Orally disintegrating olanzapine induces less weight gain in adolescents than standard oral tablets

We compared the changes in weight (kg) and body mass index (BMI) (kg/m²) in 52 hospitalized adolescents between baseline and after 12 weeks of monotherapy with either (i) olanzapine (OLZ) orally disintegrating tablets (ODT) (N = 16; 16.6 mg/day ± 4.4 [SD]), or (ii) OLZ standard oral tablets (SOT) (N = 10; 18.0 mg/day ± 4.2), or (iii) risperidone (N = 26; 2.8 mg/day ± 1.2). Significantly greater increases in mean weight and BMI were observed in the patients treated with OLZ SOT (8.9 ± 5.1 [SD] kg; 1.9 ± 0.6 kg/m², respectively) than in those with ODT (3.0 ± 2.1 kg; 1.1 ± 0.8 kg/m²). Similarly, OLZ ODT treatment was associated with significantly greater increases in weight and BMI than risperidone (1.0 ± 1.8 kg; 0.4 ± 0.7 kg/m²). These findings suggest that adolescents gain less weight with OLZ ODT than OLZ SOT, possibly because the former formulation shortens the time of interaction with digestive serotonin receptors mediating satiety.     

Oocytes from stem cells

Folliculogenesis describes the process of activating an oocyte-containing primordial follicle from the ovarian reserve and its development to the mature ovulatory stage. This process is highly complex and is controlled by extra- and intra-ovarian signaling events. Oocyte competence and capacity for fertilization to support a viable pregnancy are acquired during folliculogenesis. Cancer and cancer-based therapies can negatively affect this process, compromising fertility. Currently, preservation of fertility in these patients remains limited to surrogacy, oocyte freezing, oocyte donation, or in vitro maturation (IVM). Recent reports of stem cells being used to produce fully competent oocytes and subsequently healthy offspring in mice have opened up a novel avenue for fertility preservation. However, translating these findings into human health first relies on enhancing our understanding of follicle growth and mimicking its intricacies in vitro. Indeed, the future of oocytes from stem cells in humans comes with many possibilities but currently faces several technical and ethical obstacles.     

NOS1 and SNAP25 polymorphisms are associated with Attention-Deficit/Hyperactivity Disorder symptoms in adults but not in children

Several investigations documented that Attention-Deficit/Hyperactivity Disorder (ADHD) is better conceptualized as a dimensional disorder. At the same time, the disorder seems to have different neurobiological underpinnings and phenotypic presentation in children compared to adults. Neurodevelopmental genes could explain, at least partly these differences. The aim of the present study was to examine possible associations between polymorphisms in SNAP25, MAP1B and NOS1 genes and ADHD symptoms in Brazilian samples of children/adolescents and adults with ADHD. The youth sample consisted of 301 patients whereas the adult sample comprises 485 individuals with ADHD. Diagnoses of ADHD and comorbidities were based on the Diagnostic and Statistical Manual of Mental Disorders–4th edition criteria. The Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV) was applied by psychiatrists blinded to genotype. The total SNAP-IV scores were compared between genotypes. Impulsivity SNAP-IV scores were also compared according to NOS1 genotypes. Adult patients homozygous for the C allele at SNAP25 rs8636 showed significantly higher total SNAP-IV scores (F = 11.215; adjusted P-value = 0.004). Impulsivity SNAP-IV scores were also significantly different according to NOS1 rs478597 polymorphisms in adults with ADHD (F = 6.282; adjusted P-value = 0.026). These associations were not observed in children and adolescents with ADHD. These results suggest that SNAP25 and NOS1 genotypes influence ADHD symptoms only in adults with ADHD. Our study corroborates previous evidences for differences in the genetic contribution to adult ADHD compared with childhood ADHD.     

C3, C3AR1, HLA-DRA,and HLA-E as potential prognostic biomarkers for renal clear cell carcinoma

BackgroundPrognostic biomarkers play a vital role in the early detection of the cancer and assessment of prognosis. With advances in technology, a large number of biomarkers of kidney renal clear cell carcinoma (KIRC) have been discovered, but their prognostic value has not been fully investigated, and thus have not been widely used in clinical practice. We aimed to identify the reliable markers associated with the prognosis of KIRC patients.MethodsWe obtained 72 normal samples and 539 tumor samples from The Cancer Genome Atlas (TCGA), and 23 normal samples and 32 tumor samples from the Gene Expression Omnibus (GEO). Overlapping differentially expressed genes (ODEGs) were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, followed by construction of a protein-protein interaction (PPI) network to screen hub genes. Kaplan-Meier analysis, univariate Cox analysis, multivariate Cox analysis, Wilcoxon signed-rank test, Kruskal-Wallis test, and gene set enrichment analysis (GSEA) were performed to verify the prognostic value and function of the markers we selected. The relationships among gene expression level, tumor immune cell infiltration, and immune-checkpoints were also analyzed.ResultsA total of 910 genes were screened out, and C3, C3AR1, HLA-DRA, and HLA-E were identified as potential tumor markers. The expression of each gene was closely associated with tumor immune cell infiltration, survival rate, and the patients’ clinical characteristics (P<0.05). C3AR1, HLA-DRA, and HLA-E were also verified as independent prognostic factors of KIRC (P<0.05), and all these potential biomarkers had a close correlation with immune checkpoints.ConclusionsC3, C3AR1, HLA-DRA, and HLA-E could be reliable biomarkers of KIRC and may have a significant contribution to make in immunotherapy, thus playing an important role in the improvement of prognosis.     

