3,855 research outputs found
Effects of focal frontal lesions on response inhibition
This study examined the performance of 38 normal subjects and 43 patients with focal lesions of the frontal lobes on a simple go-nogo task where the probability of the nogo stimulus was either 75% or 25%. Patients with lesions to the superior medial parts of the frontal lobes, in particular to the left superior portion of Brodmann area 6 (which includes the supplementary motor areas and the premotor areas for the right hand) had an increased number of false alarms (incorrect responses to the nogo stimulus). These results indicate that area 6 is specifically involved in the inhibition of response. Patients with lesions to the right anterior cingulate (areas 24 and 32) were slower and more variable in their reaction time. These findings could be explained by an inability to sustain stimulus-response contingencies. Lesions to the right ventrolateral prefrontal cortex (Brodmann areas 44, 45, 47) also increased the variability of response, perhaps by disrupting monitoring performance
Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform
Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/CoVasc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases.This work was funded by the Swiss National Science Foundation NRP78 4078P0_198297 to Nadia Mercader and
Grant 310030_189136 to Stephen Leib.S
Clostridium difficile ribotypes in Austria: a multicenter, hospital-based survey
A prospective, noninterventional survey was conducted among Clostridium difficile positive patients identified in the time period of July until October 2012 in 18 hospitals distributed across all nine Austrian provinces. Participating hospitals were asked to send stool samples or isolates from ten successive patients with C.difficile infection to the National Clostridium difficile Reference Laboratory at the Austrian Agency for Health and Food Safety for PCR-ribotyping and in vitro susceptibility testing. A total of 171 eligible patients were identified, including 73 patients with toxin-positive stool specimens and 98 patients from which C. difficile isolates were provided. Of the 159 patients with known age, 127 (74.3 %) were 65 years or older, the median age was 76 years (range: 9–97 years), and the male to female ratio 2.2. Among these patients, 73 % had health care-associated and 20 % community-acquired C. difficile infection (indeterminable 7 %). The all-cause, 30-day mortality was 8.8 % (15/171). Stool samples yielded 46 different PCR-ribotypes, of which ribotypes 027 (20 %), 014 (15.8 %), 053 (10.5 %), 078 (5.3 %), and 002 (4.7 %) were the five most prevalent. Ribotype 027 was found only in the provinces Vienna, Burgenland, and Lower Austria. Severe outcome of C. difficile infection was found to be associated with ribotype 053 (prevalence ratio: 3.04; 95 % CI: 1.24, 7.44), not with the so-called hypervirulent ribotypes 027 and 078. All 027 and 053 isolates exhibited in vitro resistance against moxifloxacin. Fluoroquinolone use in the health care setting must be considered as a factor favoring the spread of these fluoroquinolone resistant C. difficile clones
Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events
Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base
Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care
Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses
Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities
Identifying patients at risk of traumatic brain injury (TBI) is important
because research suggests prophylactic treatments to reduce risk of long-term
sequelae. Blast pressure waves can cause TBI without penetrating wounds or
blunt force trauma. Similarly, bullet impacts distant from the brain can
produce pressure waves sufficient to cause mild to moderate TBI. The fluid
percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to
moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the
thigh produce pressure waves in the brain of 18-45 psi and measurable injury to
neurons and neuroglia. Analyses of research in goats and epidemiological data
from shooting events involving humans show high correlations (r > 0.9) between
rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case
study has documented epilepsy resulting from a pressure wave without the bullet
directly hitting the brain. Taken together, these results support the
hypothesis that bullet impacts distant from the brain produce pressure waves
that travel to the brain and can retain sufficient magnitude to induce brain
injury. The link to long-term sequelae could be investigated via
epidemiological studies of patients who were gunshot in the chest to determine
whether they experience elevated rates of epilepsy and other neurological
sequelae
Efficient and long-lived quantum memory with cold atoms inside a ring cavity
Quantum memories are regarded as one of the fundamental building blocks of
linear-optical quantum computation and long-distance quantum communication. A
long standing goal to realize scalable quantum information processing is to
build a long-lived and efficient quantum memory. There have been significant
efforts distributed towards this goal. However, either efficient but
short-lived or long-lived but inefficient quantum memories have been
demonstrated so far. Here we report a high-performance quantum memory in which
long lifetime and high retrieval efficiency meet for the first time. By placing
a ring cavity around an atomic ensemble, employing a pair of clock states,
creating a long-wavelength spin wave, and arranging the setup in the
gravitational direction, we realize a quantum memory with an intrinsic spin
wave to photon conversion efficiency of 73(2)% together with a storage lifetime
of 3.2(1) ms. This realization provides an essential tool towards scalable
linear-optical quantum information processing.Comment: 6 pages, 4 figure
Exponential Random Graph Modeling for Complex Brain Networks
Exponential random graph models (ERGMs), also known as p* models, have been
utilized extensively in the social science literature to study complex networks
and how their global structure depends on underlying structural components.
