Cytological clues of bone marrow findings in Kala-Azar

A case-control study was done on 77 cases in divided groups in order to test the sensitivity and specificity of new diagnostic morphologic criteria for visceral leishmaniasis. We found cytological findings other rather than the presence of intracytoplasmic Leishman Donovan bodies, i.e., the following interrelated items: 1) hypolymphopoiesis; 2) dyserythropoiesis; 3) blebbing of the granulocytic series and exfoliation of the blebs as "granular stippling;" and 4) various-sized damaged of the activated macrophages to apoptotic ones and cytoplasmic blebbing of the parasitophorous vacuoles and exfoliation of them as empty "basophilic bare cells." These two latter findings were based on our own observations over the past few years. Statistical analysis showed that these new criteria have more efficacy in diagnosis than previous ones; the differences were statistically significant. Findings obtained from this study could increase the values of diagnostic histopathological methods for detecting visceral leishmaniasis.     

Characterization of hepatitis B virus genome variability in Iranian patients with chronic infection, a nationwide study

Hepatitis B virus (HBV) isolates from Iranian patients around the country were characterized. Eighty-one complete genomes from HBV isolates were sequenced and analyzed. The studied population was grouped into three categories including inactive carriers, patients with chronic hepatitis, and patients with liver cirrhosis. Molecular and phylogenetic analyses revealed that Iranian patients were infected with HBV genotype D and subgenotype D1. The most common subtype was ayw2, followed by ayw3 and ayw4. Several deletions and insertions that had no correlation with disease outcome were observed in the HBV genomes. The most frequent mutation in the major hydrophilic region (MHR) of HBV surface antigen (HBsAg) was sP120S. Almost half of the patients studied carried precore (PC) mutant variants and one-third of the studied population was infected with variants carrying basal core promoter (BCP) mutations. PC and BCP mutations were observed in older patients, especially in those with chronic liver disease. Sixty-seven patients (82.7%) were HBeAg negative, and the prevalence of precore mutant isolates (G1896A) was higher in this group than in HBeAg-positive patients. Lamivudine drug resistance mutations were detected after 1 year of treatment in about 30% of lamivudine-treated patients. In conclusion, these results demonstrate that HBV subgenotype D1 is the only subgenotype circulating in Iran, and there is no evidence of any exotic genotype in the region. The HBV PC (G1896A) mutation may play an important role in the clinical outcome of the disease by increasing the risk of progressive liver disease among Iranian patients infected with HBV.     

Image-Guided Spinal Ablation: A Review

The image-guided thermal ablation procedures can be used to treat a variety of benign and malignant spinal tumours. Small size osteoid osteoma can be treated with laser or radiofrequency. Larger tumours (osteoblastoma, aneurysmal bone cyst and metastasis) can be addressed with radiofrequency or cryoablation. Results on the literature of spinal microwave ablation are scarce, and thus it should be used with caution. A distinct advantage of cryoablation is the ability to monitor the ice-ball by intermittent CT or MRI. The different thermal insulation, temperature and electrophysiological monitoring techniques should be applied. Cautious pre-procedural planning and intermittent intra-procedural monitoring of the ablation zone can help reduce neural complications. Tumour histology, patient clinical-functional status and life-expectancy should define the most efficient and least disabling treatment option.     

Social network analysis of Iranian researchers in the field of violence

Purpose: The social network analysis (SNA) is a paradigm for analyzing structural patterns in social relations, testing knowledge sharing process and identifying bottlenecks of information flow. The purpose of this study was to determine the status of research in the field of violence in Iran using SNA. Methods: Research population included all the papers with at least one Iranian affiliation published in violence field indexed in SCIE, PubMed and Scopus databases. The co-word maps, co-authorship network and structural holes were drawn using related software. In the next step, the active authors and some measures of our network including degree centrality (DC), closeness, eigenvector, betweeness, density, diameter, compactness and size of the main component were assessed. Likewise, the trend of the published articles was evaluated based on the number of documents and their citations from 1972 to 2014. Results: Five hundred and seventy one records were obtained. The five main clusters and hot spots were mental health, violence, war, psychiatric disorders and suicide. The co-authorship network was complex, tangled and scale free. The top nine authors with cut point role and top ten active authors were identified. The mean (standard deviation) of normalized DC, closeness, eigenvector and betweeness were 0.449 (0.805), 0.609 (0.214), 2.373 (7.353) and 0.338 (1.122), respectively. The density, diameter and mean compactness of our co-authorship network were 0.0494, 3.955 and 0.125, respectively. The main component consisted of 216 nodes that formed 17% of total size of the network. Both the number of the documents and their citations has increased in the field of violence in the recent years. Conclusion: Although the number of the documents has recently increased in the field of violence, the information flow is slow and there are not many relations among the authors in the network. However, the active authors have ability to influence the flow of knowledge within the network.     

