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.

Perceived levels of stress, emotions and physical activity in outpatients with diffuse connective tissue diseases.

BACKGROUND: Diffuse connective tissue diseases (DCTD) are autoimmune diseases that can cause comorbidities, influencing physical and psychological aspects and increase stress. The latter may also be related to the practice of physical activity (PPA). Although evidence shows that it can contribute to patients' health, the level of PPA can decrease after the diagnosis. The aim was to evaluate the basic emotions, perceived stress (PS) and PPA levels of patients with DCTD. METHODS: This is a field study with a random approach of 55 participants. We used a clinical and sociodemographic profile form for the verification of emotions, a picture with emojis of the basic emotions, the PSS-14 and the IPAQ-Brief. Data were analyzed with Mann-Whitney U and Kruskal-Wallis tests with 5% of significance. RESULTS: The average age was 49.1±12.9, mostly female (58.7%). High PS was reported by 54.5%; emotions such as joy (38.2%) and anxiety/fear (25.5%), as well as sadness (7.3%), were reported. About 87.3% were classified as having insufficient levels of PPA. Female patients (U=137.0; P<0.05) and insufficient PPA levels (U=86.5%; P<0.05) had higher PS scores, as well as those feeling sadness (χ2=19.0; P<0.05). CONCLUSIONS: The results point to the need for care with the emotional domain of these patients and suggest studies that analyze the impact of implementing PPA for this population.

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.

Morphine promotes renal pathology in sickle mice.

Patients with sickle cell disease (SCD) are often treated with opioids for severe pain. Although opioids are known to have renal-specific effects, their role in nephropathy in SCD remains unknown. Because a subset of patients receives opioids for long periods of time, we examined the influence of chronic morphine treatment on mice with pre-existing renal disease expressing varying amounts of sickle hemoglobin. Morphine treatment for 3-6 weeks resulted in a variety of defects in renal morphology observed using light and electron microscopy. Notably, morphine induced glomerular pathology, resulting in increased glomerular volume, mesangial expansion, mesangial cell proliferation, parietal cell metaplasia, podocyte effacement, and microvillus transformation. Cystic tubulopathy and hemeoxygenase-1 expression and activity were also increased in morphine-treated mice. Naloxone, a non-selective opioid receptor (OR) antagonist, ameliorated these effects. Functionally, the urine albumin to creatinine ratio was increased following acute as well as chronic morphine treatment. These results suggest that clinically relevant doses of morphine induce renal pathology and that OR antagonists may be effective for ameliorating morphine-induced renal disease.

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.