Age-stratified risk of suicide in patients with schizophrenia.

OBJECTIVES: Schizophrenia is associated with an increased risk of suicide. Few studies have investigated the risk of suicide across different ages, likely due to limitations around sample size. METHODS: From the National Health Insurance Research Database in Taiwan, this study identified 195,787 patients with schizophrenia from January 1, 2000, to December 31, 2019. During the study period, 3848 patients died from suicide. We calculated the standardized mortality ratio (SMR) for suicide stratified by age. In this age-stratified, nested case-control study, risk set sampling was used to match each case with 4 living controls by age, sex, and the year of the first diagnosis with schizophrenia. Conditional logistic regression was used for estimating age-stratified risk profiles. RESULTS: The SMR was the highest in the <25 years age group (52.8) and inversely correlated with age. Unemployment was associated with an increased risk of suicide in the 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years age groups. Depressive and sleep disorders before suicide were more common among suicide cases with schizophrenia than among controls across all age groups. Drug-induced and alcohol-induced mental disorders were significantly associated with suicide but were observed only in the age group younger than 54. Heart disease, pneumonia, and moderate or severe renal disease were risk factors for suicide in the age groups less than 65. CONCLUSIONS: The risk factors for suicide differ by age. This study's findings can be used to optimize health-care interventions for preventing suicide in patients with schizophrenia.

Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain.

BACKGROUND: Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD. METHODS: In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer's type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain. RESULTS: In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster. CONCLUSIONS: We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer's type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.

Antipsychotic medications and severe sepsis in schizophrenia: A nested case-control study.

BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.

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.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

OBJECTIVES: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature. METHODS: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. RESULTS: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42). CONCLUSION: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities.

Therapeutic Drug Monitoring of Paliperidone in Patients With Schizophrenia in Taiwan.

BACKGROUND: The blood level of antipsychotics affects clinical responses to the drug; it can be influenced by race and several individual factors. This study analyzed the therapeutic plasma concentrations (Cps) of paliperidone for both oral and long-acting injectable (LAI) formulations in clinical samples from Taiwanese patients. METHODS: Patients diagnosed with schizophrenia and treated with either oral paliperidone for at least 4 weeks or LAI paliperidone for at least 6 months were enrolled. Blood samples were taken before the morning dose of oral paliperidone or the injection of LAI paliperidone to obtain the trough Cps. RESULTS: Among the patients in this study, 51 were taking oral paliperidone, and 26 were receiving LAI paliperidone. In the oral group, the mean Cps were 40.2 ± 19.8 ng/mL in patients taking 9 mg/d and 44.2 ± 15.9 ng/mL in those taking 12 mg/d. In the LAI group, the mean Cps were 32.9 ± 12.7 ng/mL in patients receiving 100 mg per 28 days and 49.9 ± 25.9 ng/mL in those receiving 150 mg per 28 days. The mean Cps per daily dose (Cps/DD) were 4.11 ± 1.99 ng/mL/mg in the oral group and 9.24 ± 3.78 ng/mL/mg in the LAI group. CONCLUSIONS: Under the suggested DD for oral and LAI paliperidone treatment, most Taiwanese patients with schizophrenia can reach the suggested therapeutic Cps range. Wide interindividual differences were observed in the Cps/DD for both the oral (7-fold) and LAI paliperidone (4-fold) groups. Compared with Western reports, no difference was observed in the body weight-adjusted Cps/DD.

Excess mortality and risk factors for mortality among patients with severe mental disorders receiving home care case management.

