Primary aortoduodenal fistula: As a first presentation of brucellosis; a case report.

INTRODUCTION: The etiologies of primary aortoenteric fistula include aneurysm (most common), foreign body, tumor, radiation therapy, and infection (e.g., tuberculosis, syphilis). Brucellosis is a rare cause of primary aortoenteric fistula. PRESENTATION OF CASE: In this study, we reported the case ofa 55-years-old male with an aortoenteric fistula and a positive brucellosis test. DISCUSSION: In regions where brucellosis is endemic, the coexistence of aortitis and aneurysm should prompt consideration of brucella infection as a relatively uncommon cause of aortoenteric fistula. CONCLUSION: While aortitis due to brucellosis is rare, it can lead to life-threatening manifestations such as aortoduodenal fistula. Therefore, we recommend the use of Wright, Coombs Wright, and 2ME tests in similar cases.

Revealing the grammar of small RNA secretion using interpretable machine learning.

Small non-coding RNAs can be secreted through a variety of mechanisms, including exosomal sorting, in small extracellular vesicles, and within lipoprotein complexes. However, the mechanisms that govern their sorting and secretion are not well understood. Here, we present ExoGRU, a machine learning model that predicts small RNA secretion probabilities from primary RNA sequences. We experimentally validated the performance of this model through ExoGRU-guided mutagenesis and synthetic RNA sequence analysis. Additionally, we used ExoGRU to reveal cis and trans factors that underlie small RNA secretion, including known and novel RNA-binding proteins (RBPs), e.g., YBX1, HNRNPA2B1, and RBM24. We also developed a novel technique called exoCLIP, which reveals the RNA interactome of RBPs within the cell-free space. Together, our results demonstrate the power of machine learning in revealing novel biological mechanisms. In addition to providing deeper insight into small RNA secretion, this knowledge can be leveraged in therapeutic and synthetic biology applications.

Genetic Risk Variants for Class Switching Recombination Defects in Ataxia-Telangiectasia Patients.

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations. METHODS: To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier variants found in the exomes of these two groups of patients were performed. RESULTS: For the first time, we identified some variants in the exomes of the CSR-D group that were significantly associated with antigen processing and presentation pathway. Moreover, in this group of patients, the variants in four genes involved in DNA double-strand breaks (DSB) repair signaling, in particular, XRCC3 were observed, suggesting an association with CSR defect. CONCLUSION: Additional impact of certain variants, along with ATM mutations, may explain the heterogeneity in CSR defect phenotype among A-T patients. It can be concluded that genetic modulators play an important role in the course of A-T disease and its clinical severity.

Effect of Neuromuscular Exercises on Strength, Proprioceptive Receptors, and Balance in Females with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is the third most common cause of adult neurologic disabilities. The aim of this study was to determine the effect of 8 weeks of neuromuscular exercises on strength, proprioceptive receptors, and balance of women with MS. METHODS: In this randomized controlled trial study, 20 female volunteers with relapsing-remitting MS were randomly assigned into the experimental group (n = 10) and control group (n = 10). Maximum muscular strength of knee extensor and flexor muscles, knee joint proprioceptive error (Biodex), and balance (Berg Balance Scale) was measured at baseline and after 8 weeks of neuromuscular exercise. The data were analyzed using paired t-test and independent t-test. RESULTS: The results showed a significant improvement (P < 0.05) in the quadriceps strength, hamstring strength, proprioceptive receptor error, and the balance in the experimental group, but not in the control group. A significant difference was evident between the experimental and control groups in terms of strength, balance, and proprioceptive receptor error (P < 0.05). CONCLUSIONS: Neuromuscular exercise training is effective in improving balance, strength, and reducing the proprioceptive error in people with MS, and it could be recommended as modalities for these patients.

Apical Debris Extrusion with Conventional Rotary and Reciprocating Instruments.

Introduction: The aim of the present study was to compare the amount of apical debris extrusion after preparation using hand files, reciprocating files, and full rotary nickel-titanium systems. Methods and Materials: One hundred extracted human mandibular molars with two separated canals in mesial root were divided into five groups and prepared using reciprocating systems (Reciproc file and Safesider endodontic reamers file), full rotary systems (Mtwo and Neoniti A1 files) and hand instrumentation systems. Endodontic access was prepared and a #15 K-file was passed beyond the apex of the mesiobuccal canal by 1 mm to ensure the canal patency. All mesiobuccal canals were prepared 1 mm shorter than the anatomic apex. In each case, extruded debris was collected in an Eppendorf tube and weighed after desiccation. The mean weight of extruded material was calculated in each group. The analysis was carried out using the Kruskal-Wallis test followed by two tailed and Mann-Whitney U test at a significance level of 0.05. The Bonferroni correction was also applied to correct multiple comparisons. Results: There was a statistically significant difference between the reciprocal and other techniques in debris extrusion (P<0.05). The order of groups ranked in terms of debris extrusion from the lowest to highest was as follows: 1) Hand instrumentation group (with crown down technique), 2) Mtwo group, 3) Neoniti A1 group, 4) Safesider endodontic reamer group, and 5) Reciproc group. Conclusion: Based on this in vitro study, all systems have some apical debris extrusion; however, using the hand instrumentation system resulted in extrusion of significantly less debris compared to the Reciproc group. It seems that hand and rotary instrumentation systems are better than reciprocating instrumentation systems in terms of the amount of debris extrusion.

