The latest medical research on Clinical Paediatric Genetics
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about clinical paediatric genetics gathered by our medical AI research bot.
The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.
Want more personalised results?
Request AccessExploring the Molecular Interaction Between NR2E3 and NR1D1 in Retinitis Pigmentosa: A Docking and Molecular Dynamics Study.
Clinical LaboratoryRetinitis pigmentosa (RP) is a hereditary retinal disorder that gradually leads to vision loss due to photoreceptor cell degeneration. This study aims to investigate the clinical features and genetic underpinnings of RP within a large Iranian family. Our focus centered on mutations in the NR2E3 gene, which plays a critical role in the development and maintenance of the retina.
Twenty-five family members showed symptoms of RP, and fourteen of them underwent clinical examinations conducted by geneticists and ophthalmologists. The DNA samples of five individuals diagnosed with RP from the family were subjected to whole-exome sequencing (WES) as part of the study. The candidate variant identified through WES was subsequently confirmed using bidirectional sequencing in additional family members. Additionally, in silico analysis, including molecular modeling, protein-protein docking, and molecular dynamics simulation (MD), was employed to assess potential pathogenic effects associated with the candidate variants.
Ophthalmic examination revealed night blindness, which is a common symptom among affected individuals. Genetic analysis identified a homozygous missense variant (c.934G>A/p.R311Q) in NR2E3 exon 6, which co-segregates with other affected family members. Furthermore, molecular docking analysis indicated potential disruption in the binding affinity between NR2E3 and NR1D1 proteins. In-depth, molecular dynamics analysis, considering parameters such as RMSD, RMSF, and hydrogen bonding, revealed notable differences between normal and mutant protein complexes.
Exploring the molecular interaction between NR2E3 and NR1D1 provides new insights into the pathogenic mechanism of the p.R311Q mutation in RP.
Impact of Overweight on Renal Prognosis in Malignant Hypertension Patients With Thrombotic Microangiopathy.
Clinical LaboratoryOverweight and obesity is a risk factor for hypertension. Malignant hypertension (MHT) is the most severe form of hypertension, and thrombotic microangiopathy (TMA), one of its complications, has been linked to significant renal outcomes. However, the impact of overweight and obesity on renal prognosis in MHT patients with TMA is not well understood.
This was a prospective cohort enrolled 288 MHT patients with renal TMA from 2008 to 2023. The clinical and histopathological characteristics were recorded based on body mass index (BMI, < 25 and ≥ 25 kg/m2). The outcome was the incidence of kidney failure. The associations of BMI with kidney failure were examined in logistic regression models.
Among 288 patients, 180 (62.5%) progressed to kidney failure, including 113 (68.5%) patients with BMI < 25 kg/m2. Participants with obesity had higher levels of hemoglobin, estimated glomerular filtration rate and C3, but lower levels of serum creatinine and IgA nephropathy. BMI ≥ 25 kg/m2 was associated with a better outcome of kidney failure in MHT patients with TMA (odd ratios [ORs]: 0.49 [95% confidence interval (CI): 0.27-0.91], p = 0.025). Male, uric acid, onion skin lesions, and global sclerosis ratio were correlated with higher risk of kidney failure; serum albumin and treatment with renin-angiotensin system blockers were related to lower risk of kidney failure.
In MHT patients with renal TMA, normal-weight rather than overweight was found to associate with a worse renal prognosis. Management efforts for MHT may be directed toward controlling body weight within a reasonable range for patients.
Comparison of MIB-1-Specific Membrane Staining in Hyalinising Trabecular Tumor Using Mainstream Automated Immunohistochemical Staining Platforms.
Clinical LaboratoryMIB-1, a monoclonal antibody against Ki-67, exhibits specific membrane staining in the immunohistochemistry of hyalinising trabecular tumor (HTT). This specific staining pattern is crucial in diagnosing HTT. Although manual immunohistochemical staining remains the established method for MIB-1 staining, this process is complicated, inconsistent, and prone to false negatives.
