Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency

BACKGROUND Defects of the mitochondrial respiratory chain complex II (succinate dehydrogenase (SDH) complex) are extremely rare. Of the four nuclear encoded proteins composing complex II, only mutations in the 70 kDa flavoprotein (SDHA) and the recently identified complex II assembly factor (SDHAF1) have been found to be causative for mitochondrial respiratory chain diseases. Mutations in the other three subunits (SDHB, SDHC, SDHD) and the second assembly factor (SDHAF2) have so far only been associated with hereditary paragangliomas and phaeochromocytomas. Recessive germline mutations in SDHB have recently been associated with complex II deficiency and leukodystrophy in one patient. METHODS AND RESULTS We present the clinical and molecular investigations of the first patient with biochemical evidence of a severe isolated complex II deficiency due to compound heterozygous SDHD gene mutations. The patient presented with early progressive encephalomyopathy due to compound heterozygous p.E69 K and p.*164Lext*3 SDHD mutations. Native polyacrylamide gel electrophoresis and western blotting demonstrated an impaired complex II assembly. Complementation of a patient cell line additionally supported the pathogenicity of the novel identified mutations in SDHD. CONCLUSIONS This report describes the first case of isolated complex II deficiency due to recessive SDHD germline mutations. We therefore recommend screening for all SDH genes in isolated complex II deficiencies. It further emphasises the importance of appropriate genetic counselling to the family with regard to SDHD mutations and their role in tumorigenesis.

Does flow experience lead to risk? How and for whom

Background: Previous research has focused on the positive consequences of flow, an intrinsically rewarding state of deep absorption. In contrast, the present research links flow to impaired risk awareness and to risky behaviour. We expected flow to enhance self-efficacy beliefs, which in turn were hypothesised to result in low risk awareness and risky behaviour in sports. In addition, we predicted that individuals' level of experience in the activity would moderate the expected effects. Methods: One study with kayakers (Study 1) and two studies with rock climbers (Studies 2 and 3) were conducted. Kayakers completed a survey while still on the river; climbers responded during and upon completion of a climb. Results: In all studies flow was related to risk awareness. Study 2 additionally showed its association with risky behaviour. Studies 2 and 3 revealed that these relationships were mediated by self-efficacy. The mediations were moderated by level of experience (Study 3). Conclusions: The results indicated that inexperienced but not experienced participants respond to self-efficacy beliefs evoked by flow with impaired risk awareness and with risky behaviour. Theoretical implications for flow and risk research as well as practical implications for risk prevention are discussed.

The optimal lead insertion depth for esophageal ECG recordings with respect to atrial signal quality

BACKGROUND Diagnosing supraventricular arrhythmias by conventional long-term ECG can be cumbersome because of poor p-waves. Esophageal long-term electrocardiography (eECG) has an excellent sensitivity for atrial signals and may overcome this limitation. However, the optimal lead insertion depth (OLID) is not known. METHODS We registered eECGs at different lead insertion depths in 27 patients and analyzed 199,716 atrial complexes with respect to signal amplitude and slope. Correlation and regression analyses were used to find a criterion for OLID. RESULTS Atrial signal amplitudes and slopes significantly depend on lead insertion depth. OLID correlates with body height (rSpearman=0.71) and can be estimated by OLID [cm]=0.25*body height[cm]-7cm. At this insertion depth, we recorded the largest esophageal atrial signal amplitudes (1.27±0.86mV), which were much larger compared to conventional surface lead II (0.19±0.10mV, p<0.0001). CONCLUSION The OLID depends on body height and can be calculated by a simple regression formula.

Outflow tract tachycardia with R/S transition in lead V3: six different anatomic approaches for successful ablation.

OBJECTIVES The aim of this study was to analyze different anatomic mapping approaches for successful ablation of outflow tract tachycardia with R/S transition in lead V(3). BACKGROUND Idiopathic ventricular tachycardia can originate from different areas in the outflow tract, including the right and left ventricular endocardium, the epicardium, the pulmonary artery, and the aortic sinus of Valsalva. Although electrocardiographic criteria may be helpful in predicting the area of origin, sometimes the focus is complex to determine, especially when QRS transition in precordial leads is in V(3). METHODS We analyzed surface electrocardiograms of 33 successfully ablated patients with outflow tract tachycardia: 20 from the right ventricular outflow tract (RVOT) and 13 from different sites. The R/S transition was determined, and the different anatomic approaches needed for successful catheter ablation were studied. RESULTS Overall, R/S transition in lead V(3) was present in 19 (58%) of all patients. In these patients, mapping was started and successfully completed in the RVOT in 11 of 19 (58%) patients. The remaining eight patients with R/S transition in lead V(3) needed five additional anatomic accesses for successful ablation: from the left ventricular outflow tract (n = 3), aortic sinus of Valsalva (n = 2), coronary sinus (n = 1), the epicardium via pericardial puncture (n = 1), and the trunk of the pulmonary artery (n = 1), respectively. CONCLUSIONS A R/S transition in lead V(3) is common. In patients with outflow tract tachycardia with R/S transition in lead V(3), a stepwise endocardial and epicardial mapping through up to six anatomic approaches can lead to successful radiofrequency catheter ablation.

