A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients.

Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease-modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein data sets visualized using Gephi, based on protein--protein interactions in the STRING database. The top modules of NDP and RP networks were assessed using Enrichr. Based on the findings, a set of proteins, including ATP binding cassette subfamily C member 1 (ABCC1), neurogenic locus notch homologue protein 1 (NOTCH1), hepatocyte growth factor receptor (MET), RAF proto-oncogene serine/threonine-protein kinase (RAF1) and proto-oncogene vav (VAV1) was found in NDP and was involved in over-represented terms correlated with cell-mediated immunity and cancer. In contrast, transcription factor RelB (RELB), histone acetyltransferase p300 (EP300), acetyl-CoA carboxylase 2 (ACACB), adiponectin (ADIPOQ) and phosphoenolpyruvate carboxykinase 2 mitochondrial (PCK2) had major contributions to viral infections and lipid metabolism as significant events in RP. According to these findings, further research is required to demonstrate the pathogenic roles of such proteins and autoantibodies targeting them in MS and to develop therapeutic agents which can ameliorate disease severity.

EGFR rs11506105 and IFNL3 SNPs but not rs8099917 are strongly associated with treatment responses in Iranian patients with chronic hepatitis C.

Interferon lambda 3 (IFNL3) and epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) may play a key role in the spontaneous clearance of hepatitis C virus (HCV) and treatment responses. The aim of this study was to evaluate the effect of IFNL3 SNPs and EGFR rs11506105 on treatment outcomes in patients with chronic HCV (CHC). IFNL3 SNPs and EGFR rs11506105 were genotyped by PCR-restriction fragment length polymorphism and PCR-sequencing, respectively, in 235 naïve patients with CHC infection. The frequency of rapid virologic response (RVR), complete early virologic response (cEVR) and sustained virologic response (SVR) were 52.3%, 76.2% and 64.7% respectively. The results of this study showed that RVR was associated with ALT (P=0.015), AST (P=0.020), IFNL3 rs12979860 (CC) (P=0.043), rs12980275 (AA) (P=1 × 10-4), and EGFR rs11506105 (AA) (P=0.010), and IFNL3 rs12979860 (CC) (P=0.048), rs12980275 (AA) (P=0.022), and EGFR rs11506105 (AA) (P=0.006) were correlated with cEVR. HCV genotype (P=0.007), IFNL3 rs12979860 (CC) (P=0.023), IFNL3 rs12980275 (AA) (P=1 × 10-4), EGFR rs11506105 (AA) (P=0.005), RVR (P=1 × 10-4), and cEVR (P=0.003) were significant predictors for SVR. These results, for the first time, revealed that beside IFNL3 SNPs, EGFR rs11506105 is strongly associated with RVR, cEVR and SVR. EGFR rs11506105 besides IFNL3 SNPs could predict treatment responses in CHC patients.

Burden of Cardiac Siderosis in a Thalassemia-Major Endemic Population: A Preliminary Report From Pakistan.

OBJECTIVE: To describe the initial experience and demographics of T2* cardiac magnetic resonance-based myocardial-iron quantification of transfusion-dependent thalassemia-major (TM) patients from Pakistan and the correlation with serum ferritin. METHODS: Eligible TM patients presenting between April 2014 and April 2015 to Aga Khan University Hospital, Pakistan, for T2*CMR were included. The severity of myocardial-iron deposition was defined as follows: normal T2*>20 ms, mild-moderate T2*10 to 20 ms, and severe T2*<10 ms. Cardiac symptoms were classified using the NYHA functional classification. Echocardiographic systolic and diastolic functions were performed. Continuous variables were presented as the median (minimum-maximum value). Correlation was measured using the Spearman rank correlation. Multivariate logistic regression was used to determine factors associated with the NYHA functional class. RESULTS: A total of 83 patients (49 male and 34 female) with TM, age 19 (5 to 45) years at presentation for T2*CMR, were reviewed. At presentation, 70% of the patients were classified as NYHA class II or worse. T2*<20 ms was observed in 62.6% of the patients, with 47% showing severe iron deposition (T2<10 ms). No correlation of T2*<20 ms (r=-0.157, P=0.302) and T2*<10 ms (r=-0.128, P=0.464) was observed with serum ferritin. On multivariate analysis, lower T2* values correlated with a worsening NYHA functional class. CONCLUSIONS: There is a high prevalence of severe myocardial iron load in Pakistani TM patients. Serum ferritin did not correlate with T2* values. Lower T2* was the only clinical factor associated with the NYHA functional class.

