Rational design of a conformation-specific antibody for the quantification of A beta oligomers

The accurate quantification of the amounts of small oligomeric assemblies formed by the amyloid β (Aβ) peptide represents a major challenge in the Alzheimer’s field. There is therefore great interest in the development of methods to specifically detect these oligomers by distinguishing them from larger aggregates. The availability of these methods will enable the development of effective diagnostic and therapeutic interventions for this and other diseases related to protein misfolding and aggregation. We describe here a single-domain antibody able to selectively quantify oligomers of the Aβ peptide in isolation and in complex protein mixtures from animal models of disease

Is the use of videotape recording superior to verbal feedback alone in the teaching of clinical skills?

<p>Abstract</p> <p>Background</p> <p>In recent times, medical schools have committed to developing good communication and history taking skills in students. However, there remains an unresolved question as to which constitutes the best educational method. Our study aims to investigate whether the use of videotape recording is superior to verbal feedback alone in the teaching of clinical skills and the role of student self-assessment on history taking and communication skills.</p> <p>Methods</p> <p>A randomized controlled trial was designed. The study was conducted with 52 of the Dokuz Eylul University Faculty of Medicine second year students. All students' performances of communication and history taking skills were assessed twice. Between these assessments, the study group had received both verbal and visual feedback by watching their video recordings on patient interview; the control group received only verbal feedback from the teacher.</p> <p>Results</p> <p>Although the self-assessment of the students did not change significantly, assessors' ratings increased significantly for videotaped interviews at the second time.</p> <p>Conclusions</p> <p>Feedback based on videotaped interviews is superior to the feedback given solely based on the observation of assessors.</p

Extending the tephra and palaeoenvironmental record of the Central Mediterranean back to 430 ka: A new core from Fucino Basin, central Italy

Here we present the first tephrostratigraphic, palaeomagnetic, and multiproxy data from a new ∼98 m-deep sediment core retrieved from the Fucino Basin, central Italy, spanning the last ∼430 kyr. Palaeoenvironmental proxy data (Ca-XRF, gamma ray and magnetic susceptibility) show a cyclical variability related to interglacial-glacial cycles since the Marine Isotope Stage (MIS) 12-MIS 11 transition. More than 130 tephra layers are visible to the naked eye, 11 of which were analysed (glass-WDS) and successfully correlated to known eruptions and/or other equivalent tephra. In addition to tephra already recognised in the previously investigated cores spanning the last 190 kyr, we identified for the first time tephra from the eruptions of: Tufo Giallo di Sacrofano, Sabatini (288.0 ± 2.0 ka); Villa Senni, Colli Albani (367.5 ± 1.6 ka); Pozzolane Nere and its precursor, Colli Albani (405.0 ± 2.0 ka, and 407.1 ± 4.2 ka, respectively) and Castel Broco, Vulsini (419–490 ka). The latter occurs at the bottom of the core and has been 40Ar/39Ar dated at 424.3 ± 3.2 ka, thus providing a robust chronological constrain for both the eruption itself and the base of the investigated succession. Direct 40Ar/39Ar dating and tephra geochemical fingerprinting provide a preliminary radioisotopic-based chronological framework for the MIS 11-MIS 7 interval, which represent a foundation for the forthcoming multiproxy studies and for investigating the remaining ∼110 tephra layers that are recorded within this interval. Such future developments will contribute towards an improved MIS 11-MIS 7 Mediterranean tephrostratigraphy, which is still poorly explored and exploited

The regional differences in prevalence, medical expenditures and risk factors for injury in Taiwanese teenagers

BACKGROUND: Injury is the leading cause of death in teenagers worldwide. In Taiwan, people in mountainous areas have a 4 to 8 years shorter life span than the general population. Injury among teenagers is likely a major cause. The objective of this study was to investigate the regional differences in the prevalence, the risk factors, and the medical expenditures for injury among Taiwanese teenagers. METHOD: An equal probability national sample was used. In addition, representative samples from mountainous areas and offshore islands were used. Only those who aged between 12 and 21 years, and signed the consent form permitting us to link their National Health Insurance (NHI) claim data were included in the analysis. Injury-related visits and expenditures in outpatient services were extracted from the NHI data. Logistic regression was used to examine the factors associated with injury. For those who had injury related outpatient visits, mixed model was used to examine the factors associated with medical expenditures accounting for multiple visits by the same individual. RESULTS: The prevalence of nonfatal injury was around 30% of teenagers in Taiwan. It was 10% higher in mountainous areas. Factors associated with injury were those who lived in mountainous areas (adjusted odds ratio [OR]: 1.7; 95%; confidence interval [CI]: 1.3–2.3), males (OR: 1.3; 95%; CI: 1.1–1.6), older teens (18–21 years old), and those with risk behavior were positively associated with injury. These factors were also associated with the number of injury-related outpatient visits. However, teenagers in mountainous areas did not spend more on medical care than those who lived in metropolitan Taiwan. CONCLUSION: Around 30% of the teenagers were injured in a year, not including the dead. Each of the injured spent at least 851.4NTD (~27USD) for outpatient visits. The scope of the problem was not trivial. Hazardous environments and high-risk behaviors were the universal causes. In remote areas, lack of medical resources was another possibility. Empowering local people to design prevention programs according to their needs is recommended

