Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults.

Neuroprotective Effects of a Multi-Herbal Extract on Axonal and Synaptic Disruption in Vitro and Cognitive Impairment in Vivo.

Background: Alzheimer's disease (AD) is a multifactorial disorder characterized by cognitive decline. Current available therapeutics for AD have limited clinical benefit. Therefore, preventive therapies for interrupting the development of AD are critically needed. Molecules targeting multifunction to interact with various pathlogical components have been considered to improve the therapeutic efficiency of AD. In particular, herbal medicines with multiplicity of actions produce cognitive benefits on AD. Bugu-M is a multi-herbal extract composed of Ganoderma lucidum (Antler form), Nelumbo nucifera Gaertn., Ziziphus jujuba Mill., and Dimocarpus longan, with the ability of its various components to confer resilience to cognitive deficits. Objective: To evaluate the potential of Bugu-M on amyloid-ß (Aß) toxicity and its in vitro mechanisms and on in vivo cognitive function. Methods: We illustrated the effect of Bugu-M on Aß25-35-evoked toxicity as well as its possible mechanisms to diminish the pathogenesis of AD in rat cortical neurons. For cognitive function studies, 2-month-old female 3×Tg-AD mice were administered 400 mg/kg Bugu-M for 30 days. Behavioral tests were performed to assess the efficacy of Bugu-M on cognitive impairment. Results: In primary cortical neuronal cultures, Bugu-M mitigated Aß-evoked toxicity by reducing cytoskeletal aberrations and axonal disruption, restoring presynaptic and postsynaptic protein expression, suppressing mitochondrial damage and apoptotic signaling, and reserving neurogenic and neurotrophic factors. Importantly, 30-day administration of Bugu-M effectively prevented development of cognitive impairment in 3-month-old female 3×Tg-AD mice. Conclusion: Bugu-M might be beneficial in delaying the progression of AD, and thus warrants consideration for its preventive potential for AD.

Risk Factors for the Development of Colistin Resistance during Colistin Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections.

Colistin is one of the last-resort options for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections if novel antibiotics are unavailable, where the development of colistin resistance during treatment represents a major challenge for clinicians. We aimed to investigate the risk factors associated with the development of colistin resistance in patients with CRKP infections following colistin treatment. We conducted a retrospective case-control study of patients with CRKP strains available before and after colistin treatment at a medical center in Taiwan, between October 2016 and November 2020. Cases (n = 35) included patients with an initial colistin-susceptible CRKP (ColS-CRKP) strain and a subsequent colistin-resistant CRKP (ColR-CRKP) strain. Controls (n = 18) included patients with ColS-CRKP as both the initial and subsequent strains. The 30-day mortality rate after the subsequent CRKP isolation was not different between cases and controls (12/35 [34%] versus 5/18 [28%] [P = 0.631]). blaKPC (n = 38) and blaOXA-48 (n = 11) accounted for the major mechanisms of carbapenem resistance. Alterations in mgrB were found in 18/35 (51%) ColR-CRKP strains, and mcr-1 was not detected in any of the strains. More patients received combination therapy in the control group than in the case group (17/18 versus 21/35 [P = 0.008]). The logistic regression model indicated that combination therapy with tigecycline was protective against the acquisition of colistin resistance (odds ratio, 0.17; 95% confidence interval, 0.05 to 0.62 [P = 0.008]). We observed that the inclusion of tigecycline in colistin treatment mitigated the risk of acquiring colistin resistance. These results offer insight into using the combination of tigecycline and colistin for the treatment of CRKP infections in antimicrobial stewardship. IMPORTANCE Treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is challenging due to the limited options of antibiotics. Colistin is one of the last-resort antibiotics if novel antimicrobial agents are not available. It is crucial to identify modifiable clinical factors associated with the emergence of resistance during colistin treatment. Here, we found that the addition of tigecycline to colistin treatment prevented the acquisition of colistin resistance. Colistin-tigecycline combination therapy is therefore considered a hopeful option in antimicrobial stewardship to treat CRKP infections.

Nationwide analysis of medical utilization in people with severe mental illness receiving home care case management.

AIM: This nationwide study investigated the change in medical utilization of psychiatric home care case management (CM). METHODS: This nationwide study enrolled patients receiving CM (N = 10,274) from January 1, 1999 to December 31, 2010, from Taiwan's National Health Insurance Research Database. Through a 2-year mirror-image comparison weighted by the contributed person-time for each subject, we evaluated changes in medical utilization. Furthermore, a case-crossover analysis was used to verify the independent effect of CM in changing medical utilization by adjusting the time-variant variables between the pre-2-year (within 2 years before receiving CM) and post-2-year (within years after receiving CM) periods. The same methodology was applied for the subsequent 2-year comparison to assess the maintenance effect. RESULTS: Of the 10,274 patients receiving CM, 69.7% had schizophrenia. The results showed a chronological trend for the intervention of CM. The adjusted mirror-image analysis revealed a significant decrement of psychiatric and involuntary admissions after the intervention, and the utilization shifted toward psychiatric outpatient service. The case-crossover analysis with the adjustment of time-variant covariates confirmed the independent effect of CM on the changes of medical utilization. The comparable effect persisted after the next 2 years of intervention. However, CM showed no impact on lowering the admission rate for comorbid physical illnesses after the intervention. CONCLUSIONS: The CM model can effectively reduce psychiatric hospitalization and involuntary admission frequency but has no effect on comorbid physical illnesses. Care models aimed at ameliorating physical problems in such patients are needed.

