Calcium Uptake and Release through Sarcoplasmic Reticulum in the Inferior Oblique Muscles of Patients with Inferior Oblique Overaction

We characterized and compared the characteristics of Ca2+ movements through the sarcoplasmic reticulum of inferior oblique muscles in the various conditions including primary inferior oblique overaction (IOOA), secondary IOOA, and controls, so as to further understand the pathogenesis of primary IOOA. Of 15 specimens obtained through inferior oblique myectomy, six were from primary IOOA, 6 from secondary IOOA, and the remaining 3 were controls from enucleated eyes. Ryanodine binding assays were performed, and Ca2+ uptake rates, calsequestrins and SERCA levels were determined. Ryanodine bindings and sarcoplasmic reticulum Ca2+ uptake rates were significantly decreased in primary IOOA (p<0.05). Western blot analysis conducted to quantify calsequestrins and SERCA, found no significant difference between primary IOOA, secondary IOOA, and the controls. Increased intracellular Ca2+ concentration due to reduced sarcoplasmic reticulum Ca2+ uptake may play a role in primary IOOA

Lead and Cadmium Levels and Balance and Vestibular Dysfunction among Adult Participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2004

Background: Few studies have been conducted to identify risk factors for balance and vestibular dysfunction in general populations, but previous studies have reported evidence of adverse effects of lead and cadmium on balance control in high-risk groups

A complex regional intervention to implement advance care planning in one town's nursing homes: Protocol of a controlled inter-regional study

<p>Abstract</p> <p>Background</p> <p>Advance Care Planning (ACP) is an emerging strategy to ensure that well-reflected, meaningful and clearly documented treatment preferences are available and respected when critical decisions about life-sustaining treatment need to be made for patients unable to consent. In Germany, recent legislation confirms that advance directives (AD) have to be followed if they apply to the medical situation, but implementation of ACP has not yet been described.</p> <p>Methods/Design</p> <p>In a longitudinal controlled study, we compare 1 intervention region (4 nursing homes [n/hs], altogether 421 residents) with 2 control regions (10 n/hs, altogether 985 residents). Inclusion went from 01.02.09 to 30.06.09, observation lasted until 30.06.10. Primary endpoint is the prevalence of ADs at follow-up, 17 (12) months after the first (last) possible inclusion. Secondary endpoints compare relevance and validity of ADs, process quality, the rate of life-sustaining interventions and, in deceased residents, location of death and intensity of treatment before death. The regional multifaceted intervention on the basis of the US program Respecting Choices^®comprises training of n/h staff as facilitators, training of General Practitioners, education of hospital and ambulance staff, and development of eligible tools, including Physician Orders for Life-Sustaining Treatment in case of Emergency (POLST-E).</p> <p><it>Participation data: </it>Of 1406 residents reported to live in the 14 n/hs plus an estimated turnover of 176 residents until the last possible inclusion date, 645 (41%) were willing to participate. Response rates were 38% in the intervention region and 42% in the control region. Non-responder analysis shows an equal distribution of sex and age but a bias towards dependency on nursing care in the responder group. <it>Outcome analysis </it>of this study will become available in the course of 2011.</p> <p>Discussion</p> <p>Implementing an ACP program for the n/hs and related health care providers of a region requires a complex community intervention with the effect of nothing less than a cultural shift in this health care sector. This study is to our knowledge the first to develop a strategy for regional implementation of ACP, and to evaluate its feasibility in a controlled design.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN99887420">ISRCTN99887420</a></p

Life satisfaction and confidence in national institutions: evidence from South America

A number of South American countries experienced turbulent democratic, political and economic upheaval over the last 40 years in the form of coup d’états in the 1970s, tumultuous elections, and repeated severe economic crises, some of which happened fairly recently. Starting in 2010, a number of court proceedings across the region have made past military coup d’états the focus of national conversations. South American citizens may, therefore, have lost confidence in national institutions that have repeatedly disappointed their trust and expectations; a situation with potentially detrimental effects on their well-being. Using eight waves of the Gallup World Poll collected between 2009 and 2016 across ten South American countries, we investigate to what extent people’s confidence in financial institutions, the honesty of elections, the military, the judicial system, the national government and the police is associated with people’s current and expectation of future life satisfaction. We find that people who report confidence in these six institutions rate their current and expected life satisfaction, on average, to be higher than those who lack these types of institutional confidence, even after controlling for demographic factors and macroeconomic indicators. In addition, we investigate changes over time for all six measures of confidence in institutions as well as for current and expectation of future life satisfaction. Our results suggest that governments’ investments in well-functioning institutions may contribute positively to subjective well-being in a society. However, our analysis is correlational and we thus cannot rule out reverse causality

CHD7 Mutational Analysis and Clinical Considerations for Auditory Rehabilitation in Deaf Patients with CHARGE Syndrome

