-free individuals with major depressive disorder performing an attentional task during scanning, have been investigated by Gilbert et al. Dynamic causal modeling was used to model effective connectivity of excitatory and inhibitory pathways. The authors provide additional support for the GABA disinhibition hypotheses of depression and the role of AMPA receptors in ketamine's antidepressant effects.
Dong et al. in their article address the impact of another oral NMDAR antagonist, D-cycloserine, combined with lurasidone on glutamate and glutamine in bipolar depression. This preliminary pilot study demonstrated that a lower mean glutamate level post-treatment after administration of NMDAR antagonist in combination with lurasidone predicts a better antidepressant response in bipolar depression. Authors propose that in the future, attenuation of the glutamate response to NMDAR antagonists could potentially be used as a biomarker for screening of NMDAR antagonists for their antidepressant potential.
Recent studies suggested that ketamine's rapid-acting antidepressant effect is potentially mediated by the opioid system (5). Bowman et al. have investigated the resting state electroencephalography profiles induced by co-administration of ketamine with either antipsychotic clozapine, or opioid receptor antagonist naltrexone, in freely moving rats to clarify this issue further. They demonstrated that the effect of clozapine, ketamine and naltrexone on local field potentials (LFP) depends of the locomotor state and that both clozapine and naltrexone modulated the effect of ketamine LFPs.
Balanced NMDAR activity is required for optimal brain and neurocognitive function (6). In an overview, Orzylowski et al. summarize the potential role of D-serine in normal and pathological aging such as AD. They review both preclinical and human studies of D-serine's modulation of cognition. Albeit controversial, it has been suggested that, in normal aging, decreased serine racemase expression, lower D-serine concentration, and NMDARs downregulation may lead to impaired synaptic plasticity and declined cognitive function. On the other hand, in AD, increased serine racemase expression, higher D-serine levels, and NMDAR overactivation tend to generate neurotoxicity and dementia. D-Serine and DAAO have been proposed as possible biomarkers and D-serine and DAAO inhibitors as potential therapeutics in early-phase AD.
Besides its role in schizophrenia and depression, the glutamatergic system and NMDARs have also been implicated in the pathophysiology of alcohol use disorder (7). Alcohol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit. Thompson et al. showed that saracatinib, the Src/Fyn kinase inhibitor, at the doses and regimen used in the study did not affect alcohol-seeking/craving or consumption in habitual mice or heavy drinking human participants
The Dose-and Duration-Dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta-Analysis of Randomized Placebo-Controlled Trials
No full text[[abstract]]Background: While Alzheimer’s dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials.
Objective: The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric).
Methods: The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer’s dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported).
Results: The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo.
Conclusion: The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD
Effects of Team-Based Learning on Students’ Teamwork, Learning Attitude, and Health Care Competence for Older People in the Community to Achieve SDG-3
No full text[[abstract]]Background: Team-based learning (TBL) was studied in several preclinical settings, but evidence for its effectiveness in community nursing education is scant. A community health care nursing course was developed, and nursing students engaged in TBL to achieve Sustainable Development Goal 3.
Purpose: This study aimed to examine the effect of TBL model integration on students' learning attitude, community understanding, and community care competence for achieving SDG 3 and determine the extent to which the TBL model altered students' nursing competence for providing community health care. We compared the effect of TBL and traditional learning (TL) in terms of community health care knowledge objectives.
Methods: TBL was employed as the teaching strategy to guide students' discussion of community care issues, allowing them to fully utilize the knowledge acquired in their community practice. We used an unblinded crossover design, and 99 students participated in the community health nursing course.
Results: The results demonstrated that TBL improved participants' community understanding and enhanced their skills for assessing and fulfilling community needs. The experimental and control groups differed significantly in their TBL performance, learning attitude, and nursing competencies. The performance of those who engaged in TBL was higher than that of those who engaged in TL on all community issues. TBL appears to be a more effective method than TL in terms of achieving nursing students' knowledge objectives.
Conclusions: Regarding practical application, the proposed intervention enables nursing students to acquire professional knowledge related to community aging health care and nursing skills, and establish partnerships with community residents. This facilitates the achievement of the United Nations' sustainable development goal of ensuring healthy living and promoting well-being at all ages
Hericium erinaceus Mycelium Ameliorates In Vivo Progression of Osteoarthritis
No full text[[abstract]]Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability. Hericium erinaceus is a large edible mushroom with several known medicinal functions. However, the therapeutic effects of H. erinaceus in OA are unknown. In this study, data from Sprague-Dawley rats with knee OA induced by anterior cruciate ligament transection (ACLT) indicated that H. erinaceus mycelium improves ACLT-induced weight-bearing asymmetry and minimizes pain. ACLT-induced increases in articular cartilage degradation and bone erosion were significantly reduced by treatment with H. erinaceus mycelium. In addition, H. erinaceus mycelium reduced the synthesis of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in OA cartilage and synovium. H. erinaceus mycelium shows promise as a functional food in the treatment of OA
Joint effect of blood pressure and glycemic variation on the risk of cardiovascular morbidity and mortality in persons with type 2 diabetes
No full text[[abstract]]Objective: Few studies have explored the association of visit-to-visit variation in blood pressure (BP) and glycemic factors with cardiovascular disease (CVD) morbidity and mortality. This study aimed to examine the independent and joint effect of visit-to-visit BP and glycemic variation on CVD morbidity and mortality in persons with T2DM.
Methods: The present study consisted of two retrospective cohort studies. The Taiwan Diabetes Study was based on a database of the National Diabetes Care Management Program (DCMP) and linked with cardiovascular morbidity incidence. The Taichung Diabetes Study was based on the DCMP database of a medical center, which can be linked with the National Death Registry dataset. The outcomes were analyzed by using Cox's proportional hazard models.
Results: A total of 13,280 and 10,894 persons with T2DM in Taiwan and Taichung Diabetes Study, respectively, were included. SBP-CV, FPG-CV, and HbA1c-CV were significant predictors of stroke, CVD event or death, all-cause mortality, and expanded CVD mortality, whereas DBP-CV was a significant predictor of all-cause mortality and expanded and non-expanded CVD mortality. The joint effect of SBP, FPG, and HbA1c predicted the incidence of stroke and CVD event or death with increased risks of 16 %-35 %. In addition, the joint effect of SBP, DBP, FPG, and HbA1c was associated with all-cause and expanded CVD mortality with increased risks of 29 %-81 %.
Conclusions: The joint effect of BP and glucose variation improved the prediction of cardiovascular morbidity and mortality. Moreover, simultaneous measurement of visit-to-visit BP and glycemic variation may stratify persons with cardiovascular risks and may be regarded as important therapeutic goals in the care of T2DM
Urban–Rural Disparity in the Incidence of Diagnosed Autism Spectrum Disorder in Taiwan: A 10-Year National Birth Cohort Follow-up Study
No full text[[abstract]]Autism spectrum disorder (ASD) is reportedly more prevalent in urban areas partly because of better accessibility and affordability to healthcare. With universal health insurance coverage in Taiwan, a previous study has shown no urban-rural disparity in the utilization rate of a child's preventive healthcare. Under this circumstance, we followed a birth cohort of 176,273 live births from 2006 to 2015 to detect the differences in ASD incidence between urbanicities. After adjusting for socioeconomic factors, children were 1.28 (95% confidence interval (CI): 1.13-1.44) and 1.54 (95% CI: 1.36-1.75) more likely to acquire ASD in satellite and urban areas compared with those in rural areas, respectively. A gradient association between parental educational attainment and ASD incidence was also noted. Greater ASD incidences in more urbanized areas and more advanced educated parents' children were detected under a circumstance with low barriers to healthcare