OPRM1 A118G polymorphism modulating motor pathway for pain adaptability in women with primary dysmenorrhea.

Introduction: Primary dysmenorrhea (PDM) is a common condition among women of reproductive age, characterized by menstrual pain in the absence of any organic causes. Previous research has established a link between the A118G polymorphism in the mu-opioid receptor (OPRM1) gene and pain experience in PDM. Specifically, carriers of the G allele have been found to exhibit maladaptive functional connectivity between the descending pain modulatory system and the motor system in young women with PDM. This study aims to explore the potential relationship between the OPRM1 A118G polymorphism and changes in white matter in young women with PDM. Methods: The study enrolled 43 individuals with PDM, including 13 AA homozygotes and 30 G allele carriers. Diffusion tensor imaging (DTI) scans were performed during both the menstrual and peri-ovulatory phases, and tract-based spatial statistics (TBSS) and probabilistic tractography were used to explore variations in white matter microstructure related to the OPRM1 A118G polymorphism. The short-form McGill Pain Questionnaire (MPQ) was used to access participants' pain experience during the MEN phase. Results: Two-way ANOVA on TBSS analysis revealed a significant main effect of genotype, with no phase effect or phase-gene interaction detected. Planned contrast analysis showed that during the menstrual phase, G allele carriers had higher fractional anisotropy (FA) and lower radial diffusivity in the corpus callosum and the left corona radiata compared to AA homozygotes. Tractographic analysis indicated the involvement of the left internal capsule, left corticospinal tract, and bilateral medial motor cortex. Additionally, the mean FA of the corpus callosum and the corona radiata was negatively correlated with MPQ scales in AA homozygotes, but this correlation was not observed in G allele carriers. No significant genotype difference was found during the pain-free peri-ovulary phase. Discussion: OPRM1 A118G polymorphism may influence the connection between structural integrity and dysmenorrheic pain, where the G allele could impede the pain-regulating effects of the A allele. These novel findings shed light on the underlying mechanisms of both adaptive and maladaptive structural neuroplasticity in PDM, depending on the specific OPRM1 polymorphism.

Adaptive neuroplasticity in the default mode network contributing to absence of central sensitization in primary dysmenorrhea.

Introduction: Primary dysmenorrhea (PDM), the most prevalent gynecological problem among women of reproductive age, presents as a regular pattern of cyclic menstrual pain. The presence or absence of central sensitization (i.e., pain hypersensitivity) in cases of PDM is a contentious issue. Among Caucasians, the presence of dysmenorrhea is associated with pain hypersensitivity throughout the menstrual cycle, indicating pain amplification mediated by the central nervous system. We previously reported on the absence of central sensitization to thermal pain among Asian PDM females. In this study, functional magnetic resonance imaging was used to reveal mechanisms underlying pain processing with the aim of explaining the absence of central sensitization in this population. Methods: Brain responses to noxious heat applied to the left inner forearm of 31 Asian PDM females and 32 controls during their menstrual and periovulatory phases were analyzed. Results and discussion: Among PDM females experiencing acute menstrual pain, we observed a blunted evoked response and de-coupling of the default mode network from the noxious heat stimulus. The fact that a similar response was not observed in the non-painful periovulatory phase indicates an adaptive mechanism aimed at reducing the impact of menstrual pain on the brain with an inhibitory effect on central sensitization. Here we propose that adaptive pain responses in the default mode network may contribute to the absence of central sensitization among Asian PDM females. Variations in clinical manifestations among different PDM populations can be attributed to differences in central pain processing.

1,2,3,4,6-Penta-O-galloyl-d-glucose Interrupts the Early Adipocyte Lifecycle and Attenuates Adiposity and Hepatic Steatosis in Mice with Diet-Induced Obesity.

