Friedmannolan6026
rove with new therapies for ATTR cardiac amyolidosis.
Cerebral palsy (CP) associates cerebral function damages with strong locomotor defects and premature sarcopenia. We previously showed that fibroblast growth factor 19 (FGF19) exerts hypertrophic effects on skeletal muscle and improves muscle mass and strength in mouse models with muscle atrophy. Facing the lack of therapeutics to treat locomotor dysfunctions in CP, we investigated whether FGF19 treatment could have beneficial effects in an experimental rat model of CP.
Cerebral palsy was induced in male Wistar rat pups by perinatal anoxia immediately after birth and by sensorimotor restriction of hind paws maintained until Day 28. Daily subcutaneous injections with recombinant human FGF19 (0.1mg/kg bw) were performed from Days 22 to 28. Locomotor activity and muscle strength were assessed before and after FGF19 treatment. At Day 29, motor coordination on rotarod and various musculoskeletal parameters (weight of tibia bone and of soleus and extensor digitorum longus (EDL) muscles; area of skeletal muscle f, P<0.05) and soleus and EDL muscle weight (+28.6% and +27.3%, respectively, P<0.05). In addition, it reduced a number of very small fibres in both muscles (P<0.05). Finally, gene expression analyses revealed that FGF19 might counteract the immature state of skeletal muscles induced by CP.
These results demonstrate that pharmacological intervention with recombinant FGF19 could restore musculoskeletal and locomotor dysfunction in an experimental CP model, suggesting that FGF19 may represent a potential therapeutic strategy to combat the locomotor disorders associated with CP.
These results demonstrate that pharmacological intervention with recombinant FGF19 could restore musculoskeletal and locomotor dysfunction in an experimental CP model, suggesting that FGF19 may represent a potential therapeutic strategy to combat the locomotor disorders associated with CP.
Some risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions.
We performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other paramet CI 0.62-0.70) and 0.63 (95% CI 0.59-0.67), respectively.
Data indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.
Data indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.
Fabry disease (FD) is an X-linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi-organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum of FD in Chinese families.
Five male probands with unexplained left ventricular hypertrophy and their family members were investigated. Genetic screening was available in 11 subjects of the 5 families, 10 of whom proved to be carriers of either GLA gene mutation, including 3 previous reported missense mutations (c.128G>A, c.811G>A, c.950T>C), 1 novel missense mutation (c.37G>C), and 1 novel deletion mutation (c.1241delT). A total of 17 patients were definitely or possibly diagnosed of FD, given their clinical manifestations and hereditary nature of FD. Echocardiography demonstrated normal cardiac structure and function in six female patients. Electrocardiographic pre-excitation occurred in 80% (4/5) of menen male and female patients even within the same family. Female patients showed relatively low risks of structural heart disease and renal insufficiency. However, the long-term outcomes might be adverse in both sexes. Our study underlines the importance of molecular screening of the GLA gene for early identification and clinical decision making in patients with FD.The novel HLA-DPA1*0253 allele differs from HLA-DPA1*02010102 by one nucleotide substitution in exon 3.Although there are several reports in the literature of SARS-CoV-2 infection in cats, few SARS-CoV-2 sequences from infected cats have been published. In this study, SARS-CoV-2 infection was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS-CoV-2 infection in two cats, infection status was confirmed by RT-qPCR and, in one cat, serological analysis for antibodies against N-protein and S-protein, as well as neutralizing antibodies. Comparative analysis of five SARS-CoV-2 sequence fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS-CoV-2. Vemurafenib mw This study provides additional information on the clinical, molecular, and serological aspects of SARS-CoV-2 infection in cats.
To assess the independent contributions of clinical measures (relapses, Expanded Disability Status Scale [EDSS] scores, and neuroperformance measures) and nonclinical measures (new brain magnetic resonance imaging [MRI] activity and serum neurofilament light chain [sNfL] levels) for distinguishing natalizumab-treated from placebo-treated patients.
We conducted post hoc analyses using data from the AFFIRM trial of natalizumab for multiple sclerosis. We used multivariable regression analyses with predictors (EDSS progression, no relapse, new or enlarging MRI activity, brain atrophy, sNfL levels, and neuroperformance worsening) to identify measures that independently discriminated between treatment groups.
The multivariable model that best distinguished natalizumab from placebo was no new or enlarging T2 or gadolinium-enhancing activity on MRI (odds ratio; 95% confidence interval 7.2; 4.7-10.9), year 2 sNfL levels <97.5th percentile (4.1; 2.6-6.2), and no relapses in years 0-2 (2.1; 1.5-3.0). The next best-fitting model was a two-component model that included no MRI activity and sNfL levels <97.5th percentile at year 2. There was little difference between the three- and two-component models.
Nonclinical measures (new MRI activity and sNfL levels) discriminate between treatment and placebo groups similarly to or better than clinical outcomes composites and have implications for patient monitoring.
Nonclinical measures (new MRI activity and sNfL levels) discriminate between treatment and placebo groups similarly to or better than clinical outcomes composites and have implications for patient monitoring.
No international standards include vitamin D levels at diagnosis or during treatment. It is included in the Children's Oncology Group long-term follow-up guidelines. However, bone health complications (like osteopenia and atraumatic fractures) can occur at diagnosis or during treatment as well.
In this small case series, we illustrate the complexity of bone health complications among our broad paediatric oncology population. If the vitamin D level is low we supplement the patient with one standard oral dose (150 000 units for 1-2year olds, 300 000 units for 2-5year olds and 600 000 units for >5year olds). We do not adjust depending on diagnosis.
Because of the potentially negative outcomes on short, medium and long term, we recommend checking vitamin D levels on diagnosis for all newly diagnosed patients. It is a simple, low cost test and one dose of oral supplementation can easily treat the deficiency.
Because of the potentially negative outcomes on short, medium and long term, we recommend checking vitamin D levels on diagnosis for all newly diagnosed patients. It is a simple, low cost test and one dose of oral supplementation can easily treat the deficiency.
To investigate the association of subtle alterations in thyroid function with presarcopenia among patients with type 2 diabetes mellitus (T2DM).
A total of 1,865 adult patients with T2DM were enrolled in this cross-sectional study, excluding patients with overt thyroid dysfunction. Skeletal muscle mass measured by dual energy X-ray absorptiometry (DXA) was used to assess presarcopenia. Logistic regression models were used to estimate the effects of thyroid hormones (THs) on presarcopenia and subgroup analyses performed in different strata of age, sex and body mass index [BMI], respectively.
Compared to the euthyroid group (Euthy), subclinical hyperthyroidism group (SCHyper) had an increased odds of presarcopenia (multivariate-adjusted odds ratio [OR]) = 1.99, 95% confidence interval [CI] = 1.09-3.63), but the subclinical hypothyroidism group (SCHypo) did not (P > 0.05). In SCHyper group, age and BMI < 24kg/m
were independent risk factors for presarcopenia. In the overall euthyroid group, an increased odds of presarcopenia was correlated with the elevated FT4/FT3 ratio (all P for trend <0.05), while not with increment in FT3 level (P for trend >0.05). Additionally, in euthyroid subgroup analyses stratified by middle-age, gender, BMI, the similar association was noted (all P for trend <0.05), but not in the older-aged patients (P for trend >0.05).
SCHyper was an independent risk factor for presarcopenia in patients with T2DM, but SCHypo was not. In the Euthy group with T2DM, a high FT4/FT3 ratio was a good index of presarcopenia in addition to the elderly.
SCHyper was an independent risk factor for presarcopenia in patients with T2DM, but SCHypo was not. In the Euthy group with T2DM, a high FT4/FT3 ratio was a good index of presarcopenia in addition to the elderly.
Circular RNAs (circRNAs) play critical roles in tumorigenesis, but their clinical efficacy in esophageal squamous cell carcinoma (ESCC) still retains controversial. This meta-analysis aims at evaluating the associations between circRNA expressions and clinicopathologic features as well as the diagnostic and prognostic values of circRNAs in ESCC.
PubMed, EMBASE, and other online databases were systematically searched to collect studies on circRNAs and clinicopathological features, diagnostic, and/or prognostic assessments of ESCC. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Newcastle-Ottawa Scale (NOS) scales. The included studies were quantitatively weighted and merged, and diagnostic indicators, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. P values were merged by Fisher᾽s method. Sources of heterogeneity were traced using subgroup, sensitivity, and meta-regression analyses.
As a result, 12 studies were included, representing 769 ESCC patients.
