Anorectal anomalies associated with or as part of other anomalies.

Anorectal anomalies occurring with other anomalies or as part of syndromes were analyzed to determine how their epidemiological characteristics differed from those of isolated anal anomalies. Almost 15% of cases were chromosomal, monogenic or teratogenic syndromes, whereas the rest were of unknown cause including sequences (9.3%), VACTERL associations (15.4%) and multiple congenital anomalies (MCA) (60.2%). Almost half of babies with MCA had one or two VACTERL anomalies with distribution frequencies that did not differ significantly from those in babies with the full VACTERL association. There were considerable differences in the frequency of the VACTERL association among babies with different types of anorectal anomaly. Babies with anal anomalies occurring with sequences, VACTERL or MCA showed the same sex differences as babies with isolated anal anomalies, namely male predominance in anal atresia without fistula or cloaca, no sex difference in anal atresia with fistula, and female predominance in ectopic anus and congenital anal fistula. These anomalies, however, were associated with significantly lower mean gestational lengths and birth weights, and higher frequencies of fetal death and pregnancy termination than babies with isolated anal anomalies. Twins were more frequent in sequences, VACTERL and MCA than in isolated anomalies, monogenic syndromes or chromosome anomalies. Five cases were conjoined twins, representing 15% of all cases of twin pregnancies with an anal anomaly. Indeterminate sex was more frequent in babies with anal atresias without fistula than in those with fistula. Anal anomalies are defects of blastogenesis attributable to disorders in expression of pattern determining genes. The differential sex involvement in different types of anal anomaly may be manifestations of expression of the HY/SRY genes during blastogenesis or of X-linkage.

Sulfur isotope variations from orebody to hand-specimen scale at the Mezica lead-zinc deposit, Slovenia: a predominantly biogenic pattern

The Mississippi Valley-type (MVT) Pb-Zn ore district at Mezica is hosted by Middle to Upper Triassic platform carbonate rocks in the Northern Karavanke/Drau Range geotectonic units of the Eastern Alps, northeastern Slovenia. The mineralization at Mezica covers an area of 64 km(2) with more than 350 orebodies and numerous galena and sphalerite occurrences, which formed epigenetically, both conformable and discordant to bedding. While knowledge on the style of mineralization has grown considerably, the origin of discordant mineralization is still debated. Sulfur stable isotope analyses of 149 sulfide samples from the different types of orebodies provide new insights on the genesis of these mineralizations and their relationship. Over the whole mining district, sphalerite and galena have delta(34)S values in the range of -24.7 to -1.5% VCDT (-13.5 +/- 5.0%) and -24.7 to -1.4% (-10.7 +/- 5.9%), respectively. These values are in the range of the main MVT deposits of the Drau Range. All sulfide delta(34)S values are negative within a broad range, with delta(34)S(pyrite) < delta(34)S(sphalerite) < delta(34)S(galena) for both conformable and discordant orebodies, indicating isotopically heterogeneous H(2)S in the ore-forming fluids and precipitation of the sulfides at thermodynamic disequilibrium. This clearly supports that the main sulfide sulfur originates from bacterially mediated reduction (BSR) of Middle to Upper Triassic seawater sulfate or evaporite sulfate. Thermochemical sulfate reduction (TSR) by organic compounds contributed a minor amount of (34)S-enriched H(2)S to the ore fluid. The variations of delta(34)S values of galena and coarse-grained sphalerite at orefield scale are generally larger than the differences observed in single hand specimens. The progressively more negative delta(34)S values with time along the different sphalerite generations are consistent with mixing of different H(2)S sources, with a decreasing contribution of H(2)S from regional TSR, and an increase from a local H(2)S reservoir produced by BSR (i.e., sedimentary biogenic pyrite, organo-sulfur compounds). Galena in discordant ore (-11.9 to -1.7%; -7.0 +/- 2.7%, n=12) tends to be depleted in (34)S compared with conformable ore (-24.7 to -2.8%, -11.7 +/- 6.2%, n=39). A similar trend is observed from fine-crystalline sphalerite I to coarse open-space filling sphalerite II. Some variation of the sulfide delta(34)S values is attributed to the inherent variability of bacterial sulfate reduction, including metabolic recycling in a locally partially closed system and contribution of H(2)S from hydrolysis of biogenic pyrite and thermal cracking of organo-sulfur compounds. The results suggest that the conformable orebodies originated by mixing of hydrothermal saline metal-rich fluid with H(2)S-rich pore waters during late burial diagenesis, while the discordant orebodies formed by mobilization of the earlier conformable mineralization.

Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells

Background PPP1R6 is a protein phosphatase 1 glycogen-targeting subunit (PP1-GTS) abundant in skeletal muscle with an undefined metabolic control role. Here PPP1R6 effects on myotube glycogen metabolism, particle size and subcellular distribution are examined and compared with PPP1R3C/PTG and PPP1R3A/GM. Results PPP1R6 overexpression activates glycogen synthase (GS), reduces its phosphorylation at Ser-641/0 and increases the extracted and cytochemically-stained glycogen content, less than PTG but more than GM. PPP1R6 does not change glycogen phosphorylase activity. All tested PP1-GTS-cells have more glycogen particles than controls as found by electron microscopy of myotube sections. Glycogen particle size is distributed for all cell-types in a continuous range, but PPP1R6 forms smaller particles (mean diameter 14.4 nm) than PTG (36.9 nm) and GM (28.3 nm) or those in control cells (29.2 nm). Both PPP1R6- and GM-derived glycogen particles are in cytosol associated with cellular structures; PTG-derived glycogen is found in membrane- and organelle-devoid cytosolic glycogen-rich areas; and glycogen particles are dispersed in the cytosol in control cells. A tagged PPP1R6 protein at the C-terminus with EGFP shows a diffuse cytosol pattern in glucose-replete and -depleted cells and a punctuate pattern surrounding the nucleus in glucose-depleted cells, which colocates with RFP tagged with the Golgi targeting domain of β-1,4-galactosyltransferase, according to a computational prediction for PPP1R6 Golgi location. Conclusions PPP1R6 exerts a powerful glycogenic effect in cultured muscle cells, more than GM and less than PTG. PPP1R6 protein translocates from a Golgi to cytosolic location in response to glucose. The molecular size and subcellular location of myotube glycogen particles is determined by the PPP1R6, PTG and GM scaffolding.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia (Spain).

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Alcohol use and frailty in community-dwelling older persons aged 65 to 70 years.

Background: Alcohol use has beneficial as well as adverse consequences on health, but few studies examined its role in the development of age-related frailty. Objectives: To describe the cross-sectional and longitudinal association between alcohol intake and frailty in older persons. Design: The Lausanne cohort 65+ population-based study, launched in 2004. Setting: Community. Participants: One thousand five hundred sixty-four persons aged 65-70 years. Measurements: Annual data collection included demographics, health and functional status, extended by a physical examination every 3 years. Alcohol use (AUDIT-C), and Fried's frailty criteria were measured at baseline and 3-year follow-up. Participants were categorized into robust (0 frailty criterion) and vulnerable (1+ criteria). Results: Few participants (13.0%) reported no alcohol consumption over the past year, 57.8% were light-to-moderate drinkers, while 29.3% drank above recommended thresholds (18.7% "at risk" and 10.5% "heavy" drinkers). At baseline, vulnerability was most frequent in non-drinkers (43.0%), least frequent in light-to-moderate drinkers (26.2%), and amounted to 31.9% in "heavy" drinkers showing a reverse J-curve pattern. In multivariate analysis, compared to light-to-moderate drinkers, non-drinkers had twice higher odds of prevalent (adjOR: 2.24; 95%CI:1.39-3.59; p=.001), as well as 3-year incident vulnerability (adjOR: 2.00; 95%CI:1.02-3.91; p=.043). No significant association was observed among "at risk" and "heavy" drinkers. Conclusion: Non-drinkers had two-times higher odds of prevalent and 3-year incident vulnerability, even after adjusting for their baseline poorer health status. Although residual confounding is still possible, these results likely reflect a healthy survival effect among drinkers while those who experienced health- or alcohol-related problems stopped drinking earlier.