Light absorption enhancement in thin film GaAs solar cells using dielectric nanoparticles.

Cost-effective and lightweight solar cells are currently demanded in strategic fields such as space applications or integrated-wearable devices. A reduction of the active layer thickness, producing thin-film devices, has been a traditional solution to accomplish both requirements. However, this solution also reduces the efficiency of the device. For this reason, alternative strategies are being proposed. In this work, light trapping effects of an array of semiconductor nanoparticles located on the top surface of a thin-film GaAs solar cell are investigated to improve the optical absorption and current density in active layer, under the standard AM-1.5 solar spectrum. The numerical results are compared with other previous proposals such as an aluminum nanoparticle array, as well as conventional solar cells with and without a standard anti-reflective coating (ARC). The inclusion of semiconductor nanoparticles (NPs) shows an improved response of the solar cells at different angles of incidence in comparison to solar cell with an ARC. Furthermore, the efficiency increases a 10% respect to the aluminum nanoparticles (NPs) architecture, and a 21% and a 30% respect to solar cells with and without ARC, respectively.

A monolithic nanostructured-perovskite/silicon tandem solar cell: feasibility of light management through geometry and materials selection.

The use of several layers of different materials, taking advantage of their complementary bandgap energies, improves the absorption in multi-junction solar cells. Unfortunately, the inherent efficiency increment of this strategy has a limitation: each interface introduces optical losses. In this paper, we study the effects of materials and geometry in the optical performance of a nanostructured hybrid perovskite - silicon tandem solar cell. Our proposed design increases the performance of both subcells by managing light towards the active layer, as well as by minimizing reflections losses in the interfaces. We sweep both refractive index and thickness of the transport layers and the dielectric spacer composing the metasurface, obtaining a range of these parameters for the proper operation of the device. Using these values, we obtain a reduction in the optical losses, in particular they are more than a 33% lower than those of a planar cell, mainly due to a reduction of the reflectivity in the device. This approach leads to an enhancement in the optical response, widens the possibilities for the manufacturers to use different materials, and allows wide geometrical tolerances.

Patterns of pituitary dysfunction three months or more after traumatic brain injury.

PURPOSE: Chronic posttraumatic brain injury (TBI) pituitary dysfunction is not a newly discovered subject, it has been reported more frequently, probably due to increasing chances of exposure to its causes, mainly the road traffic accidents, sport-related injuries, falls, and injuries during wars. This study aims to estimate the frequency of pituitary dysfunction 3 months or more after head trauma and the patterns of hormonal deficiencies. METHODS: A cross-sectional study was conducted between January 2016 and August 2017. Participants were patients having a history of moderate-to-severe TBI at least 3 months before enrolment. Pituitary function test was done for all patients to determine the frequency of pituitary dysfunction, the number of axes deficiencies, and which hormone is mostly affected. Statistical Package for the Social Sciences (SPSS) version 23.0 was used for univariate analysis, P < 0.05 was considered statistically significant. RESULTS: Out of the 28 patients involved in this study, 17 (61%) had pituitary dysfunction, while 11 (39%) had not. Single hormonal defect was the most prevalent abnormality in 12 (43%), and the most affected hormone was the growth hormone (GH) in 14 patients (50%), followed by gonadal axis, thyroid stimulating hormone, and finally adrenocorticotropic hormone (ACTH), 6 (21%), 3 (11%), and 1 (4%), respectively. CONCLUSION: TBI pituitary dysfunction is more prevalent than was predicted in the population studied, single hormonal defect was found to be the most prevalent abnormality, being the GH is the most affected axis, and the ACTH seems to be the least.

Endosonographic examination of thyroid gland among patients with nonthyroid cancers.

