Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs.

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells.

OBJECTIVE: Pancreatic beta-cells exposed to proinflammatory cytokines display alterations in gene expression resulting in defective insulin secretion and apoptosis. MicroRNAs are small noncoding RNAs emerging as key regulators of gene expression. Here, we evaluated the contribution of microRNAs to cytokine-mediated beta-cell cytotoxicity. RESEARCH DESIGN AND METHODS: We used global microarray profiling and real-time PCR analysis to detect changes in microRNA expression in beta-cells exposed to cytokines and in islets of pre-diabetic NOD mice. We assessed the involvement of the microRNAs affected in cytokine-mediated beta-cell failure by modifying their expression in insulin-secreting MIN6 cells. RESULTS: We found that IL-1beta and TNF-alpha induce the expression of miR-21, miR-34a, and miR-146a both in MIN6 cells and human pancreatic islets. We further show an increase of these microRNAs in islets of NOD mice during development of pre-diabetic insulitis. Blocking miR-21, miR-34a, or miR-146a function using antisense molecules did not restore insulin-promoter activity but prevented the reduction in glucose-induced insulin secretion observed upon IL-1beta exposure. Moreover, anti-miR-34a and anti-miR-146a treatment protected MIN6 cells from cytokine-triggered cell death. CONCLUSIONS: Our data identify miR-21, miR-34a, and miR-146a as novel players in beta-cell failure elicited in vitro and in vivo by proinflammatory cytokines, notably during the development of peri-insulitis that precedes overt diabetes in NOD mice.

Lymphomes des annexes de l'oeil au cours du syndrome de Gougerot-Sjögren [Lymphomas of the ocular adnexa in Gougerot-Sjögren syndrome. Apropos of 4 cases].

The risk of malignant B cell lymphoma is increased in Sjögren's syndrome (SS). Orbital localization seems infrequent. We report 4 cases of malignant lymphoma (ML) occurring in 4 women aged 47 to 77 years, with primary SS in 3 cases, located to the conjunctiva in 2 cases, the lacrymal gland in 1 case and the eyelid in 1 case. The interval between the diagnosis of SS and orbital ML varied from 6 months to 15 years. All 4 lymphomas were of the B cell type, low histopathologic grade, with monoclonal gammopathy in 1 case. Extraocular lymphoma was initially present in 1 case. ML remained localized in 2 cases with a follow-up of 4 and 6 years. Two patients treated by excisional biopsy alone are in complete remission 3 and 6 years later. The 2 other patients treated with orbital radiotherapy and chemotherapy died rapidly (transformation into a high grade malignancy in 1 case). We conclude that clinical, immunopathologic features, as well as prognosis and treatment of ocular adnexa ML in SS are similar to those of primary ML without SS.

Interhemispheric distribution of Alzheimer disease and vascular pathology in brain aging

BACKGROUND AND PURPOSE: Most of the neuropathological studies in brain aging were based on the assumption of a symmetrical right-left hemisphere distribution of both Alzheimer disease and vascular pathology. To explore the impact of asymmetrical lesion formation on cognition, we performed a clinicopathological analysis of 153 cases with mixed pathology except macroinfarcts. METHODS: Cognitive status was assessed prospectively using the Clinical Dementia Rating scale; neuropathological evaluation included assessment of Braak neurofibrillary tangle and Ass deposition staging, microvascular pathology, and lacunes. The right-left hemisphere differences in neuropathological scores were evaluated using the Wilcoxon signed rank test. The relationship between the interhemispheric distribution of lesions and Clinical Dementia Rating scores was assessed using ordered logistic regression. RESULTS: Unlike Braak neurofibrillary tangle and Ass deposition staging, vascular scores were significantly higher in the left hemisphere for all Clinical Dementia Rating scores. A negative relationship was found between Braak neurofibrillary tangle, but not Ass staging, and vascular scores in cases with moderate to severe dementia. In both hemispheres, Braak neurofibrillary tangle staging was the main determinant of cognitive decline followed by vascular scores and Ass deposition staging. The concomitant predominance of Alzheimer disease and vascular pathology in the right hemisphere was associated with significantly higher Clinical Dementia Rating scores. CONCLUSIONS: Our data show that the cognitive impact of Alzheimer disease and vascular lesions in mixed cases may be assessed unilaterally without major information loss. However, interhemispheric differences and, in particular, increased vascular and Alzheimer disease burden in the right hemisphere may increase the risk for dementia in this group.

Mortality, complications and loss of pulmonary function after pneumonectomy vs. sleeve lobectomy in patients younger and older than 70 years.

Retrospective single institution analysis of all patients undergoing sleeve lobectomy or pneumonectomy between 2000 and 2005. Seventy-eight patients underwent pneumonectomy (65 patients <70 years, 13 patients >70 years) and 69 sleeve lobectomy (50 patients <70 years, 19 patients >70 years). Pre-existing co-morbidity, surgical indication and induction therapy was similarly distributed between treatment by age-groups. In patients <70 years, pneumonectomy and sleeve lobectomy resulted in a 30-day mortality of 3% vs. 0 and an overall complication rate of 26% vs. 44%, respectively. In patients >70 years, pneumonectomy and sleeve lobectomy resulted in a 30-day mortality of 15% vs. 0 and an overall complication rate of 23% vs. 32%. In both age groups, pneumonectomy was associated with more airway complications (NS) and a significantly higher postoperative loss of FEV(1) than sleeve lobectomy (P<0.0001, P<0.03). Age per se did not influence the loss of FEV(1) and DLCO for a given type of resection. Sleeve lobectomy may have a therapeutic advantage over pneumonectomy in the postoperative course of elderly patients.

Comparison of the single-use Ambu(®) aScope? 2 vs the conventional fibrescope for tracheal intubation in patients with cervical spine immobilisation by a semirigid collar*.

