Optimal side of implant for single-lead VDD pacing: right-sided versus left-sided implantation

BACKGROUND: Atrial undersensing occurs in a considerable number of patients with single-lead VDD pacing. This study tried to determine the role of implant side in maintenance of the VDD mode in patients with isolated atrioventricular (AV) block. METHODS: Eighty-two patients with isolated AV block (46 females; mean age, 58 +/- 17 years) received a single-lead VDD pacemaker (Medtronic Kappa, n = 70 and St. Jude Medical Affinity, n = 12). The patients were randomly assigned to one of two implantation groups (group I: right-sided VDD and group II: left-sided VDD). In each group, the P-wave amplitudes were determined at implantation, predischarge, 2-month, and 6-month follow-up. At each follow-up visit, stored event histograms of pacemaker were also retrieved. The atrial sensing measurements were compared between two groups. RESULTS: Implantation was easier from right side (1.7 +/- 1.0 vs 2.8 +/- 1.7 attempts, P = 0.001). Implant P-wave was higher in group I compared to group II (4.2 +/- 1.7 vs 2.7 +/- 1.0 mV, P < 0.0001). During follow-up, higher P-wave amplitudes were obtained in group I both at predischarge (2.6 +/- 1.3 vs 1.4 +/- 1.1 mV, P < 0.0001), 2-month (2.8 +/- 1.8 vs 1.3 +/- 1.0 mV, P < 0.0001), and 6-month (2.9 +/- 1.7 vs 1.3 +/- 0.9 mV, P < 0.0001) evaluations but remained stable throughout the 6 months in both groups. After implantation, VDD function was better maintained in group I than group II (100% vs 90%, P = 0.026). Incidence of atrial undersensing was lower in group I than group II (P = 0.026) in last follow-up visit. CONCLUSIONS: Implant side has a significant influence on atrial sensing performance in single-lead VDD pacing. Thus, right-side implantation should be the preferred approach for the implantation of VDD single-lead systems.     

Status epilepticus and the presence of SARS‐COV‐2 in the cerebrospinal fluid: A case report

A growing number of studies indicate a broad range of neurological manifestations, including seizures, occur in patients with COVID‐19 infection. We report a 29‐year‐old female patient with status epilepticus and positive SARS‐CoV‐2 in the cerebrospinal fluid. Our findings support previous reports suggesting seizure as a possible symptom of COVID‐19 infection.     

Erythropoietin and IGF-1 signaling synchronize cell proliferation and maturation during erythropoiesis

Tight coordination of cell proliferation and differentiation is central to red blood cell formation. Erythropoietin controls the proliferation and survival of red blood cell precursors, while variations in GATA-1/FOG-1 complex composition and concentrations drive their maturation. However, clear evidence of cross-talk between molecular pathways is lacking. Here, we show that erythropoietin activates AKT, which phosphorylates GATA-1 at Ser310, thereby increasing GATA-1 affinity for FOG-1. In turn, FOG-1 displaces pRb/E2F-2 from GATA-1, ultimately releasing free, proproliferative E2F-2. Mice bearing a Gata-1^S310A mutation suffer from fatal anemia when a compensatory pathway for E2F-2 production involving insulin-like growth factor-1 (IGF-1) signaling is simultaneously abolished. In the context of the GATA-1^V205G mutation resulting in lethal anemia, we show that the Ser310 cannot be phosphorylated and that constitutive phosphorylation at this position restores partial erythroid differentiation. This study sheds light on the GATA-1 pathways that synchronize cell proliferation and differentiation for tissue homeostasis.     

