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Rare cases of suspected spinal muscular atrophy (SMA) have been found to have cytochrome c oxidase (COX) deficiency. To date, four cases with SMA features have been reported in children with mutations in the synthesis of cytochrome oxidase 2 (SCO2) gene. We report a male neonate who was born hypotonic, with persistent lactic acidosis, spontaneous activity with EMG testing, development of respiratory distress in the first few hours of life, and died at 30 days of age with progressive cardiomyopathy. Testing for survival motor neurone (smn) and NAIP deletions were negative and a skeletal muscle biopsy showed neurogenic features with severe reductions of COX enzymatic and histochemical staining intensity. Post-mortem muscle, heart, and liver biopsies showed severe, moderate, and mild reductions in COX activity, respectively, with parallel findings in the protein content for the mitochondrial DNA (COII) and nuclear DNA (COIV) encoded subunits. DNA sequencing of exon 2 of the SCO2 gene revealed compound heterozygosity with mutations at G1541A (common mutation, E140K) and also at a novel site in the copper binding region (G1521A in the current case (converting a highly conserved cysteine to serine (C133S)); mother heterozygous for G1521A; and father heterozygous for G1541A). This case provides strong support that SCO2 mutations can result in neonatal hypotonia with an SMA 1 phenotype. SCO2 mutations should be screened in suspected SMA cases with normal smn mutation analysis and any one of; cardiomyopathy, lactic acidosis, or COX deficiency in muscle. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease with a significant and growing impact on Canadians. The "Awareness, Care and Treatment In Obesity MaNagement" (ACTION) Study investigated perceptions, attitudes and perceived barriers to obesity management among Canadian people with obesity (PwO), healthcare providers (HCPs) and employers. In this study adult PwO (body mass index ≥30 kg/m 2 , based on self-reported height/weight), HCPs (physicians and allied HCPs managing PwO) and employers (≥20 employees; offering health insurance), completed online surveys between 3 August and 11 October 2017 in a cross-sectional design. Survey respondents (N = 2545) included 2000 PwO, 395 HCPs and 150 employers. Obesity was viewed as a "chronic medical condition" by most PwO (60%), HCPs (94%) and employers (71%) and deemed to have a large impact on overall health (74%, 78%, 81%, respectively). Many PwO (74%) believed weight management was their own responsibility. While PwO (55%) reportedly knew how to manage their weight, only 10% reported maintaining ≥10% weight reduction for >1 year. Despite low success rates, the most commonly reported effective long-term weight loss methods tried and/or recommended were "improvements in eating habits" (PwO 38%; HCP 63%) and "being more active" (PwO 39%; HCP 54%). PwO and HCPs reported very different perceptions of the quality and content of their interaction during obesity management discussions. These findings highlight the communication gaps and misunderstanding between PwO, HCPs and employers. This underscores the importance of, and need for, evidence-based management of obesity and a collaborative approach and understanding of the complex nature of this chronic disease., (© 2019 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23%. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB are catalytic and SDHC and SDHD are anchoring. Mutations in SDHA and SDHAF1 (assembly factor) have been found in patients with CII deficiency and a mitochondrial phenotype. We present a patient with CII deficiency with a previously undescribed phenotype of dilated cardiomyopathy, left ventricular noncompaction, failure to thrive, hypotonia, and developmental delay. Also, a comprehensive review of 36 cases published in the literature was undertaken. The results show that CII deficiency has a variable phenotype with no correlation with residual complex activity in muscle although the phenotype and enzyme activities are comparable within a family. For some, the condition was fatal in infancy, others had multisystem involvement and some had onset in adulthood with mild symptoms and normal cognition. Neurological involvement is most commonly observed and brain imaging commonly shows leukoencephalopathy, Leigh syndrome, or cerebellar atrophy. Mutations in SDHAF1 are associated with leukoencephalopathy. Other organ systems like heart, muscle, and eyes are only involved in about 50% of the cases but cardiomyopathy is associated with high mortality and morbidity. In some patients, riboflavin has provided clinical improvement., (Copyright © 2013 Wiley Periodicals, Inc.)

We have diagnosed dihydrolipoamide dehydrogenase (DLD) deficiency in two male second cousins, who presented with markedly different clinical phenotypes. Patient 1 had a recurrent encephalopathy, and patient 2 had microcephaly and lactic acidosis. Their presentation is unusual, in that the DLD subunit deficiency had little effect on pyruvate dehydrogenase complex activity, but caused a severe reduction in the activities of other enzymes that utilize this subunit. We have identified two mutations in the DLD gene in each patient. The second cousins have one novel mutation in common resulting in a substitution of isoleucine for threonine (I47T), which has not been previously reported in the literature. Patient 1 has a second mutation that has been reported to be common in the Ashkenazi Jewish population, G229C. Patient 2 has a second mutation, E375K, which has also been previously reported in the literature. Enzyme kinetic measurements on patient fibroblasts show that under certain conditions, one heteroallelic mutation may have a higher K(m). This may account for the differing clinical phenotypes. These findings have important repercussions for other patients with similar clinical phenotypes, as DLD activity is not normally measured in cases with normal PDHc activity., (Copyright 2006 Wiley-Liss, Inc.)

