Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content.

Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4. We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.

Immunocompromised cutaneous district, isotopic, and isopathic phenomena-Systematic review.

BACKGROUND: Although the development of lesions in skin areas that have undergone injury has long been known, understanding of its pathogenesis is limited. Depending on their peculiarities, those events have been described as isomorphic, reverse isomorphic, pseudoisomorphic, isotopic, and isopathic phenomena. Ruocco's immunocompromised cutaneous district (ICD) concept was proposed to include all those phenomena. AIMS: We performed a systematic review and critically evaluated the current understanding about ICD and its relationship with the isotopic and isopathic phenomena. METHODS: To illustrate the complexity of the theme, we present a case of subclinical leprosy, whose manifestation was brisk in an old tattoo. The possible interaction between the approached phenomena, acting in the genesis of the disease, made this a pertinent study. The research was conducted under the PRISMA-P guidelines, in seven biomedical databases between 1996 and 2018. The eligibility criteria were systematic reviews, meta-analyses, clinical studies, and case series, written in English, French, Italian, Portuguese, or Spanish. RESULTS: Using standardized keywords, 1220 articles were identified. After applying the eligibility criteria, 53 studies were selected. CONCLUSION: This review ratifies that all these phenomena are aspects of one single condition. They can be integrated into the ICD concept with the pathogenesis including: (a) neural damage (peripheral or central) and (b) chronic lymphedema. Both may change the local neuroimmune interaction. The identification of these phenomena and the understanding of their pathogenesis are of paramount importance, to define the diagnosis and choose the therapeutic strategy.

Detection of Bartonella henselae in defibrinated sheep blood used for culture media supplementation

Bartonella henselae was detected in defibrinated sheep blood employed in supplementing a selective bacteria culture medium by nested PCR. We recommended that highly sensitive technical tests be run to ensure a sterile culture medium for Bartonella spp. isolation, since infected blood samples used in preparation could lead to false-positive results.

Detection of Bartonella henselae in defibrinated sheep blood used for culture media supplementation.

Bartonella henselae was detected in defibrinated sheep blood employed in supplementing a selective bacteria culture medium by nested PCR. We recommended that highly sensitive technical tests be run to ensure a sterile culture medium for Bartonella spp. isolation, since infected blood samples used in preparation could lead to false-positive results.