The diabetic child in the emergency room

The WHO announced diabetes mellitus as one of the main threats to human health in the 21st century. In children and adolescents the prevalence of both the autoimmune type 1 and the obesity-related type 2 diabetes is increasing. Common to all types of diabetes is an absolute or relative lack of insulin to keep glucose homeostasis under control. Thus children and adolescents with newly diagnosed diabetes present with hyperglycemia which is often accompanied by ketoacidosis bearing the risk of cerebral edema. Children and adolescents with known diabetes treated with insulin or orale antidiabetic agents may also suffer from hyperglycemia or even ketoacidosis during times of non-compliance with diet and drugs or during concomitant illnesses. Hyperglycemia with ketoacidosis is an emergency situation for which patients need to be admitted to the next hospital for administration of insulin, fluids and potassium. In contrast, insulin treatment in diabetic patients may also lead to a hypoglycemia, the sudden drop in blood glucose, at any moment. Thus recognition and correction of mild hypoglycemia should be familiar to every diabetic child and their caretaker. Severe hypoglycemia with or without seizures may bring the diabetic child in a sudden emergency situation for which the administration of glucagon intramuscularly or glucose intravenously is mandatory. After every severe hypoglycemia the insulin and diet regimen of the diabetic child or adolescent must be reviewed with the diabetes specialist. For unexplained hypoglycemia or major treatment adjustments the diabetic child or adolescent may need to be readmitted to the diabetic ward of a hospital to avoid repeat, potentially life-threatening hypoglycemia.

Blood lead level association with lower body weight in NHANES 1999-2006

BACKGROUND Lead exposure is associated with low birth-weight. The objective of this study is to determine whether lead exposure is associated with lower body weight in children, adolescents and adults. METHODS We analyzed data from NHANES 1999-2006 for participants aged ≥3 using multiple logistic and multivariate linear regression. Using age- and sex-standardized BMI Z-scores, overweight and obese children (ages 3-19) were classified by BMI ≥85 th and ≥95 th percentiles, respectively. The adult population (age ≥20) was classified as overweight and obese with BMI measures of 25-29.9 and ≥30, respectively. Blood lead level (BLL) was categorized by weighted quartiles. RESULTS Multivariate linear regressions revealed a lower BMI Z-score in children and adolescents when the highest lead quartile was compared to the lowest lead quartile (β (SE)=-0.33 (0.07), p<0.001), and a decreased BMI in adults (β (SE)=-2.58 (0.25), p<0.001). Multiple logistic analyses in children and adolescents found a negative association between BLL and the percentage of obese and overweight with BLL in the highest quartile compared to the lowest quartile (OR=0.42, 95% CI: 0.30-0.59; and OR=0.67, 95% CI: 0.52-0.88, respectively). Adults in the highest lead quartile were less likely to be obese (OR=0.42, 95% CI: 0.35-0.50) compared to those in the lowest lead quartile. Further analyses with blood lead as restricted cubic splines, confirmed the dose-relationship between blood lead and body weight outcomes. CONCLUSIONS BLLs are associated with lower body mass index and obesity in children, adolescents and adults.

A comparison between the chemical behaviour of lead-gold and lead-bismuth eutectics towards 316L stainless steel

Lead-gold eutectic (LGE) has been recently proposed as an alternative target material for high power spallation sources. In order to compare the corrosive properties of LGE to the better-studied eutectic of lead-bismuth (LBE), an isothermal twin-loop made of SS 316L was built and operated at the Institute of Physics of the University of Latvia. We have measured the concentration of steel alloying elements dissolved in both alloys at the end of two test campaigns via ICP-OES. In case of LGE, a pronounced concentration increase of Fe, Ni, Mn and Cr is found in the liquid metal, which is significantly higher compared to LBE. Similar results were obtained during complementary investigations on material samples exposed to both alloys in this twin-loop at 400 ◦C and 450 ◦C. These findings indicate that in contact with LGE, SS 316L steel suffers from substantial chemical attack. Detailed investigations using structure materials other than SS 316L have to be undertaken before qualifying LGE as a serious alternative to LBE.

An optimized lead system for long-term esophageal electrocardiography

Long-term electrocardiography (ECG) featuring adequate atrial and ventricular signal quality is highly desirable. Routinely used surface leads are limited in atrial signal sensitivity and recording capability impeding complete ECG delineation, i.e. in the presence of supraventricular arrhythmias. Long-term esophageal ECG might overcome these limitations but requires a dedicated lead system and recorder design. To this end, we analysed multiple-lead esophageal ECGs with respect to signal quality by describing the ECG waves as a function of the insertion level, interelectrode distance, electrode shape and amplifier's input range. The results derived from clinical data show that two bipolar esophageal leads, an atrial lead with short (15 mm) interelectrode distance and a ventricular lead with long (80 mm) interelectrode distance provide non-inferior ventricular signal strength and superior atrial signal strength compared to standard surface lead II. High atrial signal slope in particular is observed with the atrial esophageal lead. The proposed esophageal lead system in combination with an increased recorder input range of ±20 mV minimizes signal loss due to excessive electrode motion typically observed in esophageal ECGs. The design proposal might help to standardize long-term esophageal ECG registrations and facilitate novel ECG classification systems based on the independent detection of ventricular and atrial electrical activity.