Objectives: The study applied Weiner's (1980, 1986) attributional model of helping behaviour to Accident and Emergency (A&E) staff's care of patients presenting with deliberate self-harm. It was hypothesized that where staff attributed precipitants of the act of deliberate self-harm to controllable, internal, and stable patient factors, then staff would display greater negative affect, less optimism, and less willingness to help the patient., Design: Using four hypothetical scenarios in a two-factor between-subjects design, contextual factors describing a self-harm patient were manipulated., Method: Participants were 89 A&E medical and nursing staff. They were asked to rate attributions for the cause of the deliberate self-harm and their emotional responses, optimism for change, and willingness to help change the behaviour. Their general attitudes towards deliberate self-harm patients and perceived needs for training in the care of these patients were also assessed., Results: The findings were consistent with Weiner's attributional model of helping. The greater attributions of controllability, the greater the negative affect of staff towards the person, and the less the propensity to help. The higher the ratings of stability of outcome, the less staff optimism for the success of their input. Male staff and medical staff had more negative attitudes, and medical staff saw less need for further training., Conclusion: Formulating A&E staff's responses to deliberate self-harm using a cognitive-emotional model offers the possibility of working with staffs' beliefs, emotions, and behaviour to improve the care and treatment of deliberate self-harm patients.

Pyruvate dehydrogenase (PDH)-complex deficiency (OMIM 312170) is a clinically heterogeneous disorder, with phenotypes ranging from fatal lactic acidosis (LA) in the newborn to chronic neurological dysfunction. To date, over 80 different mutations have been identified in the PDHA1 gene in patients with PDH complex deficiency, which are thus thought to contribute to the PDH deficient phenotype. We have identified 14 additional patients with total PDH complex deficiency, all of whom were found to contain mutations within the PDHA1 gene (E(1)alpha subunit). The mutations include both missense mutations and duplications. Eight of these patients had novel mutations, and the remaining had mutations that have been identified previously in PDH complex deficient patients, with residual fibroblast activity ranging from 2.4 to 69% of control values. The nature of these mutations illustrates the variability in phenotype for a given gene defect, with intermittent ataxia being the mildest presentation, Leigh syndrome being the most common and severe neonatal LA the most severe., ((c) 2004 Wiley-Liss, Inc.)

Rare cases of suspected spinal muscular atrophy (SMA) have been found to have cytochrome c oxidase (COX) deficiency. To date, four cases with SMA features have been reported in children with mutations in the synthesis of cytochrome oxidase 2 (SCO2) gene. We report a male neonate who was born hypotonic, with persistent lactic acidosis, spontaneous activity with EMG testing, development of respiratory distress in the first few hours of life, and died at 30 days of age with progressive cardiomyopathy. Testing for survival motor neurone (smn) and NAIP deletions were negative and a skeletal muscle biopsy showed neurogenic features with severe reductions of COX enzymatic and histochemical staining intensity. Post-mortem muscle, heart, and liver biopsies showed severe, moderate, and mild reductions in COX activity, respectively, with parallel findings in the protein content for the mitochondrial DNA (COII) and nuclear DNA (COIV) encoded subunits. DNA sequencing of exon 2 of the SCO2 gene revealed compound heterozygosity with mutations at G1541A (common mutation, E140K) and also at a novel site in the copper binding region (G1521A in the current case (converting a highly conserved cysteine to tyrosine [corrected] (C133Y) [corrected]); mother heterozygous for G1521A; and father heterozygous for G1541A). This case provides strong support that SCO2 mutations can result in neonatal hypotonia with an SMA 1 phenotype. SCO2 mutations should be screened in suspected SMA cases with normal smn mutation analysis and any one of; cardiomyopathy, lactic acidosis, or COX deficiency in muscle., (Copyright 2003 Wiley-Liss, Inc.)

A prospective, randomised, controlled clinical study was performed to compare the incidence and severity of postoperative peripheral venous thrombophlebitis associated with a single intravenous cannula used for both intra-operative and postoperative purposes, and two cannulae, one used intra-operatively and the other postoperatively. Sixty American Society of Anaesthesiologists (ASA) physical status I or II patients aged 18-65 years undergoing elective surgery were studied. The technique of cannula insertion was standardised. After surgery, the cannulation sites were examined daily by a blinded investigator for the presence and severity of thrombophlebitis using the Baxter Scale. The two groups were similar in terms of age, gender, weight, type and duration of surgical procedures, and drugs and fluids administered both intra-operatively and postoperatively. The proportion of patients that developed phlebitis was significantly less in the two cannulae group (26.1%) than in the single cannula group (63.3%) (p < 0.0001). The severity of phlebitis was greater in the single cannula group than in the two cannulae group. These results indicate that the use of a dedicated cannula for postoperative use decreases the incidence and severity of postoperative, peripheral, cannula-related phlebitis.