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Pharmacological Reports : PR Jun 2024
Correction: Liquid chromatography-tandem mass spectrometry method for mycophenolic acid and its glucuronide determination in saliva samples from children with nephrotic syndrome.
PubMed: 38916851
DOI: 10.1007/s43440-024-00617-1 -
Journal of Neural Transmission (Vienna,... Jun 2024Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In... (Review)
Review
Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.
PubMed: 38916623
DOI: 10.1007/s00702-024-02800-3 -
Cardiology Journal 2024
Topics: Humans; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Treatment Outcome; Percutaneous Coronary Intervention
PubMed: 38913494
DOI: 10.5603/cj.98301 -
Anthropologischer Anzeiger; Bericht... Jun 2024The growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) is crucial for longitudinal bone growth and exerts several metabolic effects. It is debatable whether...
The growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) is crucial for longitudinal bone growth and exerts several metabolic effects. It is debatable whether and how the recombinant human growth hormone (rhGH) treatment affects the trunk-limb proportions. We aim to evaluate the changes in body proportions and body fat content in short children with growth hormone deficiency (GHD), children born small for gestational age (SGA), and girls with Turner syndrome (TS) during the first year of rhGH therapy. The data of 70 children with GHD, 40 children born SGA, and 36 girls with TS from 1998 to 2019 were analyzed. The following parameters were measured: height, body weight, sitting height, and two skinfolds on the arm above the triceps brachii and below the scapula at the beginning of rhGH therapy and after the first year of treatment. Sitting height and lower limb length were presented as percentages (%) of body height. Fat mass percentage (%FAT) was calculated using the Slaughter formula. At the beginning of rhGH, TS girls had the greatest height deficit (-2.7 SDS), the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and children born SGA. Moreover, TS girls had higher body weight SDS, BMI SDS compared to SGA children ( < 0.001), and higher %FAT compared to both GHD and SGA children ( < 0.001 for both). After the first year of rhGH therapy, a significant increase in lower limb share (%) and a decrease in %FAT were observed in all the study groups. TS girls still had significantly higher sitting height (%), shorter lower limbs (%), and higher %FAT, body weight SDS, and BMI SDS compared to children with GHD and children born SGA ( < 0.05 for all variables). Our results show that rhGH treatment could increase lower limb length in relation to height and reduce fat mass in treated children. Girls with TS had the largest baseline body disproportions and the highest body fat content. Despite a satisfactory reduction in height deficit, after the first year of rhGH therapy, these girls had still higher body weight SDS, BMI SDS, %FAT, the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and born SGA.
PubMed: 38912850
DOI: 10.1127/anthranz/2024/1763 -
International Journal of Biological... 2024Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new...
Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new cancer hallmark. Herein, we investigated the largely uncharacterized alternative splicing profile and the key splicing factor SF3B1 in PDAC pancreatic cells and tissues as a potential discovery source of plausible drug targets and new predictive biomarkers of clinical outcome. The research involved a transcriptome-wide analysis, comparing profiles of splicing profiles in PDAC primary cells with normal ductal cells. This revealed more than 400 significant differential splicing events in genes involved in regulation of gene expression, primarily related to mRNA splicing, and metabolism of nucleic acids. PDAC cultures were highly sensitive to the SF3B1 modulators, E7107 and Pladienolide-B, showing IC50s in the low nanomolar range. These compounds induced apoptosis, associated to induction of the MCL-1/S splice variant. and reduced cell migration, associated to RON mis-splicing. In an orthotopic mouse model, E7107 showed promising results. Furthermore, we evaluated SF3B1 expression in specimens from 87 patients and found a significant association of SF3B1 expression with progression-free and overall survival. In conclusion, SF3B1 emerges as both a potential prognostic factor and therapeutic target in PDAC, impacting cell proliferation, migration, and apoptosis. These findings warrant future studies on this new therapeutic strategy against PDAC.
Topics: Humans; RNA Splicing Factors; Pancreatic Neoplasms; Animals; Mice; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Epoxy Compounds; Prognosis; Phosphoproteins; Macrolides; Apoptosis; RNA Splicing; Alternative Splicing; Female; Cell Movement
PubMed: 38904016
DOI: 10.7150/ijbs.92671 -
Research Square Jun 2024The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP)...
The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.
