Subcutaneous granulocyte colony-stimulating factor administration for subacute traumatic spinal cord injuries, report of neurological and functional outcomes: A double-blind randomized controlled clinical trial

OBJECTIVE Granulocyte-colony stimulating factor (G-CSF) is a major cytokine that has already been clinically verified for chronic traumatic spinal cord injuries (TSCIs). In this study, the authors set out to determine the safety and efficacy of G-CSF administration for neurological and functional improvement in subacute, incomplete TSCI. METHODS This phase II/III, prospective, double-blind, placebo-controlled, parallel randomized clinical trial was performed in 60 eligible patients (30 treatment, 30 placebo). Patients with incomplete subacute TSCIs with American Spinal Injury Association Impairment Scale (AIS) grades B, C, and D were enrolled. Patients were assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, Spinal Cord Independence Measure (SCIM-III) and International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), just before intervention and at 1, 3, and 6 months, after 7 daily subcutaneous administrations of 300 μg/ day of G-CSF in the treatment group and placebo in the control group. RESULTS Among 60 participants, 28 patients (93.3) in the G-CSF group and 26 patients (86.6) in the placebo group completed the study protocol. After 6 months of follow-up, the AIS grade remained unchanged in the placebo group, while in the G-CSF group 5 patients (45.5) improved from AIS grade B to C, 5 (45.5) improved from AIS grade C to grade D, and 1 patient (16.7) improved from AIS grade D to E. The mean ± SEM change in ISNCSCI motor score in the G-CSF group was 14.9 ± 2.6 points, which was significantly greater than in the placebo group (1.4 ± 0.34 points, p < 0.001). The mean ± SEM light-touch and pinprick sensory scores improved by 8.8 ± 1.9 and 10.7 ± 2.6 points in the G-CSF group, while those in the placebo group improved by 2.5 ± 0.60 and 1.2 ± 0.40 points, (p = 0.005 and 0.002, respectively). Evaluation of functional improvement according to the IANR-SCIFRS instrument revealed significantly more functional improvement in the G-CSF group (10.3 ± 1.3 points than in the placebo group (3.0 ± 0.81 points; p < 0.001). A significant difference was also observed between the 2 groups as measured by the SCIM-III instrument (29.6 ± 4.1 vs 10.3 ± 2.2, p < 0.001). CONCLUSIONS Incomplete subacute TSCI is associated with significant motor, sensory, and functional improvement after administration of G-CSF. ©AANS 2019

Safety and efficacy of PDpoetin for management of anemia in patients with end stage renal disease on maintenance hemodialysis: Results from a phase IV clinical trial

Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7 of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49 of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis. © A.N. Javidan et al., 2014

Association of P1635 and P1655 polymorphisms in dysbindin (DTNBP1) gene with schizophrenia

Alizadeh F, Tabatabaiefar MA, Ghadiri M, Yekaninejad MS, Jalilian N, Noori-Daloii MR. Association of P1635 and P1655 polymorphisms in dysbindin (DTNBP1) gene with schizophrenia. Objectives: Schizophrenia (SCZ) is a severe psychiatric disorder with a lifetime prevalence of approximately 1 in most of the populations studied. SCZ is multifactorial with the contribution of multiple susceptibility genes that could act in conjunction with epigenetic processes and environmental factors. There is some evidence supporting the association between genetic variants in dysbindin (DTNBP1) gene and SCZ in populations. In this study, we investigated the association between polymorphisms P1635 and P1655 in dysbindin gene with SCZ. Methods: Totally, 115 unrelated patients with SCZ and 117 unrelated healthy volunteers were studied. Genomic DNA was extracted from blood. Genotyping was done with the PCR-RFLP method. The allele and genotype associations were analysed with �2 test. The Benjamini-Hochberg procedure was used to correct p values for multiple comparisons. Results: The results showed no significant difference between patients and controls in allelic frequencies or genotypic distributions of SNP P1635 (p = 0.809), but a significant difference between the case and control groups for SNP P1655 (p = 0.009) was found. We could also find a significant positive association between A-C haplotype and SCZ (OR = 1.7, 95 CI 1.18-2.42; p = 0.004, pc = 0.02) and a protective effect for A-G haplotype (p = 0.003, OR = 0.57, 95 CI 1.18-2.42; p = 0.003, pc = 0.02). Conclusion: This study may provide further support for the association between SNP polymorphisms in DTNBP1 and SCZ in the Iranian population. Studies with more markers and subjects for various populations will be necessary to understand the genetic contribution of the gene to the development of SCZ. © 2011 John Wiley &amp; Sons A/S

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOSRPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P 0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept. © 2020 Public Library of Science. All rights reserved

Early parity epigenetic footprint of FOXA1 gene body in normal breast tissue of Iranian women

