Masculinized finger-length ratios of boys, but not girls, are associated with attention-deficit/hyperactivity disorder

Gonadal hormones may exert permanent organizational effects on sexually dimorphic finger-length ratios and sexually dimorphic behavior expressed in childhood attention deficit-hyperactivity disorder (ADHD). This study extended recent work examining associations between finger-length ratios (specifically, 2D:4D) and ADHD in a well-characterized, clinically diagnosed, community-recruited sample of boys and girls. A multistage, diagnostic procedure was utilized to identify 113 children with ADHD and 137 non-ADHD comparison children. Right-hand digit ratios showed significant mean differences by gender, as well as associations with ADHD diagnosis. Boys with ADHD had more masculinized digit ratios than control-group boys. More masculine right 2D:4D and 3D:4D ratios were correlated with parent- and teacher-rated inattentive and hyperactive-impulsive symptoms in boys but not in girls. Masculinized finger-length ratios were associated with hyperactive-impulsive and oppositional- defiant symptoms, but associations were largest with symptoms of inattention. It is concluded that prenatal, organizational effects of gonadal hormones may play a role in the development of ADHD and contribute to explaining sex differences in the prevalence rates of this childhood disorder.     

Helicobacter pylori infection: CagA-specific antibodies are associated with clinical outcome,but not with HLA-class II polymorphisms of the host

In order to investigate the interrelation between immunogenetic host and bacterial factors the T-cell receptor (TCR) polymorphism TCRBV6S1 A/B, HLA-DRB1 alleles and cagA status was analyzed in 380 unrelated German individuals. H. pylori infection with cagA-positive bacterial strains was significantly associated with peptic ulcer disease in the German cohort. Patients homozygous for the non-functional TCRBV6S1B allele and presenting with peptic ulcer disease showed no CagA-specific antibodies in the majority of cases. There was no association between HLA-DRB1 alleles and the CagA status of infected individuals, although certain alleles show significant association to the infection status in different populations.     

Corticosteroids, but not NSAIDs, are associated with less Alzheimer neuropathology

The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Counts of NPs in several neocortical regions were also assessed. For each neuropathology measure, analyses of covariance controlling for age at death and sex compared subjects who received only corticosteroids (n = 54) or those who received only NSAIDs (n = 56) to the same comparison group, subjects who received neither (n = 576). Subjects receiving corticosteroids had significantly lower ratings and counts of NPs for all neuropathological measures, and NFTs overall and in the cerebral cortex and amygdala. In contrast, no measures were significant for subjects who received NSAIDs. Use of corticosteroids was associated with approximately 50% fewer NPs and NFTs in most brain regions examined, compared with nonmedicated subjects. In contrast, use of NSAIDs was not substantially associated with the reductions in hallmark lesions of AD. Because corticosteroids have anti-inflammatory as well as a myriad of other neurobiological effects, more direct studies in model systems could reveal novel therapeutic targets and mechanisms for AD lesion reduction.     

PCBs, hexachlorobenzene and DDE are not associated with recurrent miscarriage

PROBLEM: A case-control study was designed to evaluate any associations between high exposure to polychlorinated biphenyls (PCB), hexachlorobenzene (HCB) and the 1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE) and recurrent miscarriage and immunoendocrine abnormalities. METHODS OF STUDY: A total of 18 kinds of co-planer PCBs, HCB, DDE, natural killer cell (NK) activity, antiphospholipid antibodies, antinuclear antibody, prolactin, progesterone, thyroid-stimulating hormone (TSH) and free T4 were examined in 45 patients with a history of three or more (3-11) consecutive first-trimester miscarriages and 30 healthy women with no history of live birth and infertility. RESULTS: There were no differences in mean +/- S.D. values in serum samples for PCBs, HCB and DDE between patients and controls. Hypothyroidism, hyperprolactinemia, luteal phase defects, NK cell activity and the presence of autoantibodies were also not associated with levels of any of the compounds in the patients. CONCLUSION: PCBs, HCB and DDE are not associated with miscarriage and immunoendocrine abnormalities in patients with a history of recurrent miscarriage.     

Serotonin 2A receptor gene is associated with personality traits, but not to disorder, in patients with borderline personality disorder

Borderline personality disorder (BPD) is a chronic, disabling, and high-risk mental disorder characterized by a pervasive pattern of instability in regulation of emotion, interpersonal relationships, self-image, and impulse control beginning in early adulthood. BPD affects about 1%-2% of the general population and has a high mortality rate as a result of suicide and impulsive behaviour. The serotonin 2A receptor gene (HTR2A) is considered a candidate gene for BPD because multiple lines of evidence suggest that it plays an important role in suicide, impulsivity and emotional liability. To test for an association between HTR2A and BPD, we genotyped four polymorphisms, rs6313 (T102C), rs4941573, rs2296972 and rs6314 (His452Tyr), in 111 Caucasian patients with BPD and 287 Caucasian healthy controls. The program UNPHASED was used to compare allele and haplotype frequencies between cases and controls. We did not find a significant association between HTR2A and BPD based on allele, genotype or haplotype analyses. However, there were significant associations between HTR2A and personality traits in the BPD patients. The C allele of rs6313 and the A allele of rs4941573 associated with a higher Extraversion score. Our results suggest that the serotonin 2A receptor gene may not play a major role in the aetiology of borderline personality disorder, but may have a role in personality traits.     

Predicted indirectly recognizable HLA epitopes are not associated with clinical outcomes after haploidentical hematopoietic stem cell transplantation

Haploidentical stem cell transplantation (haplo-SCT) provides an alternative method to cure patients with malignant and nonmalignant hematologic diseases who lack a human leukocyte antigen (HLA) matched related or unrelated donor. HLA disparity between donor and patient was the main reason causing lots of clinical immune response. The aim of this study was to investigate whether indirect recognition of mismatched HLA could predict the clinical outcomes in haplo-SCT. The probability of indirect recognition was predicted by the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model. 577 patients with acute leukemia or myelodysplastic syndrome receiving haplo-SCT were enrolled in the study. Patients were divided into 4 quartiles according to PIRCHE-Ⅰ or PIRCHE-Ⅱ. Although the cumulative incidences of chronic graft-versus-host disease (GVHD) were significantly different among the 4 PIRCHE-Ⅰgroups, with 20.4% for group 0–6, 40.5% for group >6–11, 26.1% for group >11–19 and 23.9% for group >19 (P?=?.007), PIRCHE-Ⅰ was not significantly associated with chronic GVHD in multivariate models (RR, 0.993; 95% CI, 0.858–1.149; P?=?.926). And no significant associations were observed between PIRCHE-Ⅰ or PIRCHE-Ⅱ and other clinical outcomes. In summary, PIRCHE did not correlate with clinical outcomes and could not predict haplo-SCT outcomes.     

Posttraumatic stress disorder is associated with attenuated baroreceptor sensitivity among female, but not male, smokers

BACKGROUND: The relationship between posttraumatic stress disorder (PTSD) and parasympathetic nervous system (PNS) functioning was investigated using baroreflex sensitivity (BRS). We hypothesized that individuals with PTSD would exhibit lower BRS than those without PTSD. METHODS: Participants were 80 PTSD patients and 50 controls aged 18-68 years. All participants were smokers, many were veterans (55%), and 60 were women. Beat-to-beat BP was collected during a 5-min baseline rest periods from which estimates of BRS were derived using the sequence method. RESULTS: Women with PTSD exhibited lower BRS (M = 10.5, S.D. = 5.1) than women without PTSD (M = 14.6, S.D. = 10.7). For men, PTSD diagnosis was not associated with BRS, p > .05. CONCLUSIONS: Among women, PTSD was associated with reduced PNS functioning. Men with PTSD did not have attenuated BRS, which may be due to sample characteristics, such as age and combat veteran status. Reduced PNS activity may predispose women with PTSD to poorer cardiovascular health.     

Reduced positive emotion and underarousal are uniquely associated with subclinical depression symptoms: Evidence from psychophysiology,self‐report,and symptom clusters

Multiple models of aberrant emotional processing in depression have been advanced. However, it is unclear which of these models best applies to emotional disturbances in subclinical depressive symptoms. The current study employed a battery of psychophysiological measures and emotional ratings in a picture‐viewing paradigm to examine whether the underarousal, low positive emotion, heightened negative emotion, or emotion context insensitivity model of emotional dysfunction in subclinical depressive symptoms received greatest support. Postauricular reflex and skin conductance response potentiation for pleasant minus neutral pictures (measuring low positive emotion), overall skin conductance magnitude and late positive potential (LPP) amplitude (measuring underarousal), and pleasant minus aversive valence ratings (measuring emotion context insensitivity) and aversive minus neutral arousal ratings (measuring heightened negative emotionality) were all negatively related to depressive symptomatology. Of these, postauricular reflex potentiation and overall LPP amplitude were incrementally associated with depressive symptoms over the other measures. Postauricular reflex potentiation, overall skin conductance magnitude, and aversive minus neutral arousal ratings were incrementally associated with depressive symptomatology after controlling for other symptoms of internalizing disorders. Though no model was unequivocally superior, the low positive emotion and underarousal models received the most support from physiological measures and symptom reports, with self‐report data matching patterns consistent with the emotion context insensitivity model.     

Colony opacity, hemadsorption, hemolysis, and mitogenicity are not associated with virulence of Mycoplasma pulmonis.

Colony opacity, hemadsorption and hemolysis of erythrocytes, and the ability of whole mycoplasmal cells to induce a blastogenic response when incubated with C3H/HeN or C57BL/6 mouse lymphocytes were examined for 18 strains of Mycoplasma pulmonis to determine if any of these characteristics could be associated with virulence in vivo. Although there were differences among strains in each of these characteristics, none of these parameters were associated with virulence.     

Mutations affecting BRAF, EGFR, PIK3CA, and KRAS are not associated with sporadic vestibular schwannomas

Sporadic vestibular schwannomas are benign tumors originating from the Schwann cells of the vestibular portion of the eigth cranial nerve. An important clinical hallmark of these tumors is their variable growth rate. Investigating vestibular schwannoma biology can help to clarify this variable growth rate and may offer targets for therapeutic treatment. A recent mutation analysis on sporadic non-head and neck schwannomas detected BRAF mutations in around 20 % of tumors. BRAF is part of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. MAPK/ERK activation is associated with an uncontrolled cell growth. Mutated BRAF can function as a target to inhibit this pathway. Mutations in BRAF and other members of the MAPK/ERK pathway have not been investigated in sporadic vestibular schwannomas before. The goal of this study was to investigate if these mutations are present in vestibular schwannomas and whether these mutations correlate with tumor growth. Tumor specimens of 48 patients surgically treated for a sporadic vestibular schwannoma were analyzed. An allele-specific quantitative real-time PCR assay was performed to detect the 13 most frequent mutations affecting BRAF, EGFR, PIK3CA, and KRAS. Radiologically measured tumor growth was included in the analysis to identify potential relationships between these mutations and tumor progression. No activating hotspot mutations in BRAF, EGFR, PIK3CA, or KRAS were detected. The 13 most frequent mutations affecting BRAF, EGFR, PIK3CA, and KRAS are not involved in sporadic vestibular schwannoma development. These results are in contrast to the recent detection of these BRAF mutations in non-head and neck schwannomas.     

Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study

BackgroundThe effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial.ObjectiveTo determine if changes in erythrocyte DHA are associated with changes in LDL-C levels.MethodsIn this prospective observational study, erythrocyte DHA levels and LDL-C levels were measured in 9253 individuals who presented for at least two examinations at a medical clinic. Changes in DHA levels and the reported use of omega-3 dietary supplements were correlated with changes in LDL-C in multi-variable adjusted models including the use of LDL-C-lowering drugs.ResultsMean (standard deviation) age at baseline was 52.6 (10.6) years, and the time between exams averaged 1.9 (1.4) years. As a group, erythrocyte DHA increased from 5.0% (1.3) to 5.3% (1.3) (p < 0.001), and LDL-C was not significantly changed (109 (33) to 108 (33) mg/dL, p = 0.875). However, in multivariable-adjusted models of within-participant changes, a 1% increase in erythrocyte DHA was associated with a 1.9 mg/dL reduction in LDL-C (95% confidence interval (1.6, 2.2), p < 0.001). Similar relationships were seen with changes in erythrocyte EPA and EPA + DHA. In adjusted analyses, an increased use of omega-3 supplements was associated with a significant increase in erythrocyte DHA and a decrease in LDL-C in both users and non-users of lipid-lowering drugs.ConclusionsIn a predominantly male, normolipidemic, middle-aged cohort, increases in erythrocyte DHA were associated with decreases in LDL-C, and initiating fish oil supplement use did not increase LDL-C. These findings may serve to reassure individuals who, in adopting a more heart-healthy lifestyle, want to increase their omega-3 fatty acid intake.     

Properties of associations: Identity,nature, and clinical criteria,with a commentary on why CHARGE and Goldenhar are not associations

We report the use of fluorescent in situ hybridization (FISH) with a DNA library of chromosome 1-specific probes to confirm the karyotype, 46,XY,15, + der15,t(1;15)(q32.1; q26.3), obtained by prenatal periumbilical blood sampling from a fetus who exhibited multiple abnormalities by ultrasound examination. GTG-banding of chromosomes obtained from the mother showed a normal karyotype, while the father was unavailable for study. The propositus was born at 37 weeks gestation and survived for several weeks. Cytogenetic analysis performed after the birth of the male infant with multiple anomalies verified partial trisomy 1q. This patient is compared with other partial trisomy 1q patients reported in the literature. The usefulness of FISH is demonstrated in situations where fetal abnormalities are present with de novo chromosomal rearrangements where paternal chromosomes are unavailable for study. © 1994 Wiley-Liss, Inc.     

Severity and age of rotavirus diarrhea,but not socioeconomic conditions,are associated with rotavirus seasonality in Venezuela

Rotavirus (RV) epidemiology presents differences between developing and developed countries among which are seasonality, age at first infection, variability of strain in circulation and severity of disease. Since, in Venezuela, we have distinct seasonal patterns of RV occurrence, we examined the epidemiological profile of RV disease associated to these differences by analyzing data from previous studies conducted in Venezuela. Data were collected from children <5 years of age with diarrhea seen in six hospitals located in five cities. Socio‐demographic and clinical characteristics of RV illness were analyzed according to RV identification by ELISA assay and the seasonal patterns of RV circulation (marked versus minimal seasonality). A total of 6,742 episodes of diarrhea (1,820 rotavirus positive and 4,922 rotavirus negative) were evaluated: 1,951 in Caracas, Cumaná and Pto. Ordaz (minimal seasonality) and 4,791 in Mérida and Valencia (marked seasonality). Mean age (months) of children with RV was 8.14 ± 6.74 and 12.21 ± 9.62 (P < 0.0001) in areas with minimal and marked seasonality, respectively. RV disease was more frequent (33% vs. 24%; OR = 1.536; 95% CI: 1.36–1.73), more severe (dehydration: 64% vs. 29%; OR = 4.436; 95% CI: 3.61–5.44) and more common in infants than in older children (79% vs. 60%; OR = 2.521; 95% CI: 2.01–3.14) in cities with minimal seasonality than in those with marked seasonality. Socioeconomic conditions were not associated with seasonality. In environments with minimal seasonality, children are infected with RV at younger ages and the disease is more severe regardless of malnutrition and poverty. J. Med. Virol. 81:562–567, 2009. © 2009 Wiley‐Liss, Inc.     

Hepatic lipase promoter C-480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study

The common C‐480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high‐density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24–39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow‐mediated vasodilatation (FMD) and carotid artery intima‐media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C‐reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above‐mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.     

Interleukin 4 haplotypes of susceptibility to chronic periodontitis are associated with IL-4 protein levels but not with clinical outcomes of periodontal therapy

Different IL4 haplotypes were associated to susceptibility to/or protection against chronic periodontitis (CP). The aim of this study was to investigate if individuals carrying different haplotypes would present differences in clinical periodontal parameters and in the IL-4 levels at baseline, 45 and 90 days after non-surgical periodontal therapy. 62 patients were subdivided: genetically protected without CP (PH), genetically protected with CP (PCP), genetically susceptible with CP (SCP), genetically susceptible without CP (healthy) (SH). Clinical examination and gingival crevicular fluid (GCF) collection were performed for all patients, and IL-4 levels were measured by ELISA. At baseline, higher values for plaque index (PI, p = 0.013), gingival index (GI, p = 0.005) were observed for the SCP group in comparison to the PCP group but not after the completion of periodontal therapy. 45 and 90 days after the non-surgical therapy, PCP demonstrated significantly higher IL-4 levels than the SCP (p = 0.000002). Correlation analysis showed different results between clinical parameters and IL-4 production or GCF volume for groups with different genetic loads. The IL4 gene which was previously associated with susceptibility to CP was related with differences in the IL-4 protein levels in the GCF. However, independent of genetic carriage, individuals responded similarly to this therapy.