Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department.

BACKGROUND To date, the use of proton pump inhibitors (PPIs) has been associated with a low risk of hypomagnesaemia and associated adverse outcomes. We hypothesised that a better risk estimate could be derived from a large cohort of outpatients admitted to a tertiary emergency department (ED). METHODS A cross-sectional study was performed in 5118 patients who had measurements of serum magnesium taken on admission to a large tertiary care ED between January 2009 and December 2010. Hypomagnesaemia was defined as a serum magnesium concentration < 0.75 mmol/l. Demographical data, serum electrolyte values, data on medication, comorbidities and outcome with regard to length of hospital stay and mortality were analysed. RESULTS Serum magnesium was normally distributed where upon 1246 patients (24%) were hypomagnesaemic. These patients had a higher prevalence of out-of-hospital PPI use and diuretic use when compared with patients with magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression analyses adjusted for PPIs, diuretics, renal function and the Charlson comorbidity index score, the association between use of PPIs and risk for hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While mortality was not directly related to low magnesium levels (p = 0.67), the length of hospitalisation was prolonged in these patients even after adjustment for underlying comorbid conditions (p < 0.0001). CONCLUSION Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.

Reconstruction of femoro-acetabular offsets using a short-stem

PURPOSE Despite the fact that new and modern short-stems allow bone sparing and saving of soft-tissue and muscles, we still face the challenge of anatomically reconstructing the femoro-acetabular offset and leg length. Therefore a radiological and clinical analysis of a short-stem reconstruction of the femoro-acetabular offset and leg length was performed. METHODS Using an antero-lateral approach, the optimys short-stem (Mathys Ltd, Bettlach, Switzerland) was implanted in 114 consecutive patients in combination with a cementless cup (Fitmore, Zimmer, Indiana, USA; vitamys RM Pressfit, Mathys Ltd, Bettlach, Switzerland). Pre- and postoperative X-rays were done in a standardized technique. In order to better analyse and compare X-ray data a special double coordinate system was developed for measuring femoral- and acetabular offset. Harris hip score was assessed before and six weeks after surgery. Visual analogue scale (VAS) satisfaction, leg length difference and the existence of gluteal muscle insufficiency were also examined. RESULTS Postoperative femoral offset was significantly increased by a mean of 5.8 mm. At the same time cup implantation significantly decreased the acetabular offset by a mean of 3.7 mm, which resulted in an increased combined femoro-acetabular offset of 2.1 mm. Postoperatively, 81.7 % of patients presented with equal leg length. The maximum discrepancy was 10 mm. Clinically, there were no signs of gluteal insufficiency. No luxation occurred during hospitalization. The Harris hip score improved from 47.3 before to 90.1 points already at six weeks after surgery while the mean VAS satisfaction was 9.1. CONCLUSION The analysis showed that loss of femoro-acetabular offset can be reduced with an appropriate stem design. Consequently, a good reconstruction of anatomy and leg length can be achieved. In the early postoperative stage the clinical results are excellent.

A Genome-Wide Association Study Reveals Loci Influencing Height and Other Conformation Traits in Horses

The molecular analysis of genes influencing human height has been notoriously difficult. Genome-wide association studies (GWAS) for height in humans based on tens of thousands to hundreds of thousands of samples so far revealed ∼200 loci for human height explaining only 20% of the heritability. In domestic animals isolated populations with a greatly reduced genetic heterogeneity facilitate a more efficient analysis of complex traits. We performed a genome-wide association study on 1,077 Franches-Montagnes (FM) horses using ∼40,000 SNPs. Our study revealed two QTL for height at withers on chromosomes 3 and 9. The association signal on chromosome 3 is close to the LCORL/NCAPG genes. The association signal on chromosome 9 is close to the ZFAT gene. Both loci have already been shown to influence height in humans. Interestingly, there are very large intergenic regions at the association signals. The two detected QTL together explain ∼18.2% of the heritable variation of height in horses. However, another large fraction of the variance for height in horses results from ECA 1 (11.0%), although the association analysis did not reveal significantly associated SNPs on this chromosome. The QTL region on ECA 3 associated with height at withers was also significantly associated with wither height, conformation of legs, ventral border of mandible, correctness of gaits, and expression of the head. The region on ECA 9 associated with height at withers was also associated with wither height, length of croup and length of back. In addition to these two QTL regions on ECA 3 and ECA 9 we detected another QTL on ECA 6 for correctness of gaits. Our study highlights the value of domestic animal populations for the genetic analysis of complex traits.