BACKGROUND: Otologic manifestations are one of the most consistent findings of CHARGE syndrome found in more than 90%. Since genetic analysis of the CHD7 gene has rarely been performed in previous reports dealing with ear abnormalities, the genotypic spectrum of CHD7 mutations was analyzed in deaf patients with CHARGE syndrome, and the clinical considerations concerning auditory rehabilitation were investigated. METHODS: Nine Korean patients with CHARGE syndrome showing profound hearing loss and semicircular canal aplasia were included. All 38 exons of CHD7 were analyzed by direct sequencing. For splice site variations, in silico and exon-trapping analyses were performed to verify the pathogenicity of nucleotide variations. Clinical features and the outcome of auditory rehabilitation were also analyzed. RESULTS: Eight of 9 patients revealed alterations of the CHD7 gene including 3 frameshift, 2 nonsense, 2 splice site, and 1 missense mutations. Five of 9 patients were clinically diagnosed as atypical CHARGE syndrome but demonstrated various mutations of the CHD7 gene. One familial case showed intra-familial variability. Radiologic findings suggesting cochleovestibular nerve deficiency were identified in most of the patients. Of the 8 patients who underwent cochlear implantation, 5 patients demonstrated favorable outcome. Larger diameter of the cochleovestibular nerve on imaging and absence of severe mental retardation were factors related to better outcome after cochlear implantation rather than the type of CHD7 mutations. Auditory brainstem implantation was performed in two patients who did not benefit from cochlear implantation. CONCLUSIONS: Genetic analysis of the CHD7 gene should be performed in cases with semicircular canal aplasia even when other typical features of CHARGE syndrome are absent. For auditory rehabilitation in CHARGE syndrome, cochlear implantation should be strongly recommended in selected cases with favorable prognostic factors. Auditory brainstem implantation may be a viable option in patients with CHARGE syndrome who have failed to benefit from cochlear implantation

Politicians lie, so do I

This research analyzed whether political leaders make people lie via priming experiments. Priming is a non-conscious and implicit memory effect in which exposure to one stimulus affects the response to another stimulus. Following priming theories, we proposed an innovative concept that people who perceive leaders to be dishonest (such as liar) are likely to lie themselves. We designed three experiments to analyze and critically discussed the potential influence of prime effect on lying behavior, through the prime effect of French political leaders (inc. general politicians, presidents and parties). Experiment 1 discovered that participants with non-politician-prime were less likely to lie (compared to politician-prime). Experiment 2A discovered that, compared to Hollande-prime, Sarkozy-prime led to lying behavior both in gravity (i.e. bigger lies) and frequency (i.e. lying more frequently). Experiment 2B discovered that Republicans-prime yielded an impact on more lying behavior, and Sarkozy-prime made such impact even stronger. Overall, the research findings suggest that lying can be triggered by external influencers such as leaders, presidents and politicians in the organizations. Our findings have provided valuable insights to organizational leaders and managers in their personnel management practice, especially in the intervention of lying behavior. Our findings also have offered new insights to explain non-conscious lying behavior

Mammalian Glutaminase Gls2 Gene Encodes Two Functional Alternative Transcripts by a Surrogate Promoter Usage Mechanism

Glutaminase is expressed in most mammalian tissues and cancer cells, but the regulation of its expression is poorly understood. An essential step to accomplish this goal is the characterization of its species- and cell-specific isoenzyme pattern of expression. Our aim was to identify and characterize transcript variants of the mammalian glutaminase Gls2 gene.We demonstrate for the first time simultaneous expression of two transcript variants from the Gls2 gene in human, rat and mouse. A combination of RT-PCR, primer-extension analysis, bioinformatics, real-time PCR, in vitro transcription and translation and immunoblot analysis was applied to investigate GLS2 transcripts in mammalian tissues. Short (LGA) and long (GAB) transcript forms were isolated in brain and liver tissue of human, rat and mouse. The short LGA transcript arises by a combination of two mechanisms of transcriptional modulation: alternative transcription initiation and alternative promoter. The LGA variant contains both the transcription start site (TSS) and the alternative promoter in the first intron of the Gls2 gene. The full human LGA transcript has two in-frame ATGs in the first exon, which are missing in orthologous rat and mouse transcripts. In vitro transcription and translation of human LGA yielded two polypeptides of the predicted size, but only the canonical full-length protein displayed catalytic activity. Relative abundance of GAB and LGA transcripts showed marked variations depending on species and tissues analyzed.This is the first report demonstrating expression of alternative transcripts of the mammalian Gls2 gene. Transcriptional mechanisms giving rise to GLS2 variants and isolation of novel GLS2 transcripts in human, rat and mouse are presented. Results were also confirmed at the protein level, where catalytic activity was demonstrated for the human LGA protein. Relative abundance of GAB and LGA transcripts was species- and tissue-specific providing evidence of a differential regulation of GLS2 transcripts in mammals

Experimental Inoculation of Juvenile Rhesus Macaques with Primate Enteric Caliciviruses

Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV)-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes.Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity

Phylodynamic Reconstruction Reveals Norovirus GII.4 Epidemic Expansions and their Molecular Determinants

Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3–9.0×10−3 mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern