Primary immunodeficiency in Iran: first report of the National Registry of PID in Children and Adults

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. We extracted the patients data, by using a uniform questionnaire from their hospital records. The diagnosis of patients was based on WHO criteria. By now, 440 patients with PID, who were observed during a period of 20 years, have been registered in our registry. Among these patients, the following frequencies were found: predominantly antibody deficiency in 45.9% of patients (n = 202), phagocytic disorders in 29.09% (n = 128), T-cell disorders in 24.31% (n = 107), and complement deficiencies in 0.68% (n = 3). Common variable immunodeficiency was the most frequent disorder (n = 98), followed by chronic granulomatous disease (n = 86), ataxia telangiectasia (n = 48), x-linked agammaglobulinemia (n = 45), selective IgA deficiency (n = 42), combined immunodeficiency (n = 15), and severe combined immunodeficiency (n = 14). This study revealed that antibody deficiencies is the most frequently diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registries.     

The effects of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomized controlled trials

Besides other benefits, curcumin is getting more recognized for its antioxidant and anti‐inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta‐analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta‐analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL‐6) (SMD ?2.08; 95% CI [?3.90, ?0.25]; p = 0.02), high‐sensitivity C‐reactive protein (hs‐CRP) (SMD ?0.65; 95% CI [?1.20, ?0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD ?3.14; 95% CI [‐4.76, ?1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor‐alpha (SMD ?1.62; 95% CI [?3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [?1.06, 1.74], p = 0.63). Overall, this meta‐analysis suggests that taking curcumin‐containing supplements may exert anti‐inflammatory and antioxidant properties through a significant reduction in IL‐6, hs‐CRP, and MDA levels.     

Structural basis of DNA topoisomerase II-α (Top2-α) inhibition: a computational analysis of interactions between Top2-α and its inhibitors

Topoisomerases are enzymes that resolve winding problem of DNA during cellular processes. Because of essential roles of these enzymes in maintenance of cell function, topoisomerases are important targets for cancer chemotherapy. To date, several topoisomerase inhibitors have been introduced and applied as drugs in the treatment of cancer. Topoisomerase II α (Top2-α), a subclass of topoisomerase II enzymes, functions as the target for several anticancer agents and a variety of mutations in this protein have been associated with the development of drug resistance. Mitoxantrone and Amsacrine are among two important inhibitors of Top2 enzymes used in cancer chemotherapy. In this study, we used computational methods to analysis interactions between these compounds and Top2-α in order to identify the most important residues involved in the enzyme inhibition. In order to obtain reliable results, several docking studies have been performed on the human Top2-β to reproduce binding modes which are observed in the crystal form of Top2-β complexed with Mitoxantrone and Amsacrine. Since human Top2-β is the closest homologue to Top2-α, same docking parameters have been used for docking of Top2-α with mentioned drugs. The data also showed that the main residues involved in the interaction between Top2-α and Mitoxantrone were Lys489, Asp504, Glu506, Gly488, Ile490 and Leu491. For Top2α-Amsacrine complex, the interaction was mainly through Arg487, Glu506, Gly488, Lys489, Asn504 and Ala505. These findings clarify the mechanisms of action for these drugs and may facilitate future drug development and cancer treatment.     

Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1−/− zebrafish

Mutations in PTEN‐induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1^Y431* mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function. In contrast, genetic inactivation of the voltage dependent anion channel 1 (VDAC1), located in the outer mitochondrial membrane, did not rescue dopaminergic neurons in PINK1 deficient D. rerio. Subsequent gene expression studies revealed specific upregulation of the mcu regulator micu1 in pink1^Y431* mutant zebrafish larvae and inactivation of micu1 also results in rescue of dopaminergic neurons. The functional consequences of PINK1 deficiency and modified MCU activity were confirmed using a dynamic in silico model of Ca²⁺ triggered mitochondrial activity. Our data suggest modulation of MCU‐mediated mitochondrial calcium homeostasis as a possible neuroprotective strategy in PINK1 mutant PD.     

Novel Combination of Mesenchymal Stem Cell-Conditioned Medium with Sorafenib Have Synergistic Antitumor Effect of Hepatocellular Carcinoma Cells

Objective: Hepatocellular carcinoma (HCC) is the most common liver malignancy. Sorafenib is the first-linesystemic treatment for advanced HCCs. However, due to safety concerns, researchers are now looking for ways to boostthe efficacy of the medication. One approach for reducing toxicity is combining sorafenib with other agents so that alower dose of sorafenib is required. Mesenchymal stromal cells (MSCs) can have an inhibitory effect on HCC tumorgrowth. Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) is the substance extracted from MSC culture andcontains most of the potential cytokines secreted by MSCs. We, therefore, anticipated a synergistic Antitumor Effectof sorafenib in Combination with MSC-CM. In this study, we used HepG2 as our target cell lines. Methods: HepG2cells were treated with sorafenib alone and with sorafenib + MSC-CM. CCK-8 assay was used to evaluate and comparethe inhibition of cell growth between the two groups with different treatments. Results: The combination treatment ofcell lines with sorafenib and MSC-CM had significantly reduced the values of IC50 compared to the use of sorafenibalone (3.4 vs. 2.7 respectively). Conclusion: This study suggests that a combination of sorafenib with MSC-CM cansynergistically suppress the growth of HCC cells.     

National Spinal Cord Injury Registry of Iran (NSCIR-IR) e a critical appraisal of itsstrengths and weaknesses

The National Spinal Cord Injury Registry of Iran (NSCIR-IR) is a not-for-profit, hospital-based, and pro spective observational registry that appraises the quality of care, long-term outcomes and the personal and psychological burden of traumatic spinal cord injury in Iran. Benchmarking validity in every registry includes rigorous attention to data quality. Data quality assurance is essential for any registry to make sure that correct patients are being enrolled and that the data being collected are valid. We reviewed strengths and weaknesses of the NSCIR-IR while considering the methodological guidelines and rec ommendations for efficient and rational governance of patient registries. In summary, the steering committee, funded and maintained by the Ministry of Health and Medical Education of Iran, the inter national collaborations, continued staff training, suitable data quality, and the ethical approval are considered to be the strengths of the registry, while limited human and financial resources, poor interoperability with other health systems, and time-consuming processes are among its main weaknesses.     

Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover

We have investigated the interaction between long circulating poly(ethylene glycol)-stabilized single-walled carbon nanotubes (SWNTs) and the complement system. Aminopoly(ethylene glycol)(5000)-distearoylphosphatidylethanolamine (aminoPEG(5000)-DSPE) and methoxyPEG(5000)-DSPE coated as-grown HIPco SWNTs activated complement in undiluted normal human serum as reflected in significant rises in C4d and SC5b-9 levels, but not the alternative pathway split-product Bb, thus indicating activation exclusively through C4 cleavage. Studies in C2-depleted serum confirmed that PEGylated nanotube-mediated elevation of SC5b-9 was C4b2a convertase-dependent. With the aid of monoclonal antibodies against C1s and human serum depleted from C1q, nanotube-mediated complement activation in C1q-depleted serum was also shown to be independent of classical pathway. Nanotube-mediated C4d elevation in C1q-depleted serum, however, was inhibited by N-acetylglucosamine, Futhan (a broad-spectrum serine protease inhibitor capable of preventing complement activation through all three pathways) and anti-MASP-2 antibodies; this strongly suggests a role for activation of MASP-2 in subsequent C4 cleavage and assembly of C4b2a covertases. Intravenous injection of PEGylated nanotubes in some rats was associated with a significant rise in plasma thromboxane B2 levels, indicative of in vivo nanotube-mediated complement activation. The clinical implications of these observations are discussed.     

Soft tissue anatomy around the hip and its implications for choice of entry point in antegrade femoral nailing

Antegrade intramedullary nailing is an accepted method of treatment for femoral shaft fractures. Entrance of the nail through the trochanteric fossa is currently recommended by some surgeons. This approach results in some cases, however, in loss of abduction strength and persistent pain. Nail insertion at the tip of the greater trochanter may be more favorable. In this study the anatomical relationships of the trochanteric fossa and of the tip of the greater trochanter were explored. Dissection was carried out in 10 fresh human cadaver femurs. The risks and safety of the two entry points with respect to the adjacent soft tissues were assessed. Abductor muscles and tendons, branches of the medial circumflex femoral artery and the hip joint capsule were at risk during nail insertion through the trochanteric fossa. These structures were not endangered during insertion through the trochanteric tip. The reported clinical morbidity after nailing through the trochanteric fossa may result from direct soft tissue injury and may be reduced by choosing the route through the greater trochanter.     

Technical considerations in the Verasonics research ultrasound platform for developing a photoacoustic imaging system

Photoacoustic imaging (PAI) is an emerging functional and molecular imaging technology that has attracted much attention in the past decade. Recently, many researchers have used the vantage system from Verasonics for simultaneous ultrasound (US) and photoacoustic (PA) imaging. This was the motivation to write on the details of US/PA imaging system implementation and characterization using Verasonics platform. We have discussed the experimental considerations for linear array based PAI due to its popularity, simple setup, and high potential for clinical translatability. Specifically, we describe the strategies of US/PA imaging system setup, signal generation, amplification, data processing and study the system performance.