Fibreoptic intubation remains a key technique for the management of difficult intubation. We randomly compared the second generation single-use Ambu(®) aScope? 2 videoscope with a standard re-usable flexible intubating fibrescope in 50 tracheal intubations in patients with a difficult airway simulated by a semirigid collar. All patients' tracheas were intubated successfully with the aScope 2 or the re-usable fibrescope. The median (IQR [range]) time to intubate was significantly longer with the aScope 2 70 (55-97 [41?-226]) s vs 50 (40-59 [27-175]) s, p = 0.0003) due to an increased time to see the carina. Quality of vision was significantly lower with the aScope 2 (excellent 24 (48%) vs 49 (98%), p = 0.0001; good 22 (44%) vs 1 (2%), p = 0.0001; poor 4 (8%) vs 0, p = 0.12) but with no difference in the subjective ease to intubate (easy score of 31 (62%) vs 38 (76%), p = 0.19; intermediate 12 (24%) vs 7 (14%), p = 0.31; difficult 7 (14%) vs 5 (5%), p = 0.76). The longer times to intubate and the poorer scores for quality of vision do not support the use of the single-use aScope 2 videoscope as an alternative to the re-usable fibrescope.

Reproductive bribing and policing as evolutionary mechanisms for the suppression of within-group selfishness.

We show that a new, simple, and robust general mechanism for the social suppression of within-group selfishness follows from Hamilton's rule applied in a multilevel selection approach to asymmetrical, two-person groups: If it pays a group member to behave selfishly (i.e., increase its share of the group's reproduction, at the expense of group productivity), then its partner will virtually always be favored to provide a reproductive "bribe" sufficient to remove the incentive for the selfish behavior. The magnitude of the bribe will vary directly with the number of offspring (or other close kin) potentially gained by the selfish individual and inversely with both the relatedness r between the interactants and the loss in group productivity because of selfishness. This bribe principle greatly extends the scope for cooperation within groups. Reproductive bribing is more likely to be favored over social policing for dominants rather than subordinates and as intragroup relatedness increases. Finally, analysis of the difference between the group optimum for an individual's behavior and the individual's inclusive fitness optimum reveals a paradoxical feedback loop by which bribing and policing, while nullifying particular selfish acts, automatically widen the separation of individual and group optima for other behaviors (i.e., resolution of one conflict intensifies others).

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Rupture d'une hyperplasie nodulaire focale. A propos de deux cas [Rupture of hepatic focal nodular hyperplasia. About two cases]

The diagnostics of focal nodular hyperplasia is reached through the use of imaging. When the diagnostic is certain, surgical abstention is the rule. Nevertheless, we were confronted with two cases of a rare complication; that of intraperitoneal rupture. In this situation, we suggest to first do an arteriography to control the bleeding, then to perform surgery when the patient has reached hemodynamic stability. Spontaneous rupture as a complication of benign nodular hyperplasia remains a rare event and only five cases were reported in litterature.

Pain pattern and left internal mammary artery grafting.

BACKGROUND: This study was designed to determine whether the pain pattern in patients with an internal mammary artery (IMA) harvest differs from that in other cardiac operations and whether these patients present specific characteristics with clinical implications. METHODS: One hundred patients with left IMA grafting (IMA group) were compared prospectively with 100 patients who had a heart operation without IMA harvest (non-IMA group). Pain assessment was performed on postoperative days (POD) 1, 2, 3, and 7, and included pain intensity (10-point scale) and pain localization. RESULTS: In the IMA group, pain intensity was higher on POD 2 (4.2 +/- 2.4 versus 3.2 +/- 2.3, p < 0.01), and there were more patients without pain on POD 7 (32 versus 19, p = 0.03). In the IMA group, more patients had left basal thoracic pain throughout the entire study period and had sternal pain on POD 7, whereas more patients in the non-IMA group complained about back pain during the early postoperative period. CONCLUSIONS: The impact of IMA harvest on pain intensity is moderate, but the pain localization pattern of each group exhibits specific features that could help to better target pain management.

Metabolic and hemodynamic changes during recovery and tracheal extubation in neurosurgical patients: immediate versus delayed recovery.

Delayed recovery has been advocated to limit the postoperative stress linked to awakening from anesthesia, but data on this subject are lacking. In this study, we measured oxygen consumption (V(O2)) and plasma catecholamine concentrations as markers of postoperative stress. We tested the hypothesis that delayed recovery and extubation would attenuate metabolic changes after intracranial surgery. Thirty patients were included in a prospective, open study and were randomized into two groups. In Group I, the patients were tracheally extubated as soon as possible after surgery. In Group II, the patients were sedated with propofol for 2 h after surgery. V(O2), catecholamine concentration, mean arterial pressure (MAP), and heart rate (HR) were measured during anesthesia, at extubation, and 30 min after extubation. V(O2) and noradrenaline on extubation and mean V(O2) during recovery were significantly higher in Group II than in Group I (V(O2) for Group I: preextubation 215 +/- 46 mL/min, recovery 198 +/- 38 mL/min; for Group II: preextubation 320 +/- 75 mL/min, recovery 268 +/- 49 mL/min; noradrenaline on extubation for Group I: 207 +/- 76 pg/mL, for Group II: 374 +/- 236 pg/ mL). Extubation induced a significant increase in MAP. MAP, HR, and adrenaline values were not statistically different between groups. In conclusion, delayed recovery after neurosurgery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence from general anesthesia. IMPLICATIONS: In this study, we tested the hypothesis that delayed recovery after neurosurgery would attenuate the consequences of recovery from general anesthesia. As markers of stress, oxygen consumption and noradrenaline blood levels were higher after delayed versus early recovery. Thus, delayed recovery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence after neurosurgery.