Reduced Food Intake and Body Weight in Mice Deficient for the G Protein-Coupled Receptor GPR82

G protein-coupled receptors (GPCR) are involved in the regulation of numerous physiological functions. Therefore, GPCR variants may have conferred important selective advantages during periods of human evolution. Indeed, several genomic loci with signatures of recent selection in humans contain GPCR genes among them the X-chromosomally located gene for GPR82. This gene encodes a so-called orphan GPCR with unknown function. To address the functional relevance of GPR82 gene-deficient mice were characterized. GPR82-deficient mice were viable, reproduced normally, and showed no gross anatomical abnormalities. However, GPR82-deficient mice have a reduced body weight and body fat content associated with a lower food intake. Moreover, GPR82-deficient mice showed decreased serum triacylglyceride levels, increased insulin sensitivity and glucose tolerance, most pronounced under Western diet. Because there were no differences in respiratory and metabolic rates between wild-type and GPR82-deficient mice our data suggest that GPR82 function influences food intake and, therefore, energy and body weight balance. GPR82 may represent a thrifty gene most probably representing an advantage during human expansion into new environments

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.

Protocol for a randomized controlled trial on risk adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients

<p>Abstract</p> <p>Background</p> <p>Fractures of the long bones and femur fractures in particular are common in multiple trauma patients, but the optimal management of femur fractures in these patients is not yet resolved. Although there is a trend towards the concept of "Damage Control Orthopedics" (DCO) in the management of multiple trauma patients with long bone fractures as reflected by a significant increase in primary external fixation of femur fractures, current literature is insufficient. Thus, in the era of "evidence-based medicine", there is the need for a more specific, clarifying trial.</p> <p>Methods/Design</p> <p>The trial is designed as a randomized controlled open-label multicenter study. Multiple trauma patients with femur shaft fractures and a calculated probability of death between 20 and 60% will be randomized to either temporary fracture fixation with fixateur externe and defined secondary definitive treatment (DCO) or primary reamed nailing (early total care). The primary objective is to reduce the extent of organ failure as measured by the maximum sepsis-related organ failure assessment (SOFA) score.</p> <p>Discussion</p> <p>The Damage Control Study is the first to evaluate the risk adapted damage control orthopedic surgery concept of femur shaft fractures in multiple trauma patients in a randomized controlled design. The trial investigates the differences in clinical outcome of two currently accepted different ways of treating multiple trauma patients with femoral shaft fractures. This study will help to answer the question whether the "early total care" or the „damage control” concept is associated with better outcome.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN10321620</p

Socioeconomic status and non-fatal injuries among Canadian adolescents: variations across SES and injury measures

BACKGROUND: While research to date has consistently demonstrated that socioeconomic status (SES) is inversely associated with injury mortality in both children and adults, findings have been less consistent for non-fatal injuries. The literature addressing SES and injury morbidity among adolescents has been particularly inconclusive. To explore potential explanations for these discrepant research findings, this study uniquely compared the relationship across different measures of SES and different causes of injury (recreation versus non-recreation injuries) within a sample of Canadian adolescents. METHODS: The sample included adolescent participants (aged 12 to 19 years) in the Canadian 1996–1997 cross-sectional National Population Health Survey (n = 6967). Five SES measures (household income, two neighbourhood-level proxy measures, two parental indicators) were examined in relation to three injury outcomes (total, recreation, and non-recreation injuries) using multivariable logistic regression. RESULTS: Among males, a clear relationship with injury was observed only for a parental SES index, which was positively associated with total and recreation injuries (odds ratios for the highest versus lowest SES category of 1.9 for total and 2.5 for recreation injuries). Among females, there was some evidence of a positive relationship between SES and injuries, particularly for a neighbourhood-level education measure with total and recreation injuries (odds ratios of 1.7 for total and 2.0 for recreation injuries). CONCLUSION: The results suggest that differences related to the measures of SES chosen and the causes of injury under study may both contribute to discrepancies in past research on SES and non-fatal injuries among adolescents. To clarify the potential SES-injury relationship among youth, the findings emphasize a need for a greater understanding of the meaning and relevance of different SES measures for adolescents, and for an exploration of the pathways through which SES may be related to injury risk

Paediatricians’ Practice About SUDDEN Infant Death Syndrome in Catalonia, Spain

Background SIDS is the major cause of death among healthy born infants in developed countries. Its causes are still unclear, but its risk can be reduced by implementing some simple active interventions. In Spain, limited attention was given to SIDS by the national healthcare system, and actual data on healthcare professionals’ practice on this topic was not available. This study explored for the first time paediatricians’ knowledge and practice about SIDS. Methods A cross-sectional survey was carried out between November 2012 and April 2013 in Catalonia, and reached 1202 paediatricians. The response rate was 46%. Results 94% of respondents perceived themselves as qualified for giving advice and recommendations about SIDS to parents, but only 58% recognized the supine position as the safest position and recommended the supine position exclusively to parents. Seniority and ‘having received a specific training about SIDS’ were detrimental to paediatricians’ knowledge. Discussion Efforts should be made in order to improve paediatricians’ knowledge and practice about SIDS. Specific refresher trainings are highly recommended, and should especially target paediatricians with higher seniority. These trainings could be provided as optional modules, as we could see that the paediatricians who would most benefit from them are already aware of the need to refresh their knowledge