AIM: Home care case management (CM) is the main intervention for patients with severe mental disorders (SMDs) requiring outreach care. This study investigated the long-term mortality outcome and associated risk factors in patients who received home care CM. METHODS: This nationwide study enrolled patients who received home care CM (n = 10,255) between 1 January 1999 and 31 December 2010. Each patient was followed up from the baseline (when patients underwent home case CM for the first time during the study period) to the censor (i.e. mortality or the end of the study). We calculated the standardized mortality ratio (SMR) and presented by age and diagnosis. Multivariate regression was performed to assess independent risk factors for mortality. RESULTS: Among 10,255 patients who received home care CM, 1409 died during the study period; the overall SMR was 3.13. Specifically, patients with organic mental disorder had the highest SMR (4.98), followed by those with schizophrenia (3.89), major depression (2.98), and bipolar disorder (1.97). In the multivariate analysis, patients with organic mental disorder or dementia had the highest risk, whereas the mortality risk in patients with schizophrenia was comparable to that in patients with bipolar disorder or major depression. Deceased patients had a significantly higher proportion of acute or chronic physical illnesses, including cancer, chronic hepatic disease, pneumonia, diabetes mellitus, cardiovascular disease, and asthma. CONCLUSION: This study presented the gap of mortality in patients with SMDs receiving home care CM in Taiwan. We highlight the need for effective strategies to improve medical care for this specified population.

Excessive mortality and causes of death among patients with personality disorder with comorbid psychiatric disorders.

PURPOSE: Excessive mortality has been seen in patients with personality disorder (PD), but it has not been well-studied when patients also have other psychiatric comorbidities. This study investigated the mortality rates and causes of death in an Asian cohort with PD. METHOD: We enrolled patients ≥ 18 years of age with PD as defined by DSM-IV criteria (N = 1172), who had been admitted to a psychiatric service center in northern Taiwan between 1985 and 2008. By linking with the national mortality database (1985-2008), cases of mortality (n = 156, 13.3%) were obtained. We calculated the standardized mortality ratios (SMRs) to estimate the mortality gap between patients with PD and the general population. Stratified analyses of mortality rates by Axis I psychiatric comorbidity and sex were performed. RESULTS: Borderline PD (n = 391, 33.4%) was the dominant disorder among the subjects. The SMRs for all-cause mortality of PD alone, PD comorbid with non-substance use disorder(non-SUD), and PD comorbid with SUD were 4.46 (95% CI 1.94-6.98), 7.42 (5.99-8.85), and 15.96 (11.07-20.85), respectively. Among the causes of death, the SMR for suicide was the highest (46.92, 95% CI 34.29-59.56). The SMR for suicide in PD patients with comorbid SUD was unusually high (74.23, 95% CI 33.88-114.58). Women had a significant increase in suicide with an SMR of 59.00 (95% CI 37.89-80.11). Men had significant increase in SMRs for cardiovascular disease and gastrointestinal disease. CONCLUSIONS: We found significant synergistic effects of PD and SUD on mortality risk. A personality assessment should be mandatory in all clinical settings to prevent premature death and detect SUD early.

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.

Comparison of Subjective Experiences and Effectiveness of First-Generation Long-Acting Injectable Antipsychotics and Risperidone Long-Acting Injectables in Patients With Schizophrenia.

We conducted a cross-sectional study to compare the subjective experiences and clinical effects of first-generation long-acting injectable (FGA-LAI) antipsychotics with those of risperidone long-acting injectables (RIS-LAIs) in 434 schizophrenia patients. Compared with the RIS-LAI group, the patients treated with FGA-LAIs had a significantly longer duration of illness and LAI treatment and were older. Our results suggest that patients treated with FGA-LAI have more satisfactory subjective experiences compared with patients treated with RIS-LAI and that both FGA-LAI and RIS-LAI treatments can prevent relapses and hospitalization. Additional longitudinal studies determining the long-term benefits of RIS-LAI are warranted.

Quetiapine-associated leucopenia and thrombocytopenia: a case report.