Phytochemicals that interrupt adipocyte lifecycle can provide anti-obesity effects. 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG) is a tannin with two isomers that occurs widely in plants and exhibits various pharmacological activities. The aim of the investigation is to comprehensively examine effects of PGG isomer(s) on adipocyte lifecycle and diet-induced obesity. Human mesenchymal stem cells (hMSC), 3T3-L1 fibroblasts, and H4IIE hepatoma cells were used to determine the effects of PGG isomers on cell viability and adipogenesis. Mice with diet-induced obesity were generated from male C57/BL6 mice fed with a 45% high fat diet. Oral administration of ß-PGG (0.1 and 5 mg/kg) lasted for 14 weeks. Viability was reduced by repeated PGG treatment in hMSC, preadipocytes, and cells under differentiation. PGG mainly induces apoptosis, and this effect is independent of its insulin mimetic action. In vivo, administration of ß-PGG attenuated shortening of the colon, hyperlipidaemia, fat cells and islet hypertrophy in DIO mice. Hepatic steatosis and related gene expression were improved along with glucose intolerance. Increased serum adiponectin, leptin, and glucagon-like peptide-1 levels were also observed. In conclusion, repeated PGG treatment interrupts the adipocyte lifecycle. PGG administration reduces adiposity and fatty liver development in DIO mice, and therefore, PGG could aid in clinical management of obesity.

Effects of boschnaloside from Boschniakia rossica on dysglycemia and islet dysfunction in severely diabetic mice through modulating the action of glucagon-like peptide-1.

BACKGROUND: Boschniakia rossica is a well-known traditional Chinese medicine for tonifying kidney and improving impotence. Boschnaloside is the major iridoid glycoside in this herb but therapeutic benefits for diabetes remained to be evaluated. HYPOTHESIS/PURPOSE: The current investigation aims to study the antidiabetic effect and the underlying pharmacological mechanisms. STUDY DESIGN AND METHODS: Receptor binding, cAMP production, Ins secretion, glucagon-like peptide 1 (GLP-1) secretion, and dipeptidyl peptidase-4 activity assays were performed. Therapeutic benefits of orally administrated boschnaloside (150 and 300 mg/kg/day) were evaluated using severely 12-week old female diabetic db/db mice (Hemoglobin A1c >10%). RESULTS: Oral treatment of boschnaloside for 4 weeks improved diabetic symptoms including fasting blood sugar, hemoglobin A1c, glucose intolerance, and Homeostatic Model Assessment of Ins Resistance, accompanied by circulating GLP-1active and adiponectin levels. In addition, bochnaloside treatment improved islet/ß cell function associated with an alteration of the pancreatic and duodenal homeobox 1 level. It was shown that boschnaloside interacted with the extracellular domain of GLP-1 receptor and enhanced glucose stimulated Ins secretion. Boschnaloside also augmented the insulinotropic effect of GLP-1. Finally, the presence of boschnaloside caused a reduction of dipeptidyl peptidase-4 activity while enhanced GLP-1 secretion from STC-1 cells. CONCLUSION: It appears that bochnaloside at oral dosage greater than 150 mg/kg/day exerts antidiabetic effects in vivo through modulating the action of GLP-1.

Plasmapheresis for hypertriglyceridemia: The association between blood viscosity and triglyceride clearance rate.

OBJECTIVES: Several factors in double filtration plasmapheresis (DFPP) were associated with triglyceride (TG) clearance rate. This study examines whether baseline whole blood viscosity was a predictor for efficient TG removal. METHODS: Adult subjects who receiving DFPP for hyperlipidemia in Taoyuan General Hospital from January 2015 to March 2018 were classified into efficient and inefficient TG removal according to TG removal rate ≥50% vs <50%. TG removal rate was defined as following formula: (pre-apheresis TG- post-apheresis TG)/pre-apheresis TG. Whole blood viscosity (WBV) was estimated by following equation: WBV = 0.12 × hematocrit +0.17 × (total protein -2.07). Univariate linear regression was used to assess the association between TG removal rate and WBV. Odds ratios (ORs) and 95% confidence interval (95%CI) for associations between variables and efficient TG removal were evaluated by logistic regression model to including univariate and multivariate adjustment. RESULTS: From a total of 66 subjects receiving DFPP, 37 subjects reached efficient TG removal. The difference in pre-apheresis TG levels, hematocrit, and WBV between efficient vs. inefficient TG removal groups was 4.1 vs 6.7 mmol/L; 43.1% vs 39.5%; and 6.0cP vs 5.cP (Ps <0.05). After multivariate adjustment, WBC was a significant predictor for efficient TG removal (ORs and 95% CI were 3.192 (1.300-7.838), P < 0.05). The correlation between WBV and extraction of TG was significant (r = -0.255, P = 0.039). CONCLUSION: Hyperviscosity reduced the efficiency of TG removal in those receiving DFPP.