The CMYA5 gene confers risk for both schizophrenia and major depressive disorder in the Han Chinese population

Objectives. A recent genome-wide association study (GWAS) of the European population implicated the CMYA5 gene in schizophrenia. Previous functional studies showed that the CMYA5 protein can interact with DTNBP1 and PKA, providing further support for a role of CMYA5 in the pathogenesis of schizophrenia. However, this association requires additional validation in independent populations. Methods. To validate the association between CMYA5 and schizophrenia and major depressive disorder, we genotyped 16 SNPs within the CMYA5 gene and performed case–control studies in 1330 schizophrenia patients, 1045 patients with major depressive disorder, and 1235 normal controls. All patients were of Han Chinese origin. Results. rs6883197 and rs259127 were significantly associated with schizophrenia, and rs12514461, rs259127, and rs7343 were associated with major depressive disorder. Additionally, one risk haplotype of rs16877109–rs3828611 (G–G) was associated with both schizophrenia (P = 0.0000784, after correction) and major depressive disorder (P = 0.00230, after correction). Conclusions. Our findings support the idea that specific alleles and haplotype in the CMYA5 confer genetic risk for both schizophrenia and major depressive disorder in the Han Chinese population.     

Identification of novel microsatellite markers flanking GJB2 gene in order to use in preimplantation genetic diagnosis of hearing loss: A comparison of whole-genome amplification and semi-nested PCR

Hearing loss is the most prevalent sensorineural disorder which can be caused by genetic factors in more than half of the cases. GJB2 mutations with the frequency of 18.7% are the most common cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in the Iranian population. The aim of the current study was to genotype 100 healthy individuals for eight microsatellite markers flanking the GJB2 gene, and to study markers on ten blastomeres using semi-nested PCR and Whole-genome amplification (WGA). All microsatellite markers within 1 Mb flanking the GJB2 gene were identified. From the identified markers, four with potentially high heterozygosity values were selected. The heterozygosity indices of four newly discovered markers and four previously reported markers were calculated. The markers and the GJB2 gene were also validated on single lymphocytes and blastomeres. Totally, 77 alleles were observed in eight loci. D13S046 showed the highest polymorphism and D13S141 showed the lowest. The observed heterozygosities of all markers, except D13S141, were higher than 50%. All single cells were genotyped successfully by the two techniques. Our findings indicate a high degree of polymorphism of the selected markers. Due to the high rate of successful amplification of markers in all ten blastomeres and the low level of allelic drop out (ADO), a combination of these eight microsatellite markers in conjunction with direct mutation detection is suggested for performing preimplantation genetic diagnosis (PGD) of hearing loss due to GJB2 mutations.     

Expression of the monoclonal antibody-defined CAR-3 epitope on neoplastic and preneoplastic lesions of the colon mucosa

The AR-3 monoclonal antibody, which defines the tumor-associated antigen CAR-3, was previously found to be able to discriminate between neoplastic cells in gastric, pancreatic, colonic, ovarian and endometrial carcinomas and their normal counterparts. In fact, it strongly reacts with carcinomatous cells at the level of both the glycocalix and the cytoplasm, while its reactivity with normal tissues is restricted to the glycocalix of few mucin-producing epithelial cells. We have now investigated the reactivity of this antibody with immunohistochemical techniques on a series of formalin-fixed paraffin-embedded specimens, from precancerous and cancerous lesions of the large bowel which were classified as adenomas with mild, moderate or severe dysplasia, adenomas with cancer and adenocarcinomas, respectively. It was found that the intensity and extent of the staining correlated with the degree of dysplasia and that the highest expression of the CAR-3 epitope was detectable in adenocarcinomas. Also the localization of the staining in the lesions displayed an increasingly complex pattern, going from linear in adenomas with mild dysplasia to a very strong intracytoplasmic and/or intraluminal expression in adenomas with severe dysplasia or adenocarcinomas.     

Serum cholinesterase levels after thermal injury. Is treatment required?

Changes in serum cholinesterase (also known as pseudo- or non-specific cholinesterase) activity have been measured in 20 patients after thermal injury. In 19 patients a marked fall was noted at around day 5 post-burn, and recovery to normal levels was variable and in some cases prolonged.A variety of symptoms, for example, dyspnoea and confusion, have been attributed to lowered serum cholinesterase activity and some workers have gone so far as to advocate blood transfusion to treat such a condition (Price et al., 1970; Frohlich, 1977). In this study we found 13 patients (65 per cent) with such symptoms coexisting with a low serum cholinesterase activity. However, we do not believe these symptoms were directly attributable to the low enzyme activity for the following reasons:

• 1.1. In only three of the 13 patients were symptoms observed at times when the lowest cholinesterase activity was recorded.
• 2.2. A conventional explanation for these symptoms was available, except in three cases with abdominal distension.
• 3.3. In six cases no symptoms were observed despite very low cholinesterase levels.