Social and medical vulnerability factors of frequent users at the emergency department: a case-control study

BACKGROUND: Up to 5% of patients presenting to the emergency department (ED) four or more times within a 12 month period represent 21% of total ED visits. In this study we sought to characterize social and medical vulnerability factors of ED frequent users (FUs) and to explore if these factors hold simultaneously. METHODS: We performed a case-control study at Lausanne University Hospital, Switzerland. Patients over 18 years presenting to the ED at least once within the study period (April 2008 toMarch 2009) were included. FUs were defined as patients with four or more ED visits within the previous 12 months. Outcome data were extracted from medical records of the first ED attendance within the study period. Outcomes included basic demographics and social variables, ED admission diagnosis, somatic and psychiatric days hospitalized over 12 months, and having a primary care physician.We calculated the percentage of FUs and non-FUs having at least one social and one medical vulnerability factor. The four chosen social factors included: unemployed and/or dependence on government welfare, institutionalized and/or without fixed residence, either separated, divorced or widowed, and under guardianship. The fourmedical vulnerability factors were: ≥6 somatic days hospitalized, ≥1 psychiatric days hospitalized, ≥5 clinical departments used (all three factors measured over 12 months), and ED admission diagnosis of alcohol and/or drug abuse. Univariate and multivariate logistical regression analyses allowed comparison of two JGIM ABSTRACTS S391 random samples of 354 FUs and 354 non-FUs (statistical power 0.9, alpha 0.05 for all outcomes except gender, country of birth, and insurance type). RESULTS: FUs accounted for 7.7% of ED patients and 24.9% of ED visits. Univariate logistic regression showed that FUs were older (mean age 49.8 vs. 45.2 yrs, p=0.003),more often separated and/or divorced (17.5%vs. 13.9%, p=0.029) or widowed (13.8% vs. 8.8%, p=0.029), and either unemployed or dependent on government welfare (31.3% vs. 13.3%, p<0.001), compared to non-FUs. FUs cumulated more days hospitalized over 12 months (mean number of somatic days per patient 1.0 vs. 0.3, p<0.001; mean number of psychiatric days per patient 0.12 vs. 0.03, p<0.001). The two groups were similar regarding gender distribution (females 51.7% vs. 48.3%). The multivariate linear regression model was based on the six most significant factors identified by univariate analysis The model showed that FUs had more social problems, as they were more likely to be institutionalized or not have a fixed residence (OR 4.62; 95% CI, 1.65 to 12.93), and to be unemployed or dependent on government welfare (OR 2.03; 95% CI, 1.31 to 3.14) compared to non-FUs. FUs were more likely to need medical care, as indicated by involvement of≥5 clinical departments over 12 months (OR 6.2; 95%CI, 3.74 to 10.15), having an ED admission diagnosis of substance abuse (OR 3.23; 95% CI, 1.23 to 8.46) and having a primary care physician (OR 1.70;95%CI, 1.13 to 2.56); however, they were less likely to present with an admission diagnosis of injury (OR 0.64; 95% CI, 0.40 to 1.00) compared to non-FUs. FUs were more likely to combine at least one social with one medical vulnerability factor (38.4% vs. 12.1%, OR 7.74; 95% CI 5.03 to 11.93). CONCLUSIONS: FUs were more likely than non-FUs to have social and medical vulnerability factors and to have multiple factors in combination.

Metabolic activation pattern of distinct hippocampal subregions during spatial learning and memory retrieval.

Activation dynamics of hippocampal subregions during spatial learning and their interplay with neocortical regions is an important dimension in the understanding of hippocampal function. Using the (14C)-2-deoxyglucose autoradiographic method, we have characterized the metabolic changes occurring in hippocampal subregions in mice while learning an eight-arm radial maze task. Autoradiogram densitometry revealed a heterogeneous and evolving pattern of enhanced metabolic activity throughout the hippocampus during the training period and on recall. In the early stages of training, activity was enhanced in the CA1 area from the intermediate portion to the posterior end as well as in the CA3 area within the intermediate portion of the hippocampus. At later stages, CA1 and CA3 activations spread over the entire longitudinal axis, while dentate gyrus (DG) activation occurred from the anterior to the intermediate zone. Activation of the retrosplenial cortex but not the amygdala was also observed during the learning process. On recall, only DG activation was observed in the same anterior part of the hippocampus. These results suggest the existence of a functional segmentation of the hippocampus, each subregion being dynamically but also differentially recruited along the acquisition, consolidation, and retrieval process in parallel with some neocortical sites.

