Lymphomas in Golestan province of Iran: Results of a population-based cancer registry

Introduction: Malignancies of lymphoid cells can be divided into Hodgkin and non-Hodgkin lymphomas (NHL) on the basis of pathologic features, clinical manifestations and treatment. In this paper we present data on lymphomas in Golestan province, in the northeast of Iran, during 2004-2006, using three years results of the Golestan population-based cancer registry (GPCR), a voting member of the International Association of Cancer Registries (IACR). Methods: GPCR started collecting data on all cancers from all public and private diagnostic and therapeutic centers (hospitals, specialist physicians' offices, pathology, laboratory, and imaging centers) of Golestan province in 2004. Here, we used the Iranian national census data to identify the population characteristics of this geographical area. The last census was done in 2006 and the next one will be done in 2011. The population data for years between the national census intervals are retrieved from provincial census done annually by health deputy of Golestan University of Medical Sciences (GOUMS). Results: A total of 5,076 cancer cases were diagnosed in the GPCR between 2004 and 2006. Of these, 237 (4.67 %) were lymphomas, among the ten top cancers of this area, the patients having a mean (±SD) age of 45.2 (±20.9) years. The number of cases, frequency, age specific rates, crude rates and age standardized incidence rates (ASR) (per 100,000 personyears) for lymphomas in males and females are presented. Conclusion: It could be concluded that according to available therapies for HL and NHL, the outcome of the patients could be improved in this area, due to the better diagnostic and therapeutic methods now available

Cancer incidence in Golestan province: Report of an ongoing population-based cancer registry in Iran between 2004 and 2008

Background: Golestan Province, at the western end of the Asian esophageal cancer (EC) belt in northeastern Iran, was reported to have one of the highest worldwide rates of EC in the 1970s. We have previously shown a declining incidence of EC in Golestan during the last decades. This study reports additional new results from the Golestan Population-based Cancer Registry (GPCR). Methods: The GPCR collected data from newly diagnosed (incident) cancer cases from all 68 public and private diagnostic and therapeutic centers in Golestan Province. CanReg-4 software was used for data entry and analysis based on the guidelines of the International Agency for Research on Cancer (IARC). Age-standardized incidence rates (ASR) of cancers were calculated using the 2000 world standard population. Results: From 2004 through 2008, 9007 new cancer cases were reported to the GPCR. The mean (SD) age was 55.5 (18.6) years, and 54 were diagnosed in men. The ASRs of all cancers were 175.3 and 141.1 per 100,000 person-years for males and females, respectively. Cancers of the stomach (ASR:30.7), esophagus (24.3), and lung (15.4) were the most common cancers in males. In females, breast cancer (ASR:26.9) was followed by malignancies of the esophagus (19.1) and stomach (12.4). The diagnosis of cancer was based on histopatho- logical reports in 71 and on death certificate only in 9 ofcases. Conclusions: The EC incidence rate continues to decline in Golestan, while the incidence rates of stomach, colorectal, and breast cancers continue to increase

Consanguineous marriage, prepregnancy maternal characteristics and stillbirth risk: A population-based case-control study

Introduction. Consanguineous marriage is associated with increased risks for congenital anomalies, low birthweight, and other adverse perinatal outcomes. In this population-based, case-control study we investigated the association between consanguineous marriage (first-cousin marriage) and stillbirth risk, using prospectively collected information from prepregnancy visits. Material and methods. From 2007 to 2009, we identified 283 stillbirths (cases) and 2088 randomly selected live control births through prepregnancy visits in rural Golestan, Iran. The associations between consanguinity and prepregnancy maternal characteristics and stillbirth risk were examined using multivariate logistic regression. Results. The rate of consanguineous marriage was 19.4% among cases and 13.6% among controls. Consanguinity was associated with increased stillbirth risk [odds ratio (OR) 1.53; 95% CI 1.10-2.14]. The association was significantly increased for preterm stillbirth (< 37 gestational weeks) (OR 2.43; 95% CI 1.46-4.04) but not for term stillbirth (≥ 37 weeks) (OR 1.14; 95% CI 0.75-1.74). Low and high maternal age, underweight, obesity, nulliparity, a history of infertility or miscarriage, previous obstetric complications (preeclampsia, preterm delivery, and stillbirth in previous pregnancies) were also associated with increased stillbirth risks. Conclusions. Consanguineous marriage is associated with increased risk of stillbirth, particularly preterm stillbirth. Findings for other maternal risk factors for stillbirth in rural Iran are consistent with previously reported findings from high-income countries. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology

Modeling and predicting drug pharmacokinetics in patients with renal impairment

Current guidance issued by the US FDA to assess the impact of renal impairment on the pharmacokinetics of a drug under development has recently been updated to include evaluation of drugs with nonrenal elimination routes. Renal impairment not only affects elimination of the drug in the kidney, but also the nonrenal route of drugs that are extensively metabolized in the liver. Renal failure may influence hepatic drug metabolism either by inducing or suppressing hepatic enzymes, or by its effects on other variables such as protein binding, hepatic blood flow and accumulation of metabolites. Prior simulation of the potential exposure of individuals with renal impairment may help in the selection of a safe and effective dosage regimen. In this article, we discuss the application of a systems biology approach to simulate drug disposition in subjects with renal impairment. © 2011 Expert Reviews Ltd

Correlation of invalidation with symptom severity and health status in fibromyalgia

Objective. Invalidation is a new construct in health psychology, especially in diseases with inherently invisible symptoms such as FM. It can potentially affect both the quality of life and disease severity in patients with FM. This study aimed to investigate the correlation of illness invalidation with health status and symptom severity in FM. Methods. A total of 112 consecutive patients with FM referred to the rheumatology clinic were enrolled. Invalidation was measured by the Illness Invalidation Inventory (3*I). To measure patient status and progress of FM, the Revised Fibromyalgia Impact Questionnaire (FIQR) was used and patients' quality of life was assessed by the 12-item Short Form Health Survey (SF-12). Multiple linear regression analyses were performed and Spearman's correlations were calculated. Results. All the patients were female and aged between 18 and 61 years. No significant differences in discounting and lack of understanding between various sources of invalidation were found. The strongest correlation was observed between FIQR symptom score and discounting by work (r = 0.519, P < 0.05). Multiple linear regression analyses revealed that only discounting from the spouse significantly predicted FIQR total scores of FM patients P = 0.03 (CI 0.28, 10.64). Conclusion. Discounting correlated more strongly with SF-12 subscales and FIQR domains than did lack of understanding. The current study revealed that active negative social responses and the source of invalidation are important in predicting symptom severity and quality of life in FM. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved

Impact of Baseline Magnetic Resonance Imaging on Neurologic, Functional, and Safety Outcomes in Patients With Acute Traumatic Spinal Cord Injury

Study Design: Systematic review. Objective: To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI). Methods: An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI. Results: The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved outcomes; however, the quality of evidence was deemed very low due to selection bias. Seven studies reported MRI predictors of neurologic or functional outcomes. There was moderate-quality evidence that longer intramedullary hemorrhage (2 studies) and low-quality evidence that smaller spinal canal diameter at the location of maximal spinal cord compression and the presence of cord swelling are associated with poor neurologic recovery. There was moderate-quality evidence that clinical outcomes are not predicted by SCI lesion length and the presence of cord edema. Conclusions: Certain MRI characteristics appear to be predictive of outcomes in acute SCI, including length of intramedullary hemorrhage (moderate-quality evidence), canal diameter at maximal spinal cord compression (low-quality evidence), and spinal cord swelling (low-quality evidence). Other imaging features were either inconsistently (presence of hemorrhage, maximal canal compromise, and edema length) or not associated with outcomes. The paucity of literature highlights the need for well-designed prospective studies. © 2017, © The Author(s) 2017

Sulfonylurea Receptor 1, Transient Receptor Potential Cation Channel Subfamily M Member 4, and KIR6.2:Role in Hemorrhagic Progression of Contusion