The application of post-translational modification oriented serum proteomics to assess experimental diabetes with complications.

Proteome analysis of serum from type 2 diabetics with complications may lead to the discovery of diagnostic or prognostic biomarkers. To circumvent the principal barrier of serum proteomics, our investigation aimed to evaluate whether a study of post-translational modification enriched serum proteins could be valuable for the discovery of biomarkers or metabolic pathways related to type 2 diabetes pathogenesis. Type 2 diabetes was induced from high-fat diet fed Sprague Dawley rats with streptozotocin injection. Once diabetic status was confirmed, serum samples from either fasted healthy or diabetic rats were pooled and profiled by two-dimensional difference gel electrophoresis or comparative 2D electrophoresis after protein enrichments using immobilized metal ion, concanavalin A, and lentil affinity chromatography, respectively. Differential expressed proteins were identified and the associated networks were established by an Ingenuity Pathway Analysis. As a result, induced rats became severe diabetic and accompanied by hyperlipidemia, fatty liver, and glomerular hypertrophy. There were 3 total, 14 phosphorylated and 23 glycosylated protein targets differentially expressed. Proteins could be linked to HNF4A, HNF1A, and NFκB transcriptional factors and antigen presentation, humoral immune response, and inflammatory response pathways. Predicted organ toxicity in kidney, heart, and liver matched with our histopathological results. In conclusion, post-translational modification based serum protein enrichment could be a valuable approach to enhance the resolution of serum proteomics without depleting potentially valuable abundant proteins. Our results also indicated the potential association of the hepatic secretome and hepatocyte nuclear factors in the pathogenesis of type 2 diabetes and its complications.

Neuroimaging Studies of Primary Dysmenorrhea.

Primary dysmenorrhea (PDM), cyclic menstrual pain in the absence of pelvic anomalies, is one of the most common gynecological disorders in reproductive females. Classified as chronic pelvic pain syndrome, PDM encompasses recurrent spontaneous painful ("on") and pain-free ("off") states and is thus a good clinical model to study state- and trait-related changes of pain in the brain. In this chapter, we summarize state-of-the-art neuroimaging studies of primary dysmenorrhea from phenotype and endophenotype to genotype facets. Structural and functional brain alterations associated with primary dysmenorrhea are discussed.

Unaltered intrinsic functional brain architecture in young women with primary dysmenorrhea.

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen's d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.

The association between serum testosterone and mortality among elderly men on hemodialysis.

OBJECTIVES: This study examines the associations between total testosterone levels and dialysis mortality. METHODS: Elderly men who initiate hemodialysis in Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We reviewed clinical characteristics and biochemical data from start of dialysis and followed over a 5-year period after dialysis. Body composition parameters were assessed 3-6 months after dialysis. Skeletal muscle mass index (SMMI) was defined by skeletal muscle mass divided by squared height. We defined those with lowest tertile of testosterone values as low testosterone group. Adjusted hazard ratios (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival curves were evaluated by Cox hazards model and Kaplan-Meier method. The discriminative power of SMMI and testosterone levels was calculated according to the area under the curve and the receiver operating characteristic curve (AUROC). RESULTS: From a total of 137 elderly hemodialysis patients, the range of lowest, middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25-10.5 nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total testosterone levels at baseline were a significant predictor for mortality aHR(95% CI): 0.79 (0.70-0.91). The unadjusted and adjusted c-statistics of SMMI vs testosterone values to predict overall were 770 (0.688-0.852) vs 0.779 (0.691-0.866) and 855 (0.812-0.886) vs 0.812 (0.744-0.856) (Ps < .05), whereas the capacity of c-statistics was similar (χ2  = 0.143 and 2.709, Ps > .05). CONCLUSIONS: Total testosterone value was a predictor for mortality. It was noninferior to SMMI in predicting dialysis mortality.

Synergistic effects of aerobic exercise and cognitive training on cognition, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline: study protocol for a randomized controlled trial.

BACKGROUND: Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes. METHODS/DESIGN: Stroke survivors (n = 75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments. DISCUSSION: This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.

Association between obesity with low muscle mass and dialysis mortality.

BACKGROUND/AIM: To examine the association between body composition and dialysis mortality. METHODS: Adult patients who underwent haemodialysis in Taoyuan General Hospital from 2012 to 2016 were enrolled. We reviewed their baseline characteristics and followed up their treatment over 5 years after dialysis. Patients with body mass index >25 kg/m2 were defined as obese. High or low muscle mass were classified by skeletal muscle mass index (SMMI) based on consensus from Chinese population. All age-matched subjects were classified into four groups: (A) optimal; (B) obesity; (C) low muscle mass; and (D) obesity with low muscle mass. Adjusted hazard ratios for mortality and cumulative survival curves were evaluated by Cox proportional hazard model and Kaplan-Meier method. The discriminative power of SMMI was calculated according to the area under the curve and the receiver operating characteristic curve. RESULTS: From a total of 176 age-matched patients, the incidence rates of mortality for different groups were 3.7, 7.8, 10.3 and 16.5 per 1000 person-months. After adjusting for continuous variables, SMMI was independently associated with mortality. The difference between groups A and D was more significant in women than in men after multivariate adjustment (adjusted hazard ratios: 7.465 vs 1.682) (P = 0.035 and 0.553). The discriminative power of SMMI to predict 5-year mortality was 0.700 for men and 0.750 for women, and the best cut-off values were 11.1 and 8.4 kg/m2 CONCLUSIONS: Low muscle mass was associated with dialysis mortality. Obesity with low muscle mass was a predictor for dialysis mortality in women.

Associations among Serum Beta 2 Microglobulin, Malnutrition, Inflammation, and Advanced Cardiovascular Event in Patients with Chronic Kidney Disease.

OBJECTIVES: This study examines the associations among serum ß2 microglobulin (B2M), malnutrition, inflammation, and atherosclerosis (MIA) in those with chronic kidney disease (CKD). METHODS: CKD patients who were followed in Taoyuan General Hospital from 2009 to 2015 were enrolled. Demographic and biochemical data, including B2M and C-reactive protein (CRP) were reviewed. The participants were stratified according to B2M tertiles. Adjusted hazard ratios (AHRs) and cumulative survival curves for death and MIA syndrome were evaluated by Cox hazard model and Kaplan-Meier method. We also calculated the area under the curve for the receiver operating characteristic curve (AUROC). RESULTS: From a total of 312 CKD patients, mean follow-up time was 39.7 months. Compared to those with lowest tertile of B2M, the highest tertile group had lower serum albumin, hemoglobin, and estimated glomerular filtration rate. After multivariate adjustment, the associations among tertiles of B2M, death or dialysis, cardiovascular events (CVEs), and MIA syndrome remained significant. The AHRs for the highest tertile group in death or dialysis, CVEs, and MIA syndrome were 25.91 and 65.84 and 152.50(all Ps <0.05).The AUROC for B2M in death or dialysis, CVEs, and MIA syndrome were greater than that for creatinine. The best cut-off value of B2M for predicting death or dialysis, CVEs, and MIA syndrome were 5.39 mg/dL(sensitivity: 67.1%, specificity 62.5%), 4.21 mg/dL(sensitivity: 85.1%, specificity 52.1%), and 5.40 mg/dL(sensitivity: 79.7%, specificity 64.1%). CONCLUSIONS: In those with CKD, serum B2M was more sensitive than creatinine in predicting CVEs and MIA syndrome.

Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO.