A characteristic EEG pattern in 4p-syndrome: case report and review of the literature.

Deletions on the short arm of chromosome 4 cause Wolf-Hirschhorn syndrome (WHS) and Pitt-Rogers-Danks syndrome (PRDS). WHS is associated with severe growth and mental retardation, microcephaly, a characteristic facies and congenital malformations. The PRDS phenotype is similar to WHS but generally less severe. Seizures occur in the majority of WHS and PRDS patients. Sgrò et al. [17] described a stereotypic electroclinical pattern in four unrelated WHS patients, consisting of intermittent bursts of 2-3 Hz high voltage slow waves with spike wave activity in the parietal areas during drowsiness and sleep associated with myoclonic jerks. We report a patient with PRDS and the typical EEG pattern and review 14 WHS patients with similar EEG findings reported in the literature. CONCLUSION: Awareness and recognition of the characteristic electroclinical findings in Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome might help in the early diagnosis of such patients.

Cerebral aneurysm exclusion by CT angiography based on subarachnoid hemorrhage pattern: a retrospective study

Contexte : Identifier les patients avec une hémorragie sous-arachnoïdienne spontanée chez qui l'angio-CT suffit pour exclure des anévrysmes rompus.Méthodes : Une étude rétrospective a été effectuée de tous les patients avec une hémorragie sous-arachnoïdienne qui ont eu un angio-CT ainsi qu'une angiographie par cathéter dans le but d'exclure un anévrysme. Les cas négatifs de l'angio-CT (sans anévrysmes) ont été classés d'après leur schéma hémorragique au CT dans les catégories suivantes : « anévrysmale », « périmésencéphalique » puis « sans hémorragie ».Résultats : Deux-cent-quarante-et-un patients ont été inclus. Une sensibilité de 96.4% et une spécificité de 96.0% ont été observée pour l'exclusion d'anévrysmes par l'angio-CT. Parmi les 78 cas négatifs de l'angio-CT, chacun des 35 cas avec un motif hémorragique périmésencéphalique ou sans hémorragie au CT n'ont pas eu d'anévrysmes démontrés à l'angiographie par cathéter.Conclusions: L'angio-CT est fiable pour exclure les anévrysmes rompus lorsqu'un motif hémorragique périmésencéphalique ou pas d'hémorragie sont visibles au CT à une semaine depuis le début des symptômes.

Injury pattern of the Flash-Ball, a less-lethal weapon used for law enforcement: report of two cases and review of the literature.

Less-lethal weapons are used in law enforcement to neutralize combative individuals and to disperse riot crowds. Local police recently used such an impact weapon, the Flash-Ball, in two different situations. This gun fires large rubber bullets with kinetic energies around 200 J. Although it is designed to avoid skin penetration, impacts at such energies may still create major trauma with associated severe injuries to internal organs. This is a report of 2 patients shot with the Flash-Ball who required medical attention. One could be discharged quickly, but the other required hospitalization for heart and lung contusion. Both patients required advanced investigations including computed tomography (CT) scan. The medical literature on injuries induced by less-lethal impact weapons is reviewed. Impacts from the Flash-Ball can cause significant injury to internal organs, even without penetration. Investigations as for other high-energy blunt traumas are called for in these cases.

Owl melanin-based plumage redness is more frequent near than away from the equator: implications on the effect of climate change on biodiversity

Climate change acts as a major new selective agent on many organisms, particularly at high latitudes where climate change is more pronounced than at lower latitudes. Studies are required to predict which species are at a high risk of extinction and whether certain phenotypes may be more affected by climate change than others. The identification of susceptible phenotypes is important for evaluating the potential negative effect of climate change on biodiversity at the inter- and intraspecific levels. Melanin-based coloration is an interesting and easily accessible candidate trait because, within certain species, reddish pheomelanin-based coloration is associated with adaptations to warm climates. However, it is unclear whether the same holds among species. We tested one prediction of this hypothesis in four owl genera (wood, scops, screech, and pygmy owls), namely that darker reddish species are more prevalent near the equator than polewards. Our comparative analysis is consistent with this prediction for the northern hemisphere, suggesting that pale reddish species may be adapted to cold climates and dark reddish species to warmer climates. Thus, climate change may have a larger negative impact on pale pheomelanic owls and favour dark pheomelanic species.