This study aimed to explore whether the classical reaction pattern can be replicated by utilizing the current mainstream automated immunohistochemical staining platforms. Furthermore, we examined the effect of different conditions on staining efficiency and their value in clinical diagnosis assistance.
Specimens obtained from eight and six cases of HTT and non-HTT, respectively, from a single center were stained using the manual staining method and the Dako Autostainer Link 48 (AS48), Dako Omnis, Ventana BenchMark ULTRA, and Leica BOND-III automated immunohistochemical staining platforms. The Autostainer Link 48 was found to be the most stable staining platform, while the BenchMark ULTRA with primary antibody incubation at room temperature (RT) and the Omnis platform with antigen retrieval at pH 9.0 were able to reproduce membrane-positive staining for MIB-1 in the HTT specimens.
Our results offer crucial reference value for clinical diagnostic assistance.
An Optimized CRISPR/Cas12a Assay to Facilitate the BRAF V600E Mutation Detection.
Clinical LaboratoryAccurate detection of the BRAF V600E (1799T > A) mutation status can significantly contribute to selecting an optimal therapeutic strategy for diverse cancer types. CRISPR-based diagnostic platforms exhibit simple programming, cost-effectiveness, high sensitivity, and high specificity in detecting target sequences. The goal of this study is to develop a simple BRAF V600E mutation detection method.
We combined the CRISPR/Cas12a system with recombinase polymerase amplification (RPA). Subsequently, several parameters related to CRISPR/Cas12a reaction efficiency were evaluated. Then, we conducted a comparative analysis of three distinct approaches toward identifying BRAF V600E mutations in the clinical samples.
Our data suggest that CRISPR/Cas detection is considerably responsive to variations in buffer conditions. Magnesium acetate (MgOAc) demonstrated superior performance compared to all other examined additive salts. It was observed using 150 nM guide RNA (gRNA) in an optimized reaction buffer containing 14 mM MgOAc, coupled with a reduction in the volumes of PCR and RPA products to 1 μL and 3 μL, respectively, resulted in an enhanced sensitivity. Detection time was decreased to 75 min with a 2% limit of detection (LOD), as evidenced by the results obtained from the blue light illuminator. The CRISPR/Cas12a assay confirmed the real-time PCR results in 31 of 32 clinical samples to identify the BRAF V600E mutation status, while Sanger sequencing detected BRAF V600E mutations with lower sensitivity.
We propose a potential diagnostic approach that is facile, fast, and affordable with high fidelity. This method can detect BRAF V600E mutation with a 2% LOD without the need for a thermocycler.
A Narrative Review of Bedaquiline and Delamanid: New Arsenals Against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis.
Clinical LaboratoryThe treatment of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is a formidable challenge. Treatment of MDR- and XDR-TB using bedaquiline (BDQ) and delamanid (DLM), two newly introduced medications, is steadily increasing. This narrative review aimed to present a concise overview of the existing information regarding BDQ and DLM, and elucidate their antimicrobial characteristics, resistance mechanisms, synergism with other drugs, and side effects.
To collect the required information about the antimicrobial properties, a search for scientific evidence from the Scopus, PubMed, and Embase databases was performed, and all recently published articles up to May 2024 were considered.
BDQ had potent antimicrobial effects on various types of nontuberculous mycobacteria (NTM), including rapid-growing and slow-growing species, and MDR/XDR Mycobacterium tuberculosis. The mechanisms of BDQ resistance in M. tuberculosis primarily involve mutations in three genes: atpE, mmpR (Rv0678) and pepQ. BDQ may have synergistic effects when combined with DLM, pyrazinamide, and pretomanid/linezolid. BDQ has a low incidence of side effects. The use of BDQ may prolong the QTc interval. Similarly, DLM showed potent antimicrobial effects on NTM and MDR/XDR M. tuberculosis. The main resistance mechanisms to DLM are induced by mutations in fbiA, fbiB, fbiC, fgd1, and ddn genes. The DLM had synergistic effects with BDQ and moxifloxacin. The DLM also has few side effects in some patients including QTc prolongation.
BDQ and DLM are suitable antibiotics with few side effects for the treatment of MDR/XDR-TB. These antibiotics have synergistic effects when combined with other antituberculosis drugs.
Serum Lipid Profile and Electrolytes Reference Intervals for Apparently Healthy Children and Adolescents in Addis Ababa, Ethiopia.
Clinical LaboratoryAccurate reference intervals generated from an apparently healthy population and stratified by crucial variables such as age and gender are required to guarantee appropriate interpretation of test results. Since there were no local reference intervals in the study area, the present study aimed to establish reference intervals on serum lipid profiles and electrolytes for children and adolescents in Addis Ababa.
This community-based cross-sectional study was conducted from April to October 2019. Laboratory analysis was performed using the automatic biochemical analyzer Cobas 6000 (c501) from Roche. According to Clinical and Laboratory Standards Institute (CLSI) guidelines, reference intervals for lipid profile and electrolyte tests for apparently healthy children and adolescents were established. We used a non-parametric method to calculate the 2.5th and 97.5th percentiles with a 90% confidence interval.
In children, the reference intervals for serum potassium, sodium, chloride, calcium, magnesium, and phosphate in mmol/L were 4.37-5.20, 137-145.50, 101.90-107.90, 2.34-2.70, 0.74-0.97, and 1.42-1.85, respectively; and for total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, the respective values were 100.76-171.70, 44.16-126.36, 60.60-105.60, and 31.60-53.70 in mg/dL, for both genders. For adolescents, the reference intervals were 4.03-5.58, 137-146, 98.90-120.90, 2.39-2.70, 0.73-0.96, and 0.96-1.80 for serum potassium, sodium, chloride, calcium, magnesium, and phosphate in mmol/L, respectively; and 97.20-189.10, 40.50-143.60, 41.70-120.90, and 21.30-57.0 in mg/dL for total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, respectively, for both genders.
The established reference intervals in the current study revealed that both the lower and upper limits contradicted the manufacturer values as well as the available literature. The study also discovered significant gender differences in reference values for TC, TG, LDL-C, potassium, phosphate, and chloride in the adolescent age groups.
Cutoff Values for Glycated Albumin, 1,5-Anhydroglucitol, and Fructosamine as Alternative Markers for Hyperglycemia.
Clinical LaboratoryGlycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), and fructosamine have attracted considerable interest as markers of hyperglycemia. This study aimed to evaluate the optimal cutoff values for GA, 1,5-AG, and fructosamine and to determine their respective diagnostic efficacies in relation to hyperglycemia.
We enrolled 6012 individuals who had undergone fasting blood glucose (FBG) and Hemoglobin A1c (HbA1c) tests along with at least one alternative glycemic marker. Receiver operating characteristic (ROC) curves and the upper or lower limit of the reference range (97.5 or 2.5 percentiles) were used to ascertain the optimal cutoff values. Follow-up data from healthy individuals were used to identify patients who developed diabetes mellitus (DM).
The ROC cutoff values for GA, 1,5-AG, and fructosamine were 13.9%, 13.3 μg/mL, and 278 μmol/L, respectively, with corresponding area under the curve (AUC) values of 0.860, 0.879, and 0.834. The upper limits of the reference intervals for GA and fructosamine were 15.1% and 279 μmol/L, respectively, and the lower limit for 1,5-AG was 5.3 μg/mL. Among the GA cutoff values, the ROC cutoff had the highest sensitivity. Analyzing the follow-up data showed that lowering the GA cutoff from 16.0% to 13.9% identified an additional 40 people with DM progression.
Lowering the GA cutoff values significantly increased the sensitivity of DM diagnosis and enhanced its potential as a screening marker by identifying more individuals with diabetes progression. Conversely, modifications to the cutoff values for 1,5-AG and fructosamine did not confer any discernible diagnostic or predictive advantages.
The Bacterial Species Behind the Wound and Their Antibacterial Resistant Pattern: A Three-Year Retrospective Study at St. Dominic Hospital, Akwatia, Ghana.