Wheat allergy: clinical and laboratory findings

BACKGROUND: Food allergy affects 6-8% of infants and wheat allergy is one of the common food allergies among children. The clinical and laboratory manifestations of wheat allergy were evaluated in this study. METHODS: Thirty-two children (< or =12 years old) with suspected wheat allergy were evaluated for wheat allergy. The patients underwent wheat skin prick test (SPT), measurement of wheat-specific IgE and wheat challenge test. The patients with a convincing history of anaphylaxis following ingestion of wheat or with a positive challenge test, and those with a history of immediate hypersensitivity reaction following ingestion of wheat in addition to a positive wheat SPT and/or positive wheat-specific IgE were considered wheat allergic. Then, the laboratory and clinical manifestations of their disease were studied. RESULTS: Among patients with suspected wheat allergy, 24 patients with definite wheat allergy were identified. Anaphylaxis was a dominant clinical feature, accounting for 54.1% of acute symptoms. Chronic allergy symptoms like asthma and eczema were noted in 50% of the patients. Wheat-specific IgE was higher in patients with anaphylaxis (p<0.02) and the risk of anaphylaxis was 14.4 times more in patients with wheat-specific IgE equal to or more than 3+. CONCLUSIONS: Anaphylaxis had occurred in a remarkable number of patients repeatedly, which demonstrates the severity of the reactions, poor knowledge of the disease and probable existence of more patients with mild reactions. Regarding the higher level of wheat-specific IgE in patients with anaphylaxis, wheat-specific IgE could be used to predict the severity of symptoms.     

Assessment of Obstructive Sleep Apnea and its Severity during Wakefulness

In this article, a novel technique for assessment of obstructive sleep apnea (OSA) during wakefulness is proposed; the technique is based on tracheal breath sound analysis of normal breathing in upright sitting and supine body positions. We recorded tracheal breath sounds of 17 non-apneic individuals and 35 people with various degrees of severity of OSA in supine and upright sitting positions during both nose and mouth breathing at medium flow rate. We calculated the power spectrum, Kurtosis, and Katz fractal dimensions of the recorded signals and used the one-way analysis of variance to select the features, which were statistically significant between the groups. Then, the maximum relevancy minimum redundancy method was used to reduce the number of characteristic features to two. Using the best two selected features, we classified the participant into severe OSA and non-OSA groups as well as non-OSA or mild vs. moderate and severe OSA groups; the results showed more than 91 and 83% accuracy; 85 and 81% specificity; 92 and 95% sensitivity, for the two types of classification, respectively. The results are encouraging for identifying people with OSA and also prediction of OSA severity. Once verified on a larger population, the proposed method offers a simple and non-invasive screening tool for prediction of OSA during wakefulness.     

Molecular epidemiology of human herpesvirus 8 variants in Kaposi's sarcoma from Iranian patients

Kaposi's sarcoma (KS) is a rare cancer in Iran and there is no epidemiological and molecular information about HHV-8 variants circulating among the Iranian population. In this study HHV-8 sequences have been analyzed in 43 cutaneous KS biopsies from Iranian patients mainly affected by classic KS. DNA samples were subjected to PCR amplification of HHV-8 ORF26, T0.7 and K1 followed by direct nucleotide sequencing and phylogenetic analysis. The analysis of ORF26 showed that 30 (69.8%) and 13 (30.2%) samples belonged to subtypes A/C and K, respectively. In general, the clustering of HHV-8 T0.7 variants paralleled that of ORF26. Genotyping of K1 sequences showed that the majority of samples (39 out of 41) fall into the large C clade with only 2 belonging to the A clade. In conclusion, HHV-8 variants identified among classic Iranian KS are largely related to Eurasian genotypes previously identified in KS from Mediterranean, Middle East, and East Asian regions.     

