Intractable Seizure Disorders: Efficacy of The Classic Ketogenic Diet

 ObjectiveThe ketogenic diet is a high-fat, low carbohydrate, adequate protein diet,developed in the 1920s for the management of intractable seizure disorders in children. To evaluate efficacy and tolerability of the classic  ketogenic diet, we analyzed records of the children started on the diet from 1999 to 2006 at the Mofid children's hospital.Materials & Methods The subjects were 87 children, mean age 55 months. Before initiation of the diet, 55% of the patients had seizures, at least 1-4 times per day, 36% - 5 or more per day and 9% - 2 to 4 times per week. Mean number of Anti Epileptic Drugs (AEDs) tried for them was 8 and 67% were receiving three or more drugs.Results The ketogenic diet showed drastic improvement, with at least 50% reduction in seizure frequency in 87% of our patients, 39% of whom showed complete seizure control in the third month. After one year, in 80% of the patients who returned, improvement  continued, with 26% of them being seizure free; besides, 23% had one AED decreased, 36% had two or three AEDs decreased, and 25% (one child) had all AEDs discontinued. Of the 30 improved cases, 20%, at the end of the first year, had improved behavior as  well, and 23% of them had become more alert. The median diet duration of the improved group was 15 months.Conclusion The improvement in our patients, low  side effects, and the duration of diet by families reveal that the ketogenic diet can still be a very useful alternative therapy in certain epileptic children.

EFFECTS OF ORAL IRON SUPPLEMENT ON BREATH-HOLDING SPELLS IN CHILDREN

Objectives:Breath holding spells are one of the most frequent and important diagnostic challenges in pediatrics. The aim of this study, conducted on pediatric patients referring to the pediatric neurology clinic in Hormozgan province, was to evaluate therapeutic effects of iron on breath holding spellsMaterials and Methods:35 children (19 males and 16 females), aged between 3 to 60 months, with a history of breath-holding spells, were included in the trial. To obtain all relevant data a specifically designed questionnaire requiring information on sex, age, age of onset of spells, type of spells, frequency of attacks before and after treatment with oral iron supplement, and determinants of body iron stores was completed for all the patients, based on the mother's statements. The patients were treated by an oral iron preparation for three months.Results:The age of onset of spells ranged between 6 to 24 months. The cyanotic type of spell was detected in 31 children, the pallid type in 3, and the mixed type in one child. There were 14 children with iron deficiency anemia and 20 children with reduced iron stores. Just one child had a normal iron profile. Complete therapeutic response was documented in 24 children, good response in 9, and poor response in one and in one child no change in frequency of spells was seen.Conclusion:Although no significant therapeutic difference was seen in the different response groups, it seems that iron supplement may play an important role in reducing breath holding spells in children.Keywords:Iron, Breath holding spell, children, Iron deficiency Anemi

Heisenberg-limited metrology with a squeezed vacuum state, three-mode mixing, and information recycling

We have previously shown that quantum-enhanced atom interferometry can be achieved by mapping the quantum state of squeezed optical vacuum to one of the atomic inputs via a beamsplitter-like process [Phys. Rev. A 90, 063630 (2014)]. Here we ask the question: is a better phase sensitivity possible if the quantum state transfer (QST) is described by a three-mode-mixing model, rather than a beamsplitter? The answer is yes, but only if the portion of the optical state not transferred to the atoms is incorporated via information recycling. Surprisingly, our scheme gives a better sensitivity for lower QST efficiencies and with a sufficiently large degree of squeezing can attain near-Heisenberg-limited sensitivities for arbitrarily small QST efficiencies. Furthermore, we use the quantum Fisher information to demonstrate the near optimality of our scheme

Reporting a rare form of myopathy, myopathy with extrapyramidal signs, in an Iranian family using next generation sequencing: A case report

Background: Myopathy with extrapyramidal signs (MPXPS) is an autosomal recessive mitochondrial disorder which is caused by mutation in mitochondrial calcium uptake 1 (MICU1) gene located on chromosome 10q22.1. Next Generation Sequencing (NGS) technology is the most effective method for identification of pathogenic variants with the ability to overcome some limitations which Sanger sequencing may encountered. There are few reports on this rare disease around the world and here in this study we first revealed genetic identification of two affected individuals in an Iranian family with a novel mutation. Case presentation: The proband was a 5-year-old girl from consanguenous parents. She was first clinically suspicious of affected with limb-girdle muscular dystrophy (LGMD). Muscle biopsy studies and autozygosity mapping, using four short tandem repeat (STR) markers linked to 6 genes of the most prevalent forms of LGMD, ruled out calpainopathy, dysferlinopathy, and sarcoglycanopathis. DNA sample of the proband was sent for NGS. Whole exome sequencing (WES) revealed a novel mutation c.1295delA in exon 13 of MICU1 gene. This homozygous deletion creates a frameshift and a premature stop codon downstream of canonical EF4 calcium binding motif of MICU1. According to the American College of Medical Genetics and Genomics (ACMG) guidline for sequence interpretation, this variant was a pathogenic one. Sanger sequencing in all family members confirmed the results of the WES. Conclusions: This study was the first report of MPXPS in Iranian population which also revealed a novel mutation in the MICU1 gene. © 2020 The Author(s)