Un modèle animal simple pour l'apprentissage des techniques de microanastomoses vasculaires de congruences diefférentes

BACKGROUND Since the pioneering work of Jacobson and Suarez, microsurgery has steadily progressed and is now used in all surgical specialities, particularly in plastic surgery. Before performing clinical procedures it is necessary to learn the basic techniques in the laboratory. OBJECTIVE To assess an animal model, thereby circumventing the following issues: ethical rules, cost, anesthesia and training time. METHODS Between July 2012 and September 2012, 182 earthworms were used for 150 microsurgical trainings to simulate discrepancy microanastomoses. Training was undertaken over 10 weekly periods. Each training session included 15 simulations of microanastomoses performed using the Harashina technique (earthworm diameters >1.5 mm [n=5], between 1.0 mm and 1.5 mm [n=5], and <1.0 mm [n=5]). The technique is presented and documented. A linear model with main variable as the number of the week (as a numeric covariate) and the size of the animal (as a factor) was used to determine the trend in time of anastomosis over subsequent weeks as well as differences between the different size groups. RESULTS The linear model showed a significant trend (P<0.001) in time of anastomosis in the course of the training, as well as significant differences (P<0.001) between the groups of animal of different sizes. For diameter >1.5 mm, mean anastomosis time decreased from 19.6±1.9 min to 12.6±0.7 min between the first and last week of training. For training involving smaller diameters, the results showed a reduction in execution time of 36.1% (P<0.01) (diameter between 1.0 mm and 1.5 mm) and 40.6% (P<0.01) (diameter <1.0 mm) between the first and last weeks. The study demonstrates an improvement in the dexterity and speed of nodes' execution. CONCLUSION The earthworm appears to be a reliable experimental model for microsurgical training of discrepancy microanastomoses. Its numerous advantages, as discussed in the present report, show that this model of training will significantly grow and develop in the near future.

Glacier advances in northeastern Turkey before and during the global Last Glacial Maximum

Abstract Our study in the Başyayla Valley in northeastern Anatolia showed evidence of four glacier advances that built terminal and lateral moraines. Surface exposure dating of boulders on these moraines showed that the Maximum Ice Extent (MIE) was asynchronous with the global Last Glacial Maximum (LGM; 22.1 ± 4.3 thousand years; ka). The local {MIE} took place at least 57.0 ± 3.5 ka ago. The extent of the Başyayla Glacier during this advance is not known exactly because the boulders are only preserved on a lateral moraine. The next advance was prior to 41.5 ± 2.5 ka, and it descended down the valley to approximately 2320 m above sea level (m a.s.l.), with a glacier length of 5.3 km. During the early global LGM, the Başyayla Glacier extended for a distance of 4.9 km down to approx. 2430 m a.s.l. The last recorded advance occurred during the global LGM. This extension was 0.7 km smaller than the local {MIE} and its terminus reached 2490 m a.s.l. only. The exposure ages of boulders in a retreat position at an altitude of approx. 3045 m a.s.l. indicate that the valley has remained ice-free since the Lateglacial period. Therefore, the Lateglacial extent was limited to the cirque system in the uppermost part of the catchment. Furthermore, Holocene glacier oscillations seem to be either absent or restricted to solifluction in the whole catchment and to rock glacier movements in the southern tributary of the Başyayla Valley system.

A 5'-3' exonuclease activity involved in forming the 3' products of histone pre-mRNA processing in vitro.

Histone RNA 3' processing in vitro produces one or more 5' cleavage products corresponding to the mature histone mRNA 3' end, and a group of 3' cleavage products whose 5' ends are mostly located several nucleotides downstream of the mRNA 3' end. The formation of these 3' products is coupled to the formation of 5' products and dependent on the U7 snRNP and a heat-labile processing factor. These short 3' products therefore are a true and general feature of the processing reaction. Identical 3' products are also formed from a model RNA containing all spacer nucleotides downstream of the mature mRNA 3' end, but no sequences from the mature mRNA. Again, this reaction is dependent on both the U7 snRNP and a heat-labile factor. Unlike the processing with a full-length histone pre-mRNA, this reaction produces only 3' but no 5' fragments. In addition, product formation is inhibited by addition of cap structures at the model RNA 5' end, indicating that product formation occurs by 5'-3' exonucleolytic degradation. This degradation of a model 3' product by a 5'-3' exonuclease suggests a mechanism for the release of the U7 snRNP after processing by shortening the cut-off histone spacer sequences base paired to U7 RNA.

