Association of polymorphisms of the estrogen receptor gene with anxiety-related traits in children and adolescents: a longitudinal study

Anxiety problems and associated temperamental traits are multifactorial, determined by the interaction of genetic and environmental factors. Genetic effects may involve both neurotransmitters and hormones. A good candidate gene for association with anxiety-related traits is the estrogen receptor (ESRalpha). Estrogen exerts an effect on mood and behavior in humans through gene regulation on binding to estrogen receptor protein. Association between ESRalpha polymorphism and anxiety-related traits was investigated in a cohort of 680 Australian adolescents studied from 4-8 months to 15-16 years of age. Genotype frequencies were estimated for polymorphic PvuII and XbaI restriction sites in intron 1 and a microsatellite [(TA)(n)] locus 5' of ESRalpha. There was strong linkage disequilibrium between the three loci and a significant sex difference was observed in allele (for (TA)(n), PvuII) and genotype (for XbaI) frequencies. There were no significant allelic or genotypic differences in anxiety-related traits for the three loci tested. However, some significant associations were found for PvuII/(TA)(n) and XbaI/(TA)(n) two-locus genotypes and anxiety, accounting for between 1.6% and 2.8% of the total variance for anxiety in this population. The discordance in Hardy-Weinberg proportions at the XbaI locus between the sexes is an important finding, perhaps indicating a sex-specific role for ESRalpha in fetal survival.     

Latent structure of depression in a community sample: a taxometric analysis

BACKGROUND: The latent structure of depression was examined using taxometric analysis, a family of statistical procedures designed specifically to test whether a given construct is best conceptualized as a distinct category or a continuous dimension. METHOD: Data were derived from the Australian National Survey of Mental Health and Well-Being, a large epidemiological survey that measured the prevalence of the major DSM-IV and ICD-10 mental disorders. Two taxometric procedures, maximum covariance (MAXCOV) and mean above minus below a cut (MAMBAC), were carried out on a sample of 1933 community volunteers. Simulated categorical and dimensional datasets aided in the interpretation of the research data. RESULTS: The results of the taxometric analyses in the subsample who endorsed at least one symptom of depression were consistent with a dimensional latent structure of depression. CONCLUSIONS: The findings of the current study suggest that depression, as measured in this subsample, is best conceptualized, measured and classified as a continuously distributed syndrome rather than as a discrete diagnostic entity. Incorporation of dimensional measurement into psychiatric classification systems remains a challenge for the future.     

Mapping of gene loci in the Q13–Q15 region of chromosome 12

The gene loci CDK4, GLI, CHOP and MDM2 have been mapped to the q13–q15 region of chromosome 12. Using fluorescencein situ hybridization onto simultaneously DAPI-banded metaphase chromosomes and interphase nuclei, we have more precisely mapped and ordered these loci, together with a number of Genethon microsatellite markers. GLI and CHOP localize to 12q13.3–14.1, CDK4 to 12q14 and MDM2 to 12q14.3–q15, and the gene order is cen-GLI/CHOP-CDK4-MDM2. The Genethon microsatellites D12S80 and D12S83 flank MDM2.     

Neuroanatomical Correlates of Skin Conductance Orienting in Normal Humans: A Magnetic Resonance Imaging Study

Although little is known about the neuroanatomical basis of skin conductance orienting in intact normal humans, the limited literature on animals and humans with neurological and clinical disorders implicate prefrontal, temporal/amygdala, and pons brain areas in mediating skin conductance orienting. This study relates area of these structures using magnetic resonance imaging techniques to skin conductance orienting responses in 17 normal humans in order to test hypotheses that larger area of these excitatory structures will be associated with more orienting responses. Left and right hand skin conductance orienting was significantly associated with left and right prefrontal area (r = .44-.60), area of the pons (r = .43-.54), and left but not right temporal/amygdala area (r = .47-.53). No relationships were observed with areas thought to be unrelated to skin conductance activity (cerebellum, nonfrontal cortical area), medial prefrontal cortex, or the third ventricle. This appears to be the first study relating brain structure to skin conductance orienting in intact normal humans. Although preliminary at the present time, these results implicate prefrontal, pons, and temporal/amygdala areas in the mediation of skin conductance orienting in normal humans.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

Influence of birth weight on primary surgical management of newborns with esophageal atresia

BackgroundTo determine if birth-weight (BW) influences primary surgical management of newborns undergoing operation for esophageal atresia and tracheo-esophageal fistula (EA-TEF).MethodsNewborns undergoing repair of esophageal atresia at a single specialist centre between 1999 and 2017 were categorised into three groups based on BW; Group A < 1.5 kg, Group B <2.5 kg and Group C >2.5 kg. Outcome data analysed were (i) technical ability of the surgeon to perform primary esophageal anastomosis, (ii) anastomotic leak, (iii) anastomotic stricture, (iv) esophageal replacement, (v) need for other procedures notably fundoplication, aortopexy, tracheostomy and (vi) mortality. Statistical analysis was performed using a two-tailed Fisher's exact test and logistic regression.Results198 patients underwent surgery for EA-TEF during the study period, Group A (n = 13), Group B (n = 73) and Group C (n = 112). Inability to perform a primary anastomosis was significantly higher in Group A vs Group B (p = 0.003) and Group C (p = 0.004). Birthweight was a significant variable in the ability to perform a primary esophageal anastomosis (OR 1.009, p = 0.004). Mortality rate was significantly higher in Group A vs Group C (P = 0.0158).ConclusionsVery low birth weight infants are less likely to achieve a definitive primary anastomosis during emergent repair of esophageal atresia, and have a higher mortality.     

Basismaßnahmen zur Wiederbelebung Erwachsener (Basic Life Support)

Notfall + Rettungsmedizin - Der Europäische Rat für Wiederbelebung hat diese Leitlinie –&nbsp;Basismaßnahmen zur Wiederbelebung&nbsp;– auf Grundlage des...     

Behavioural analysis of the anorectic effects of fluoxetine and fenfluramine

Two sets of experiments were carried out to compare the effects of fenfluramine and fluoxetine on consummatory and operant behaviour. In food-deprived rats allowed access to a 35% sucrose solution, an initial period of sucrose consumption was followed by a short period of grooming and exploratory behaviour, later superceded by resting. This behavioural satiety sequence was advanced by fluoxetine, but disrupted bydl-fenfluramine, which suppressed post-prandial resting, even at sub-anorectic doses. Fluoxetine also elicited resting behaviour following water drinking. However, this did not appear to be a non-specific sedative effect, since fluoxetine increased post-prandial grooming. In rats performing on random interval schedules of food reinforcement, fluoxetine caused proportionally greater decreases in responding on a reinforcement-lean schedule (RI-300s), as compared to a reinforcement-rich schedule (RI-7.5s); this effect is similar to that of a reduction in level of food deprivation. By contrast, fenfluramine reduced responding equally on both schedules. In both paradigms, the effects of fluoxetine were compatible with an increase in postprandial satiety, but the effects of fenfluramine were not.     

Assessment of the value and pattern of use of a target controlled propofol infusion system

Summary Thirty one anaesthetists were supplied with a pharmacokinetic based target controlled propofol infusion system for evaluation. Twenty seven of 30 replies to a questionnaire sent to them indicated that the system had changed their use of propofol for maintenance of anaesthesia. The main reasons were greater ease of use and more confidence regarding the predictability of anaesthetic effects compared with manually controlled infusion. Data obtained from 770 patients anaesthetised with the system were analysed. The median maximum target concentration selected was 6.6 g/ml. Younger patients (18–35 yr) required significantly greater target concentrations than older patients (65–80 yr). The mean time during which the system was in maintenance mode, when the predicted blood concentration of propofol was held constant for at least one minute, was 26.1 minutes. The median number of alterations in propofol concentration was 6. The target controlled infusion system provided an inexpensive and acceptable method of delivering intravenous anaesthesia.