OBJECTIVES: There is limited endosonographic literature regarding thyroid gland pathology, which is frequently visualized during upper endoscopic ultrasound (EUS). Our objective was to assess the prevalence of benign and malignant thyroid lesions encountered during routine upper EUS within a cancer center setting. MATERIALS AND METHODS: The data were prospectively collected and retrospectively analyzed. All upper EUS procedures performed between October 2012 and July 2014 were reviewed at a large referral cancer center. Data collected included patient demographics, preexisting thyroid conditions, thyroid gland dimensions, the presence or absence of thyroid lesions, and EUS morphology of lesions if present, and interventions performed to characterize thyroid lesions and pathology results when applicable. RESULTS: Two hundred and forty-five EUS procedures were reviewed. Of these, 100 cases reported a detailed endosonographic examination of the thyroid gland. Most of the thyroid glands were endosonographically visualized when the tip of the scope was at 18 cm from the incisors. Twelve cases showed thyroid lesions, out of which three previously undiagnosed thyroid cancers were visualized during EUS (two primary papillary thyroid cancers and one anaplastic thyroid cancer). Transesophageal EUS-guided fine needle aspiration of thyroid lesions was feasible when the lesion was in the inferior portion of the thyroid gland, and the tip of the scope was at 18 cm or more from the incisors. CONCLUSIONS: Routine EUS examination may detect unexpected thyroid lesions including malignant ones. We encourage endosonographers to screen the visualized portions of the thyroid gland during routine withdrawal of the echoendoscope.

Periosteum: biology and applications in craniofacial bone regeneration.

The bone-regenerative potentials of the periosteum have been explored as early as the 17th century. Over the past few years, however, much has been discovered in terms of the molecular and cellular mechanisms that control the periosteal contribution to bone regeneration. Lineage tracing analyses and knock-in transgenic mice have helped define the relative contributions of the periosteum and endosteum to bone regeneration. Additional studies have shed light on the critical roles that BMP, FGF, Hedgehog, Notch, PDGF, Wnt, and inflammation signaling have or may have in periosteal-mediated bone regeneration, fostering the path to novel approaches in bone-regenerative therapy. Thus, by examining the role that each pathway has in periosteal-mediated bone regeneration, in this review we analyze the status of the current research on the regenerative potential of the periosteum. The provided analysis aims to inform both clinician-scientists who may have interest in the current studies about the biology of the periosteum as well as dental surgeons who may find this review useful to perform periosteal-harnessing bone-regenerative procedures.

Primary papillary thyroid carcinoma diagnosed by using endoscopic ultrasound with fine needle aspiration.

There is paucity in the literature on the use of endoscopic ultrasound (EUS) for evaluating the thyroid gland. We report the first case of primary papillary thyroid cancer diagnosed by using EUS and fine needle aspiration (FNA). A 66-year-old man underwent EUS for the evaluation of mediastinal lymphadenopathy. FNA of the lymph nodes showed benign findings. A hypoechoic mass was noted in the right lobe of the thyroid gland. Therefore, FNA was performed. The cytological results were consistent with primary papillary thyroid cancer.

HSP65-PRA identification of non-tuberculosis mycobacteria from 4892 samples suspicious for mycobacterial infections.

Various molecular methods have been used for the rapid identification of mycobacterial species. In this survey, evaluation of antibiotic resistance and PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene was carried out for identification of non-tuberculosis mycobacteria (NTM) isolates from different clinical specimens. Forty-eight different mycobacterial isolates were selected and followed by the conventional and PRA of hsp65 for species identification. The antibiotic susceptibility test was carried out according to standard methods. A 439 bp PCR product of hsp65 in all selected isolates was amplified and digested with the BstEII and HaeIII restriction enzymes. The restriction fragment length polymorphism (RFLP) patterns were analyzed for species identification. Using PRA for 48 mycobacterial selected isolates, including 15 M. tuberculosis, one M. bovis and all 32 isolates of NTM, revealed 11 different species among the NTM isolates. The most frequent NTM isolates were M. kansasii, M. gordonae III, M. marinum, M. chelonae, M. scrofluaceum and M. gastri. In most cases, the PRA results were perfectly in accordance with the classical biochemical method. Combination of resistance to rifampin and isoniazid was present among M. kansasi, M. gordoniae III, M. scrofluaceum, M. chelonae, M. marinum, M. gastri, M. gordoniae II and M. trivale isolates. A high incidence of co-resistance to six, five, four and three anti-TB drugs was observed in 18.5%, 9.1%, 6.6% and 11.7% of all NTM isolates, respectively. Our results showed that PRA, in comparison with classical methods, is rapid and accurate enough for the identification of mycobacterial species from LJ medium. Additionally, we found that in Iran we have a highly diverse population of NTM isolates among patients suspected of having TB.