Trajectories of psychological adaptation to marital breakup after a long-term marriage

Background: Marital dissolution is known to be among the most stressful life events with long- reaching negative consequences on individuals’ lives. A limitation in research to date is that most studies have focused on the impact of marital disruption on well-being outcomes in younger adults. Furthermore, although population-based studies on divorce document a broad range of negative effects, more fine-grained analyses reveal a large heterogeneity in people’s adjustment, which is still not well understood. Objective: To explore trajectories of psychological adaptation to marital breakup after a long-term marriage, and to examine variables accounting for recovery or chronicity in terms of intrapersonal resources (personality, trait resilience, personal growth), relationship variables (satisfaction with ex- relationship, length of marriage, time since divorce) and socio-demographic variables (age, gender, financial situation). Methods: Latent transition analysis is used to examine the course of psychological adaptation (i.e., depressive symptoms, life satisfaction, hopelessness, mourning and subjective health) to divorce over two years among five profiles of 308 divorcees (mean age: 55.6 years; average duration of former marriage: 23.62 years): Two larger groups of individuals, the one which adapted very well (‘resilients’, 29%), the other quite well (‘average copers’, 49%), and three groups with major difficulties (‘vulnerables’, 6%; ‘malcontents’, 12%; and ‘resigned’, 4%). In a second step the differences among transition patterns were explored on the basis of the distal variables (i.e., intrapersonal resources, relationship variables, socio-demographics). Results: Although the probability of upward changes was higher for those individuals with lower adaptation at time 1, only a small number of individuals made an upward change from the maladapted to the well-adapted groups throughout the two years. The groups of copers and resilients remained stable in their psychological adaption. The most consistent results related to upward changes were intrapersonal resources, namely the NEO personality traits and trait resilience. Conclusion: The majority of individuals divorcing after a long-term marriage adapt successfully over time. Adaptation trajectories depend primarily on intrapersonal resources. However, a minority of divorcees exhibit enduring difficulties. Knowledge about the diversity of these trajectories of vulnerability could be of great help for designing psychological interventions to better tackle this critical life event.

An automated method for mapping physical soil and water conservation structures on cultivated land using GIS and remote sensing techniques

An efficient and reliable automated model that can map physical Soil and Water Conservation (SWC) structures on cultivated land was developed using very high spatial resolution imagery obtained from Google Earth and ArcGIS, ERDAS IMAGINE, and SDC Morphology Toolbox for MATLAB and statistical techniques. The model was developed using the following procedures: (1) a high-pass spatial filter algorithm was applied to detect linear features, (2) morphological processing was used to remove unwanted linear features, (3) the raster format was vectorized, (4) the vectorized linear features were split per hectare (ha) and each line was then classified according to its compass direction, and (5) the sum of all vector lengths per class of direction per ha was calculated. Finally, the direction class with the greatest length was selected from each ha to predict the physical SWC structures. The model was calibrated and validated on the Ethiopian Highlands. The model correctly mapped 80% of the existing structures. The developed model was then tested at different sites with different topography. The results show that the developed model is feasible for automated mapping of physical SWC structures. Therefore, the model is useful for predicting and mapping physical SWC structures areas across diverse areas.

Comparison of Mixed and Kinematic Uniform Boundary Conditions in Homogenized Elasticity of Femoral Trabecular Bone Using Microfinite Element Analyses

Mechanical properties of human trabecular bone play an important role in age-related bone fragility and implant stability. Micro-finite element (microFE) analysis allows computing the apparent elastic properties of trabecular bone biopsies, but the results depend on the type of applied boundary conditions (BCs). In this study, 167 femoral trabecular cubic biopsies with a side length of 5.3 mm were analyzed using microFE analysis to compare their stiffness systematically with kinematic uniform boundary conditions (KUBCs) and periodicity-compatible mixed uniform boundary conditions (PMUBCs). The obtained elastic constants were then used in the volume fraction and fabric-based orthotropic Zysset-Curnier model to identify their respective model parameters. As expected, PMUBCs lead to more compliant apparent elastic properties than KUBCs, especially in shear. The differences in stiffness decreased with bone volume fraction and mean intercept length. Unlike KUBCs, PMUBCs were sensitive to heterogeneity of the biopsies. The Zysset-Curnier model predicted apparent elastic constants successfully in both cases with adjusted coefficients of determination of 0.986 for KUBCs and 0.975 for PMUBCs. The role of these boundary conditions in finite element analyses of whole bones and bone-implant systems will need to be investigated in future work.

