Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency

3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is considered to be a rare cause of congenital microcephaly, infantile onset of intractable seizures and severe psychomotor retardation. Here, we report for the first time a very mild form of genetically confirmed 3-PGDH deficiency in two siblings with juvenile onset of absence seizures and mild developmental delay. Amino acid analysis showed serine values in CSF and plasma identical to what is observed in the severe infantile form. Both patients responded favourably to relatively low dosages of serine supplementation with cessation of seizures, normalisation of their EEG abnormalities and improvement of well-being and behaviour. These cases illustrate that 3-PGDH deficiency can present with mild symptoms and should be considered as a treatable disorder in the differential diagnosis of mild developmental delay and seizures. Synopsis: we present a novel mild phenotype in patients with 3-PGDH deficiency

Spin-dependent resonant tunneling through semimetallic ErAs quantum wells

Resonant tunneling through semimetallic ErAs quantum wells embedded in GaAs structures with AlAs barriers was recently found to exhibit an intriguing behavior in magnetic fields which is explained in terms of tunneling selection rules and the spin-polarized band structure including spin-orbit coupling.Comment: 4 pages, figures supplied as self-unpacking figures.uu, uses epsfig.sty to incorporate figures in preprin

An in vitro comparison between two methods of electrical resistance measurement for occlusal caries detection

Because of different measurement techniques and the easier design of the CRM prototype, this in vitro study aimed to compare the diagnostic performance and reproducibility of two electrical methods (Electronic Caries Monitor III, ECM and Cariometer 800, CRM) for occlusal caries detection, and to evaluate the effect of staining/ discoloration of fissures on diagnostic performance. Hundred and seventeen third molars with no apparent occlusal cavitation were selected. Six examiners inspected all specimens independently, using the CRM, and a subgroup of 4 using the ECM. Histological validation using a stereomicroscope was performed after hemisectioning. Intra- and interexaminer reproducibility was assessed by Lin's concordance correlation coefficient (CCC) and Bland and Altman analysis. Diagnostic performance parameters included sensitivity (SE), specificity (SP) and area under the ROC curve (A(z)). The CCC yielded an intra- and interexaminer reproducibility of 0.69/0.62 (ECM) and of 0.79/0.74 (CRM). The mean intra- and interexaminer 95% range of measurements (range between Bland and Altman limits of agreement) given in percentages of the instrument reading were 67%/65% for the ECM and 28%/33% for the CRM. A(z) at the D3-4 level was 0.74 (ECM) and 0.78 (CRM). The CRM showed at least equivalent diagnostic performance to the ECM. However, improvement is still desirable. Diagnostic performance appeared to be enhanced in discolored lesions; however, this may be related to sample lesion distribution characteristics. Copyright (C) 2006 S. Karger AG, Basel

Therapeutic approaches to pediatric pseudotumor cerebri: new insights from literature data

The pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is characterized by signs and symptoms of increased intracranial pressure such as headache and cranial nerve palsies, in the absence of any space-occupying mass. This condition commonly affects overweight women of childbearing age, even if it is also frequent in men and children. Children with PTCS may present with atypical signs and symptoms, with a different prognosis compared to adults. However, the treatment is the same for both children and adults, even if there are no strict treatment guidelines in regards. All treatment strategies in children are based on retrospective studies and none has been evaluated in prospective or randomized controlled trial studies. This review focuses on literature data on PTCS treatment in children

Diagnosis of acute toxoplasmosis in pregnant women referred to therapeutic centers of Alborz Province (Iran) using immunoglobulin G avidity ELISA technique

Objective To evaluate immunoglobulin G (IgG) avidity as a useful and reliable technique in diagnosing toxoplasmosis in pregnant women referring to therapeutic centers of Alborz Province (Iran) in 2014, against two other tests, IgG and immunoglobulin G (IgM) anti-Toxoplasma. Methods Serum samples (468 in total) were obtained from different therapeutic centers in Karaj City. ELISA method was used to test the anti-Toxoplasma avidity of IgG, IgM and IgG. The data were analyzed by descriptive statistical methods and Chi-square test (P < 0.05) using SPSS 17.0. Results Anti-Toxoplasma avidity tests of IgM and IgG were positive in 9 and 86 samples respectively. Also, a borderline IgM avidity was detected in 2 suspected samples. In addition, among all positive and suspected samples, 79 cases indicated high titers of IgG avidity, 7 cases were of low titers and 1 case was of a borderline titer. The prevalence of anti-Toxoplasma antibodies was 20. The sera which showed high avidity index was obtained from patients at chronic phase of infection (77.7) while those which showed low avidity levels were from patients at acute toxoplasmosis (92). Conclusions This study clearly showed that acute and chronic phases of toxoplasmosis could be differentiated with the aid of IgG avidity test. This test may also assist in recognizing old and newly acquired infections. © 2016 Asian Pacific Tropical Medicine Pres

Parasitic helminth infections of dogs, wolves, foxes, and golden jackals in Mazandaran Province, North of Iran