DeePathology: Deep Multi-Task Learning for Inferring Molecular Pathology from Cancer Transcriptome.

Despite great advances, molecular cancer pathology is often limited to the use of a small number of biomarkers rather than the whole transcriptome, partly due to computational challenges. Here, we introduce a novel architecture of Deep Neural Networks (DNNs) that is capable of simultaneous inference of various properties of biological samples, through multi-task and transfer learning. It encodes the whole transcription profile into a strikingly low-dimensional latent vector of size 8, and then recovers mRNA and miRNA expression profiles, tissue and disease type from this vector. This latent space is significantly better than the original gene expression profiles for discriminating samples based on their tissue and disease. We employed this architecture on mRNA transcription profiles of 10750 clinical samples from 34 classes (one healthy and 33 different types of cancer) from 27 tissues. Our method significantly outperforms prior works and classical machine learning approaches in predicting tissue-of-origin, normal or disease state and cancer type of each sample. For tissues with more than one type of cancer, it reaches 99.4% accuracy in identifying the correct cancer subtype. We also show this system is very robust against noise and missing values. Collectively, our results highlight applications of artificial intelligence in molecular cancer pathology and oncological research. DeePathology is freely available at https://github.com/SharifBioinf/DeePathology .

Effect of local papaverine on arteriovenous fistula maturation in patients with end-stage renal disease.

BACKGROUND: Arteriovenous fistula (AVF) maturation is one of the main concerns in patients with end-stage renal disease (ESRD) and finding a strategy for increasing success rate and accelerating fistula maturation is valuable. The aim of this study was to evaluate the effects of papaverine injection on AVF maturation and success rate. METHOD: This study was a randomized clinical trial that involved 110 patients with ESRD that were referred for AVF construction. Patients were allocated in papaverine group and control group with block randomization according to age and sex. In the case group, papaverine (0.1 or 0.2 cc) was injected locally within the subadventitia of artery and vein after proximal and distal control during AVF construction and in the control group, AVF construction was done routinely without papaverine injection. RESULTS: Maturation time in case and control groups was 37.94 ± 11.49 and 44.23 ± 9.57 days, respectively (p=0.004). Hematoma was not seen in the case group but occurred in one patient in the control group. One patient of the case group developed venous hypertension. Four functional fistulas, 1 (1.8%) in the case group and 3 (5.5%) in the control group, failed to mature (p=0.618). Maturation rate did not differ between the two groups statistically (p=0.101). CONCLUSION: Local papaverine injection increased vessel diameter and blood flow, increasing shearing stress in both arterial and venous segment of recently created AVF. In this way, papaverine probably can decrease AVF maturation time without an increase in complications.

Effect of local papaverine on arteriovenous fistula maturation in patients with end-stage renal disease / Efeito da papaverina local na maturação de fístulas arteriovenosas em pacientes com doença renal terminal

Abstract Background: Arteriovenous fistula (AVF) maturation is one of the main concerns in patients with end-stage renal disease (ESRD) and finding a strategy for increasing success rate and accelerating fistula maturation is valuable. The aim of this study was to evaluate the effects of papaverine injection on AVF maturation and success rate. Method: This study was a randomized clinical trial that involved 110 patients with ESRD that were referred for AVF construction. Patients were allocated in papaverine group and control group with block randomization according to age and sex. In the case group, papaverine (0.1 or 0.2 cc) was injected locally within the subadventitia of artery and vein after proximal and distal control during AVF construction and in the control group, AVF construction was done routinely without papaverine injection. Results: Maturation time in case and control groups was 37.94 ± 11.49 and 44.23 ± 9.57 days, respectively (p=0.004). Hematoma was not seen in the case group but occurred in one patient in the control group. One patient of the case group developed venous hypertension. Four functional fistulas, 1 (1.8%) in the case group and 3 (5.5%) in the control group, failed to mature (p=0.618). Maturation rate did not differ between the two groups statistically (p=0.101). Conclusion: Local papaverine injection increased vessel diameter and blood flow, increasing shearing stress in both arterial and venous segment of recently created AVF. In this way, papaverine probably can decrease AVF maturation time without an increase in complications.

