CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature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

The effects of organophosphate pesticide exposure on Hispanic children's cognitive and behavioral functioning

OBJECTIVE: This study investigates the effects of Organophosphate (OP) pesticides exposure on the cognitive and behavioral functioning of Hispanic children living in an agricultural community. METHODS: Forty-eight children were administered a battery of cognitive measures, and their parents and teachers completed behavior rating scales. Children provided a urine sample for analysis of OP pesticides metabolites. RESULTS: All children had a detectable level of at least one OP pesticide metabolite. Higher OP pesticide metabolite concentration levels were significantly correlated with poorer performance on some subtests of the Wisconsin Card Sorting Test. However, the significance of this association was dependent upon the inclusion of two samples with noticeable higher OP pesticide metabolite concentration levels. CONCLUSIONS: Short-term OP pesticide exposure seems to have deleterious effects on children's speed of attention, sequencing, mental flexibility, visual search, concept formation, and conceptual flexibility. This study is among a relatively small number of studies investigating an extremely complex problem. Limitations and suggestions for future studies are discussed.     

Effects of a phorbol ester and diacyglycerols on secretion of mucin and arginine esterase by rat submandibular gland cells

The effects of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and a diacylglyceride, 1-oleoyl-2-acetyl-glycerol (OAG) on the secretion of two major exocrine products by dispersed rat submandibular cells were investigated. TPA stimulated the release of acinar cell mucin and ductal cell protease (arginine esterase) in a dose- and time-dependent manner. Mucin secretion was also provoked by OAG, which, however, had no effect on arginine esterase release. The unsaturated diacylglycerol, 1,2-diolein, elicited a greater mucosecretory response than did OAG at the same concentration, while the saturated 1,2-distearin produced a smaller response.Mucin and enzyme secretion caused by TPA or OAG in the rat submandibular model was not inhibited by either of two putative antagonists, the antipsychotic drug, fluphenazine, and the antibiotic, polymyxin B.The involvement of extracellular Ca²⁺ in TPA-induced secretion was examined by comparing responses of cells maintained in normal or Ca²⁺-free medium, or in medium containing the ionophore A23187. Although extracellular Ca²⁺ was not an absolute requirement for a secretory response, the results indicate a synergistic relationship between TPA and Ca²⁺ in stimulating the release of both mucin and arginine esterase.These results suggest a role for the Ca²⁺-, phospholipid-dependent enzyme, protein kinase C in the secretory mechanism of mucous and serous cells in the submandibular gland. This is consistent with the proposal that receptor-mediated hydrolysis of membrane phosphoinositides is an initial event in stimulus-response coupling in exocrine cells.     

Effect of short-term digoxin treatment on ouabain-sensitive sodium transport of erythrocytes

In hemodialyzed patients, the serum albumin concentration determined by the bromcresol purple (BCP) method was lower than that determined by an immunological method. The degree of underestimation appeared to be well correlated to the serum concentration of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), a major endogenous ligand substance present in uremic serum. CMPF inhibited in vitro the binding of BCP to serum protein and human serum albumin. Our results suggest that CMPF is a major interferent in the underestimation of the serum albumin concentration by the BCP method in uremia.     

Infliximab‐related weight gain in inflammatory bowel disease: associations and financial impacts

Association between tumour necrosis alpha inhibitors and weight gain has been reported. We examined weight change in our cohort of inflammatory bowel disease patients treated with infliximab (IFX) for over 12 months, its associations and financial implications. Two‐thirds of patients gained weight during the course of therapy. The mean change in weight after 12 months of IFX therapy was 3.3 (±6.5) kg.     

World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists—Part 1. A methodological guide

Advances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step “recipe” for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.     

Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae)

Aim of the study

Cocos nucifera cultivated in Brazil is known as “coco-da-Bahia” or “coqueiro-da-Índia”. The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera “common variety” were evaluated to test the anti-inflammatory and antinociceptive activities.

Materials and methods

Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50 mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50 mg/kg), and the references drugs morphine (5 mg/kg), acetilsalicilic acid (200 mg/kg), prometazine (30 mg/kg), and metisergide (5 mg/kg) were evaluated on models of analgesia and inflammation.

Results

CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5 mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin.

Conclusions

results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.