Adlerkappel3277
The variant did not reduce TNNT1 protein levels or affect its localization but impaired its ability to modulate muscle contraction in response to Ca2+ levels. Identification of the causative variant in TNNT1 finally clarifies that the OCPMD sheep is in fact a large animal model of TNNT1 congenital myopathy. This model could now be used for testing molecular or gene therapies.
Magnetic resonance imaging (MRI) features are typical findings in Hirayama disease (HD) and are useful diagnostic entities but may not be present in all patients.
We present the case of a 22-year-old Nepalese man who presented with insidious onset of weakness of his right upper limb of more than 5 years duration. His weakness was progressive for the first 3 years, and then remained static. On examination, weakness of the interossei, thenar, hypothenar, flexor, and extensor muscles were present in his right upper limb, power was normal in his left upper and bilateral lower limbs. Minipolymyoclonus was present in both upper limbs, less prominent on the left side. Electrophysiological findings showed motor axonal neuropathy in his right upper limb, neurogenic discharges and fibrillations, and fasciculations in both upper limbs. Contrast magnetic resonance imaging (MRI) of his cervical spine in flexion was normal. Our patient was diagnosed with HD based on clinical and electrophysiological findings. Our patient was advised to use a cervical collar and regular physiotherapy and was found to have subjective benefit.
A normal cervical MRI does not rule out HD and the diagnosis can also be made based on clinical and electrophysiological studies. Progressive distal upper limb weakness or tremor in young patients should be evaluated for HD, because early diagnosis and intervention might halt the progression.
A normal cervical MRI does not rule out HD and the diagnosis can also be made based on clinical and electrophysiological studies. Progressive distal upper limb weakness or tremor in young patients should be evaluated for HD, because early diagnosis and intervention might halt the progression.Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.
Instruments for monitoring the clinical status of adolescents with emotional problems are needed. The Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) according to theory measures problems/symptoms, well-being, functioning and risk. Documentation of whether the theoretical factor structure for CORE-OM is applicable for adolescents is lacking.
This study examined the factor structure and psychometric properties of the CORE-OM based on two samples of adolescents (age 14-18) youths seeking treatment for emotional problems (N = 140) and high school students (N = 531). A split half approach was chosen. An exploratory factor analysis (EFA) was performed on the first half of the stratified samples to establish the suitability of the model. A Confirmatory Factor Analysis (CFA) with the chosen model from the EFA was performed on the second half. Internal consistency and clinical cut-off scores of the CORE-OM were investigated.
The best fitting model only partially confirmed the theoretical model analysis on CORE-OM for adolescents resulted in a five-factor solution, and opens up for new subscales concerning positive resources and problems with others. A 17-item solution for the general problems/symptoms scale is suggested. We advise developers of self-report instruments not to reverse items, if they do not intend to measure a separate factor, since these seem to affect the dimensionality of the scales. Comparing means for gender in non-clinical samples should not be done without modification of the general emotional problem and the positive resources scales. Slightly elevated CORE-OM scores (up to 1.3) in adolescents may be normal fluctuations.
Metastasectomy is performed on a select cohort of patients with advanced and/or recurrent bone and soft tissue sarcomas because of the potential for long term relapse free and overall survival associated with the procedure. However, the evidence supporting metastasectomy is difficult to summarize without a systematic examination of existing literature. Cytidine supplier The objective of this systematic review will be to examine survival among both adults and children with advanced and recurrent bone and STS who undergo metastasectomy.
We designed and registered a study protocol for a systematic review and meta-analysis. We will include data from survival studies (e.g., randomized trials, cohort studies, routine case registries, and case control) conducted in children and adults with advanced and recurrent bone and soft tissue sarcoma who undergo metastasectomy. The primary outcome will be overall survival. Secondary outcomes will be 30-day post-operative mortality, recurrence-free survival, time off systemic therapy, and ptify, evaluate, and integrate data on survival of metastasectomy of bone and soft tissue sarcoma by organ of metastasis. Our findings may have implications for clinicians, patients, and their families when considering selection for resection of oligometastatic disease in de novo, or recurrent bone and soft tissue sarcoma. Implications for future research will be identified to improve the outcomes of these complex patients.
PROSPERO CRD42019126906.
PROSPERO CRD42019126906.
Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due to genetic variants that affect diffusible elements. Previous studies have mostly assessed the impact of cis and trans effects at the gene level. However, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we use massively parallel reporter assays to directly measure the transcriptional outputs of thousands of individual regulatory elements in embryonic stem cells and measure cis and trans effects between human and mouse.
Our approach reveals that cis effects are widespread across transcribed regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we find that trans effects are rare but stronger in enhancers than promoters and are associated with a subset of transcription factors that are differentially expressed between human and mouse. While we find that cis-trans compensation is common within promoters, we do not see evidence of widespread cis-trans compensation at enhancers. Cis-trans compensation is inversely correlated with enhancer redundancy, suggesting that such compensation may often occur across multiple enhancers.
Our results highlight differences in the mode of evolution between promoters and enhancers in complex mammalian genomes and indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.
Our results highlight differences in the mode of evolution between promoters and enhancers in complex mammalian genomes and indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.
The optimal MAP target for patients with cardiogenic shock (CS) remains unknown. We sought to determine the relationship between mean arterial pressure (MAP) and mortality in the cardiac intensive care unit (CICU) patients with CS.
Using a single-center database of CICU patients admitted between 2007 and 2015, we identified patients with an admission diagnosis of CS. MAP was measured every 15 min, and the mean of all MAP values during the first 24 h (mMAP
) was recorded. Multivariable logistic regression determined the relationship between mMAP
and adjusted hospital mortality.
We included 1002 patients with a mean age of 68 ± 13.7 years, including 36% females. Admission diagnoses included acute coronary syndrome in 60%, heart failure in 74%, and cardiac arrest in 38%. Vasoactive drugs were used in 72%. The mMAP
was higher (75 vs. 71 mmHg, p < 0.001) among hospital survivors (66%) compared with non-survivors (34%). Hospital mortality was inversely associated with mMAP
(adjusted OR 0.9 per 5 mmHg higher mMAP
, p = 0.01), with a stepwise increase in hospital mortality at lower mMAP
. Patients with mMAP
< 65 mmHg were at higher risk of hospital mortality (57% vs. 28%, adjusted OR 2.0, 95% CI 1.4-3.0, p < 0.001); no differences were observed between patients with mMAP
65-74 vs. ≥ 75 mmHg (p > 0.1).
In patients with CS, we observed an inverse relationship between mMAP
and hospital mortality. The poor outcomes in patients with mMAP
< 65 mmHg provide indirect evidence supporting a MAP goal of 65 mmHg for patients with CS.
In patients with CS, we observed an inverse relationship between mMAP24 and hospital mortality. The poor outcomes in patients with mMAP24 less then 65 mmHg provide indirect evidence supporting a MAP goal of 65 mmHg for patients with CS.
Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso.
Blood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction.
In the study area, infected people harbour season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.
In high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.