T- and B-cell responses and previous exposure to hepatitis B virus in 'anti-HBc alone' patients.

A serologic response to hepatitis B virus (HBV) defined as 'anti-HBc alone' is commonly observed, but its significance remains unclear. This study aimed to define the relationship between 'anti-HBc alone' serostatus and HBV infection, including HBV-specific T- and B-cell memory responses. We enrolled 31 'anti-HBc alone' patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 'anti-HBc alone' patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN-γ secretion by HBV-specific T cells was compared in individuals who were 'anti-HBc alone' (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme-linked immunospot (ELISpot) assays. An HBsAg-IgG B-cell ELISpot assay was performed in 'anti-HBc alone' patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the 'anti-HBc alone' individuals were co-infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV-specific T-cell responses were similar between 'anti-HBc alone' individuals and HBV resolvers. Circulating HBV-memory B-cell responses were detected in all 'anti-HBc alone' individuals, consistent with an HBsAg-specific memory pool. After one HBV vaccine dose, increased anti-HBs antibody levels were observed, accompanied by an expansion of HBsAg-specific memory B cells (P = 0.0226). 'Anti-HBc alone' individuals showed HBV-specific T-cell and memory B-cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.

Long-term hyperexcitability of sensory and motor axons in Aplysia californica: Induction by axotomy, serotonin, and transient depolarization

Neuropathic pain is a debilitating neurological disorder that may appear after peripheral nerve trauma and is characterized by persistent, intractable pain. The well-studied phenomenon of long-term hyperexcitability (LTH), in which sensory somata become hyperexcitable following peripheral nerve injury may be important for both chronic pain and long-lasting memory formation, since similar cellular alterations take place after both injury and learning. Though axons have previously been considered simple conducting cables, spontaneous afferent signals develop from some neuromas that form at severed nerve tips, indicating intrinsic changes in sensory axonal excitability may contribute to this intractable pain. Here we show that nerve transection, exposure to serotonin, and transient depolarization induce long-lasting sensory axonal hyperexcitability that is localized to the treated nerve segment and requires local translation of new proteins. Long-lasting functional plasticity may be a general property of axons, since both injured and transiently depolarized motor axons display LTH as well. Axonal hyperexcitability may represent an adaptive mechanism to overcome conduction failure after peripheral injury, but also displays key features shared with cellular analogues of memory including: site-specific changes in neuronal function, dependence on transient, focal depolarization for induction, and requirement for synthesis of new proteins for expression of long-lasting effects. The finding of axonal hyperexcitability after nerve injury sheds new light on the clinical problem of chronic neuropathic pain, and provides more support for the hypothesis that mechanisms of long-term memory storage evolved from primitive adaptive responses to injury. ^

A COMPARISON OF COUNTY HOSPITAL UTILIZATION BEFORE AND AFTER INTERVENTION BY THE HOSPITAL'S ALCOHOLISM SERVICES PROGRAM

This study examines the reduction in hospital utilization of 393 public hospital patients who were referred to the hospital's alcoholism screening program for intervention. The 393 patients were the total patient population of the alcoholism screening program for the period of September through December, 1982. Medical records of these patients were investigated to assess the total number of hospital days six months before and six months after intervention. The findings support the hypothesis of decreased utilization. The total number of hospital days for 393 patients before intervention of the alcoholism program was 3,458, with a mean length of stay of 8.80 days. The total number of hospital days after intervention was 458 days, with a mean length of stay of 6.50 days. The average individual difference (decrease) was 7.63 days for one year. From a total of 393 patients counseled by the alcoholism program, 106 (27%) went to treatment for their alcoholism. Other aims were to examine the referral sources (physicians, nurses, social workers and the MAST); study the impact of familial history of alcoholism on referrals, and explore the MAST scores of patients successfully referred. Implications of the study are that it would benefit the public hospital, with their disproportionate numbers of alcoholics, to intervene in the behavioral patterns of alcoholism. Such intervention would be a factor in reducing the overall hospitalization of the alcoholic. ^