BACKGROUND: There have been few reports regarding quetiapine-associated hematological effects other than white-blood-cell alteration. We present the first reported Han-Chinese case that developed leucopenia and thrombocytopenia after taking quetiapine. CASE PRESENTATION: We present a case of a person with a bipolar I disorder who experienced leucopenia and thrombocytopenia after taking 400 mg/day of quetiapine and 1000 mg/day of valproic acid for three and one-half months. The hematological toxicity abated upon the discontinuation of both drugs. However, due to the intolerable side effects of the replaced antipsychotic (haloperidol), and according to the patient's preference, we prescribed quetiapine and valproic acid again. There was a recurrence of leucopenia and a decreased platelet count by the sixth day. The adverse effects disappeared soon after we discontinued quetiapine, while keeping valproic acid treatment. CONCLUSION: Quetiapine-associated leucopenia and thrombocytopenia seems reversible but possibly fatal. Therefore, clinical practitioners should be aware of this adverse reaction.

Predictors for identifying patients with patellofemoral pain syndrome responding to femoral nerve mobilization.

OBJECTIVE: To identify the predictors for successful neurodynamic management in patients with patellofemoral pain syndrome. DESIGN: Prospective cohort, prediction rule study. SETTING: Hospital. PARTICIPANTS: Patients with patellofemoral pain syndrome (N=51) underwent clinical examination and measurement of physical parameters, including femoral slump test, lower-extremity alignment, flexibility and muscle strength, and functional level. INTERVENTION: Patients received 6 treatment sessions of femoral nerve mobilization within 2 weeks. MAIN OUTCOME MEASURES: Pain level during functional testing was assessed before and after the first and sixth session of treatment. Patients were then grouped into responder and nonresponder groups. Criteria for the responder group was a pain score decrease ≥50% or Global Rating Scale score ≥4. Chi-square and independent t tests were used to identify potential variables with a significance level of .10, and stepwise logistic regression was used to find predictors with a significance level of .05. RESULTS: Twenty-five patients responded to the initial treatment (immediate effect), and 28 patients responded after 6 sessions (longer-term effect). A positive femoral slump test was identified as the predictor for the immediate treatment effect. The prediction factors for the longer-term effect included responding to femoral nerve mobilization the first time and a bilateral difference in hip extension angles. Application of the clinical predictors improved the success rate to 90% for 1 treatment session and 93% for 6 treatment sessions. CONCLUSIONS: Clinicians could use the positive femoral slump test and a bilateral difference in hip extension angles during the femoral slump test to determine whether or not patients with patellofemoral pain syndrome might benefit from femoral nerve mobilization.

Incidence and Risk Profiles for Suicide Mortality in Patients With Schizophrenia Receiving Homecare Case Management in Taiwan.

Case management (CM)-based community therapy for patients with schizophrenia had little effect on reducing suicide mortality. We investigate the long-term suicide mortality outcome and associated risk factors in patients with schizophrenia receiving homecare (CM) in Taiwan. We enrolled a nationwide cohort of patients with schizophrenia who newly received homecare CM intervention (n = 13 317) between January 1, 2001, and December 31, 2015; their data were derived from Taiwan's National Health Insurance Research Database. We calculated the incidence rate of suicide methods. We examined the demographic and medical utilization profile for suicide and then performed a nested case-control study and multivariate regression to identify independent risk factors for suicide mortality. Among the 13 317 patients who received homecare CM intervention, 1766 died during the study period, of whom 213 died by suicide, which is the leading cause of unnatural death. Jumping from a high place, self-poisoning, and hanging were the top 3 suicide methods. Increased medical utilization was noted for both psychiatric and non-psychiatric services within 3 months of suicide mortality. Comorbidities of depressive disorder, nonspecific heart diseases, pneumonia, and gastrointestinal ulcers were identified as independent risk factors for suicide mortality. Suicide was the leading cause of unnatural mortality in patients with schizophrenia receiving homecare CM intervention in Taiwan. We noted the preferred suicide methods, high medical utilization, and comorbidities before suicide. Thus, we suggest that the CM team should assess lethal methods for suicide and ensure that patients adhere to psychiatry treatment for improving the current care model for this specified population.