Effects of Kinesiology Taping on Scapular Reposition Accuracy, Kinematics, and Muscle Activity in Athletes With Shoulder Impingement Syndrome: A Randomized Controlled Study.

CONTEXT: Scapular proprioception is a key concern in managing shoulder impingement syndrome (SIS). However, no study has examined the effect of elastic taping on scapular proprioception performance. OBJECTIVE: To investigate the immediate effect of kinesiology taping (KT) on scapular reposition accuracy, kinematics, and muscle activation in individuals with SIS. DESIGN: Randomized controlled study. SETTING: Musculoskeletal laboratory, National Yang-Ming University, Taiwan. PARTICIPANTS: Thirty overhead athletes with SIS. INTERVENTIONS: KT or placebo taping over the upper and lower trapezius muscles. MAIN OUTCOME MEASURES: The primary outcome measures were scapular joint position sense, measured as the reposition errors, in the direction of scapular elevation and protraction. The secondary outcomes were scapular kinematics and muscle activity of the upper trapezius, lower trapezius, and serratus anterior during arm elevation in the scapular plane (scaption). RESULTS: Compared with placebo taping, KT significantly decreased the reposition errors of upward/downward rotation (P = .04) and anterior/posterior tilt (P = .04) during scapular protraction. KT also improved scapular kinematics (significant group by taping effect for posterior tilt, P = .03) during scaption. Kinesiology and placebo tapings had a similar effect on upper trapezius muscle activation (significant taping effect, P = .003) during scaption. CONCLUSIONS: Our study identified the positive effects of KT on scapular joint position sense and movement control. Future studies with a longer period of follow-up and clinical measurement might help to clarify the clinical effect and mechanisms of elastic taping in individuals with SIS.

Antipsychotic medications and stroke in schizophrenia: A case-crossover study.

BACKGROUND: The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia. METHODS: Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug. RESULTS: Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015). CONCLUSIONS: Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats.

In traditional Chinese medicine, Ligusticum wallichii Franchat (Chuan Xiong) and its active ingredient tetramethylpyrazine (TMP) have been used to treat cardiovascular diseases and to relieve various neurological symptoms such as ischemic deficits. However, scientific evidence related to their effectiveness or precise modes of neuroprotective action is largely unclear. In the current study, we elicited the neuroprotective mechanisms of TMP after focal cerebral ischemic/reperfusion (I/R) by common carotid arteries and middle cerebral artery occlusion model in rats. TMP was administrated 60 min before occlusion via intraperitoneal injection. TMP concentration-dependently exhibited significant neuroprotective effect against ischemic deficits by reduction of behavioral disturbance. Neuronal loss and brain infarction in the ischemic side of rats were markedly lowered by treatment with TMP. Cerebral I/R-induced internucleosomal DNA fragmentation, caspase-8, caspase-9, and caspase-3 activation, and cytochrome c release were reduced by TMP treatment. Western blot analysis revealed the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax and Bad by cerebral I/R insult. Among them, only the alteration in Bcl-xL expression was reversed by TMP treatment. Moreover, the activation of microglia and/or recruitment of inflammatory cells within the ischemic side and the consequent production of monocyte chemoattractant protein 1 (MCP-1) were suppressed by TMP pre-treatment. Our findings suggest that TMP might provide neuroprotection against ischemic brain injury, in part, through suppression of inflammatory reaction, reduction of neuronal apoptosis, and prevention of neuronal loss.

Tetramethylpyrazine reduces ischemic brain injury in rats.

Tetramethylpyrazine (TMP), which is widely used in the treatment of ischemic stroke by Chinese herbalists, is one of the most important active ingredients of the traditional Chinese herbal medicine, Ligusticum wallichii Franchat (Chung Xiong). However, the mechanism by which TMP protects the brain is still not clear. We examined neuroprotective effects of TMP after transient focal cerebral ischemia using common carotid artery and middle cerebral artery occlusion model in rats and evaluated the involvement of anti-inflammation. TMP administrated intraperitoneally significantly protected the brain against ischemic insult as evidenced by the reduction in infarction volume, preservation of neurons, and decrease in brain edema. TMP markedly reduced cerebral ischemia/reperfusion-induced inflammatory cell activation and proinflammatory mediator production. Moreover, TMP suppressed lipopolysaccharide/interferon-gamma-induced inflammation and prostaglandin E(2) production in cultured glial cells. Our findings suggest that one of neuroprotective effects of TMP against ischemic brain injury might involve its anti-inflammatory potential.