THE BACON CHOW STUDY: THE RELATIONSHIP BETWEEN INFECTIOUS ILLNESS AND GROWTH OF INFANTS

Multiple dietary deficiencies and high rates of infectious illness are major health problems leading to malnutrition and limitation of growth of children in developing countries. Longitudinal studies which provide information on illness incidence and growth velocity are needed in order to untangle the complex interrelationship between nutrition, illness and growth. From 1967 to 1973, researchers led by Dr. Bacon Chow of the Johns Hopkins University School of Hygiene undertook a quasi-experimental prospective study in Suilin Township, Taiwan to determine the effects of a nutritional supplement to the diets of pregnant and lactating women on the growth, development and resistance to disease of their offspring. This dissertation presents results from the analysis of infant morbidity and postnatal growth.^ Maternal nutritional supplementation has no apparent effect on the postnatal growth or morbidity of infants. Significant sex differences exist in growth response to illness and in illness susceptibility. Male infants have more diarrhea and upper respiratory illness. Respiratory illness is positively associated with growth rate in weight in the first semester of life. Diarrhea is significantly negatively associated with growth in length in the second semester. Small-for-date infants are more susceptible to illness in general and have a different pattern of growth response than large-for-date infants.^ Principal components analysis of illness data is shown to be an effective technique for making more precise use of ambiguous morbidity data. Multiple regression with component scores is an accurate method for estimating variance in growth rate predicted by indepenent illness variables. A model is advanced in which initial postnatal growth rate determines subsequent susceptibility to nutritional stress and infection. Initial growth rate is a function of prenatal nutrition, but is not significantly affected by maternal supplementation during gestation or lactation. Critical evaluation is made of nutritional supplementation programs which do not afford disease control.^

IL -12 inhibits the metastatic potential of osteosarcoma cells and induces tumor regression via a mechanism involving Fas /Fas ligand pathway

Despite multiple changes in the adjuvant chemotherapy regimens used to treat osteosarcoma (OS), the 2-year metastasis-free survival has remained at 65–70% for the past 10 years. Characterizing the molecular determinants that permit metastatic spread of tumor cells is a crucial element in developing new approaches for the treatment of osteosarcoma. Since OS metastasizes almost exclusively to the lung, an organ with constitutive Fas ligand (FasL) expression, we hypothesized that the expression of Fas (CD95, APO-1) by OS cells may play a role in the ability of these cells to form lung metastases. Fas expression was quantified in human SAOS-2 OS cells and selected variants (LM2, LM4, LM5, LM6, LM7). Using northern blot, FACS and RT-PCR analysis, low Fas expression was found to correlate with higher metastatic potential in these cell lines. The highly metastatic LM7 cell line was transfected with the full-length human Fas gene and injected into athymic nude mice. The median number of metastatic nodules per mouse fell from over 200 to 1.1 and the size of the nodules decreased from a range of 0.5–9.0 mm to less than 0.5 mm in the Fas-transfected cell line compared to the native LM7 cell line. Additionally, the subsequent incidence of lung metastases was lower in the Fas-expressing cell line. IL-12 was seen to upregulate Fas expression in the highly metastatic LM sublines in vitro. To visualize the effects of IL-12 in vivo, nude mice were injected with LM7 cells and treated biweekly for 4 weeks with Ad.mIL-12, saline control or Ad.βgal. Lung sections were analyzed via immunchistochemistry for Fas expression. A higher expression of Fas was found in tumors from mice receiving IL-12. To study the mechanism by which IL-12 upregulates Fas, LM7 cells were transfected with a luciferase reporter gene construct containing the full-length human fas promoter. Treatment with IL-12 increased luciferase activity. We therefore conclude that IL-12 influences the metastatic potential of OS cells by upregulating the fas promoter, resulting in increased cell surface Fas expression and susceptibility to Fas-induced cell death. ^

Abundance and biomass of zooplankton from 1986-1994 collected in front of Constanta city, Black Sea

The Est Constanta 1986-1994 dataset contains zooplankton data collected allong a 5 station transect in front of the city Constanta (44°10'N, 28°41.5'E - EC1; 44°10'N, 28°47'E - EC2; 44°10'N, 28°54'E - EC3; 44°10'N, 29°08'E - EC4; 44°10'N, 29°22'E - EC5). Zooplankton sampling was undertaken at 5 stations where samples were collected using a Juday closing net in the 0-10, 10-25, 25-50m layer (depending also on the water masses). The dataset includes samples analysed for mesozooplankton species composition and abundance. Sampling volume was estimated by multiplying the mouth area with the wire length. Taxon-specific mesozooplankton abundance was count under microscope. Total abundance is the sum of the counted individuals. Total biomass Fodder, Rotifera , Ctenophora and Noctiluca was estimated using a tabel with wet weight for each species an stage.