However, the literature on their use in biological networks (especially brain
networks) has remained sparse. Descriptive models based on a specific feature
of the graph (clustering coefficient, degree distribution, etc.) have dominated
connectivity research in neuroscience. Corresponding generative models have
been developed to reproduce one of these features. However, the complexity
inherent in whole-brain network data necessitates the development and use of
tools that allow the systematic exploration of several features simultaneously
and how they interact to form the global network architecture. ERGMs provide a
statistically principled approach to the assessment of how a set of interacting
local brain network features gives rise to the global structure. We illustrate
the utility of ERGMs for modeling, analyzing, and simulating complex
whole-brain networks with network data from normal subjects. We also provide a
foundation for the selection of important local features through the
implementation and assessment of three selection approaches: a traditional
p-value based backward selection approach, an information criterion approach
(AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF
approach serves as the best method given the scientific interest in being able
to capture and reproduce the structure of fitted brain networks
Autoimmune hepatitis in India: profile of an uncommon disease
BACKGROUND: Autoimmune hepatitis (AIH) has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. METHODS: Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver biopsy if possible. RESULTS: Forty-one of 2401 (1.70%) patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the duration of symptoms was 20.3 (20.5) months. Nineteen (50%) of them presented with chronic hepatitis, 13 (34.2%) as cirrhosis, 5 (13.1%) with acute hepatitis and 1 (2.6%) with cholestatic hepatitis. The presentations were jaundice in 21 (55.2%), pedal edema and hepatomegaly in 17 (44.7%), splenomegaly in 13 (34.2%), encephalopathy, abdominal pain in 9 (23.6%) and fever in 8 (21%). Twelve had esophageal varices and 3 had bled. Biochemical parameters were ALT 187 (360) U/L, AST 157 (193) U/L, ALP 246 (254) U/L, globulin 4.1 (1.6) g/dL, albumin 2.8 (0.9) g/dL, bilirubin 5.2 (7.4) mg/dL, prothrombin time 17 (7) sec and ESR 47 (17) sec. The autoimmune markers were SMA (24), ANA (15), both SMA and ANA (4), AMA (1), rheumatoid factor (2), pANCA (1), and Anti-LKM in none. Thirty (79%) patients had definite AIH and eight (21%) had probable AI hepatitis. Associated autoimmune diseases was seen in 15/38 (39.4%), diabetes 4, hypothyroidism 3, vitiligo 2, thrombocytopenia 2, rheumatoid arthritis 2, Sjogren's syndrome 1 and autoimmune polyglandular syndrome III in 1. Viral markers were positive in two patients, one presenting as acute hepatitis and HEV-IgM positive and another anti-HCV positive. CONCLUSION: In India, autoimmune hepatitis is uncommon and usually presents with chronic hepatitis or cirrhosis, acute hepatitis being less common. Age at presentation was earlier but clinical parameters and associated autoimmune diseases were similar to that reported from the west. Primary biliary cirrhosis is rare. Type II AIH was not observed
Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus
BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy
- …