Altres ajuts: J.M.S is supported by grants from the Department of Veterans Affairs (I01BX002889), the Department of Defense (SCI170199), the National Heart, Lung and Blood Institute (R01HL082517) and the National Institute of Neurological Disorders and Stroke (NINDS) (R01NS060801; R01NS102589; R01NS105633); V.G. is supported by a grant from NINDS (NS061934).In severe traumatic brain injury (TBI), contusions often are worsened by contusion expansion or hemorrhagic progression of contusion (HPC), which may double the original contusion volume and worsen outcome. In humans and rodents with contusion-TBI, sulfonylurea receptor 1 (SUR1) is upregulated in microvessels and astrocytes, and in rodent models, blockade of SUR1 with glibenclamide reduces HPC. SUR1 does not function by itself, but must co-assemble with either KIR6.2 or transient receptor potential cation channel subfamily M member 4 (TRPM4) to form K (SUR1-KIR6.2) or SUR1-TRPM4 channels, with the two having opposite effects on membrane potential. Both KIR6.2 and TRPM4 are reportedly upregulated in TBI, especially in astrocytes, but the identity and function of SUR1-regulated channels post-TBI is unknown. Here, we analyzed human and rat brain tissues after contusion-TBI to characterize SUR1, TRPM4, and KIR6.2 expression, and in the rat model, to examine the effects on HPC of inhibiting expression of the three subunits using intravenous antisense oligodeoxynucleotides (AS-ODN). Glial fibrillary acidic protein (GFAP) immunoreactivity was used to operationally define core versus penumbral tissues. In humans and rats, GFAP-negative core tissues contained microvessels that expressed SUR1 and TRPM4, whereas GFAP-positive penumbral tissues contained astrocytes that expressed all three subunits. Förster resonance energy transfer imaging demonstrated SUR1-TRPM4 heteromers in endothelium, and SUR1-TRPM4 and SUR1-KIR6.2 heteromers in astrocytes. In rats, glibenclamide as well as AS-ODN targeting SUR1 and TRPM4, but not KIR6.2, reduced HPC at 24 h post-TBI. Our findings demonstrate upregulation of SUR1-TRPM4 and K after contusion-TBI, identify SUR1-TRPM4 as the primary molecular mechanism that accounts for HPC, and indicate that SUR1-TRPM4 is a crucial target of glibenclamide

Serum vitamin D status in Iranian fibromyalgia patients: According to the symptom severity and illness invalidation

Background: This study was designed to assess serum vitamin D status (25-OHD) in the fibromyalgia (FM) patients and to compare it with a healthy control group. It also aimed to investigate the correlation of serum vitamin D level with FM symptom severity and invalidation experiences. Methods: A total of 74 consecutive patients with FM and 68 healthy control participants were enrolled. The eligible FM patients completed the Illness Invalidation Inventory (3*I), the Revised Fibromyalgia Impact Questionnaire (FIQR) and a short-form health survey (SF-12). Venous blood samples were drawn from all participants to evaluate serum 25-OHD levels. Mann-Whitney tests and multiple logistic regression analyses were performed and Spearman's correlations were calculated. Results: 88.4 of FM patients had low levels of serum 25-OHD. FM patients had significantly higher level of serum 25-OHD than the control group (17.24 ± 13.50 and 9.91 ± 6.47 respectively, P = 0.0001). There were no significant correlations between serum 25-OHD levels and the clinical measures of disease impact, invalidation dimensions, and health status. Multiple logistic regression analyses revealed that an increased discounting of the disease by the patient's spouse was associated with a 4-fold increased risk for vitamin D deficiency (OR = 4.36; 95 CI, 0.95-19.87, P = 0.05). Conclusions: This study showed that although high rates of vitamin D insufficiency or deficiency were seen among FM patients and healthy non-FM participants, but it seems there was no intrinsic association between FM and vitamin D deficiency. Addressing of invalidation experience especially by the patient's spouse is important in management of FM. © The Korean Pain Society, 2016

The Sub-axial Cervical Spine Injury Classification System (SLIC): A Novel Approach to Recognize The Importance of Morphology, Neurology and Integrity of the Disco-ligamentous complex