Relationships between Locus of Control and Adherence to Diabetes Regimen

Abstract Background: Adequate self-care in diabetes causes quality of life promotion and decreases the number of inpatient cases. The health locus of control theory is used to assess adherence to diabetes regimen in some studies in developed countries. The purpose of this study was to determine the status of diabetes locus of control in a sample of diabetic patients in Iran and investigation of it's relationship to adherence to diabetes regimen. Methods: This analytical and cross-sectional study was carried out on 120 patients referred to Yazd Diabetes Research Center. The Iranian versions of Diabetes Locus of Control scale and Diabetes Selfcare Activities scale were used for data collection. Results: Men were more internal locus of control and women were more chance locus of control. The attributions of external locus of control increased by age, while the internal locus of control increased by education level and chance locus of control decreased by education level. A positive association between internal locus of control and adherence to diabetes regimen was found and there was a negative association between chance locus of control and adherence to diabetes regimen. Conclusion: Findings suggest that interventions aimed at improving internal locus of control may improve adherence to diabetes regimen but different diabetic patients have different attribution styles and interventional programs to enhance diabetes self-care will be more successful if patient's locus of control is addressed

Infection with hepatitis B virus carrying novel pre-S/S gene mutations in female siblings vaccinated at birth: two case reports

<p>Abstract</p> <p>Introduction</p> <p>After the initiation of a mass hepatitis B vaccination program in Taiwan, the prevalence of hepatitis B virus infection has declined progressively. However, about 1 percent of the young generation, who received hepatitis B vaccination at birth, remain carriers. Infection with vaccine-escape hepatitis B virus mutants always occurs shortly after birth. Here, we report two female siblings in whom the infection occurred in their adolescence. This report raises the question of whether a booster for hepatitis B vaccination is needed.</p> <p>Case presentation</p> <p>Two 19 and 14-year-old Taiwanese female siblings were born to a mother infected with hepatitis B virus and received a complete course of hepatitis B vaccination at birth. They remained negative for serum hepatitis B surface antigen and positive for serum anti-hepatitis B surface antibody throughout their childhood. However, both were infected with the hepatitis B virus in their adolescence. Hepatitis B virus DNA was extracted from serum samples from the mother and two siblings. Hepatitis B virus pre-S/S sequence was amplified by polymerase chain reaction followed by nucleotide sequencing. When compared with the sequence obtained from the mother, multiple amino acid substitutions located near or in the major hydrophilic region of the surface antigen were identified in the elder sister. Four of these mutations (sL97S, sL98S, sG102R, and sA159P) were novel. A novel in-frame deletion (14 amino acids deleted, pre-S 127-140) was found in the hepatitis B virus pre-S2 region in the younger sister.</p> <p>Conclusions</p> <p>Despite having received hepatitis B vaccination at birth, hepatitis B virus infection can still occur in adolescence with the emergence of novel mutations in the pre-S/S gene. This is a rare event and, to the best of our knowledge, has not been previously reported.</p

Prediction of response to treatment in children with epilepsy

Abstract Objective: This study was conducted to predict the response to treatment in patients treated with anti-epilepsy drugs. Material and Methods: This analytical questionnaire-based study was conducted in 2014 among 128 patients with epilepsy admitted to Mofid Children's Hospital, Tehran, Iran. The inclusion criteria were children 2 months to 12 yr of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. Patients were followed up for 6 months and the response to their treatment was recorded. The good response to treatment was defined as the absence of seizure with two drugs during follow up. Results: Seventy-two patients (56.3%) were boys. The age of the first seizure was under 2 yr old in 90 patients (70.3%). History of febrile convulsion, family history of epilepsy and history of asphyxia was found in 16 (12.5%), 41 (32%), and 27 (21.1%) patients, respectively. Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1-2 in 36 patients (28.1%). Overall, 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. History of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment. Conclusion: Abnormal EEG is an effective factor in treatment response in the children studied. Key Words: Pediatric, Anti-seizure drug, Response to treatment, Children, Epileps

Genetics of intellectual disability in consanguineous families

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence

Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.We gratefully acknowledge funding that supported this research support from the Ryerson University Faculty of Science (CNA), as well as funding support in the form of a CIFAR Catalyst Grant (JPJ and CNA), an NSERC Alliance Grant (CNA) and the Ryerson COVID-19 SRC Response Fund award (CNA). BW is partly supported by CIFAR AI Chairs Program. This work was also supported by a Mitacs award (BW), the European Union’s Horizon 2020 research and innovation program under a Marie Sklodowska-Curie grant (ER), by the CIFAR Azrieli Global Scholar program (JPJ), by the Ontario Early Researcher Awards program (JPJ and CNA), and by the Canada Research Chairs program (JPJ). We also thank Dr. James Rini (University of Toronto) for the kind gift of the 9.8E12 antibody used to detect the 229E Spike protein, and Dr. Scott Gray-Owen (University of Toronto) for the kind gift of the NL63 human coronavirus.Peer reviewe