Packet latency of deterministic broadcasting in adversarial multiple access channels

We study broadcasting in multiple access channels with dynamic packet arrivals and jamming. Communication environments are represented by adversarial models that specify constraints on packet arrivals and jamming. We consider deterministic distributed broadcast algorithms and give upper bounds on the worst-case packet latency and the number of queued packets in relation to the parameters defining adversaries. Packet arrivals are determined by a rate of injections and a number of packets that can be generated in one round. Jamming is constrained by a rate with which an adversary can jam rounds and by a number of consecutive rounds that can be jammed

Perinatal manifestations of congenital disorders of glycosylation—A clue to early diagnosis

N-glycosylation defects—isolated or mixed with other glycosylation defects—are the most frequent congenital disorders of glycosylation and present mostly in childhood, with a specific combination of non-specific phenotypic features. The diagnosis, however, is often delayed. The aim of this study is to describe the perinatal phenotype of congenital disorders of N-glycosylation. We present an analysis of perinatal symptoms in a group of 24 one-center Polish patients with N-glycosylation defects—isolated or mixed. The paper expands the perinatal phenotype of CDGs and shows that some distinctive combinations of symptoms present in the perinatal period should raise a suspicion of CDGs in a differential diagnosis

Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report

Introduction Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes. Case report Clinical symptoms of a 47 year old proband (and independently described in his 20 year old son) as well as differential diagnosis are discussed in the presented report. The most characteristic were recurrent attacks of blurred vision, paresthesias and hemiparesis often accompanied by speech disturbances and followed by severe headache with vomiting. Advanced morphological and genetic procedures were required to exclude MELAS, CADASIL and Call-Fleming syndrome. Finally, the definite diagnosis was possible after the application of the whole exome sequencing technique. It confirmed, for the first time in the Polish population, a heterozygous T666M mutation (c.1997C>T; p.Thr666Met) in the CACNA1A gene in the proband, the proband's son and in several other family members. Conclusion The presented report provides clinical and genetic insight into familial hemiplegic migraine 1 resulting from a mutation in the CACNA1A gene

Hyaline fibromatosis syndrome inducing mutations in the ectodomain of anthrax toxin receptor 2 can be rescued by proteasome inhibitors.

Hyaline Fibromatosis Syndrome (HFS) is a human genetic disease caused by mutations in the anthrax toxin receptor 2 (or cmg2) gene, which encodes a membrane protein thought to be involved in the homeostasis of the extracellular matrix. Little is known about the structure and function of the protein or the genotype-phenotype relationship of the disease. Through the analysis of four patients, we identify three novel mutants and determine their effects at the cellular level. Altogether, we show that missense mutations that map to the extracellular von Willebrand domain or the here characterized Ig-like domain of CMG2 lead to folding defects and thereby to retention of the mutated protein in the endoplasmic reticulum (ER). Mutations in the Ig-like domain prevent proper disulphide bond formation and are more efficiently targeted to ER-associated degradation. Finally, we show that mutant CMG2 can be rescued in fibroblasts of some patients by treatment with proteasome inhibitors and that CMG2 is then properly transported to the plasma membrane and signalling competent, identifying the ER folding and degradation pathway components as promising drug targets for HFS

The potential of dietary treatment in patients with glycogen storage disease type IV

There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initiated this observational study to assess the outcomes of medical diets, which limit the accumulation of glycogen. Clinical, dietary, laboratory, and imaging data for 15 GSD IV patients from three centres are presented. Medical diets may have the potential to delay or prevent liver transplantation, improve growth and normalize serum aminotransferases. Individual care plans aim to avoid both hyperglycaemia, hypoglycaemia and/or hyperketosis, to minimize glycogen accumulation and catabolism, respectively. Multidisciplinary monitoring includes balancing between traditional markers of metabolic control (ie, growth, liver size, serum aminotransferases, glucose homeostasis, lactate, and ketones), liver function (ie, synthesis, bile flow and detoxification of protein), and symptoms and signs of portal hypertension

Pregnancy, delivery and puerperium in a patient with lysinuric protein intolerance – a case report

The paper presents the course of pregnancy, delivery and early postpartum period in a 23-year-old woman with lysinuric protein intolerance (LPI). The pregnancy was uneventful and resulted in a caesarean birth to a healthy baby at 37 weeks gestation. Nevertheless, the course of pregnancy in women with LPI is associated with a significantly increased risk of serious complications, including acute hyperammonemia, preeclampsia and postpartum bleeding, as well as fetus intrauterine growth retardation. In many cases, intensive metabolic monitoring and a proper diet with protein limitation and appropriate amino acids supplementation may significantly reduce the risk for both the mother and the newborn

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective?

BACKGROUND: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy. RESULTS: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers. CONCLUSIONS: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: Is riboflavin supplementation effective?

Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy. Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and

Current diagnosis and treatment of pyridoxine dependent epilepsy due to antiqutin deficiency

Drgawki pirydoksynozależne (pyridoxine-dependent epilepsy – PDE) to rzadko występująca encefalopatia padaczkowa uwarunkowana autosomalnie recesywnie. Charakteryzuje się uporczywymi, nawracającymi drgawkami u noworodków i niemowląt, nieodpowiadającymi na standardowe leczenie przeciwpadaczkowe, a ustępującymi przy podaży terapeutycznych dawek witaminy B6 (pirydoksyny). Najczęstszą przyczyną PDE jest deficyt ALDH7A1 (antykwityny) – enzymu biorącego udział w przemianie lizyny, który prowadzi do nagromadzenia w płynach ustrojowych (w tym także w płynie mózgowo-rdzeniowym) szkodliwych metabolitów, które inaktywują aktywną postać witaminy B6. Podaż leczniczych dawek pirydoksyny w większości przypadków pozwala opanować drgawki, a dodatkowo wprowadzenie diety ubogolizynowej i/lub suplementacja argininy prawdopodobnie poprawia rokowanie co do rozwoju intelektualnego pacjentów.Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive epileptic encephalopathy. It is characterized by persistent, recurrent seizures in newborns and infants resistant to conventional antyepileptic drugs but responsive to pharmacological dosages of vitamin B6 (pyridoxine). The most common cause of PDE is the deficit of ALDH7A1 (antiquitin) – an enzyme involved in the lysine degeneration pathway which leads to the accumulation of harmful metabolites in body fluids (including the cerebrospinal fluid CSF) which inactivate the pirydoxal phosphate. Vitamin B6 supplementation enables control seizures, in addition the introduction of lysine-restricted diet and / or arginine fortification is likely to improve the prognosis for the intellectual development

Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease