CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature

PurposeRare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation.MethodsWe obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine–based classifier distinguishing CDK13-RD and non–CDK13-RD samples.ResultsWe reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance.ConclusionWe describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder.     

Evaluation of Schistosomiasis Mansoni Morbidity by Hepatic and Splenic Elastography

In patients with Mansoni schistosomiasis, it is fundamental to evaluate the disease morbidity, which is reflected by the severity of periportal fibrosis (PPF) and parameters of portal hypertension, as analyzed by ultrasonography (US). This study aimed to evaluate the morbidity of schistosomiasis by hepatic and splenic point shear-wave elastography (pSWE) and relate this to US parameters. The PPF pattern, the diameter of the portal and splenic veins and the size of the spleen were evaluated by US. Then, liver and spleen pSWEs were assessed in 74 patients using the same equipment. As the PPF pattern progressed, the splenic pSWE values significantly increased. Significant correlations between splenic pSWE, the longitudinal and transverse lengths of the spleen and the diameters of the portal and splenic veins were observed. These findings, however, were not observed through hepatic pSWE. In conclusion, the splenic pSWE has the potential for assessing morbidity in schistosomiasis mansoni.     

Evaluation of the Semmes–Weinstein filaments and a questionnaire to assess chemotherapy-induced peripheral neuropathy

Objective

This study aims to assess the use of Semmes–Weinstein monofilaments (SWMs) and of the Chemotherapy-Induced Neurotoxicity Questionnaire (CINQ) in the detection of chemotherapy-induced peripheral neuropathy (CIPN).

Method

It is a comparative and cross-sectional study performed in a philanthropic general hospital, located in the state of Minas Gerais, Brazil. One hundred seventeen individuals have participated in this study; they were divided into two groups: patients (n?=?87) treated with oxaliplatin, paclitaxel, or docetaxel and controls (n?=?30) without malignant disease.

Results

There were statistically significant differences between groups for all symptoms assessed by means of the CINQ. Lower limbs were more severely affected. Patients had increased frequency and severity of changes in all points assessed with SWM compared with controls. In the analyses of concordance between CINQ and SWM, kappa?=?0.320 (p?ρ?=?0.357; p?Conclusion CINQ and SWM may be valid tools for diagnosing CIPN in oncology practice. SWM may identify subclinical CIPN.     

Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin

Clinical Oral Investigations - This study evaluated the effect of embedding simvastatin (SIM) on the osteoinductive capacity of PLGA?+?HA/βTCP scaffolds in stem cells from human...     

Testosterone is essential for cocaine sensitization in male rats

Most studies agree that males and females respond differently to drugs of abuse. In females, estradiol enhances the behavioral response to cocaine. However, studies on the role of testosterone and the locomotor response to psychostimulants in the male rat are inconclusive. Our study was designed to determine the behavioral effects of testosterone on the development and persistence of cocaine sensitization in male rats. We tested different doses of cocaine (10, 15 and 30 mg/kg) to determine which dose induced locomotor sensitization in intact (INT) and gonadectomized (GDX) animals. We also investigated if GDX males with testosterone replacement (GDX-T) showed a similar locomotor response to cocaine as INT males.Our data showed that gonadectomy enhanced the locomotor response to a single cocaine injection. This effect was not observed in gonadectomized rats that received testosterone replacement. However, GDX rats did not show a progressive increase in their locomotor response to repeated cocaine administration (15 and 30 mg/kg) (sensitization) as did INT and GDX-T animals. It is possible that in GDX males, the initial high locomotor response to cocaine creates a ceiling effect that limits further increase in cocaine-induced hyperactivity. These findings indicate that testosterone not only modulates the behavioral response to a single and to repeated cocaine injections, but is also essential for male rats to become sensitized to cocaine.     

Meckel's diverticulum in children: eleven cases

We report 11 cases of Meckel's diverticulum in children admitted to the department of Paediatrics Surgery of Lomé (Togo). None of the cases was identified before surgery. A systematic search during appendectomy identified 3 cases. It was fortuitously discovered four times, and due to complications in four cases. There was one complication related death. Segmental intestinal resection was the only technique used.