Disruption to control network function correlates with altered dynamic connectivity in the wider autism spectrum.

Autism is a common developmental condition with a wide, variable range of co-occurring neuropsychiatric symptoms. Contrasting with most extant studies, we explored whole-brain functional organization at multiple levels simultaneously in a large subject group reflecting autism's clinical diversity, and present the first network-based analysis of transient brain states, or dynamic connectivity, in autism. Disruption to inter-network and inter-system connectivity, rather than within individual networks, predominated. We identified coupling disruption in the anterior-posterior default mode axis, and among specific control networks specialized for task start cues and the maintenance of domain-independent task positive status, specifically between the right fronto-parietal and cingulo-opercular networks and default mode network subsystems. These appear to propagate downstream in autism, with significantly dampened subject oscillations between brain states, and dynamic connectivity configuration differences. Our account proposes specific motifs that may provide candidates for neuroimaging biomarkers within heterogeneous clinical populations in this diverse condition

Knowledge, attitudes and practices (KAP) regarding menstruation among girls in Aurangabad, India and their correlation with sociodemographic factors

Background: Menstruation has always been surrounded by different perceptions throughout the world. Nowadays, there is some openness toward menstruation, but differences in attitude still persist between different populations depending upon the education, socioeconomic status and the surroundings. We conducted this study to assess the knowledge regarding menstruation, their attitudes and the practises undertaken by the young girls of India .A prewritten questionnaire was distributed to these girls and the answers were analysed.Methods: A school based cross-sectional study design was employed in Aurangabad, Maharashtra. A multi stage sampling technique was used to select 1000 female high school and junior college and pharmacy college students. Data collection was carried out from May 2018 to August 2018 using a pre- tested structured questionnaire. The data were entered into a computer using Epi-info version 3.5.1 and then exported to SPSS for Windows version 20.0 for analysis. Bivariate and multivariate logistic regression analysis was done at 95 % confidence interval.Results: In this study 682and 552 respondents had good knowledge and practice of menstruation respectively. The findings of the study showed a significant positive association between good knowledge of menstruation and educational status of mothers (AOR = 1.51, 95% CI = 1.02-2.22), (AOR = 2.42, 95% CI:1.64-3.56). Educational status of the mother (AOR = 2.03, 95 % CI =1.38-2.97), revealed significant positive association with good practice and attitude of menstrual process.Conclusions: The findings showed that the knowledge and practice of menstruation is low. Hence awareness programmed should be conducted in schools regularly. Participation of mothers can also add to the knowledge and good practice scores of the young girls

Drivers of reptile and amphibian assemblages outside the protected areas of Western Ghats, India

Biodiversity conservation in forested landscapes outside protected areas is important to sustain populations of species with restricted ranges. However, such habitats face many anthropogenic threats, including logging, extraction of firewood and leaf-litter for mulch in plantations. In this study, we determined the effects of forest degradation on amphibians and reptiles in forests outside protected areas by measuring their species richness and community composition across a disturbance gradient from near pristine to highly degraded forests in Agumbe, Western Ghats, India. Twenty-one strip 15. m. ×. 150. m transects were laid across the disturbance gradient and diurnal visual encounter surveys were conducted. Sampling was repeated three times per transect covering the dry, intermediate and wet seasons. Amphibian and reptile communities were affected by the decrease in canopy cover and leaf litter volume, respectively. Our results indicate that the collection of firewood and leaf-litter can severely affect amphibian and reptile populations. Structured conservation planning outside of protected areas is therefore imperative. © 2014 Elsevier GmbH.Divya Balaji, Rachakonda Sreekar, Siddharth Ra

Non-pollinator fig wasp impact on the reproductive success of an invasive fig tree: why so little?

Classical biological control agents fail to achieve an impact on their hosts for a variety of reasons and an understanding of why they fail can help shape decisions on subsequent releases. Ornamental Ficus microcarpa is a widely planted avenue fig tree that is invasive in countries where its pollinator (Eupristina verticillata) is also introduced. This tree also supports more than 20 species of non-pollinating fig wasps (NPFW) that feed in the figs and have the potential to reduce the plant’s reproduction. Odontofroggatia galili, one of the most widely introduced NPFW, has larvae that develop in galled ovules that might otherwise develop into seeds or support pollinator larvae. We examined the distribution and relative abundance of the pollinator and O. galili on F. microcarpa in China, towards the northern limit of the tree’s natural range, and in Italy where the two species have been introduced. Where they co-existed, we also recorded the impact of varying densities of O. galili on F. microcarpa seed and pollinator production. O. galili and E. verticillata displayed contrasting habitat preferences in China, with O. galili almost absent from warmer sites. O. galili abundance and sex ratios varied between the natural and introduced ranges. Figs with more O. galili contained fewer seeds and pollinator offspring, but reproduction was rarely inhibited totally. Additional species with a greater impact in the figs they occupy are needed if biocontrol of F. microcarpa is to be effective

Somatic mutations in exocrine pancreatic tumors: association with patient survival.

KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application

Telomere length and survival in primary cutaneous melanoma patients

Dermatology-oncolog

Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs).

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c. − 124 and c. − 146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c. − 124C4T mutation was the most common event, present in 2.3% (3/130), and the c. − 146C4T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient’s clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.This project was partially supported by Barretos Cancer Hospital internal research funds (PAIP) and CNPq Universal Grant (476192/2013-7) to RMR. NCC is a recipient of an FAPESP Doctoral Fellowship (2013/25787-3). Further funding from the project ‘Microenvironment, metabolism and cancer’ that was partially supported by Programa Operacional Regional do Norte (ON.2—O Novo Norte) under the Quadro de Referência Estratégico Nacional (QREN) and the Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education that is partially supported by the FCT

Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways

Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH.This study was funded by Grant 5K08AA017622 from the National Institutes of Health and a University of Pittsburgh Medical Center Pilot Grant to JB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target