Efficacy of neuromodulation on the treatment of fibromyalgia: A network meta-analysis.

OBJECTIVE: Several types of neuromodulation have been investigated for the treatment of fibromyalgia, but they show varied efficacy on pain, functioning, comorbid depression and comorbid anxiety. Whether some types of neuromodulation or some factors are associated with a better response also awaits clarification. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials to evaluate the efficacy of neuromodulation in patients with fibromyalgia. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and PsycINFO before March 2022. We employed a frequentist random-effects network meta-analysis. RESULTS: Forty trials involving 1541 participants were included. Compared with sham control interventions, several types of transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) were associated with significant reduction of pain, depression, anxiety, and improvement in functioning. Many significantly effective treatment options involve stimulation of the primary motor cortex or dorsolateral prefrontal cortex. CONCLUSION: We concluded that several types of rTMS, tDCS and tRNS may have the potential to be applied for clinical purposes.

Cluster analysis exploring the impact of childhood neglect on cognitive function in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder related to neurocognitive deficits. Exposure to childhood trauma is associated with worse cognitive performance. Different compositions of childhood trauma in BD and their impacts on cognition are rarely reported. METHODS: We used the Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognitive performance and the Chinese version of the Short Form of the Childhood Trauma Questionnaire (C-CTQ-SF) to assess childhood trauma experience among 55 euthymic BD patients. Cluster analysis was applied to dissect their childhood trauma experiences, which revealed three distinct clusters: a low trauma group, neglect-focus group, and multiple-trauma-experience group. We compared the cognitive function between the three clusters and used a generalized linear model to evaluate the impact of childhood neglect on cognitive domains. RESULTS: The neglect-focus cluster showed prominent exposures to physical and emotional neglect (41.8%). BD patients in this cluster performed worse in BAC-A compared with patients in the multiple trauma cluster, especially in working memory and processing speed. The neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002) after adjusting sex, age, education year, BMI and total psychotropic defined daily dose. CONCLUSIONS: Distinct patterns of childhood trauma experience are seen in BD patients and are related with different cognitive profiles. Early exposure of neglect-focus trauma was associated with the worst cognitive performance in current study. Further studies investigating the intensity of the neglect, as well as individual resilience and coping mechanisms in BD, are warranted.

Effects of early aquatic exercise intervention on trunk strength and functional recovery of patients with lumbar fusion: a randomized controlled trial.

This study investigated the effectiveness of an early aquatic exercise program on trunk muscle function and functional recovery of patients with lumbar fusion. Twenty-eight subjects were divided into two equal groups. Patients in the aquatic group performed two 60-min aquatic exercise sessions and three 60-min home exercise sessions per week for 6 weeks, whereas those in the control group performed five sessions of 60-min home exercises per week for 6 weeks. The primary outcomes were the Numerical Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI), and the secondary outcomes were Timed Up and Go Test (TUGT), trunk flexor and extensor muscle strength, lumbopelvic stability, and lumbar multifidus muscle thickness measured pre- and post-intervention. Compared with participants in the control group, those in the experimental group showed significant improvement in NPRS, ODI, trunk extensor strength, lumbopelvic control, lumbar multifidus muscle thickness, and relative change in multifidus muscle thickness (significant time by group interactions, P < 0.05). Participants in both groups showed significant time effects (P < 0.001) for TUGT and trunk flexor strength outcome. Aquatic exercise combined with home exercise was superior to home exercise alone in reducing pain, disability and improving muscle strength, lumbopelvic stability, and lumbar multifidus muscle thickness.

Clozapine and its protective effect on all-cause, natural, and suicide mortality in patients with schizophrenia: A nationwide cohort study in Taiwan.