BACKGROUND: The accumulation of soluble oligomeric amyloid-ß peptide (oAß) proceeding the formation of senile plaques contributes to synaptic and memory deficits in Alzheimer's disease. Our previous studies have indentified scavenger receptor A (SR-A), especially SR-A type I (SR-AI), as prominent scavenger receptors on mediating oAß clearance by microglia while glycan moiety and scavenger receptor cysteine-rich (SRCR) domain may play the critical role. Macrophage receptor with collagenous structure (MARCO), another member of class A superfamily with a highly conserved SRCR domain, may also play the similar role on oAß internalization. However, the role of N-glycosylation and SRCR domain of SR-AI and MARCO on oAß internalization remains unclear. RESULT: We found that oAß internalization was diminished in the cells expressing SR-AI harboring mutations of dual N-glycosylation sites (i.e. N120Q-N143Q and N143Q-N184Q) while they were normally surface targeted. Normal oAß internalization was observed in 10 SR-AI-SRCR and 4 MARCO-SRCR surface targeted mutants. Alternatively, the SRCR mutants at ß-sheet and α-helix and on disulfide bone formation obstructed receptor's N-glycosylation and surface targeting. CONCLUSION: Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAß internalization.

Incidence and mortality of postoperative acute kidney injury in non-dialysis patients: comparison between the AKIN and KDIGO criteria.

OBJECTIVES: This retrospective study determines whether the kidney disease: improving global outcomes (KDIGO) criteria are superior to acute kidney injury network (AKIN) criteria in detecting non-dialysis AKI events and predicting mortality in chronic kidney disease (CKD) patients after surgery. METHODS: Surgical patients who were admitted to the intensive care unit were enrolled. Non-dialysis AKI cases were defined using either KDIGO or AKIN creatinine criteria and stratified by CKD stages. The adjusted hazard ratios (AHRs) for in-hospital mortality are compared to those without AKI. The cumulative survival curves and the predictability for mortality are accessed by Kaplan-Meier method and calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve, respectively. RESULTS: From a total of 826 postoperative patients, the overall in-hospital mortality rate was 11.6% (96 cases) and that for AKI according to KDIGO and AKIN criteria was 30.0% (248 cases) and 31.0% (256 cases). The cumulative survival curve stratified by CKD and AKI stages were comparable between KDIGO and AKIN criteria. The discriminative power for mortality stratified by CKD stages for KDIGO and AKIN criteria are as followed: all subjects: 0.678 versus 0.670 (both ps <0.001); non-CKD: 0.800 versus 0.809 (both ps <0.001); early-stage CKD: 0.676 versus 0.676 (both ps <0.001); late-stage CKD: 0.674 versus 0.660 (ps were <0.001 and 0.003). CONCLUSION: The KDIGO criteria are superior to AKIN criteria in predicting mortality after surgery, especially in those with advanced CKD.

Associations among time-average mineral values, mortality and cardiovascular events in hemodialysis patients.

UNLABELLED: Mineral and bone disease (CKD-MBD), disorders of mineral metabolism, is associated with mortality and cardiovascular disease in dialysis patients. However, the associations among time average mineral values (P, Ca and PTH) and clinical outcomes are not well investigated. OBJECTIVES: This study examines the associations among mineral values and clinical outcomes from a single medical center. METHODS: Adult patients who initiate hemodialysis in Taoyuan General Hospital from 2008 to 2013 were enrolled. We examined these associations using baseline and time-average model. The clinical outcomes included mortality, major adverse cardiovascular events (MACE) and cardiovascular events. We also examined the association between achieve K/DOQI guidelines' targets and clinical outcomes. RESULTS: From a total of 284 hemodialysis patients, none of the baseline mineral values is associated with mortality and cardiovascular event, except hyperphosphatemia. Compared to patients achieved K/DOQI guidelines' targets, time average hyperphosphatemia is associated with MACE and first cardiovascular event [the adjusted hazard ratios (AHRs) are 6.343 and 3.278); whereas time average hypercalcemia is associated with MACE marginally (the AHR is 5.964). None of above clinical outcomes is related to hyperparathyroidism. The AHRs for mortality in those who only met PTH targets and none of the mineral value targets are 1.73 and 1.74, whereas the AHRs for cardiovascular events in those who met only Ca, only PTH, and none of the targets are 1.73, 1.81 and 2.54 (all ps < 0.05). CONCLUSION: Time-average phosphate is associated with cardiovascular events after initiation of dialysis. Among mineral values, serum phosphate is still the strongest predictor for mortality and cardiovascular events.

Effectiveness of hyaluronic acid administration in treating adhesive capsulitis of the shoulder: a systematic review of randomized controlled trials.

INTRODUCTION: Adhesive capsulitis (AC) of the shoulder presents with an insidious onset of pain and progressive limitation of shoulder movement. OBJECTIVES: To investigate whether intra-articular hyaluronic acid (HA) administration alone is superior to conventional therapies and whether the addition of intra-articular HA administration to conventional therapies improves clinical outcomes in patients with AC. METHODS: The PubMed, EMBASE, CINAHL, and Cochrane Library electronic databases were searched without language restrictions in July 2014 with a priori defined inclusion and exclusion criteria. RESULTS: Four randomized controlled trials (273 participants, 278 shoulders) were included in this review. Two trials compared intra-articular HA administration with conventional therapies and 2 trials evaluated intra-articular HA administration as an addition to conventional therapies. Pain and shoulder function/disability outcomes in the HA injection group were not superior to those achieved in the conventional therapy groups. No significant differences in pain or shoulder function/disability outcomes were noted between the groups with and without adjunctive HA administration. CONCLUSIONS: Intra-articular HA administration alone is not superior to conventional AC treatments, and the addition of intra-articular HA administration to conventional therapies does not provide significant added benefits. HA administration in AC patients who are receiving conventional therapies should be evaluated to avoid unnecessary medical expenditure.

Association of brain-derived neurotrophic factor gene Val66Met polymorphism with primary dysmenorrhea.

Primary dysmenorrhea (PDM), the most prevalent menstrual cycle-related problem in women of reproductive age, is associated with negative moods. Whether the menstrual pain and negative moods have a genetic basis remains unknown. Brain-derived neurotrophic factor (BDNF) plays a key role in the production of central sensitization and contributes to chronic pain conditions. BDNF has also been implicated in stress-related mood disorders. We screened and genotyped the BDNF Val66Met polymorphism (rs6265) in 99 Taiwanese (Asian) PDMs (20-30 years old) and 101 age-matched healthy female controls. We found that there was a significantly higher frequency of the Met allele of the BDNF Val66Met polymorphism in the PDM group. Furthermore, BDNF Met/Met homozygosity had a significantly stronger association with PDM compared with Val carrier status. Subsequent behavioral/hormonal assessments of sub-groups (PDMs = 78, controls = 81; eligible for longitudinal multimodal neuroimaging battery studies) revealed that the BDNF Met/Met homozygous PDMs exhibited a higher menstrual pain score (sensory dimension) and a more anxious mood than the Val carrier PDMs during the menstrual phase. Although preliminary, our study suggests that the BDNF Val66Met polymorphism is associated with PDM in Taiwanese (Asian) people, and BDNF Met/Met homozygosity may be associated with an increased risk of PDM. Our data also suggest the BDNF Val66Met polymorphism as a possible regulator of menstrual pain and pain-related emotions in PDM. Absence of thermal hypersensitivity may connote an ethnic attribution. The presentation of our findings calls for further genetic and neuroscientific investigations of PDM.

Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption.

Tension pneumocephalus as a complication of hyperbaric oxygen therapy in a patient with chronic traumatic brain injury.

Although hyperbaric oxygen therapy has not been accepted as a standard therapy for traumatic brain injuries, it has been used, along with rehabilitative exercises, for traumatic brain injuries, and the standard protocol has a low risk of complications. We report a case of chronic traumatic brain injury that progressed to tension pneumocephalus after hyperbaric oxygen therapy. The patient was a 25-yr-old man who presented with left occipital bone fracture and subarachnoid and subdural hemorrhage after being hit by a car. He underwent craniectomy to remove the hematoma and cerebrospinal fluid diversion with a ventriculoperitoneal shunt for the treatment of hydrocephalus. Fifteen months after the trauma, the patient received hyperbaric oxygen therapy to promote functional recovery. Tension pneumocephalus developed after the first session of hyperbaric oxygen therapy, and immediate burr hole drainage followed by ligation of the ventriculoperitoneal shunt was performed. The patient's consciousness recovered gradually, and he was discharged home. We suggest that patients with unrepaired skull base fracture and cerebrospinal fluid diversion should be carefully evaluated before receiving hyperbaric oxygen therapy.