Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder

ObjectiveAdult bipolar disorder (BP) has been associated with lifetime history of physical and sexual abuse. However, there are no reports of the prevalence of abuse in BP youth. The objective of this study was to examine the prevalence and correlates of physical and/or sexual abuse among youth with BP spectrum disorders.MethodsFour hundred forty-six youths, ages 7 to 17 years (12.7 ± 3.2), meeting DSM-IV criteria for BP-I (n = 260), BP-II (n = 32) or operationalized definition of BP-NOS (n = 154) were assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children—Present and Lifetime version (K-SADS-PL). Abuse was ascertained using the K-SADS.ResultsTwenty percent of the sample experienced physical and/or sexual abuse. The most robust correlates of any abuse history were living with a non-intact family (OR = 2.6), lifetime history of posttraumatic stress disorder (PTSD) (OR = 8.8), psychosis (OR = 2.1), conduct disorder (CD) (OR = 2.3), and first-degree family history of mood disorder (OR = 2.2). After adjusting for confounding demographic factors, physical abuse was associated with longer duration of BP illness, non-intact family, PTSD, psychosis, and first-degree family history of mood disorder. Sexual abuse was associated with PTSD. Subjects with both types of abuse were older, with longer illness duration, non-intact family, and greater prevalence of PTSD and CD as compared with the non-abused group.LimitationsRetrospective data. Also, since this is a cross-sectional study, no inferences regarding causality can be made.ConclusionSexual and/or physical abuse is common in youth with BP particularly in subjects with comorbid PTSD, psychosis, or CD. Prompt identification and treatment of these youth is warranted.     

TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients

BackgroundToll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response.ObjectivesTo analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients.Study designWe performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate^® assay with VeraCode^®. The outcome variables were early virologic response (EVR) and sustained virologic response (SVR).ResultsIn a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039).ConclusionsOur study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients.     

The validity of the severity-psychosis hypothesis in depression

BackgroundPsychotic depression (PD) is classified as a subtype of severe depression in the current diagnostic manuals. Accordingly, it is a common conception among psychiatrists that psychotic features in depression arise as a consequence of depressive severity. The aim of this study was to determine whether the severity of depressive and psychotic symptoms correlate in accordance with this “severity–psychosis” hypothesis and to detect potential differences in the clinical features of PD and non-psychotic depression (non-PD).MethodsQuantitative analysis of Health of the Nation Outcome Scales (HoNOS) scores from all patients admitted to a Danish general psychiatric hospital due to a severe depressive episode in the period between 2000 and 2010 was performed.ResultsA total of 357 patients with severe depression, of which 125 (35%) were of the psychotic subtype, formed the study sample. Mean HoNOS scores at admission differed significantly between patients with non-PD and PD on the items hallucinations and delusions (non-PD = 0.33 vs. PD = 1.37, p < 0.001), aggression (non-PD = 0.20 vs. PD = 0.36, p = 0.044) and on the total score (non-PD = 10.55 vs. PD = 11.87, p = 0.024). The HoNOS scores on the two items “depression” and “hallucinations and delusions” were very weakly correlated.LimitationsDiagnoses were based on normal clinical practice and not formalized research criteria.ConclusionsThe symptomatology of PD and non-PD differs beyond the mere psychosis. Furthermore, severity ratings of depressive and psychotic symptoms are very weakly correlated. These findings offer further support to the hypothesis stating that the psychotic- and non-psychotic subtypes of depression may in fact be distinct clinical syndromes.     