PubMed: 38903062
DOI: 10.21203/rs.3.rs-4438861/v1 -
Asian Journal of Surgery Jun 2024
PubMed: 38902171
DOI: 10.1016/j.asjsur.2024.05.206 -
Frontiers in Immunology 2024Anti-SSA antibodies target two unrelated proteins, Ro52 (E3 ligase) and Ro60 (RNA binding protein). Previous studies indicate that anti-Ro52 antibodies are frequently...
INTRODUCTION
Anti-SSA antibodies target two unrelated proteins, Ro52 (E3 ligase) and Ro60 (RNA binding protein). Previous studies indicate that anti-Ro52 antibodies are frequently associated with various myositis-specific autoantibodies (MSAs)-including anti-tRNA synthetase antibodies-and that the coexistence of MSAs and anti-Ro52 antibodies may portend worse clinical outcomes. Although not well-described in the setting of myositis, work from our animal model of HRS (histidyl-tRNA synthetase)-induced myositis suggests that anti-Ro60 antibodies may also be linked to specific MSAs such as anti-HRS/Jo-1. We therefore aimed to demonstrate the prevalence and clinical characteristics of Ro52 and Ro60 antibody positivity in patients possessing Jo-1 antibodies.
METHODS
To establish the immunological link between anti-synthetase, anti-Ro52, and anti-Ro60 antibodies, we evaluated the relative titers of these antibodies in blood and bronchoalveolar lavage fluid (BALF) of mice following immunization with HRS/Jo-1. In parallel, we used ELISA-based approaches to assess sera from 177 anti-Jo1 antibody-positive patients for the presence of anti-Ro52 and/or anti-Ro60 antibodies. We then determined statistical associations between co-existing anti-Jo-1, anti-Ro52, and/or anti-Ro60 antibodies and clinical manifestations associated with the anti-synthetase syndrome.
RESULTS
Mice immunized with HRS had higher levels of anti-Ro52 and anti-Ro60 antibodies in serum and BALF than PBS-immunized mice. In 177 anti-Jo-1 antibody-positive patients, the prevalence of anti-Ro52 and anti-Ro60 antibodies was 36% and 15%, respectively. The frequency of dry eye/dry mouth, interstitial pneumonia, and pulmonary events over time differed between patients with various combinations of anti-Ro52 and anti-Ro60 antibodies. While anti-Ro52 antibodies generally correlated with statistically significant increases in each of these clinical manifestations, the presence of Ro60 antibodies alone was associated with decreased frequency of ILD.
DISCUSSION
Anti-Ro52 and/or anti-Ro60 antibodies are often co-expressed with anti-Jo1 antibodies, defining clinical subsets with different disease course/outcomes.
Topics: Animals; Humans; Ribonucleoproteins; Myositis; Female; Mice; Male; Middle Aged; Antibodies, Antinuclear; Autoantibodies; Aged; Adult; Histidine-tRNA Ligase; Disease Models, Animal; Autoantigens; RNA, Small Cytoplasmic
PubMed: 38895121
DOI: 10.3389/fimmu.2024.1399451 -
Diabetes, Obesity & Metabolism Jun 2024To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D).
AIM
To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D).
METHODS
The study group included 350 patients with T1D and 250 healthy control subjects. The analysis focused on the genotyping of KLF14 rs4731702 single nucleotide polymorphism (SNP), as well as evaluating serum concentrations of inflammatory markers, blood pressure, lipid profiles, and the quantitative status of CD4 + CD25highFOXP3+ T cells.
RESULTS
Patients with T1D carrying the T allele of KLF14 rs4731702 SNP had higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, as well as lower glycated haemoglobin and serum concentration of proinflammatory markers than C allele carriers. They also developed hypertension less often than carriers of the C allele. The analysis of CD4 + CD25highFOXP3+ regulatory T-cell status based on KLF14 genotype showed that, in T1D patients, those with the TT genotype had the highest frequency of these cells compared to carriers of the CC and CT genotypes.
CONCLUSION
Our study suggests that the T allele of the KLF14 rs4731702 SNP might confer a protective effect against the development of obesity, hypertension, dyslipidaemia, and chronic inflammatory state in patients diagnosed with T1D.
PubMed: 38894632
DOI: 10.1111/dom.15707 -
Movement Disorders : Official Journal... Jun 2024
PubMed: 38894500
DOI: 10.1002/mds.29868