Resumo Introdução: A maturação da fístula arteriovenosa (FAV) é uma das principais preocupações em pacientes com doença renal terminal (DRT). Assim, é importante identificar estratégias para aumentar as taxas de sucesso e acelerar a maturação da fístula. O objetivo do presente estudo foi avaliar os efeitos da infiltração de papaverina sobre a maturação da FAV e suas taxas de sucesso. Método: O presente ensaio clínico randomizado incluiu 110 pacientes com DRT encaminhados para colocação de FAV. Os pacientes foram randomizados em bloco em função de idade e sexo e alocados nos grupos caso ou controle. Os indivíduos no grupo caso receberam infiltração local de papaverina (0,1 ou 0,2 ml) no plano da sub-adventícia da artéria e veia após o controle proximal e distal durante a construção da FAV. No grupo controle, a construção da FAV foi realizada rotineiramente sem infiltração de papaverina. Resultados: Os tempos de maturação dos grupos caso e controle foram 37,94 ± 11,49 e 44,23 ± 9,57 dias, respectivamente (p = 0,004). Foi observado hematoma em apenas um paciente do grupo controle. Um paciente do grupo caso desenvolveu hipertensão venosa. Quatro fístulas funcionais, uma (1,8%) no grupo caso e três (5,5%) no grupo controle, não amadureceram (p = 0,618). A taxa de maturação não diferiu estatisticamente entre os dois grupos (p = 0,101). Conclusão: A infiltração local de papaverina aumentou o diâmetro do vaso e o fluxo sanguíneo, elevando a tensão de cisalhamento nos segmentos arterial e venoso da FAV recentemente criada. Desta forma, a papaverina provavelmente consegue reduzir o tempo de maturação da FAV sem aumentar as complicações.

A novel alpha-thalassemia nonsense mutation in HBA2: C.382 A > T globin gene.

In this study, a new alpha globin gene mutation on the α2-globin gene is reported. This mutation resulted in a Lys > stop codon substitution at position 127 which was detected in four individuals (three males and one female). DNA sequencing revealed this mutation in unrelated persons in Khuzestan province, Southwestern Iran of Lor ethnicity. This mutation caused no severe hematological abnormalities in the carriers. From the nature of substituted residues in α2-globin, it is widely expected that this mutation leads to unstable and truncated protein and should be detected in couples at risk for α-thalassemia.

Exon sequencing of PKD1 gene in an Iranian patient with autosomal-dominant polycystic kidney disease.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. ADPKD is genetically heterogeneous with two genes identified: PKD1 (16p13.3, 46 exons) and PKD2 (4q21, 15 exons). Eighty five percent of the patients with ADPKD have at least one mutation in the PKD1 gene. Genetic studies have demonstrated an important allelic variability among patients, but very few data are known about the genetic variation among Iranian populations. METHODS: In this study, exon direct sequencing of PKD1 was performed in a seven-year old boy with ADPKD and in his parents. The patient's father was ADPKD who was affected without any kidney dysfunction, and the patient's mother was congenitally missing one kidney. RESULTS: Molecular genetic testing found a mutation in all three members of this family. It was a missense mutation GTG>ATG at position 3057 in exon 25 of PKD1. On the other hand, two novel missense mutations were reported just in the 7-year-old boy: ACA>GCA found in exon 15 at codon 2241 and CAC>AAC found in exon 38 at codon 3710. For checking the pathogenicity of these mutations, exons 15, 25, and 38 of 50 unrelated normal cases were sequenced. CONCLUSION: our findings suggested that GTG>ATG is a polymorphism with high frequency (60%) as well as ACA>GCA and CAC>AAC are polymorphisms with frequencies of 14% and 22%, respectively in the population of Southwest Iran.

Association of high LDH and low glucose levels in pleural space with HER2 expression in non-small cell lung cancer.

BACKGROUND: Evidence shows direct link of HER2 to increased glycolysis and over production of lactate dehydrogenase (LDH). HER2 overexpression, high LDH and low glucose pleural levels are associated with poor prognosis in lung cancer. Here, their relationships were investigated. MATERIALS AND METHODS: HER2 positivity was studied using immunohistochemistry in non-small cell lung cancer. Glucose and LDH levels were measured using commercial colorimetric kits. RESULTS: Of 42 patients (29 adenocarcinoma and 13 squamous cell carcinoma), 28 (66.7%) were HER2-negative, 14 (33.3%) were HER2- positive, including 9 (21.4%) weakly stained (1+) and 5 (11.9%) moderately stained (2+) samples. The relationship between HER2 and glucose and LDH levels were tested in 20 newly diagnosed lung cancer patients who had simultaneous pleural and serum samples. Pleural and serum LDH levels were increased, and pleural glucose levels were decreased with the scale of HER2 positivity, and that the difference in glucose levels between HER2-negative group and HER2- positive patients scored at 2+ reached statistical significance (p=0.02). This latter group all had pleural glucose levels below 40 mg/dl. CONCLUSIONS: For the first time, we showed a significant association between low pleural glucose level and overexpression of HER2 in lung cancer. Further investigations are warranted to disclose the association of HER2 with low pleural glucose levels in other populations, with a larger sample size, in malignant pleural effusions caused by other types of cancer, and finally to assess employment as a screening tool for finding HER2-positive cases of lung cancer.