PPARα polymorphisms as risk factors for dyslipidemia in a Brazilian population

Background and aimsPeroxisome proliferator-activated receptor α is a nuclear receptor involved in the regulation of several biochemical pathways. Polymorphisms within its gene have been associated with several metabolic traits. We aimed to investigate the association of L162V and Intron 7G > C polymorphisms with serum level markers and common morbidities affecting an older adult/elderly cohort from Cuiaba City, Mato Grosso State, Brazil, as well as to compare the results with a previously studied population from São Paulo City, Brazil.Methods and resultsThe studied population consisted of 570 subjects from Cuiaba City, Brazil, who were subjected to clinical interviews and blood collection for laboratory examinations and DNA extraction. Dyslipidemia was defined when participants were taking oral hypolipemiants or those with total cholesterol above 200 mg/dL, HDL-c below 40 mg/dL, LDL-c above 130 mg/dL and TG above 150 mg/dL. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) was used for polymorphism genotyping. Individual polymorphism and haplotype data were available for analyses. In the studied sample, allele frequencies were 0.052 and 0.292 for 162V and Intron 7C, respectively. In brief, 162V allele was associated with dyslipidemia (p = 0.025), and after correction for alcohol consumption and waist-to-rip ratio, a tendency of association could still be observed (p = 0.050). In addition, Intron 7C allele was associated with dyslipidemia even after correction for the same variables (p = 0.029). When compared to our previous study from São Paulo, we found some divergences regarding these results, which may be explained by differences between the two populations. Haplotype association analyses revealed an association between L/C haplotype and dyslipidemia (p = 0.021) and between V/C haplotype and lower LDL-c levels when compared to L/G haplotype (p = 0.044).ConclusionThese results may help to clarify the role of PPARα gene in lipid and lipoprotein metabolism and the evaluation of its polymorphisms and haplotypes as being characterized as genetic risk factors for metabolic disturbances.     

CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population

BackgroundSingle nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).MethodsGenotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C>G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.ResultsCRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA–2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA–2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.ConclusionsCRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.     

A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men

This study assessed associations between the CYP4F2 gene and myocardial infarction (MI), using a haplotype-based case-control study of 234 MI patients and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of rs2108622 and frequency of the T-C-G haplotype were significantly higher, and frequency of the T-C-A haplotype was significantly lower for MI patients than for controls (P = 0.006, P = 0.001 and P = 0.002, respectively).     

Association between polymorphisms in catechol‐O‐methyltransferase (COMT) and cocaine‐induced paranoia in European‐American and African‐American populations

Catechol‐O‐methyltransferase (genetic locus, COMT) is a major enzyme involved in catecholamine metabolism and has been associated with numerous psychiatric phenotypes. We studied COMT SNPs and haplotypes in cocaine‐induced paranoia (CIP) in African‐American (AA) and European‐American (EA) populations. We genotyped 17 SNPs across the COMT locus in 319 AA pedigrees (848 individuals) and 302 EA pedigrees (707 individuals). Family‐controlled association analyses were conducted using FBAT. We found SNP rs737865 to be nominally significantly associated in the AA family population (P = 0.05). In EAs, the best‐known marker, rs4680 (Val158Met), was nominally significant in additive models (P = 0.03). SNP rs174696 also showed nominal significance in additive models (P = 0.02). We considered the three SNPs (rs737866–rs4680–rs174696) together in haplotype analysis in both family populations, using HBAT. The A–A–T haplotype was significantly associated with CIP in EAs (Z = 2.845; P = 0.0044, global P = 0.020). We then studied COMT SNPs in an additional 738 AA and 404 EA unrelated cocaine dependent individuals with and without paranoia. The A–A–T haplotype was significantly associated to CIP in the AA unrelated population (P = 0.0015). Two haplotypes, A–G–C and A–A–C, were significant in the EA unrelated population (P = 0.001 and 0.0003). We also identified rs4680 and three other SNPs, rs933271, rs5993883, and rs740603, as potentially functional variants, as predicted by a signature of positive selection in unrelated EAs and AAs. Based on our robust family‐controlled and unrelated‐affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine. © 2011 Wiley‐Liss, Inc.     