Clinical LaboratoryWound infections are often underestimated issues that can lead to chronic illnesses, and since the introduction of antibiotics, wound complications have become less common. However, due to the increased and irrational use of these antibiotics, the resistance in the bacterial isolates has become very common. This has led to reduced treatment options, delay in wound healing, and high treatment costs. This study aimed to investigate bacterial wound infections and their antibiotic resistance at St. Dominic Hospital, Ghana.
A total of 517 records of wound swab culture and susceptibility testing, and patient demographics from 2020 to 2022 were collected from the microbiology unit of St. Dominic Hospital in the Eastern Region of Ghana. The data were entered into Microsoft Excel 2019, cleaned, and exported into IBM SPSS v26 for the statistical analysis. p < 0.05 was considered statistically significant for all analyses.
The overall prevalence of bacteriological agents causing wound infection in individuals who visited the St. Dominic Hospital from 2020 to 2022 was 70.21% (363/517), with S. aureus 79/363 (21.76%) being the most abundant isolate. Out of the 79 S. aureus isolated, 40 (50.63%) and 39 (49.37%) were resistant to ampicillin and cephalexin, respectively. More than 50% of the predominant Gram-negative isolate, K. pneumoniae, were resistant to clindamycin 45/72 (62.50%) but susceptible to levofloxacin 70/72 (97.22%), cefotetan 69/72 (95.83%), and chloramphenicol 67/72 (93.06%).
Antibacterial susceptibility patterns revealed significant resistance trends, particularly among Gram-negative isolates, emphasizing the urgent need for prudent antibiotic use and ongoing surveillance to combat resistance.
Detection of Rifampicin Resistance rpoB Gene Using GeneXpert MTB/RIF Assay in Pulmonary Tuberculosis Cases at Debre Tabor Comprehensive Specialized Hospital, Northwest Ethiopia.
Clinical LaboratoryTuberculosis (TB) is a preventable and treatable disease leading to the second death globally. The evolution of drug resistance in Mycobacterium tuberculosis (MTB), particularly rifampicin resistance (RR), has hampered TB control efforts. Thus, this study aimed to provide information regarding the magnitude of MTB and rifampicin resistance among patients tested using the GeneXpert method.
A retrospective analysis was carried out at DTCSH. The study included TB registration logbook data from all patients who visited the hospital and were tested for MTB with the Xpert MTB/RIF assay from 2017 to 2024. The laboratory-based data were entered, cleaned, and analyzed using SPSS version 26 software. Multilogistic regression analysis was employed, and a p value ≤ 0.05 was considered statistically significant.
A total of 12,981 patient results were included, of which 8.9% (1160/12,981) were MTB-positive and 7.1% (82/1160) were RR. Individuals aged 15-29 years (AOR = 2.13; 95% CI = 1.55-2.93, p < 0.001), living in rural areas (AOR = 1.23; 95% CI = 1.08-1.41, p = 0.003), and HIV+ (AOR = 1.79; 95% CI = 1.48-2.33, p < 0.001) had a higher risk of developing tuberculosis. While RR was identified in 63.4% (52/82) of new, 24.4% (20/82) of re-treated, and 12.2% (10/82) of failed presumptive TB patients.
In this study, MTB and RR trends were high. Productive age groups, rural populations, and HIV patients were at risk. To lessen the burden of this contagious and fatal disease, it is recommended to increase early diagnosis of drug-resistant TB and enhance infection control.
The Neutrophil Percentage-to-Albumin Ratio as a Biomarker for All-Cause and Diabetes-Cause Mortality Among Diabetes Patients: Evidence From the NHANES 1988-2018.
Clinical LaboratoryNeutrophil percentage-to-albumin ratio (NPAR) was significantly correlated with diabetes-related complications. There are little data about NPAR and mortality risk in individuals with diabetes.
This study included 3858 diabetes patients from the National Health and Nutrition Examination Survey (NHANES) conducted from 1988 to 2018. Using a restricted cubic spline (RCS), the relationship between the NPAR and mortality risk was shown. Multivariable Cox regression models were used to evaluate the relationship between the NPAR and diabetes-cause and all-cause death. An examination of the time-dependent receiver operating characteristic curve (ROC) was used to assess how well the NPAR predicted survival outcomes.
Among 3858 diabetes individuals, a total of 1198 (31.1%) died over a mean follow-up of 7.86 years; of these, 326 (8.4%) had diabetes-related deaths and 872 (22.6%) had deaths from other causes. The RCS regression analysis showed a positive linear association between the NPAR and all-cause and diabetes-cause mortality. High NPAR group had a significantly higher risk of all-cause and diabetes-cause mortality in univariate and multivariate analysis. Compared with low NPAR group, high NPAR group had a low survival rate of diabetes cases in all-cause death and diabetes-cause mortality with area under the curve of the 3-, 5-, and 10-year ROC curve being 0.725, 0.739, and 0.734 for all-cause mortality and 0.754, 0.752, and 0.745 for diabetes-cause mortality, respectively.
In summary, we examined 3858 diabetes patients from NHANES database (1998-2018) and suggested NPAR as a biomarker for all-cause and diabetes-cause mortality prediction.
Prognostic Nutritional Index is Related to All-Cause Mortality in Patients With Stage IV Colorectal Cancer Treated With Capecitabine: Single-Center 24-Month Observational Study in Vietnam.
Clinical LaboratoryTo determine the mortality rate and the predictive value of the prognostic nutritional index (PNI) for all-cause mortality during the 24 months in patients with stage IV colorectal cancer treated with capecitabine.
We conducted a study on 87 stage IV colorectal cancer patients treated with capecitabine. Before the day of treatment, all patients were measured CEA and CRP-hs levels and calculated neutrophil/lympho ratio (NLR) and PNI. Patients were monitored and collected drug side effects and mortality for 24 months.
The mortality rate of study subjects was 60.9%. CRP-hs, NLR, and PNI were independent factors associated with 24-month mortality in patients with stage IV colorectal cancer (p < 0.05 to p < 0.01). At a cut-off value of 38.51, PNI was a predictor for mortality, with the area under the curve (AUC) of 0.88 and p < 0.001.
PNI was a good predictor of all-cause mortality in patients with stage IV colorectal cancer treated with capecitabine for 24 months.
Clustering Based on Laboratory Data in Patients With Heart Failure Admitted to the Intensive Care Unit.
Clinical LaboratoryHeart failure (HF) is a common condition that imposes a significant burden on healthcare systems. We aimed to identify subgroups of patients with heart failure admitted to the ICU using routinely measured laboratory biomarkers.
A large dataset (N = 1176) of patients with heart failure admitted to the ICU at the Beth Israel Deaconess Medical Center in Boston, USA, between June 1, 2001, and October 31, 2012, was analyzed. We clustered patients to identify laboratory phenotypes. Cluster profiling was then performed to characterize each cluster, using a binary logistic model.
Two distinct clusters of patients were identified (N = 679 and 497). There was a significant difference in the mortality rate between Clusters 1 and 2 (50 [7.4%] vs. 109 [21.9%], respectively, p < 0.001). Patients in the Cluster 2 were significantly older (mean [SD] age = 72.35 [14.40] and 76.37 [11.61] years, p < 0.001) with a higher percentage of chronic kidney disease (167 [24.6%] vs. 262 [52.7%], respectively, p < 0.001). The logistic model was significant (Log-likelihood ratio p < 0.001, pseudo R2 = 0.746) with an area under the curve of 0.905. The odds ratio for leucocyte count, mean corpuscular volume (MCV), red blood cell (RBC) distribution width, hematocrit (HcT), lactic acid, blood urea nitrogen (BUN), serum potassium, magnesium, and sodium were significant (all p < 0.05).
Laboratory data revealed two phenotypes of ICU-admitted patients with heart failure. The two phenotypes are of prognostic importance in terms of mortality rate. They can be differentiated using blood cell count, kidney function status, and serum electrolyte concentrations.