Using eggshell membrane as nerve guide channels in peripheral nerve regeneration.

OBJECTIVE(S): The aim of this study was to evaluate the final outcome of nerve regeneration across the eggsell membrane (ESM) tube conduit in comparison with autograft. MATERIALS AND METHODS: Thirty adult male rats (250-300 g) were randomized into (1) ESM conduit, (2) autograft, and (3) sham surgery groups. The eggs submerged in 5% acetic acid. The decalcifying membranes were cut into four pieces, rotated over the teflon mandrel and dried at 37(°)C. The left sciatic nerve was surgically cut. A 10-mm nerve segment was cut and removed. In the ESM group, the proximal and distal cut ends of the sciatic nerve were telescoped into the nerve guides. In the autograft group, the 10 mm nerve segment was reversed and used as an autologous nerve graft. All animals were evaluated by sciatic functional index (SFI) and electrophysiology testing. RESULTS: The improvement in SFI from the first to the last evalution in ESM and autograft groups were evaluated. On days 49 and 60 post-operation, the mean SFI of ESM group was significantly greater than the autograft group (P< 0.05). On day 90, the mean nerve conduction velocity (NCV) of ESM group was greater than autograft group, although the difference was not statistically significant (P> 0.05). CONCLUSION: These findings demonstrate that ESM effectively enhances nerve regeneration and promotes functional recovery in injured sciatic nerve of rat.

Role of routine pelvic radiography in initial evaluation of stable, high-energy, blunt trauma patients.

BACKGROUND: Pelvic fractures are among the most devastating traumatic injuries accompanied by high morbidity and mortality rate leading to catastrophic outcomes and haemodynamic consequences. Although Advanced Trauma Life Support (ATLS) recommends performing pelvic radiography in all major blunt trauma patients, several lines of evidence recommend that it can be limited to those blunt trauma patients who are haemodynamically unstable or have positive pelvic physical examination. Thus, we performed this study in order to evaluate the efficacy of routine pelvic radiography in haemodynamically stable, high-energy, blunt trauma patients. METHODS: This was a prospective cross-sectional study including all the haemodynamically stable, high-energy, blunt trauma patients with negative pelvic physical examination referring to our trauma centre during a 5-month period (May-September 2010). Pelvic radiographies were performed and reviewed for abnormalities. In those who had negative pelvic physical examination and the radiography was not revealing enough, CT imaging was requested and reviewed. RESULTS: During the study period, 1679 high-energy blunt trauma patients referred to our centre out of which 389 were haemodynamically stable and had negative pelvic physical examination. Pelvic radiography was found to be normal in all the patients except one (0.25%) who had pelvic fracture. Only three patients required CT imaging out of which two (0.5%) were found to be normal. CONCLUSIONS: Pelvic radiography could be eliminated from the primary survey protocol of the patients with high-energy blunt trauma who are haemodynamically stable and have negative pelvic physical examination.

Role of cervical spine radiography in the initial evaluation of stable high-energy blunt trauma patients.

BACKGROUND: Detecting cervical spine injuries in trauma patients is essential because undetected injuries in the this area may result in severe neurological disability and probably quadriplegia. Thus, radiography of the cervical spine is considered mandatory in the initial evaluation of trauma patients according to Advanced Trauma Life Support. This approach results in many unnecessary normal radiographs. Therefore, we performed this study to determine the role of routine cervical radiography in the initial evaluation of stable high-energy blunt trauma patients. METHODS: This was a prospective cross-sectional study including all hemodynamically stable high-energy blunt trauma patients with negative cervical physical examinations referred to our trauma center during a 5-month period (May to September 2010). Cervical radiographs, computed tomography (CT) scanning and magnetic resonance imaging were performed and reviewed for abnormalities. RESULTS: During the study period, 1,679 high-energy blunt trauma patients were referred to our center, of which 400 were hemodynamically stable and had negative cervical physical examinations. Cervical radiographs were found to be normal in all patients. CONCLUSION: Cross-table cervical spine radiographs can be limited to those high-energy blunt trauma patients who have a positive cervical physical examination or those in whom the physical examination is not revealing. These radiographs also have low value for detecting occult cervical spine fractures, and CT imaging is considered the modality of choice in these cases.