Association of nitric oxide synthase gene polymorphisms (−786T>C, 4a4b, 894G>T) with primary ovarian insufficiency in Korean women

ObjectivesThe aim of our study was to investigate whether the endothelial nitric oxide synthase (eNOS) gene polymorphisms ?786T>C, 4a4b, and 894G>T that affect nitric oxide (NO) generation confer a risk for primary ovarian insufficiency (POI) in Korean women.Study designWe genotyped 136 POI patients and 236 controls among Korean women for the three single nucleotide polymorphism sites with PCR-RFLP analysis. Differences in the eNOS ?786T>C (rs2070744), 4a4b (rs61722009), and 894G>T (rs1799983) genotype frequencies between patients and controls were compared, and odds ratios and 95% confidence intervals were determined as a measure of the strength of the association between the genotypes and POI.ResultsThe POI patients had significantly decreased frequencies of the eNOS 894GT and ?786TT/894GT genotypes (P = 0.025 and 0.027, respectively). However, the significant association between these eNOS polymorphisms and POI disappeared after adjustment for multiple comparisons (adjusted P = 0.075 and 0.081, respectively). The eNOS ?786T/894G haplotype is more frequent in patients than controls (P = 0.030), whereas the ?786T/894T haplotype was less frequent in patients (P = 0.031). The associations between ?786/894 haplotypes and POI were confirmed by permutation tests. We did not find associations between the eNOS ?786T>C or 4a4b polymorphisms and POI.ConclusionsOur data suggest that the eNOS ?786T/894T haplotype is associated with a decreased POI risk, and we postulate that the eNOS ?786T/894T haplotype may confer less risk on POI occurrence by reducing pathologically increased NO generation by eNOS in POI. Further study is warranted to elucidate the effect of the eNOS 894G>T polymorphism and POI occurrence.     

Genetic variation in Micro-RNA genes of host genome affects clinical manifestation of symptomatic Human Cytomegalovirus infection

BackgroundMicro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection.MethodologyHCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing.ResultsWe observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR = 3.11, p = 0.009 and adjusted OR = 3.25, p = 0.007), rs11614913 (crude OR = 3.20, p = 0.006 and adjusted OR = 3.48, p = 0.004) and rs3746444 (crude OR = 4.91, p = 0.002 and adjusted OR = 5.28, p = 0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444).ConclusionsThese results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection.     

Clinical and biological monitoring of nutritional status in severe burns

Aim of the studyBurn patients are subject to hypermetabolism and catabolic states. Aim was to evaluate our current practice in nutrition.MethodsTwenty-one severely burned patients were prospectively included during three months period. Body weight was measured at least two times in a week during all stay in burn ICU. Biological markers of inflammation (C-reactive protein, CRP) and nutrition (prealbumin) were performed weekly. Protocol included early nasogastric feeding, tolerated gastric stasis less than 250 mL at four hours nasogastric aspirations, caloric target value of 40 Kcal/kg per day and measurement of total daily calorie intakes.ResultsPatient demographics showed a mean percent total body surface burn of 51.1 ± 27 % (range 20–90), age of 38.7 ± 13.1 years (range 18–67) and 57.3 % of smoke inhalation. All patients were ventilated and 19 patients survived. Length of stay was 75.7 ± 47 days (range 22–184). Patients received only 58.9 ± 10 % of calorie intakes recommended by French burn society. Loss of body mass was 15.2 ± 9 kg (range 3–31) or 19.1 ± 10 % of admission weight (range 5–37). Erosion of body mass was not correlated with burned surface (p = 0.08), calorie intakes (p = 0.26), smoke inhalation (p = 0.46), lengths of stay (p = 0.53), lengths of ventilation (p = 0.08) or nutrition (p = 0.12), days of antibiotic (p = 0.72), number of dressing changes (p = 0.6) or surgery (p = 0.64). Biological parameters showed CRP decreasing and prealbumin improving values.ConclusionNew strategies of nutrition are necessary to improve outcome and reduce body mass loss in burns.     

Detection of human herpesvirus-6 variants in pediatric brain tumors: Association of viral antigen in low grade gliomas

BackgroundHuman herpesvirus-6 (HHV-6) has been associated with a diverse spectrum of central nervous system (CNS) diseases and reported glial tropism.ObjectiveTo determine if HHV-6 is present in a series of pediatric brain tumors.Study designPediatric gliomas from 88 untreated patients represented in a tissue microarray (TMA) were screened for HHV-6 by nested polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemistry (IHC) and compared to non-glial tumors (N = 22) and control brain (N = 32). Results were correlated with tumor grade and overall survival.ResultsHHV-6 U57 was detected by nested PCR in 68/120 (57%) tumors and 7/32 (22%) age-matched non-tumor brain (P = 0.001). HHV-6 U31 was positive in 73/120 (61%) tumors and 11/32 (34%) controls (P = 0.019). Seventy-two percent (43/60) of tumors were HHV-6 Variant A. HHV-6 U57 was confirmed by ISH in 83/150 (54%) tumors and 10/32 (31%) controls (P = 0.021), revealing a non-lymphocytic origin of HHV-6. HHV-6A/B gp116/64/54 late antigen was detected by IHC in 50/124 (40%) tumors and 6/32 (18%) controls (P = 0.013). Interestingly, 58% of low grade gliomas (N = 67) were IHC positive compared to 19% of high grade gliomas (N = 21, P = 0.002) and 25% of non-gliomas (N = 36, P = 0.001). HHV-6A/B gp116/64/54 antigen co-localized with glial fibrillary acidic protein, confirming the astrocytic origin of antigen. Overall, there was no primary association between HHV-6A/B gp116/64/54 antigen detection and survival (P = 0.861).ConclusionsWe provide the first reported series of HHV-6 detection in pediatric brain tumors. The predominance of HHV-6 in glial tumors warrants further investigation into potential neurooncologic disease mechanisms.     

The effect of relaxin on the female anterior cruciate ligament: Analysis of mechanical properties in an animal model

BackgroundThe peptide hormone relaxin, found in pregnant and non-pregnant females, has been shown to have collagenolytic effects on ligamentous tissue. Relaxin receptors have recently been identified on the human female anterior cruciate ligament (ACL). Relaxin may affect the load bearing properties of the female ACL and contribute to non-contact ACL injuries.HypothesisThe administration of recombinant relaxin ± estrogen will lead to a significant decrease in ACL integrity in the guinea pig model.Study designControlled laboratory study.MethodsAdult female guinea pigs were divided into three experimental groups. Group 1 (n = 4) was administered only 20 µg/h of recombinant porcine relaxin for 3 weeks. Group 2 (n = 4) was administered 20 µg/h of recombinant porcine relaxin and 5 µg/h of estradiol for 3 weeks. Group 3 (n = 4) served as both a normal control before surgical transection of the ACL and a positive ACL tear control after transection. All hormones were administered using separate implanted osmotic pumps. ACL laxity was tested by implanting radio-opaque markers in the femur and tibia of each leg. After applying a standard anterior force (22 N), the distance between markers was measured radiographically at day 0 and day 21. The animals were then sacrificed and the ACL's were analyzed for load-to-failure using a material testing machine.ResultsLoad-to-failure testing indicated that animals treated with relaxin only had significantly weaker ACL's (µ = 40.4 N, p = 0.001) compared to controls (µ = 64.1 N). The relaxin + estrogen group (µ = 32.7 N) was also significantly weaker than controls (p = 0.007). There were no statistical differences between relaxin and relaxin + estrogen groups. Both relaxin only and relaxin + estrogen groups showed an increase in anterior translation of the tibia after 3 weeks of infusion, but it did not achieve statistical significance.ConclusionsRelaxin significantly alters the mechanical properties of the ACL in an animal model.Clinical relevanceThe effects of relaxin, possibly in conjunction with estrogen, may contribute to a comprehensive etiology for human female non-contact ACL injuries.     

Pretreatment cerebral metabolic activity correlates with antidepressant efficacy of vagus nerve stimulation in treatment-resistant major depression: A potential marker for response?

BackgroundPretreatment brain activity in major depressive disorder correlates with response to antidepressant therapies, including pharmacotherapies and transcranial magnetic stimulation. The purpose of this trial was to examine whether pretreatment regional metabolic activity in selected regions of interest (ROIs) predicts antidepressant response following 12 months of vagus nerve stimulation (VNS) in 15 patients with treatment-resistant major depression (TRMD).MethodsFluorodeoxyglucose positron emission tomography (FDG PET) was used to assess regional mean relative cerebral metabolic rate for glucose (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices) at baseline (prior to VNS activation). Depression severity was assessed at baseline and after 12 months of VNS using the Hamilton Depression Rating Scale (HDRS), with response defined as ≥ 50% reduction in HDRS from baseline.ResultsBaseline CMRGlu in the anterior insular cortex differentiated VNS responders (n = 11) from nonresponders (n = 4) and correlated with HDRS change (r = .64, p = .01). In a regression analysis, lower anterior insular cortex CMRGlu (p = .004) and higher orbitofrontal cortex CMRGlu (p = .047) together predicted HDRS change (R² = .58, p = .005). In a whole brain, voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex correlated with HDRS change (r = .78, p = .001).LimitationsSample size was small, limiting statistical power; patients remained on their psychiatric medications; study was open-label and uncontrolled.ConclusionsThis preliminary study suggests that pretreatment regional CMRGlu may be useful in predicting response to VNS in TRMD patients.     

The effect of testosterone alone and testosterone + estradiol therapy on bladder functions and smooth muscle/collagen content in surgically menopause induced rats

ObjectivesThe aim of the study was to investigate the effect of testosterone alone and testosterone + estradiol therapy on bladder functions and smooth muscle/collagen content in surgically menopause induced rat model.MethodsThe study included 34 female Sprague-Dawley rats, and the rats were divided into four groups. After bilateral oophorectomy, during a 60 days period, six rats received IM saline injection for one time, as a control group, and nine rats received testosterone undecanoate 100 mg/kg IM for one time, and nine rats received testosterone undecanoate 100 mg/kg IM for one time + daily 0.50 mg nasal spray of 17β estradiol. Ten rats were taken as sham group. Urodynamic studies were performed in all groups before and after the study. The rats were sacrificed after 60 days, and cystometric findings and smooth muscle/collagen ratio of the bladders were compared between the groups.ResultsIncrease in maximal bladder capacity and compliance were significantly higher in the testosterone treatment group and testosterone + estradiol treatment group than in the control group (p = 0.01 and p = 0.002, respectively for bladder capacity; p = 0.04 and p = 0.005, respectively for bladder compliance). Smooth muscle/collagen ratio of the bladders was significantly higher in the testosterone and testosterone + estradiol treatment groups than in the control group (p = 0.04 and p = 0.008, respectively).ConclusionsThis study shows that bladder functions may deteriorate in postmenopausal period. In addition to estrogen replacement therapy, testosterone has a significant role to increase bladder smooth muscle, leading to improvement in bladder functions in postmenopausal women with urogenital system dysfunction.     

Prediction of antidepressant response in both 2.25xthreshold RUL and fixed high dose RUL ECT

Some forms of electroconvulsive therapy (ECT) can result in generalized seizures that lack efficacy, therefore physiological markers of treatment adequacy would be helpful. EEG measures of seizure quality, such as EEG regularity and post-ictal suppression, have largely supplanted seizure duration as a marker for seizure adequacy, yet no predictive algorithm has gained wide clinical acceptance. Electrographic seizure durations of less than 25 s still prompt re-stimulation in many settings. We re-examined the utility of EEG seizure duration and other measures of EEG seizure as predictors of antidepressant response to right unilateral (RUL) ECT.MethodsSeventy-two adult patients with major depression were randomized to either titrated RUL ECT at 2.25 times initial seizure threshold or RUL ECT at a fixed dose of 403 mC. Intent-to-treat responder status (defined by 60% reduction in HRSD scores and final score of 12 or less after the last RUL ECT session) was identified as the dependent variable in a nominal logistic regression model including EEG seizure quality candidate variables, controlled for age and gender.ResultsA model including EEG seizure duration, EEG regularity, post-ictal suppression, age and gender and randomization status was significantly predictive of intent-to-treat responder status at treatment 2 (R2 = .21 p < .003; N = 66) and treatment 4 (R2 = .27 p < .0004; N = 67). The model remained significant at these time points even when randomization status (titrated moderately suprathreshold vs. high fixed dosage) was removed (Treatment 2: R2 = .18 p < .007; Treatment 4: R2 = .23 p < .0007).ConclusionEEG markers of seizure adequacy, including EEG seizure duration, are modestly predictive of antidepressant response for both titrated moderately suprathreshold and high fixed dosage RUL ECT.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Cerebrovascular hemodynamics in Alzheimer's disease and vascular dementia: a meta-analysis of transcranial Doppler studies

Background and purposeAlteration in cerebrovascular hemodynamics has reported in both ageing and dementia. However, it is still unclear whether this alteration follows similar pattern in ageing and in different dementia pathologies. The aim of this meta-analysis was to investigate changes in cerebral blood flow velocity and pulsatility index in two most common forms of dementia; Alzheimer's disease and vascular dementia, using transcranial Doppler studies.MethodsA literature search was conducted in Pubmed, EMBASE and Web of Science. After initial screening of 304 articles and removing duplicates, a total of 53 articles, published between 1980 and 2010, were reviewed. Finally 12 articles were included in the meta-analysis. For each study, effect sizes (ES) indicating the standardized mean differences of the hemodynamic measures between two groups were calculated. Using random effect models, pooled estimates of ES were measured.ResultsPatients with Alzheimer's disease (ES = ?1.09, 95% CI ?1.77 to ?0.44, p = 0.004) and vascular dementia (ES = ?1.62, 95% CI ?2.26 to ?0.98, p < 0.001) had significantly lower cerebral blood flow velocity compared with healthy aged-matched controls. In addition, pulsatility index was significantly higher in both Alzheimer's disease (ES = 0.5, 95% CI 0.28–0.72, p < 0.001) and vascular dementia patients (ES = 2.34, 95% CI 1.39–3.29, p < 0.001). Patients with Alzheimer's disease had lower pulsatility index (ES = ?1.22, 95% CI ?1.98 to ?0.46, p = 0.002) compared to subjects with vascular type of dementia.ConclusionsPatients with Alzheimer's disease and vascular dementia have a pronounced disturbance in their cerebrovascular hemodynamics. The severity of disturbances in cerebral hemodynamics is significantly lower in Alzheimer's disease compared to vascular dementia.     

Depressive symptoms, physical activity, and weight gain in premenopausal Latina and White women

ObjectivesDescribe changes and examine the association between depressive symptoms, physical activity, body mass index (BMI), and perceived health among Latina (n = 81) and White (n = 151) women in the first year of the late-premenopausal stage.MethodsLongitudinal study focused on the biopsychosocial health of midlife women (ages 40–50 years) with regular menstrual cycles and not taking hormones. Frequency of depressive symptoms, BMI, waist to hip ratios, and self-reported physical activity levels were obtained at 6-month intervals and perceived health at 12 months. Results are reported here for 232 women who remained premenopausal (low FSH/regular cycles) for the first 12 months.ResultsDepressive symptoms were similar for Latinas (11.1 ± 9.8) and Whites (11.1 ± 8.2) and increased by 2.3 points over time for all women. Latinas had higher BMI (28 ± 5.7, p < 0.01) than Whites (26 ± 5.7). Body weight increased an average of 1.2 lbs over 12 months for both groups. Both groups reported sub-optimal levels of physical activity that did not change over time, but Latinas reported higher levels at all 3 time points. Controlling for age and ethnicity, women in service or agricultural occupations reported higher activity levels than women in other roles. Better perceived health at 12 months was predicted by lower baseline BMI (r = 0.43, p < 0.01) and fewer depressive symptoms (r = 0.38, p < 0.01).ConclusionsDepressive symptoms, weight gain and physical inactivity among women in the late-premenopausal stage point to the need for interventions focused on causal factors other than hormonal changes and menopause.     

Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study

The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (< 255 Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex (p = 0.008, p = 0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex (p = 0.005, p = 0.004 and p = 0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.