Beyond Polycystic Kidney Disease

Tuberous sclerosis(TS) is an autosomal dominant disease caused by mutations in TSC1 and TSC2 genes. TSC2 gene is located in chromosome 16p13.3, adjacent to PKD1 gene, responsible for the autosomal dominant polycystic kidney disease. In a rare subgroup of patients, the presence of a deletion which simultaneously affects the TSC2 and PKD1 genes has been confirmed. TSC2/PKD1-Contiguous Gene Syndrome is characterised by the early appearance of autosomal dominant polycystic kidney disease in combination with several phenotypic manifestations of TS. We present a 13-year-old girl with bilateral renal cysts detected at the age of 9 months. At the age of 13, she was referred to the Dermatology Outpatients Clinic due to a facial cutaneous eruption. She presented with facial erythema, fibroadenomas with malar distribution and disseminated hypomelanotic macules, meeting the criteria for TS. TSC2/PKD1 Contiguous Gene Syndrome deletion was suspected, being later confirmed by genetic testing.info:eu-repo/semantics/publishedVersio

The Government needs to catch up with early years professionals

Last month, at the height of the pandemic, we were asked by the STA (Standards and Testing Agency) to review Test Items for its third attempt at Reception Baseline Assessment (RBA) in September 2023

Women living with HIV/AIDS who are sexual partners of injecting drug users

OBJECTIVE: To analyze perceptions of risk, prevention strategies, their own relationship with drug use and that of their partner's, and future expectations among women living with HIV/AIDS whose partners are drug users. METHODS: This is a qualitative study of women living with HIV/AIDS who receive specialist treatment in São Paulo Municipality. Semi-structured interviews were carried out with 15 women, whose self-reported means of infection were heterosexual relations with a partner who is an injecting drug user. The script for the interviews covered the following areas: childhood, history of sexual relations, use of drugs, impact of seropositivity on daily life, understanding of the prevention of sexually transmitted infections, and perspectives of the future. The material from the interviews was analyzed using content analysis. RESULTS: The study pointed to a difference in the ways that the women live with their own drug use and with that of their partners. Their partners' use of injecting drugs was not primarily associated with a risk of HIV infection, due to attempts to conceal the fact or because they believed that the monogamy-fidelity-confidence trinity would take precedence as a form of protection. CONCLUSIONS: The women's different experiences of drug use should be taken into account and opportunities to discuss with them about the issue are important to ensure that more effective strategies for prevention and care are adopted.OBJETIVO: Analisar as percepções de risco, as estratégias de prevenção, sua própria relação com o uso de drogas e do parceiro e suas expectativas quanto ao futuro relatadas por mulheres vivendo com HIV/Aids parceiras de usuários de drogas. MÉTODOS: Estudo qualitativo sobre mulheres vivendo com HIV/Aids, atendidas em serviço especializado no Município de São Paulo. Foram aplicadas entrevistas semi-estruturadas a 15 mulheres, cuja via de infecção auto-referida foram as relações heterossexuais com parceiro usuário de drogas injetáveis. O roteiro das entrevistas compreendia: infância, história dos relacionamentos amorosos, uso de drogas, impacto da soropositividade no cotidiano, compreensão sobre prevenção de infecções sexualmente transmissíveis, e visão do futuro. A interpretação das entrevistas foi realizada por meio de análise de conteúdo. RESULTADOS: O estudo indicou diversidade da convivência das mulheres com o uso de drogas próprio e do parceiro. O uso de drogas injetáveis pelo parceiro não foi, prioritariamente, associado ao risco de infecção por HIV/Aids, seja por estratégias de ocultamento do fato, seja por considerarem que a tríade monogamia-fidelidade-confiança teria primazia como forma de proteção. CONCLUSÕES: A diversidade da convivência das mulheres com o uso de drogas deve ser considerada e oportunidades de fala e escuta sobre a questão podem ser importantes para a adoção de estratégias mais efetivas de prevenção e cuidado.Universidade de São Paulo Faculdade de Medicina Departamento de Medicina PreventivaUniversidade Federal de São Paulo (UNIFESP) Departamento de Ciências da SaúdePrefeitura Municipal de São Paulo Secretaria Municipal de SaúdeUNIFESP, Depto. de Ciências da SaúdeSciEL

NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms.

Mitochondrial complex I (CI) deficiency is the most common oxidative phosphorylation disorder described. It shows a wide range of phenotypes with poor correlation within genotypes. Herein we expand the clinics and genetics of CI deficiency in the brazilian population by reporting three patients with pathogenic (c.640G>A, c.1268C>T, c.1207dupG) and likely pathogenic (c.766C>T) variants in the NDUFV1 gene. We show the mutation c.766C>T associated with a childhood onset phenotype of hypotonia, muscle weakness, psychomotor regression, lethargy, dysphagia, and strabismus. Additionally, this mutation was found to be associated with headaches and exercise intolerance in adulthood. We also review reported pathogenic variants in NDUFV1 highlighting the wide phenotypic heterogeneity in CI deficiency