Imaging genomics discovery of a new risk variant for Alzheimer's disease in the postsynaptic SHARPIN gene

Molecular mechanisms underlying Alzheimer's disease (AD) are difficult to investigate, partly because diagnosis lags behind the insidious pathological processes. Therefore, identifying AD neuroimaging markers and their genetic modifiers may help study early mechanisms of neurodegeneration. We aimed to identify brain regions of the highest vulnerability to AD using a data‐driven search in the AD Neuroimaging Initiative (ADNI, n = 1,100 subjects), and further explored genetic variants affecting this critical brain trait using both ADNI and the younger UK Biobank cohort (n = 8,428 subjects). Tensor‐Based Morphometry (TBM) and Independent Component Analysis (ICA) identified the limbic system and its interconnecting white‐matter as the most AD‐vulnerable brain feature. Whole‐genome analysis revealed a common variant in SHARPIN that was associated with this imaging feature (rs34173062, p = 2.1 × 10^?10). This genetic association was validated in the UK Biobank, where it was correlated with entorhinal cortical thickness bilaterally (p = .002 left and p = 8.6 × 10^?4 right), and with parental history of AD (p = 2.3 × 10^?6). Our findings suggest that neuroanatomical variation in the limbic system and AD risk are associated with a novel variant in SHARPIN. The role of this postsynaptic density gene product in β1‐integrin adhesion is in line with the amyloid precursor protein (APP) intracellular signaling pathway and the recent genome‐wide evidence.     

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

Molecular diagnostic methods based on the detection of mutations conferring drug resistance are promising technologies for rapidly detecting multidrug-/extensively drug-resistant tuberculosis (M/XDR TB), but large studies of mutations as markers of resistance are rare. The Global Consortium for Drug-Resistant TB Diagnostics analyzed 417 Mycobacterium tuberculosis isolates from multinational sites with a high prevalence of drug resistance to determine the sensitivities and specificities of mutations associated with M/XDR TB to inform the development of rapid diagnostic methods. We collected M/XDR TB isolates from regions of high TB burden in India, Moldova, the Philippines, and South Africa. The isolates underwent standardized phenotypic drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), moxifloxacin (MOX), ofloxacin (OFX), amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) using MGIT 960 and WHO-recommended critical concentrations. Eight genes (katG, inhA, rpoB, gyrA, gyrB, rrs, eis, and tlyA) were sequenced using Sanger sequencing. Three hundred seventy isolates were INH^r, 356 were RIF^r, 292 were MOX^r/OFX^r, 230 were AMK^r, 219 were CAP^r, and 286 were KAN^r. Four single nucleotide polymorphisms (SNPs) in katG/inhA had a combined sensitivity of 96% and specificities of 97 to 100% for the detection of INH^r. Eleven SNPs in rpoB had a combined sensitivity of 98% for RIF^r. Eight SNPs in gyrA codons 88 to 94 had sensitivities of 90% for MOX^r/OFX^r. The rrs 1401/1484 SNPs had 89 to 90% sensitivity for detecting AMK^r/CAP^r but 71% sensitivity for KAN^r. Adding eis promoter SNPs increased the sensitivity to 93% for detecting AMK^r and to 91% for detecting KAN^r. Approximately 30 SNPs in six genes predicted clinically relevant XDR-TB phenotypes with 90 to 98% sensitivity and almost 100% specificity.     

α-Helical element at the hormone-binding surface of the insulin receptor functions as a signaling element to activate its tyrosine kinase

The primary hormone-binding surface of the insulin receptor spans one face of the N-terminal β-helix of the α-subunit (the L1 domain) and an α-helix in its C-terminal segment (αCT). Crystallographic analysis of the free ectodomain has defined a contiguous dimer-related motif in which the αCT α-helix packs against L1 β-strands 2 and 3. To relate structure to function, we exploited expanded genetic-code technology to insert photo-activatable probes at key sites in L1 and αCT. The pattern of αCT-mediated photo-cross-linking within the free and bound receptor is in accord with the crystal structure and prior mutagenesis. Surprisingly, L1 photo-probes in β-strands 2 and 3, predicted to be shielded by αCT, efficiently cross-link to insulin. Furthermore, anomalous mutations were identified on neighboring surfaces of αCT and insulin that impair hormone-dependent activation of the intracellular receptor tyrosine kinase (contained within the transmembrane β-subunit) disproportionately to their effects on insulin binding. Taken together, these results suggest that αCT, in addition to its hormone-recognition role, provides a signaling element in the mechanism of receptor activation.     

Relationships between cerebral structure and cognitive function in African Americans with type 2 diabetes

Background

Relationships between cognitive function and brain structure remain poorly defined in African Americans with type 2 diabetes.

Mechanism of Thyroid Calorigenesis: Role of Active Sodium Transport

The hypothesis that thyroid calorigenesis is mediated by stimulation of active Na(+) transport was tested by measuring the Q(o2) of liver slices and skeletal muscle (diaphragm) from thyroxine- and triiodothyronine-injected thyroidectomized and normal rats in media fortified with ouabain (10(-3) M) and/or free of Na(+) or K(+). In both tissues, more than 90% of the increase in Q(o2) produced by injections of thyroid hormone in euthyroid rats was derived from increased energy utilization by the Na(+) pump. In triiodothyronine-treated thyroidectomized rats, activation of Na(+) transport accounted for 90% or more of the increment in Q(o2) in liver and 40% or more of the increment in diaphragm. Intracellular Na(+), K(+), and Cl(-) concentrations were measured in euthyroid and hyperthyroid liver and diaphragm. The transmembrane Na(+) and K(+) concentration differences were significantly increased in both tissues by the administration of triiodothyronine. These results indicate that thyroid hormone activates Na(+) extrusion and K(+) accumulation either by increasing the local concentration of ATP or by direct stimulation of the Na(+) pump.