AIM: Clozapine is indicated as the last-line agent for the treatment of refractory schizophrenia due to its side effects. This study included an Asian schizophrenia population and investigated the effect of clozapine on the risks of all-cause, natural, and suicide mortality. METHODS: This study included a large-scale schizophrenia inpatient cohort derived from the National Health Insurance Research Database from January 1, 2001, to December 31, 2019 (n = 43,025). Of them, we selected those who received clozapine (clozapine cohort, n = 5800). From those who never used clozapine, we selected two individuals for each patient in the clozapine cohort by matching by age, sex, and the year of the index date (ratio: 1:2, control cohort, n = 11,583). The clozapine and nonclozapine control cohorts together were defined as the study cohort (n = 17,383). Multivariate Cox proportional-hazards regression with a time-dependent model was performed to investigate the effect of individual antipsychotic agents on mortality. RESULTS: All individual first-generation antipsychotics were not associated with mortality risk. However, most individual second-generation antipsychotics exerted protective effects against all-cause and natural mortality. Furthermore, only clozapine and risperidone were significantly associated with a low risk of suicide mortality. Only clozapine exhibited a dose-dependent relationship with all-cause, natural, and suicide mortality. CONCLUSIONS: This study provides robust evidence supporting the strong protective effect of clozapine on all-cause, suicide, and natural mortality risks in an Asian population. Under close monitoring, clozapine use can be advantageous in patients with schizophrenia who are at a high risk of suicide.

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.

Specificity of the femoral slump test for the assessment of experimentally induced anterior knee pain.

OBJECTIVE: To assess the specificity of the femoral slump test (FST) when assessing experimentally induced anterior knee pain. DESIGN: Cross-sectional, exploratory study. SETTING: Research laboratory. PARTICIPANTS: Asymptomatic subjects (N=12; 6 men; 6 women) for the study. An experimental pain model was used to simulate anterior knee pain by injecting .25 mL of hypertonic saline solution (5% NaCl) into the medial infrapatellar fat pad. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The changes in pain intensity and diameter after applying the structure differential maneuver (neck flexion/extension) during the FST were recorded and analyzed. RESULTS: Results revealed that the structure differential maneuver of the FST did not alter the pain intensity or diameter in 9 (neck extension) and 10 (neck flexion) out of 12 subjects, which meant that the FST provided appropriate testing responses in 75% to 83% cases when the anterior knee pain did not originate in neural tissues. CONCLUSIONS: The FST had a specificity of more than .75 when detecting nerve mechanosensitivity problems of anterior knee pain.

Lower extremity kinematics in children with and without flexible flatfoot: a comparative study.

BACKGROUND: A high percentage of young children present with flatfeet. Although the percentage of those with flatfeet declines with age, about 15% of the population maintains a flat arch. A reduction in longitudinal arch height usually combines with excessive subtalar joint pronation and may be related to other musculoskeletal problems of the lower extremity kinetic chain. The purpose of this study is to describe and compare the lower extremity kinematics between children with normal arches and those with flexible flatfeet, with the intent of providing practical information for decision making when treating children with flexible flatfeet. METHODS: Twenty children with flexible flatfeet (years age mean (SD), 9.7 (0.9) years) and 10 children with normal arches (yeas age mean (SD), 9.6 (1.2) years) were included. Kinematic data (maximum and minimum angles, and movement range, velocity, and excursion) of the hip, knee and rearfoot were collected during walking using Liberty Electromagnetic Tracking System. Kinematic variables were compared between the normal arches and flexible flatfeet groups using repeated measures mixed effects ANOVA. RESULTS: Movement patterns at the hip, knee and ankle joints were similar between children with flexible flatfeet and with normal arches. The results of ANOVA showed no significant main effect or interaction in any of the kinematic variables (P ≥ 0.05). CONCLUSIONS: This study identified no kinematic adaptation during walking in children with flexible flatfoot. We suggested that future research should take the influence of the mid-foot and forefoot into consideration when examining lower extremity kinematics in children with flexible flatfoot.