Conditioned stochastic particle systems and integrable quantum spin systems

We consider from a microscopic perspective large deviation properties of several stochastic interacting particle systems, using their mapping to integrable quantum spin systems. A brief review of recent work is given and several new results are presented: (i) For the general disordered symmectric exclusion process (SEP) on some finite lattice conditioned on no jumps into some absorbing sublattice and with initial Bernoulli product measure with density $\rho$ we prove that the probability $S_\rho(t)$ of no absorption event up to microscopic time $t$ can be expressed in terms of the generating function for the particle number of a SEP with particle injection and empty initial lattice. Specifically, for the symmetric simple exclusion process on $\mathbb Z$ conditioned on no jumps into the origin we obtain the explicit first and second order expansion in $\rho$ of $S_\rho(t)$ and also to first order in $\rho$ the optimal microscopic density profile under this conditioning. For the disordered ASEP on the finite torus conditioned on a very large current we show that the effective dynamics that optimally realizes this rare event does not depend on the disorder, except for the time scale. For annihilating and coalescing random walkers we obtain the generating function of the number of annihilated particles up to time $t$, which turns out to exhibit some universal features.Comment: 25 page

KCC2 is required for the survival of mature neurons but not for their development

The K+/Cl- co-transporter KCC2 (SLC12A5) allows mature neurons in the CNS to maintain low intracellular Cl- levels that are critical in mediating fast hyperpolarizing synaptic inhibition via type A γ-aminobutyric acid receptors (GABAARs). In accordance with this, compromised KCC2 activity results in seizures, but whether such deficits directly contribute to the subsequent changes in neuronal structure and viability that lead to epileptogenesis, remains to be assessed. Canonical hyperpolarizing GABAAR currents develop postnatally which reflect a progressive increase in KCC2 expression levels and activity. To investigate the role that KCC2 plays in regulating neuronal viability and architecture we have conditionally ablated KCC2 expression in developing and mature neurons. Decreasing KCC2 expression in mature neurons resulted in the rapid activation of the extrinsic apoptotic pathway. Intriguingly, direct pharmacological inhibition of KCC2 in mature neurons was sufficient to rapidly induce apoptosis, an effect that was not abrogated via blockade of neuronal depolarization using Tetrodotoxin (TTX). In contrast, ablating KCC2 expression in immature neurons had no discernable effects on their subsequent development, arborization or dendritic structure. However, removing KCC2 in immature neurons was sufficient to ablate the subsequent postnatal development of hyperpolarizing GABAAR currents. Collectively, our results demonstrate that KCC2 plays a critical role in neuronal survival by limiting apoptosis, and mature neurons are highly sensitive to the loss of KCC2 function. In contrast, KCC2 appears to play a minimal role in mediating neuronal development or architecture

Neurolymphomatosis mimicking neurosarcoidosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Both neurosarcoidosis and central nervous system lymphoma can be very difficult to diagnose. We describe the case of a patient in whom neurosarcoidosis was strongly suspected, but who was eventually found to have lymphoma. We believe the case to be of interest and practical value to neurologists, oncologists and internists with an interest in inflammatory diseases.</p> <p>Case presentation</p> <p>A diagnosis of neurosarcoidosis was considered in a 49-year-old Caucasian man on the basis of the following symptoms and indications: a cough, bilateral hilar lymphadenopathy confirmed by thoracic computed tomography, the development of an S1 radiculopathy, cerebrospinal fluid abnormalities (raised protein level), bilateral lung hilar and lachrymal gland uptake on a gallium scan, and erythema nodosum confirmed with skin biopsy. These were followed by the development of multiple cranial neuropathies, including seventh nerve palsy. Exhaustive further investigations yielded no evidence for an alternative diagnosis. Treatments with steroids, cyclophosphamide, intravenous immunoglobulin and finally infliximab were of no benefit. He eventually developed cutaneous nodules, a biopsy of which revealed lymphoma that proved resistant to therapy.</p> <p>Conclusion</p> <p>Constant diagnostic vigilance is required in disorders such as neurosarcoidosis.</p

Three-Dimensional Super-Resolution in Eukaryotic Cells Using the Double-Helix Point Spread Function

Single-molecule localization microscopy, typically based on total internal reflection illumination, has taken our understanding of protein organization and dynamics in cells beyond the diffraction limit. However, biological systems exist in a complicated three-dimensional environment, which has required the development of new techniques, including the double-helix point spread function (DHPSF), to accurately visualize biological processes. The application of the DHPSF approach has so far been limited to the study of relatively small prokaryotic cells. By matching the refractive index of the objective lens immersion liquid to that of the sample media, we demonstrate DHPSF imaging of up to 15-μm-thick whole eukaryotic cell volumes in three to five imaging planes. We illustrate the capabilities of the DHPSF by exploring large-scale membrane reorganization in human T cells after receptor triggering, and by using single-particle tracking to image several mammalian proteins, including membrane, cytoplasmic, and nuclear proteins in T cells and embryonic stem cells.We thank the Royal Society for the University Research Fellowship of S.F.L. (UF120277). This work was kindly funded by the Engineering and Physical Sciences Research Council (EP/M003663/1) and by the Wellcome Trust