Avaliação e tratamento do doente com acne – Parte I: Epidemiologia, etiopatogenia, clínica, classificação, impacto psicossocial, mitos e realidades, diagnóstico diferencial e estudos complementares

O Portuguese Acne Advisory Board (PAAB), grupo de dermatologistas portugueses que, à semelhança de grupos congéneres internacionais, tem dedicado particular atenção à definição de linhas de orientação para o tratamento da acne, pretende que o presente documento constitua uma ferramenta útil na abordagem dos doentes com esta patologia. Elaborou-se um dossier, para educação médica contínua, subdividido em 2 partes: Parte I – etiopatogenia e clínica; Parte II – abordagem terapêutica. Nesta Parte I, revêem-se os principais aspectos da clínica e da fisiopatogenia da acne à luz dos conhecimentos actuais. Discute-se a importância do impacto psicológico e social desta entidade e analisam-se os principais mitos e realidades com ela relacionados. Descrevem-se, sucintamente, as patologias mais relevantes no diagnóstico diferencial das lesões de acne. Enumeram-se as indicações para estudo hormonal, bem como os exames a efectuar nos doentes com esta patologia. The Portuguese Acne Advisory Board (PAAB), a group of Portuguese dermatologists with a special interest in acne, develop, as other international groups in this field, consensus recommendations for the treatment of acne. Overall, the goal is to provide a practice guideline to all physicians dealing with this entity. The continuing medical education dossier was divided in two parts: Part I – etiopathogeny and clinical features; Part II – therapy. This Part I reviews acne pathophysiology, clinical aspects, psychological and social impact and several myths surrounding this disease. Some other entities relevant for the differential diagnosis are described. The need of hormonal evaluation is also discusse

Autosomal dominant optic atrophy and cataract “plus” phenotype including axonal neuropathy

Objective To characterize the phenotype in individuals with OPA3-related autosomal dominant optic atrophy and cataract (ADOAC) and peripheral neuropathy (PN). Methods Two probands with multiple affected relatives and one sporadic case were referred for evaluation of a PN. Their phenotype was determined by clinical ± neurophysiological assessment. Neuropathologic examination of sural nerve and skeletal muscle, and ultrastructural analysis of mitochondria in fibroblasts were performed in one case. Exome sequencing was performed in the probands. Results The main clinical features in one family (n = 7 affected individuals) and one sporadic case were early-onset cataracts (n = 7), symptoms of gastrointestinal dysmotility (n = 8), and possible/confirmed PN (n = 7). Impaired vision was an early-onset feature in another family (n = 4 affected individuals), in which 3 members had symptoms of gastrointestinal dysmotility and 2 developed PN and cataracts. The less common features among all individuals included symptoms/signs of autonomic dysfunction (n = 3), hearing loss (n = 3), and recurrent pancreatitis (n = 1). In 5 individuals, the neuropathy was axonal and clinically asymptomatic (n = 1), sensory-predominant (n = 2), or motor and sensory (n = 2). In one patient, nerve biopsy revealed a loss of large and small myelinated fibers. In fibroblasts, mitochondria were frequently enlarged with slightly fragmented cristae. The exome sequencing identified OPA3 variants in all probands: a novel variant (c.23T>C) and the known mutation (c.313C>G) in OPA3. Conclusions A syndromic form of ADOAC (ADOAC+), in which axonal neuropathy may be a major feature, is described. OPA3 mutations should be included in the differential diagnosis of complex inherited PN, even in the absence of clinically apparent optic atrophy