Background and Aim: There is a large amount of information on intestinal parasites in stray dogs and golden jackals (Canis aureus) in Mazandaran Province, Iran. However, there is little information about foxes and wolves, which have a potential role in the spread of dangerous parasitic diseases, such as echinococcosis and toxocariasis. The aim of the present study was to identify the genus or species of parasitic worms in stool samples obtained from carnivores in Mazandaran Province, Iran, from August 2017 to April 2018. Materials and Methods: A total of 274 fecal samples were collected from carnivores, including dog, fox, wolf, and C. aureus in three areas of Mazandaran Province, Iran. All specimens were examined by centrifugal fecal flotation using a solution of Sheather's sugar to detect helminths eggs. Then, all samples were assessed using a light microscope. Data analysis was performed by SPSS version 18 (Chicago, IL, USA). Results: In this study, seven genera of helminths were observed, including Ancylostoma, Uncinaria, Toxocara, Dipylidium, Toxascaris, Taenia, and Spirocerca. The prevalence of helminth infections was 97.7 (127 out of 130), 56.7 (51 out of 90), 51.4 (18 out of 35), and 52.6 (10 out of 19), among dogs, C. aureus, foxes, and wolves, respectively. The highest prevalence of Ancylostoma and Toxocara infections occurred in the eastern and central areas of the province (42.1 and 35.7, respectively). Conclusion: Based on the results of this study, the infection with intestinal zoonotic helminths in carnivores was an important public health factor in Mazandaran. Therefore, these infections can be potentially harmful to humans and other animals. Copyright © 2020 Siyadatpanah, et al

Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center

Background: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. Methods: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan–Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. Results: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). Conclusions: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival. Electronic supplementary material The online version of this article (10.1245/s10434-018-6467-9) contains supplementary material, which is available to authorized users

Metabolic Control Analysis in a Cellular Model of Elevated MAO-B: Relevance to Parkinson’s Disease

We previously demonstrated that spare respiratory capacity of the TCA cycle enzyme alpha-ketoglutarate dehydrogenase (KGDH) was completely abolished upon increasing levels of MAO-B activity in a dopaminergic cell model system (Kumar et al., J Biol Chem 278:46432–46439, 2003). MAO-B mediated increases in H2O2 also appeared to result in direct oxidative inhibition of both mitochondrial complex I and aconitase. In order to elucidate the contribution that each of these components exerts over metabolic respiratory control as well as the impact of MAO-B elevation on their spare respiratory capacities, we performed metabolic respiratory control analysis. In addition to KGDH, we assessed the activities and substrate-mediated respiration of complex I, pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and mitochondrial aconitase in the absence and presence of complex-specific inhibitors in specific and mixed substrate conditions in mitochondria from our MAO-B elevated cells versus controls. Data from this study indicates that Complex I and KGDH are the most sensitive to inhibition by MAO-B mediated H2O2 generation, and could be instrumental in determining the fate of mitochondrial metabolism in this cellular PD model system

Amino acid synthesis deficiencies

In recent years the number of disorders known to affect amino acid synthesis has grown rapidly. Nor is it just the number of disorders that has increased: the associated clinical phenotypes have also expanded spectacularly, primarily due to the advances of next generation sequencing diagnostics. In contrast to the "classical" inborn errors of metabolism in catabolic pathways, in which elevated levels of metabolites are easily detected in body fluids, synthesis defects present with low values of metabolites or, confusingly, even completely normal levels of amino acids. This makes the biochemical diagnosis of this relatively new group of metabolic diseases challenging. Defects in the synthesis pathways of serine metabolism, glutamine, proline and, recently, asparagine have all been reported. Although these amino acid synthesis defects are in unrelated metabolic pathways, they do share many clinical features. In children the central nervous system is primarily affected, giving rise to (congenital) microcephaly, early onset seizures and varying degrees of mental disability. The brain abnormalities are accompanied by skin disorders such as cutis laxa in defects of proline synthesis, collodion-like skin and ichthyosis in serine deficiency, and necrolytic erythema in glutamine deficiency. Hypomyelination with accompanying loss of brain volume and gyration defects can be observed on brain MRI in all synthesis disorders. In adults with defects in serine or proline synthesis, spastic paraplegia and several forms of polyneuropathy with or without intellectual disability appear to be the major symptoms in these late-presenting forms of amino acid disorders. This review provides a comprehensive overview of the disorders in amino acid synthesis

Energy Consumption, Carbon Emissions and Global Warming Potential of Wolfberry Production in Jingtai Oasis, Gansu Province, China

During the last decade, China's agro-food production has increased rapidly and been accompanied by the challenge of increasing greenhouse gas (GHG) emissions and other environmental pollutants from fertilizers, pesticides, and intensive energy use. Understanding the energy use and environmental impacts of crop production will help identify environmentally damaging hotspots of agro-production, allowing environmental impacts to be assessed and crop management strategies optimized. Conventional farming has been widely employed in wolfberry (Lycium barbarum) cultivation in China, which is an important cash tree crop not only for the rural economy but also from an ecological standpoint. Energy use and global warming potential (GWP) were investigated in a wolfberry production system in the Yellow River irrigated Jingtai region of Gansu. In total, 52 household farms were randomly selected to conduct the investigation using questionnaires. Total energy input and output were 321,800.73 and 166,888.80 MJ ha−1, respectively, in the production system. The highest share of energy inputs was found to be electricity consumption for lifting irrigation water, accounting for 68.52%, followed by chemical fertilizer application (11.37%). Energy use efficiency was 0.52 when considering both fruit and pruned wood. Nonrenewable energy use (88.52%) was far larger than the renewable energy input. The share of GWP of different inputs were 64.52% electricity, 27.72% nitrogen (N) fertilizer, 5.07% phosphate, 2.32% diesel, and 0.37% potassium, respectively. The highest share was related to electricity consumption for irrigation, followed by N fertilizer use. Total GWP in the wolfberry planting system was 26,018.64 kg CO2 eq ha−1 and the share of CO2, N2O, and CH4 were 99.47%, 0.48%, and negligible respectively with CO2 being dominant. Pathways for reducing energy use and GHG emission mitigation include: conversion to low carbon farming to establish a sustainable and cleaner production system with options of raising water use efficiency by adopting a seasonal gradient water pricing system and advanced irrigation techniques; reducing synthetic fertilizer use; and policy support: smallholder farmland transfer (concentration) for scale production, credit (small- and low-interest credit) and tax breaks