Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience

Objective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. Study design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. Results: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. Conclusions: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain.info:eu-repo/semantics/publishedVersio

Stab Injury to the Preauricular Region With Laceration of the External Carotid Artery Without Involvement of the Facial Nerve: a Case Report

BACKGROUND: Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external carotid artery. Hence, external carotid artery lesions are usually associated with facial nerve dysfunction. We present an unusual case report in which the patient had an injury to this artery with no facial nerve compromise. CASE PRESENTATION: A 25-year-old Portuguese man sustained a stab wound injury to his right preauricular region with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of the wound was achieved at the place of aggression by two off-duty doctors. He was initially transferred to a district hospital, where a large arterial bleeding was observed and a temporary compressive dressing was applied. Subsequently, the patient was transferred to a tertiary hospital. At admission in the emergency room, he presented a pulsating lesion in the right preauricular region and slight weakness in the territory of the inferior buccal branch of the facial nerve. The physical examination suggested an arterial lesion superficial to the facial nerve. However, in the operating theater, a section of the posterior and lateral flanks of the external carotid artery inside the parotid gland was identified. No lesion of the facial nerve was observed, and the external carotid artery was repaired. To better understand the anatomical rationale of this uncommon clinical case, we dissected the preauricular region of six cadavers previously injected with colored latex solutions in the vascular system. A small triangular space between the two main branches of division of the facial nerve in which the external carotid artery was not covered by the facial nerve was observed bilaterally in all cases. CONCLUSIONS: This clinical case illustrates that, in a preauricular wound, the external carotid artery can be injured without facial nerve damage. However, no similar description was found in the reviewed literature, which suggests that this must be a very rare occurrence. According to the dissection study performed, this is due to the existence of a triangular space between the cervicofacial and temporofacial nerve trunks in which the external carotid artery is not covered by the facial nerve or its branches.info:eu-repo/semantics/publishedVersio

Quantifying Missing Heritability at Known GWAS Loci

Recent work has shown that much of the missing heritability of complex traits can be resolved by estimates of heritability explained by all genotyped SNPs. However, it is currently unknown how much heritability is missing due to poor tagging or additional causal variants at known GWAS loci. Here, we use variance components to quantify the heritability explained by all SNPs at known GWAS loci in nine diseases from WTCCC1 and WTCCC2. After accounting for expectation, we observed all SNPs at known GWAS loci to explain 1.29 X more heritability than GWAS-associated SNPs on average (P = 3.3 X 10[superscript -5]). For some diseases, this increase was individually significant:2.07 X for Multiple Sclerosis (MS) (P = 6.5 X 10 [superscript -9]) and for Crohn's Disease (CD) (P = 1.3 X 10[superscript -3]); all analyses of autoimmune diseases excluded the well-studied MHC region. Additionally, we found that GWAS loci from other related traits also explained significant heritability. The union of all autoimmune disease loci explained 7.15 X more MS heritability than known MS SNPs (P 20,000 Rheumatoid Arthritis (RA) samples typed on ImmunoChip, with 2.37 X more heritability from all SNPs at GWAS loci (P = 2.3 X 10[superscript -6]) and more heritability from all autoimmune disease loci (P < 1 X 10[superscript -16]) compared to known RA SNPs (including those identified in this cohort). Our methods adjust for LD between SNPs, which can bias standard estimates of heritability from SNPs even if all causal variants are typed. By comparing adjusted estimates, we hypothesize that the genome-wide distribution of causal variants is enriched for low-frequency alleles, but that causal variants at known GWAS loci are skewed towards common alleles. These findings have important ramifications for fine-mapping study design and our understanding of complex disease architecture.National Institutes of Health (U.S.) (Grant R03HG006731)National Institutes of Health (U.S.) (Fellowship F32GM106584

Parents’ marital status and child physical abuse potential: the mediation of depression symptoms

Informed by a social interactional framework of stress and parenting, the aim of this study was to examine the mediating effect of depression symptoms on the asso- ciation between parents’ marital status (married and divorced parents) and child physical abuse potential, in a Portuguese community sample. It was hypothesized that the possible observed differences between divorced and married parents in the child physical abuse potential would be explained by their depression symptoms. Parents (N = 892) were assessed in their marital status, severity of depression symptoms and child physical abuse potential. Results showed that, when compared with married parents, divorced parents had higher child physical abuse potential. However, parents’ depression symptomatology was found as a mediator of the effect of marital status differences on child physical abuse potential. The influence of the status of divorced parents on the increase of child physical abuse potential was explained by the increase of the parents’ depression symptoms. This finding suggested that parents’ divorced status had no longer an effect on child physical abuse potential when parents’ depression symptomatology was tested as a mediator vari- able. The present mediation model explained 47 % of the variability in the child physical abuse potential score. Prac- tical implications of these findings for prevention and psy- chological intervention are also discussed.info:eu-repo/semantics/publishedVersio

Tendências na utilização de antimicrobianos em um hospital universitário, 1990-1996 Trends in antimicrobial utilization in a university hospital, 1990-1996

OBJETIVO: Uma das principais preocupações mundiais quanto ao uso de medicamentos está relacionada à utilização de antimicrobianos. Nos países em desenvolvimento, poucos recursos são empregados na monitorização de ações sobre o uso racional de medicamentos. São, também, limitados os dados sobre o uso daqueles agentes em hospitais. Assim realizou-se estudo para determinar os padrões de uso de antimicrobianos em hospital num período de sete anos (1990 a 1996). MÉTODOS: O estudo foi realizado em um hospital universitário, terciário, com 690 leitos, localizado em Porto Alegre, RS. Os registros hospitalares foram revisados visando identificar o consumo de antimicrobianos por pacientes internados, sendo os resultados expressos em dose diária definida (DDD) por 100 leitos-dia. A análise de conglomerados foi realizada para determinar as tendências de consumo dos agentes individuais. RESULTADOS: O consumo de antimicrobianos aumentou com o correr dos anos, passando de 83,8 DDD por 100 leitos-dia, em 1990, a 124,58 DDD por 100 leitos-dia em 1996. O grupo de medicamentos mais utilizado foi de penicilinas (39,6%), seguido por cefalosporinas (15,0%), aminoglicosídeos (14,4%), sulfonamidas (12,8%), glicopeptídeos (3,6%) e lincosaminas (3,1%). Estes grupos foram responsáveis por cerca de 90% do consumo. A análise de conglomerados do uso de antimicrobianos mostrou 13 grupos principais de tendência de consumo. CONCLUSÕES: O consumo de antimicrobianos cresceu no período avaliado, sendo expressivamente mais alto em comparação com o relatado em outros estudos. Quando novas alternativas terapêuticas foram disponibilizadas no hospital, o uso de medicamentos antigos decresceu e, em alguns casos, existiu manutenção dos níveis de consumo. Quando foi realizada intervenção específica como uma campanha para o uso correto de cefoxitina, as mudanças esperadas ocorreram.<br>OBJECTIVE: There is a worldwide concern about rational drug use, more specifically related to antimicrobial utilization. In developing countries, few resources are intended for monitoring on rational drug use. Moreover, there are limited data on the use of antimicrobial agents in hospitals. A study was carried out to describe patterns of use of antimicrobial agents over a 7-year period (1990 to 1996). METHODS: The study was conducted in a 690-bed tertiary care university hospital in Porto Alegre, Brazil. Hospital records were reviewed to identify inpatient antibiotics use. Results were expressed in defined daily dose per 100-beds/day. Cluster analysis was performed to determine the trends in use of individual agents. RESULTS: Antimicrobials use increased year after year, from 83.8 DDD per 100 beds-day in 1990 to 124.58 DDD per 100 beds-day in 1996. Penicillins were the drug group mostly used (39.6%), followed by cephalosporins (15.0%), aminoglycosides (14.4%), sulfonamides (12.8%), glycopeptides (3.6%), and lincosamides (3.1%). These groups were responsible for around 90% of all agents used. The use of antimicrobial agents was divided into thirteen groups based on cluster analysis. CONCLUSIONS: Antimicrobial use increased dramatically in the study period, and this increase was significantly higher when compared to other studies. When newer alternative agents became available in the hospital, the use of already existing drugs decreased and in some cases remained relatively stable. After implementing specific interventions, such as an effort for the correct use of cefoxitin, the expected changes in use were observed

Descrição anatômica do terço proximal da artéria circunflexa femoral medial: estudo em cadáver Anatomical description of the proximal third of the medial femoral circumflex artery: a cadaveric study

OBJETIVO: Descrever através de estudo em cadáver a disposição anatômica do terço proximal da artéria cincunflexa femoral medial (ACFM). MÉTODOS: Foi avaliada a disposição anatômica do terço proximal da ACFM, através de dissecção em 12 quadris de cadáver, que após terem sua altura aferida em metros (M), foram determinados alguns parâmetros: Ângulo de lateralização da ACFM (Â), Profundidade da ACFM em relação a origem superomedial do músculo quadrado femoral (P), distância da ACFM em relação a inserção superolateral do músculo quadrado femoral (D). RESULTADOS: Quando comparamos a média dos parâmetros entre os sexos notamos: Masculino Â= 43.6 graus, feminino Â= 38.3 graus. Masculino D= 6mm, feminino D= 9.5mm. Masculino P= 20.8 mm, feminino P= 18.3mm. A média dos parametros  e P são menores no sexo feminino porém o parâmetro D no sexo feminino é maior. CONCLUSÃO: Devemos ter como parâmetro superficial de segurança para o terço proximal da ACFM o ponto de inserção superolateral do músculo quadrado femoral. Que o parâmetro D da ACFM no sexo feminino é maior do que no sexo masculino. Que desinserir o músculo quadrado femoral em sua origem no ísquio pode oferecer maior segurança a ACFM do que faze-lo em sua inserção femural. Nível de evidência IV, série de casos.<br>OBJECTIVE: To describe, in a cadaver study, the anatomical arrangement of the proximal third medial femoral circumflex artery (ACFM). METHODS: We evaluated the anatomic arrangement of the proximal third of the ACFM through dissection in 12 cadaver hips. After measuring their height in meters (M), several parameters were determined: angle of lateralization of ACFM (Â), Depth ACFM in relation to the superomedial origin of the quadratus femoris muscle (P), and distance of ACFM from the superolateral insertion of the muscle quadratus femoris (D). RESULTS: In the comparison of mean parameters between the sexes, it was noted that: Male  = 43.6 degrees, female  = 38.3 degrees. Male D = 6mm, female D = 9.5mm. Male P = 20.8 mm, female P = 18.3mm. The average for parameters A and P were lower in females, but parameter D was higher in females. CONCLUSION: We should use, as the secure surface parameter for the proximal third of the ACFM, the superolateral insertion point of the quadratus femoris muscle. The fact that the parameter D of ACFM is greater in females than in males. Disconnecting the quadratus femoris muscle at its point of origin in the isquio may offer greater security to ACFM than doing it at the point of femoral insertion. Level of Evidence