Abstract Background Context Despite technological advances in spine surgery, classification of sub-axial cervical spine injuries remains largely descriptive, lacking standardization and any relationship to prognosis or clinical decision making. Purpose The primary purpose of this paper is to define a classification system for sub-axial cervical spine trauma that conveys information about injury pattern and severity as well as treatment considerations and prognosis. The proposed system is designed to be both comprehensive and easy to use. The secondary objective is to evaluate the classification system in the basic principles of classification construction, namely reliability and validity. Study Design/Setting Derivation of the classification was from a synthesis of the best cervical classification parameters gleaned from an exhaustive literature review and expert opinion of experienced spine surgeons. Multi-center reliability and validity study of a cervical classification system using previously collected CT, MRI, and plain film x-ray images of sub-axial cervical trauma. Methods Important clinical and radiographic variables encountered in sub-axial cervical trauma were identified by a working section of the Spine Trauma Study Group (STSG). Significant limitations of existing injury classification systems were defined and addressed within the new system. It was then introduced to the STSG and applied to 11 cervical trauma cases selected to represent a spectrum of subaxial injury. Six weeks later, the cases were randomly re-ordered and again scored using the novel classification system. Twenty surgeons completed both intervals. Inter-rater and intra-rater reliability and several forms of validity were assessed. For comparison, the reliability of both the Harris and the Ferguson & Allen systems were also evaluated. Results Each of three main categories (injury morphology; disco-ligamentous complex integrity; and neurological status) identified as integrally important to injury description, treatment, and prognosis was assigned an ordinal score range, weighted according to its perceived contribution to overall injury severity. A composite injury severity score was modeled by summing the scores from all three categories. Treatment options were assigned based upon threshold values of the severity score. Inter-rater agreement as assessed by ICC of the DLC, Morphology, and Neurological Status scores was 0.49, 0.57, and 0.87, respectively. Intra-rater agreement as assessed by ICC of the DLC, Morphology, and Neurological Status scores was 0.66, 0.75, and 0.90, respectively. Raters agreed with treatment recommendations of the algorithm in 93.3 % of cases, suggesting high construct validity. The reliability if the SLIC treatment algorithm compared favorably to the earlier classification systems of Harris and Ferguson & Allen. Conclusions The Sub-axial Injury Classification (SLIC) and Severity Scale provides a comprehensive classification system for sub-axial cervical trauma, incorporating pertinent characteristics for generating prognoses and courses of management. Early data on validity and reliability are encouraging. Further testing is necessary before introducing the SLIC score into clinical practice

The Testicular and Epididymal Expression Profile of PLCζ in Mouse and Human Does Not Support Its Role as a Sperm-Borne Oocyte Activating Factor

Phospholipase C zeta (PLCζ) is a candidate sperm-borne oocyte activating factor (SOAF) which has recently received attention as a potential biomarker of human male infertility. However, important SOAF attributes of PLCζ, including its developmental expression in mammalian spermiogenesis, its compartmentalization in sperm head perinuclear theca (PT) and its release into the ooplasm during fertilization have not been established and are addressed in this investigation. Different detergent extractions of sperm and head/tail fractions were compared for the presence of PLCζ by immunoblotting. In both human and mouse, the active isoform of PLCζ was detected in sperm fractions other than PT, where SOAF is expected to reside. Developmentally, PLCζ was incorporated as part of the acrosome during the Golgi phase of human and mouse spermiogenesis while diminishing gradually in the acrosome of elongated spermatids. Immunofluorescence localized PLCζ over the surface of the postacrosomal region of mouse and bull and head region of human spermatozoa leading us to examine its secretion in the epididymis. While previously thought to have strictly a testicular expression, PLCζ was found to be expressed and secreted by the epididymal epithelial cells explaining its presence on the sperm head surface. In vitro fertilization (IVF) revealed that PLCζ is no longer detectable after the acrosome reaction occurs on the surface of the zona pellucida and thus is not incorporated into the oocyte cytoplasm for activation. In summary, we show for the first time that PLCζ is compartmentalized as part of the acrosome early in human and mouse spermiogenesis and is secreted during sperm maturation in the epididymis. Most importantly, no evidence was found that PLCζ is incorporated into the detergent-resistant perinuclear theca fraction where SOAF resides