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.

Bartonellosis are diseases caused by any kind of Bartonella species. The infection manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacilliformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nodules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, erythema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases.

A intradermoterapia é um procedimento médico introduzido por Pistor, em 1958, e consiste na aplicação, diretamente na região a ser tratada, de injeções intradérmicas de substâncias farmacológicas muito diluídas. Esse método é capaz de estimular o tecido que recebe os medicamentos tanto pela ação da punctura quanto pela ação dos fármacos, e apregoa-se que sua vantagem é evitar o uso de medicação sistêmica. Há relatos da utilização da intradermoterapia para tratamento de doenças dolorosas, dermatoses e condições consideradas inestéticas. Atualmente, clínicas médicas oferecem esse tratamento, utilizando, porém, o nome mais popular para essa prática, mesoterapia. Há escassa informação científica sobre o tema publicada em periódicos indexados no MedLine e poucos estudos com metodologia mais rigorosa sobre a eficácia e o mecanismo de ação da via intradérmica. A maioria das publicações indexadas sobre esse tema versa sobre as complicações dessa técnica. As dermatoses inestéticas têm se tornado queixas frequentes nos consultórios dermatológicos, sendo necessário um embasamento científico para lidar com tais pacientes, os quais, muitas vezes, estão em busca das novidades mostradas através da mídia. Assim, há necessidade de estudos cientificamente bem conduzidos sobre essa técnica. Estes estudos deverão oferecer aos médicos elementos para esclarecer os pacientes sobre quais benefícios esperar e quais os riscos de tal abordagem. Desse modo, realizou-se uma revisão bibliográfica sobre o assunto e constatou-se a necessidade de novos estudos com metodologia adequada para a confirmação dos benefícios da intradermoterapia como ferramenta útil no tratamento dermatológico.

Donovanosis is a chronic bacterial illness frequently associated with sexually transmitted infections (STI) and is under diagnosed both in endemic areas as well as in countries in which doctors have little experience with tropical diseases. The utilization of syndromic diagnosis and treatment of STIs in various parts of the world and the previous use of antibiotics make it difficult to find Donovan bodies in the cytodiagnostic and hystopathological exams, requiring the utilization of technology that is neither routine nor often accessible to confirm the hypothesized diagnosis. Therefore, it is necessary to bring medical professionals up to date about this infectious disease.

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.

We evaluated culture-negative, community-acquired endocarditis by using indirect immunofluorescent assays and molecular analyses for Bartonella spp. and Coxiella burnetii and found a prevalence of 19.6% and 7.8%, respectively. Our findings reinforce the need to study these organisms in patients with culture-negative, community-acquired endocarditis, especially B. henselae in cat owners.