A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement

The CADM family of proteins consists of four neuronal specific adhesion molecules (CADM1, CADM2, CADM3 and CADM4) that mediate the direct contact and interaction between axons and glia. In the peripheral nerve, axon-Schwann cell interaction is essential for the structural organization of myelinated fibres and is primarily mediated by the binding of CADM3, expressed in axons, to CADM4, expressed by myelinating Schwann cells. We have identified—by whole exome sequencing—three unrelated families, including one de novo patient, with axonal Charcot-Marie-Tooth disease (CMT2) sharing the same private variant in CADM3, Tyr172Cys. This variant is absent in 230 000 control chromosomes from gnomAD and predicted to be pathogenic. Most CADM3 patients share a similar phenotype consisting of autosomal dominant CMT2 with marked upper limb involvement. High resolution mass spectrometry analysis detected a newly created disulphide bond in the mutant CADM3 potentially modifying the native protein conformation. Our data support a retention of the mutant protein in the endoplasmic reticulum and reduced cell surface expression in vitro. Stochastic optical reconstruction microscopy imaging revealed decreased co-localization of the mutant with CADM4 at intercellular contact sites. Mice carrying the corresponding human mutation (Cadm3Y170C) showed reduced expression of the mutant protein in axons. Cadm3Y170C mice showed normal nerve conduction and myelin morphology, but exhibited abnormal axonal organization, including abnormal distribution of Kv1.2 channels and Caspr along myelinated axons. Our findings indicate the involvement of abnormal axon-glia interaction as a disease-causing mechanism in CMT patients with CADM3 mutations. A correction has been published: Brain, Volume 144, Issue 7, July 2021, Page e64, https://doi.org/10.1093/brain/awab18

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes

Chromium removal from aqueous solution by a PEI-silica nanocomposite

It is essential and important to determine the adsorption mechanism as well as removal efficiency when using an adsorption technique to remove toxic heavy metals from wastewater. In this research, the removal efficiency and mechanism of chromium removal by a silica-based nanoparticle were investigated. A PEI-silica nanoparticle was synthesized by a one-pot technique and exhibited uniformly well-dispersed PEI polymers in silica particles. The adsorption capacity of chromium ions was determined by a batch adsorption test, with the PEI-silica nanoparticle having a value of 183.7 mg/g and monolayer sorption. Adsorption of chromium ions was affected by the solution pH and altered the nanoparticle surface chemically. First principles calculations of the adsorption energies for the relevant adsorption configurations and XPS peaks of Cr and N showed that Cr(VI), [HCrO4](-) is reduced to two species, Cr(III), CrOH2+ and Cr3+, by an amine group and that Cr(III) and Cr(VI) ions are adsorbed on different functional groups, oxidized N and NH3+

Adverse Drug Reactions in Children—A Systematic Review

Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided

Evaluation and Treatment of Acne Patients – Part I: Epidemiology, Etiopathogeny, Clinic, Classification, Psychosocial Impact, Myths and Realities, Differential Diagnosis and Laboratory Studies

O Portuguese Acne Advisory Board (PAAB), grupo de dermatologistas portugueses que, à semelhança de grupos congéneres internacionais, tem dedicado particular atenção à definição de linhas de orientação para o tratamento da acne, pretende que o presente documento constitua uma ferramenta útil na abordagem dos doentes com esta patologia. Elaborou-se um dossier, para educação médica contínua, subdividido em 2 partes: Parte I – etiopatogenia e clínica; Parte II – abordagem terapêutica. Nesta Parte I, revêem-se os principais aspectos da clínica e da fisiopatogenia da acne à luz dos conhecimentos actuais. Discute-se a importância do impacto psicológico e social desta entidade e analisam-se os principais mitos e realidades com ela relacionados. Descrevem-se, sucintamente, as patologias mais relevantes no diagnóstico diferencial das lesões de acne. Enumeram-se as indicações para estudo hormonal, bem como os exames a efectuar nos doentes com esta patologia. The Portuguese Acne Advisory Board (PAAB), a group of Portuguese dermatologists with a special interest in acne, develop, as other international groups in this field, consensus recommendations for the treatment of acne. Overall, the goal is to provide a practice guideline to all physicians dealing with this entity. The continuing medical education dossier was divided in two parts: Part I – etiopathogeny and clinical features; Part II – therapy. This Part I reviews acne pathophysiology, clinical aspects, psychological and social impact and several myths surrounding this disease. Some other entities relevant for the differential diagnosis are described. The need of hormonal evaluation is also discusse