Purification of modified mycobacterial A60 antigen by affinity chromatography and its use for rapid diagnostic tuberculosis infection.

Tuberculosis has been declared a global emergency. The mainstay for its control is the rapid and accurate identification of infected individual. Antibodies to A60, one of the macromolecular antigen complexes of mycobacteria were commonly used in the rapid detection of Mycobacterium tuberculosis. The aim of this study was to prepare specific antibodies against A60 for detection of tuberculosis infection. Specific polyclonal antibodies against A60, (A60-Ab) were prepared in rabbits using 2 boosted injections of the antigen (A60). The antibodies were purified and treated with normal oral flora to remove any non-specific and cross-reactive antibodies. These antibodies were conjugated to CNBr-activated Sepharose 4B and used to isolate subunits of A60 with more specificity for M. tuberculosis. A new affinity column was designed to prepare modified (purified) A60 antigen. Purified A60 antigen (PA60-Ag) was used to develop antibody production by Immunoaffinity chromatography. 113 patients with a confirmed diagnosis of pulmonary TB at Pasteur Institute were selected for the study. The specificity of the results was analyzed with TB-rapid test by using PA60-antibodies. TB-rapid test revealed that normal oral flora-absorbed antibodies could lead to more specific results than that of the non-absorbed antibodies. The developed, modified A60 antibodies, (PA60-Ab)-rapid test showed higher sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and overall efficiency (93.0%, 86.0%, 90.0%, 91.0%, and 90.0% respectively) for the detection of the Mycobacterium antigen. Moreover, PA60-Ag showed only two protein bands of molecular weight 45 and 66kDa in SDS-PAGE while untreated A60 showed multiple bands. Thus, our study helped in the purification of a novel and well characterized A60 antigen and good diagnostic potential for detecting tuberculosis infection.

The gammadelta cells as marker of non-seroconverted cattle naturally infected with Mycobacterium avium subspecies paratuberculosis.

Early diagnosis of MAP infection is a pressing need to enable efficient intervention with the spread of MAP infection in herds. Hence, study of lymphocyte subsets and their expressed adhesion molecules could contribute in defining a distinct diagnostic marker (or markers) at the subclinical period of the infection that could in turn facilitate the development of effective diagnostic approach. In accordance with this objective, milk and blood samples were collected from two groups of cattle naturally infected with MAP and their corresponding negative controls. Group (C) comprised 3-4 year-old ELISA negative/PCR positive-cattle that were considered as subclinical seronegative low shedder group (early stage). Group (A) included 6-8 year-old ELISA positive-cattle, which were considered as a clinical seropositive group (late stage). Flow cytometry of B cells, CD8(+), CD4(+) and gammadelta cells and the adhesion molecules CD44(+), CD62L, LFA-1 and LPAM-1 indicated increase in CD4(+) and B cells levels, with higher levels in blood than milk of group A, and significant expression of CD44(+) in blood and milk and LPAM-1 in blood only. The CD8(+) cells count in milk was higher than blood in the late stage. The peculiar feature of the early stage (group C) was the high level of gammadelta cells in the blood and milk, with tendency to express high level of CD62L. Compelling evidence could support the assumption that the dominant gammadelta cells at early stage of MAP infection could be of CD8CD2(-)WC+1(+) phenotype. gammadelta cells appear as promising markers in defining early changes of MAP infection due to their important role in priming innate and cell mediated immunity. Possible utilization of these peculiar changes in the gammadelta cells level in the early diagnosis of MAP infection should be the subject of further research.