Effects of adipose tissue stem cell concurrent with greater omentum on experimental long-bone healing in dog

Repair of large bone defects resulting from trauma, tumors, and osteitis is a current challenge to surgeons. Adipose-derived adult stem cells (ASCs) are multipotent cells that are able to differentiate into osteoblasts in the presence of certain factors. In this study, the role of greater omentum as a scaffold incorporation of ASCs was evaluated in long-bone defect healing in dog model. Sixteen 3-4-year-old, male adult mongrel dogs, weighing 25.2 ± 3.5 kg, were used in this study. In the control group (n = 4), the defect was left empty. In the omental group (n = 4), the defect was filled with harvested omentum. In the omental-ASCs group (n = 4), the defect was filled with omentum and 1 mL of ASCs was injected into the grafted omentum. In the omental-culture medium group (n = 4), 1 mL of culture medium was injected into the grafted omentum. Finally, the injured radial bones were fixed with plate and screw. Radiographs of each forelimb was taken postoperatively on the first day and at the second, fourth, sixth, and eighth weeks postinjury to evaluate bone formation, union, and remodeling of the defect. The operated radii were removed on the 56th postoperative day and were histopathologically evaluated. In this study, both omental-culture medium and omental-ASCs groups demonstrated superior osteogenic potential in healing the radial bone defect. Compared to those of the omental and control groups, more advanced bone healing criteria were present in the omental-culture medium and omental-ASCs groups at radiological and histopathological levels at 8 weeks postsurgery.     

Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property

Context: Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded.

Objective: This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice.

Materials and methods: For the acute toxicity study, the animals orally received five different single doses of α-l-guluronic acid and were kept under observation for 14?d. In the sub-chronic study, 24 male and female BALB/c mice were divided into four groups and treated daily with test substance preparation at dose levels of 0, 50, 250, and 1250?mg/kg body weight for at least 90 consecutive days. The mortality, body weight changes, clinical signs, hematological and biochemical parameters, gross findings, histopathological, and organs weight determinants were monitored during this study.

Results: The results of acute toxicity indicated that the LD50 of α-l-guluronic acid is 4.8?g/kg. We found no mortality or abnormality in clinical signs, body weight, relative organs weight, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.

Conclusions: Our results suggest that α-l-guluronic acid has high safety when administered orally in animals.     

Genetic diagnosis of cancer by fuzzy-rough gene selection and the complementary hierarchical fuzzy classifier

Gene expression data have extremely high dimensionality with respect to traditional classifiers which causes not to be used efficiently. In this paper a Fuzzy-Rough Gene Selection and Complementary Hierarchical Fuzzy classifier (FRGS-CHF) to classify the gene expression data as a new methodology is proposed. First, some relevant genes are selected using fuzzy-rough attribute selection method. After removing redundant genes, a new complementary hierarchical fuzzy classifier is proposed. The complementary learning mechanism refers to positive and negative learning which are found in the human brain hippocampus. FRGS-CHF is made-up of two parallel hierarchical fuzzy systems; the first is trained with positive samples whilst the other is treated with negative samples. In contrast to many other methods such as statistical or neural networks, FRGS-CHF provides greater interpretability. It does not rely on the assumption of underlying data distribution. Using complementary and hierarchical approaches, the proposed method exploits the lateral inhibition between output classes and considers the problem as a multidimensional problem. Benchmarked datasets are used to demonstrate the validity and advantages of the proposed method over the other existing methods in terms of the accuracy, better transparency, time efficiency together with fewer fuzzy rules and parameters.     

Novel FARS2 variants in patients with early onset encephalopathy with or without epilepsy associated with long survival

Mitochondrial translation is essential for the biogenesis of the mitochondrial oxidative phosphorylation system (OXPHOS) that synthesizes the bulk of ATP for the cell. Hypomorphic and loss-of-function variants in either mitochondrial DNA or in nuclear genes that encode mitochondrial translation factors can result in impaired OXPHOS biogenesis and mitochondrial diseases with variable clinical presentations. Compound heterozygous or homozygous missense and frameshift variants in the FARS2 gene, that encodes the mitochondrial phenylalanyl-tRNA synthetase, are commonly linked to either early-onset epileptic mitochondrial encephalopathy or spastic paraplegia. Here, we expand the genetic spectrum of FARS2-linked disease with three patients carrying novel compound heterozygous variants in the FARS2 gene and presenting with spastic tetraparesis, axial hypotonia and myoclonic epilepsy in two cases.Subject terms: Metabolic disorders, Mutation