Versatile Effects of GABA Oolong Tea on Improvements in Diastolic Blood Pressure, Alpha Brain Waves, and Quality of Life.

Emerging evidence has demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human study was to investigate the therapeutic effects of daily GO tea consumption on improvements in blood pressure, relaxation-related brain waves, and quality of life (QOL) over a period of 28 consecutive days. Total polyphenols, major catechins, and free amino acids were analyzed via an HPLC assay. Changes in heart rate, blood pressure, α brain waves (index of relaxation), and the eight-item QOL score were investigated on days 0, 7, 14, 21, and 28. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, the daily consumption of GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p < 0.05 for both). For participants with pre-hypertension, GO tea could effectively reduce heart rate and systolic and diastolic blood pressure on day 28 (p < 0.05). At the end of the study, incremental changes in alpha brain waves and QOL scores were also demonstrated (p < 0.05 for both). This study suggests that GO tea might potentially serve as a natural source for alternative therapy to improve blood pressure, stress relief, and QOL.

Cerebral Microbleed Burdens in Specific Brain Regions Are Associated With Disease Severity of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 mutations, is characterized by recurrent ischemic strokes and progressive cognitive decline. It remains unclear whether cerebral microbleeds (CMBs) can serve as a surrogate marker for disease progression in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. We aimed to investigate the CMB burdens in NOTCH3 mutation carriers at different disease stages and test their associations with cognitive performance. Methods and Results Forty-nine individuals carrying NOTCH3 cysteine-altering mutations received brain magnetic resonance imaging with T1-weighted and susceptibility-weighted images. Whole brain images were segmented into 14 regions using Statistical Parametric Mapping and FreeSurfer software, and semiautomatic methods were used to locate and quantify the number and volume of CMBs. In our study participants, the median of CMB counts was 13, with a wide individual variation (range, 0-286). CMBs were most frequently present in thalamus, followed by temporal lobe. In the whole brain, the CMB counts and CMB volume ratios (ie, CMB volume divided by the volume of corresponding brain region) gradually increased as the disease advanced. CMB counts in the thalamus and temporal and frontal lobes increased more rapidly than other brain regions as disease progressed. There were significant associations between Mini-Mental State Examination scores and CMB counts in the frontal lobe, temporal lobe, and pons. Conclusions CMBs may have an influential role in the clinical manifestations of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CMB burdens and their distribution in different brain regions may be capable to serve as a disease marker for monitoring the disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Increased risk for venous thromboembolism among patients with concurrent depressive, bipolar, and schizophrenic disorders.

OBJECTIVE: The study aim was to investigate the risk of venous thromboembolism (VTE) in patients with concurrent depressive, bipolar, and schizophrenic disorders. METHODS: A population-based cohort study was conducted in which information regarding psychiatric illnesses and medical comorbidities in 29,467 patients with concurrent depressive, bipolar, and schizophrenic disorders and regarding 117,868 controls were extracted. We compared the incidence of VTE between the study and control cohorts. Cox proportional hazard regression models were used to analyze the risk of VTE after adjusting for potential confounders, including sex, age, and comorbidities. RESULTS: Compared with the control cohort, the overall study cohort had a 2.995-fold higher adjusted hazard ratio (aHR) for development of deep vein thrombosis (DVT) and a 2.591-fold higher aHR for development of pulmonary embolism (PE). Moreover, patients with depressive, bipolar, and schizophrenic disorders all exhibited higher aHRs for development of both DVT and PE. CONCLUSION: The relative risks of DVT and PE were higher in patients with concurrent depressive, bipolar, and schizophrenic disorders than those of the general population. Further research is needed to develop effective prevention strategies for different patient populations.

Increased prevalence and risk of anxiety disorders in adults with tinnitus: A population-based study in Taiwan.

OBJECTIVE: Tinnitus is a common disorder that may cause psychological distress and anxiety. The aim of this study was to investigate the association between anxiety disorders (ADs) and tinnitus in a large population. METHOD: We conducted a cross-sectional study using the National Health Insurance Research Database in Taiwan. Study subjects included 14,772 patients with tinnitus and 709,963 people in the general population who sought treatment in 2005. Distributions in ADs, age, sex, and medical comorbidities were compared between groups using chi-squared tests. Multivariate logistic regression models adjusted for age, sex, and medical comorbidities were used to analyze the association between tinnitus and ADs. RESULTS: Prevalence of ADs in tinnitus and general population groups was 3.9% and 1.5%, respectively, and this difference was significant (P<0.001). Diabetes mellitus, hypertension, hyperlipidemia, concussion or head injury, Meniere's disease, sensorineural hearing impairment, renal disease, coronary artery disease, and cerebrovascular disease were significantly more prevalent in the tinnitus group (all P-values<0.001). Multivariate logistic regression model demonstrated that patients with tinnitus were significantly associated with increased risk of ADs (adjusted OR=1.99; 95% CI=1.81-2.19; P<0.001). CONCLUSION: Because the risk of ADs was significantly higher in patients with tinnitus than in the general population, physicians should be aware of the importance of psychological factors in tinnitus management.

Changes in functional connectivity of pain modulatory systems in women with primary dysmenorrhea.

Menstrual pain is the most prevalent gynecological complaint, and is usually without organic cause (termed primary dysmenorrhea, PDM). The high comorbidity in the later life of PDM with many functional pain disorders (associated with central dysfunction of pain inhibition, eg, fibromyalgia) suggests possible maladaptive functionality of pain modulatory systems already occurred in young PDM women, making them vulnerable to functional pain disorders. Periaqueductal gray (PAG) matter functions as a critical hub in the neuraxis of pain modulatory systems; therefore, we investigated the functional connectivity of PAG in PDM. Forty-six PDM subjects and 49 controls received resting-state functional magnetic resonance imaging during menstruation and periovulatory phases. The PAG of PDM subjects exhibited adaptive/reactive hyperconnectivity with the sensorimotor cortex during painful menstruation, whereas it exhibited maladaptive hypoconnectivity with the dorsolateral prefrontal cortex and default mode network (involving the ventromedial prefrontal cortex, posterior cingulate cortex, or posterior parietal cortex) during menstruation or periovulatory phase. We propose that the maladaptive descending pain modulatory systems in PDM may underpin the central susceptibility to subsequent development of various functional disorders later in life. This hypothesis is corroborated by the growing body of evidence that hypoconnectivity between PAG and default mode network is a coterminal to many functional pain disorders.

Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: a systematic review and meta-analysis.

Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13-0.51; P=0.0001), 0.40 (95% CI 0.26-0.63; P<0.0001), and 0.21 (95% CI 0.09-0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29-0.70; P=0.0004) and 0.41 (95% CI 0.20-0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09-1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.

Effects of recombinant adenovirus-mediated hypoxia-inducible factor-1alpha gene on proliferation and differentiation of endogenous neural stem cells in rats following intracerebral hemorrhage.

OBJECTIVE: To investigate the effects of adenovirus (Ad)-mediated hypoxia-inducible factor-1alpha (HIF-1α) gene on proliferation and differentiation of endogenous neural stem cells (NSCs) in rats following intracerebral hemorrhage (ICH) and the underlying mechanisms. METHODS: A total of 120 specific pathogen-free, adult, male Sprague-Dawley rats were included in this study. After establishment of ICH models in rats, PBS, Ad, or Ad-HIF-1α was administered via the ischemic ventricle. On the 1st, 7th, 14th, 21st and 28th d after ICH, rat neurological deficits were scored, doublecortin (DCX) expression in the subventricular zone cells was detected by immunohistochemical staining, and 5-bromo-2'-deoxyuridine (BrdU)-, BrdU/DCX-, and BrdU/glial fibrillary acidic protein-positive cells in the subventricular zone were counted using immumofluorescence method among PBS, Ad, and Ad-HIF-1α groups. RESULTS: On the 7th, 14th, 21st and 28th d after ICH, neurological deficit scores in the Ad-HIF-1α group were significantly lower than in the PBS and Ad groups (P<0.05). In the Ad-HIF-1α group, DCX expression was significantly increased on the 7th d, peaked on the 14th d, and then gradually decreased. In the Ad-HIF-1α group, BrdU-positive cells were significantly increased over time course, and significant difference in BrdU-positive cell counts was observed when compared with the PBS and Ad groups at each time point (P<0.01 or 0.05). On the 7th, 14th, 21st and 28th d after ICH, the number of DCX-, BrdU-, BrdU/DCX-, and BrdU/DCX-positive cells in the Ad-HIF-1α group was significantly greater than in the PBS and Ad groups (P<0.05). CONCLUSIONS: HIF-1α gene can promote the proliferation, migration and differentiation of endogenous neural stem cells after ICH, thereby contributing to neurofunctional recovery after ICH.

Dimensional complexity of neuromagnetic activity reduced during finger movement of greater difficulty.

OBJECTIVE: We investigated the variation in dimensionality (D2) of neuromagnetic activity over the primary sensorimotor cortex (SM1) in healthy adults performing motor tasks of different difficulty. METHODS: Magnetoencephalography (MEG) was used to record neuromagnetic activity during self-paced, brisk unimanual finger extension at a rate of 1 and 2 Hz using the index finger of the dominant and non-dominant hands in 16 healthy subjects. Motor task difficulty was rated by the relative difference in time measurement between 1 and 2 Hz finger movements of both hands. The relative difference in dimensionality of SM1 activity was calculated by subtracting the D2 value in 2 Hz movement from that in 1 Hz one within subjects. RESULTS: Simple regression analyses show a significantly negative relationship between the relative dimensional complexity and the relative motor task difficulty in the contralateral SM1 for the left- (p<0.05), but not the right- (p=0.447) hand movement. CONCLUSIONS: The present data suggest that a motor task of greater difficulty may engender a reduction of simultaneously active quasi-independent neuronal generators in the contralateral SM1 underpinned by stronger neuronal connectivity of a relatively low dimensionality. SIGNIFICANCE: The decrease in dimensional complexity of MEG activity associated with a motor task of greater difficulty gives new insights to motor control strategy.

Effects of hypobaric hypoxia on adenine nucleotide pools, adenine nucleotide transporter activity and protein expression in rat liver.

AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a hypobaric chamber simulating 5,000 m high altitude for 23 h every day for 0 (H0), 1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP, ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS: Compared with H0 group, intra-mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group reached the lowest point (70.6%) (P<0.01) when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in H0 group. In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups. Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly lower than that in H0 group, whereas H1 group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P<0.01) when compared to H0 group. ANT activity in H30 group was higher than in H15 group, but still lower than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0 group decreased significantly, which in H5 group was the lowest, being 27.1% of that in H0 group (P<0.01). ANT protein level in H30 group was higher than in H15 group, but still lower than in H0 group. CONCLUSION: Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure. The lower level of extra-mitochondrial ATP may be related to the decrease of ANT activity during hypoxia exposure.

ICA-based spatiotemporal approach for single-trial analysis of postmovement MEG beta synchronization.

The extraction of event-related oscillatory neuromagnetic activities from single-trial measurement is challenging due to the non-phase-locked nature and variability from trial to trial. The present study presents a method based on independent component analysis (ICA) and the use of a template-based correlation approach to extract Rolandic beta rhythm from magnetoencephalographic (MEG) measurements of right finger lifting. A single trial recording was decomposed into a set of coupled temporal independent components and corresponding spatial maps using ICA and the reactive beta frequency band for each trial identified using a two-spectrum comparison between the postmovement interval and a reference period. Task-related components survived dual criteria of high correlation with both the temporal and the spatial templates with an acceptance rate of about 80%. Phase and amplitude information for noise-free MEG beta activities were preserved not only for optimal calculation of beta rebound (event-related synchronization) but also for profound penetration into subtle dynamics across trials. Given the high signal-to-noise ratio (SNR) of this method, various methods of source estimation were used on reconstructed single-trial data and the source loci coherently anchored in the vicinity of the primary motor area. This method promises the possibility of a window into the intricate brain dynamics of motor control mechanisms and the cortical pathophysiology of movement disorder on a trial-by-trial basis.

Healthy-side dominance of cortical neuromagnetic responses in sudden hearing loss.

Previous brain imaging and mapping studies have reported findings indicating functional reorganization in the central auditory pathways of patients with profound unilateral hearing loss. This study reports for the first time to our knowledge, using a whole-head neuromagnetometer with monaural stimulation of both intact and affected ears, a pattern of healthy-side dominance for cortical neuromagnetic responses in adult patients in the early stage of idiopathic sudden sensorineural hearing loss, and a pattern of contralateral dominance is verified in controls.