Background: Young age at first full-term pregnancy (FFTP) is an important factor in breast cancer risk reduction. It is postulated that this protective effect is the result of stable molecular signatures imprinted by physiological process of pregnancy, but the molecular mechanism of this protective role is unclear. The aim of the current study was to identify the effect of early FFTP on methylation status of FOXA1 gene body. FOXA1 is an essential transcription factor for mammary gland development and estrogen responsiveness of breast tissue. Methods: Fresh frozen normal breast tissues (n = 51) were collected from Iranian women who underwent cosmetic mammoplasty (27 nulliparous women and 24 parous women who have experienced first pregnancy before the age of 25). DNA was extracted and then methylated DNA immunoprecipitation (MeDIP) real-time PCR was used to assess FOXA1 gene body methylation. Results: Our results revealed that FOXA1 methylation level is significantly higher in early parous compared with nulliparous group (p = 0.041). Conclusion: Our study provides new hint about the association between early FFTP and epigenetic modifications within gene body of FOXA1 in normal breast tissue. More investigation is required for clarifying molecular mechanisms underlying this association in order to develop breast cancer prevention strategies. © 2019, Pasteur Institute of Iran. All rights reserved

Corrigendum to �Reliability of digital photography for assessing lower extremity alignment in individuals with flatfeet and normal feet types� J. Bodyw. Mov. Ther. 21 (2017) 704�710(S1360859216302790)(10.1016/j.jbmt.2016.12.006)

The authors regret that affiliation b was incorrect in the published paper �Reliability of digital photography for assessing lower extremity alignment in individuals with flatfeet and normal feet types� Journal of Bodywork &amp; Movement Therapies 21 (2017) 704�710. This affiliation is correct above. The authors would like to apologize for any inconvenience caused. © 201

Health-care access and utilization among individuals with low back pain in Iran: a WHO-ILAR COPCORD study

Background: Low back pain (LBP) is a major contributor to chronic pain and disability. The purpose of this study was to evaluate health-care access and utilization among patients with LBP in Iran. We also sought to study the pattern and characteristics of care-utilization behavior in these patients. Methods: Data from the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) were used for this study. Three cities (Zahedan, Sanandaj, Yazd) were selected to represent the Iranian population, with different socioeconomic status and ethnic, cultural, and religious background. Demographic data, acute or chronic LBP, disability index, and utilizing care from conventional medicine (CM), allied health providers (AHP), and complementary and alternative medicine (CAM) providers were recorded. Results: Of 9101 patients, 38.6 reported LBP. Only 3.3 did not utilize care of any kind, 66.7 referred to CM providers, 20.8 to AHP, and 9.2 to CAM care. Health-care utilization was higher in female patients, older age, higher education, and higher disability index. Conclusions: The findings of this study indicate a high rate of health-care utilization among patients with LBP in Iran. CM is the most prevalent health-care resource sought by patients. These findings could be used as a framework in developing more efficient health-care programs according to the needs of specific populations. © 2020 The Author(s)

Granulocyte-colony stimulating factor administration for neurological improvement in patients with postrehabilitation chronic incomplete traumatic spinal cord injuries: A double-blind randomized controlled clinical trial

OBJECTIVE Granulocyte-colony stimulating factor (G-CSF) is a major growth factor for activation and differentiation of granulocyte colonies in the bone marrow. This cytokine has been widely and safely employed in different conditions over many years. The purpose of this study was to investigate the efficacy of G-CSF administration for traumatic spinal cord injury (TSCI). METHODS This double-blind parallel randomized, placebo-controlled, clinical trial, a phase III study, was performed from June 2013 to June 2016 in the Brain and Spinal Cord Injury Research (BASIR) center at Tehran University of Medical Sciences (TUMS). It included 120 patients with incomplete chronic TSCI, American Spinal Injury Association (ASIA) Impairment Scale (AIS) B, C, or D, of at least 6 months� duration. Sixty patients were allocated into the treatment group and 60 patients into the control group. All the patients had completed an outpatient rehabilitation program in the post-acute period and were in a neurological and functional plateau. Patients were assessed with the ASIA grading system, the Spinal Cord Independence Measure (SCIM-III), and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) just before intervention and at 1, 3, and 6 months after 7 subcutaneous administrations of 300 μg/day of G-CSF in the treatment group and placebo in the control group (administered once per day over the course of 1 week). Randomization was performed with randomized block design, and the patients and evaluators were blinded regarding the treatment groups. One patient did not receive the entire allocated intervention and 5 patients were lost to follow-up. Thus data from 114 patients were included in the analysis. RESULTS One hundred twenty patients were randomized and allocated into the study groups. Among them, 56 patients (93.3) in the G-CSF group and 58 patients (96.6) in the placebo group completed the study protocol. After 6 months of follow-up, AIS in the placebo group remained unchanged, whereas in the G-CSF group, 1 patient improved from AIS B to C, and 4 patients improved from AIS C to D. The mean (± SE) improvement in ASIA motor score in the G-CSF group was 5.5 ± 0.62, which was significantly more than in the placebo group (0.77 ± 0.20) (p < 0.001). The mean light touch and pinprick sensory scores, respectively, increased by 6.1 ± 1.1 and 8.7 ± 1.5 in the G-CSF group and by 1.3 ± 0.52 and 0.89 ± 0.44 scores in the placebo group (p < 0.001). Evaluation of functional improvement by the IANR-SCIFRS instrument revealed significantly more improvement in the G-CSF group (3.5 ± 0.37) than in the placebo group (0.41 ± 0.12) (p < 0.001). Also, a significant difference was observed in functional improvement between the 2 groups as measured by SCIM-III instrument (7.5 ± 0.95 vs 2.1 ± 0.51, p < 0.001). CONCLUSIONS Administration of G-CSF for incomplete chronic spinal cord injuries is associated with significant motor, sensory, and functional improvement. © AANS 2018