Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome–Host Interaction Mechanistic Hypothesis

Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro–immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro–anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut–brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome–host interactions that may contribute to the severity of ASD by maintaining the brain–gut axis pathways in a dysregulated state.     

The miR-200c/141-ZEB2-TGFb axis is aberrant in human T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia (T-PLL) is mostly characterized by aberrant expansion of small- to medium-sized prolymphocytes with a mature post-thymic phenotype, high aggressiveness of the disease and poor prognosis. However, T-PLL is more heterogeneous with a wide range of clinical, morphological, and molecular features, which occasionally impedes the diagnosis. We hypothesized that T-PLL consists of phenotypic and/or genotypic subgroups that may explain the heterogeneity of the disease. Multi-dimensional immuno-phenotyping and gene expression profiling did not reveal clear T-PLL subgroups, and no clear T-cell receptor a or b CDR3 skewing was observed between different T-PLL cases. We revealed that the expression of microRNA (miRNA) is aberrant and often heterogeneous in T-PLL. We identified 35 miRNA that were aberrantly expressed in T-PLL with miR-200c/141 as the most differentially expressed cluster. High miR- 200c/141 and miR-181a/181b expression was significantly correlated with increased white blood cell counts and poor survival. Furthermore, we found that overexpression of miR-200c/141 correlated with downregulation of their targets ZEB2 and TGFbR3 and aberrant TGFb1- induced phosphorylated SMAD2 (p-SMAD2) and p-SMAD3, indicating that the TGFb pathway is affected in T-PLL. Our results thus highlight the potential role for aberrantly expressed oncogenic miRNA in T-PLL and pave the way for new therapeutic targets in this disease.     

A brief synopsis on scalp melanoma

Melanoma constitutes one of the most sinister and troublesome malignancies encountered by humanity. Generally, the diagnosis of advanced melanoma connotes a grave prognosis, prompting a sense of looming threat of death, however, the early‐stage detected disease responds well to robust treatment resulting in reasonable survivorship. Scalp melanomas are even more troublesome, because they typically exhibit more aggressive biologic behavior and are often diagnosed at a late stage. This review tries to comprehensively highlight the various diagnostic, therapeutic, and outcome aspects of scalp melanomas. The literature research includes peer‐reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till May 2020 and reference lists of respective articles. Only articles published in English language were included.     

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.     

Sensibilisierungstrainings gegenüber häuslicher Gewalt für medizinisches Fachpersonal. Sind diese auch effizient?

Untersuchungen der Europäischen Union folgend, sind 33 % aller Frauen ab dem 15. Lebensjahr von häuslicher Gewalt betroffen und wenden sich bei der Suche nach Hilfe vorwiegend an das Gesundheitssystem. Das Erleben von Gewalt hat schwerwiegende Folgen nicht nur auf die psychische, sondern auch auf die körperliche Gesundheit der Betroffenen. So kommt es neben Verletzungsfolgen, u. a. zu unerklärbaren Schmerzen, gastrointestinalen Beschwerden oder Problemen im Bereich der reproduktiven Medizin. Nachdem sich viele der Betroffenen auf der Suche nach Unterstützung zuerst an das Gesundheitssystem wenden, kommt dem medizinischen Fachpersonal auch hier eine Schlüsselrolle zu, wodurch Sensibilisierungstrainings für die Berufsgruppen immer bedeutender werden. Teilnehmerinnen und Teilnehmer an Sensibilisierungstrainings gegenüber häuslicher Gewalt wurden vor und nach dem Training mit Hilfe eines Fragebogens zu ihrer empfundenen Sicherheit im Umgang mit von Gewalt betroffenen Patientinnen und Patienten befragt. Die Evaluation eines Schulungszyklus am Landeskrankenhaus Innsbruck zeigte signifikante Verbesserungen im subjektiven Sicherheitsgefühl im Umgang mit gewaltbetroffenen Patientinnen und Patienten. Ein strukturierter Aufbau der Sensibilisierungstrainings mit Basiskursen und Aufbauseminaren, sowie einem Fokus auf Beziehungsaufbau und Umgang mit Emotionen erscheint sinnvoll.