Distal motor neuropathy associated with novel EMILIN1 mutation

Abstract Elastin microfibril interface-located proteins (EMILINs) are extracellular matrix glycoproteins implicated in elastogenesis and cell proliferation. Recently, a missense mutation in the EMILIN1 gene has been associated with autosomal dominant connective tissue disorder and motor-sensory neuropathy in a single family. We identified by whole exome sequencing a novel heterozygous EMILIN1 mutation c.748C>T [p.R250C] located in the coiled coil forming region of the protein, in four affected members of an autosomal dominant family presenting a distal motor neuropathy phenotype. In affected patient a sensory nerve biopsy showed slight and unspecific changes in the number and morphology of myelinated fibers. Immunofluorescence study of a motor nerve within a muscle biopsy documented the presence of EMILIN-1 in nerve structures. Skin section and skin derived fibroblasts displayed a reduced extracellular deposition of EMILIN-1 protein with a disorganized network of poorly ramified fibers in comparison with controls. Downregulation of emilin1a in zebrafish displayed developmental delay, locomotion defects, and abnormal axonal arborization from spinal cord motor neurons. The phenotype was complemented by wild-type zebrafish emilin1a, and partially the human wild-type EMILIN1 cRNA, but not by the cRNA harboring the novel c.748C>T [p.R250C]. These data suggest a role of EMILIN-1 in the pathogenesis of diseases affecting the peripheral nervous system

Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

<p>Abstract</p> <p>Background</p> <p>Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).</p> <p>Methods</p> <p>Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.</p> <p>Results</p> <p>Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m²at baseline to 128.9 after 2 years (<it>p </it>= 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (<it>p </it>= 0.0003) and in TDF+PI group (<it>p </it>= 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.</p> <p>Conclusions</p> <p>Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.</p

A TECNOLOGIA COMO DISPOSITIVO DO ATENDIMENTO HUMANIZADO NA ATENÇÃO BÁSICA À SAÚDE

Over the years, it has been observed that technology has been advancing more and more and has contributed significantly to people's lives, as well as to important areas such as health, because, based on these tools, it becomes possible to develop care faster and more humanized to patients who seek primary health care to obtain medical assistance. Thus, the research aims to explain the relevance of technology as a device for humanized care in primary health care. The methodology used consisted of the literature review method in order to obtain concise information about the objective of the work, with articles published from 2019 to 2022 available on Scielo, Lilacs and PubMed. Researches that were lower than 2019 were excluded, as well as those whose content was not in Portuguese, which would make the researchers' verification and analysis process difficult. In this way, the results pointed to the benefits caused by technology, enabling better care in terms of medical consultations, exams and guidance to patients, making humanized care in primary health care an essential factor. Concluding on the need to expand technology as a humanized device in all primary health care units, considering that some locations do not have these tools, because, in addition to promoting effectiveness in terms of faster assistance, it enables the minimization queue for appointments and exams.Com o passar dos anos, observa-se que a tecnologia vem avançando cada vez mais e contribuído de forma significativa na vida das pessoas, como também para áreas importantes como a da saúde, pois, a partir dessas ferramentas que torna-se possível desenvolver atendimento mais rápidos e humanizado aos pacientes que buscam atenção básica de saúde para obter assistência médica. Assim, a pesquisa objetiva explicar sobre a relevância da tecnologia como dispositivo do atendimento humanizado na atenção básica à saúde. A metodologia utilizada consistiu no método revisão de literatura com o intuito de obter informações concisas a respeito do objetivo do trabalho, sendo inserido artigos publicados no período de 2019 a 2022 disponíveis na Scielo, Lilacs e PubMed. Sendo excluídas pesquisas que estavam inferior a 2019, bem como aquelas cujo conteúdo não era língua portuguesa, o que dificultaria o processo de verificação e análise dos pesquisadores. Dessa forma, os resultados apontaram sobre os benefícios ocasionados pela tecnologia, possibilitando melhores atendimentos em termos de consultas médicas, exames e orientações aos pacientes, tornando o atendimento humanizado na atenção básica à saúde como um fator imprescindível. Concluindo-se sobre a necessidade de ampliar a tecnologia como dispositivo humanizado em todas as unidades de atenção básica à saúde, tendo em vista que algumas localidades não dispõem dessas ferramentas, pois, além de promover eficácia em termos de assistência mais rápida, possibilita a minimização da fila de espera por atendimentos e exames

Towards a better understanding of thermally treated polycarbophil matrix tablets for controlled release

Polycarbophil (POL), a polyacrylic acid cross-linked with divinyl glycol, is widely used in semisolid and solid dosage forms. When undergoing a thermal treatment in the range 120\u2013160 \ub0C, POL shows interesting morphological modifications, related to changes in physical properties, such as swelling of the powder granules, or hardening and matrix formation if included in the composition of a tablet. Thermal analysis conducted on POL highlighted a thermal event (Z) that can be correlated both to the shrinking of the powder granules and to the matrix formation in compacted POL powder. Modulated differential scanning calorimetry (MDSC) allowed to distinguish, inside event Z, an irreversible process overlapping with a reversible glass transition, attributable to the volatilization of residual solvents identified, through a complex TGA-FTIR-GC\u2013MS interface, as acetate esters used for the polymer production as very fine powder. A specific interaction between acetates and POL, capable of stabilizing the polymer chains in a given conformation, was highlighted. The molecular rearrangement of the POL chains, following the volatilization of the solvent-stabilizers, is therefore ascribable to a loss of energetic stability of this material, which justifies the shrinking phenomena in the granules of the powder and the matrix formation when POL is compacted

Peritoneal carcinomatosis: imaging with 64-MDCT and 3T MRI with diffusion-weighted imaging

Peritoneal carcinomatosis is usually associated with a poor overall survival rate. Recently, introduction of more aggressive surgical treatment and intraperitoneal chemotherapy appears to significantly increase the overall survival rate for these patients. A detailed preoperative assessment of peritoneal carcinomatosis could be very challenging in the field of imaging, but a new aggressive surgical approach requires an accurate preoperative assessment of the disease. Cross-sectional imaging using CT and MRI with diffusion-weighted imaging (DWI) sequences is important for appropriate management of patients with peritoneal carcinomatosis. Appreciation of the spectrum of diagnostic patterns and pitfalls as well as different sites of involvement of peritoneal carcinomatosis using CT and DWI is crucial for appropriate surgical treatment