The effect of some polymorphisms in vitamin D receptor gene in menopausal women with osteoporosis

Introduction: Vitamin D receptor gene is one of candidate genes related to osteoporosis expansion. The association of ApaI, TaqI, and BsmI polymorphisms in vitamin D receptor gene with bone metabolism and density has been already demonstrated. Aim: This study was conducted to investigate the association between the ApaI, TaqI and BsmI polymorphisms and bone density. This study was descriptive-analytical study. Centers for bone density measurement in southwestern Iran. Materials and Methods: In this descriptive-analytical study, 200 participants aged 45- and above 45-year-old women referring the centers of bone density measurement participated. The bone density of femoral neck and lumbar vertebrae was measured using dual-energy X-ray absorptiometry method. Based on t-score, the participants were assigned into patients (n=130) and healthy individuals (n=70). Different genotypes of ApaI (AA/Aa/aa), TaqI (TT/Tt/tt), and BsmI (BB/Bb/bb) were determined by PCR-RFLP. The data on bone density and PCR-RFLP were analysed by chi-square and ANOVA. Also, triad combination of the genotypes was statistically analysed. For each genotype combination, chi-square was run between the patients and control group and p-value was calculated. Results: No significant association was seen between ApaI polymorphism and bone density (p>0.05). TaqI and BsmI polymorphisms had a significant association with femoral neck’s bone density (p0.05). Patients with homozygous dominant TT genotype had the least bone density in femoral neck compared to other genotypes. Lumbar vertebrae’s bone density was similar in three TaqI genotypes. The patients with homozygous recessive bb genotype had the least bone density in femoral neck and lumbar vertebrae compared to other genotypes. Conclusion: TaqI and BsmI polymorphisms could be desirable markers in diagnosis of women at risk of osteoporosis in the studied region in Iran. Therefore, these women will receive suitable medical treatment at proper tim

Calcitonin receptor AluI (rs1801197) and TaqI calcitonin genes polymorphism in 45-and over 45-year-old women and their association with bone density

Purpose: Calcitonin receptor gene has also a polymorphism which is associated with bone mass density. This study evaluates the association between calcitonin receptor AluI (rs1801197) and Taq1 calcitonin genes polymorphism with bone density rate. Methods: In this descriptive-analytical study in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenol- chloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. Results: The genotypic distribution of polymorphism AluI for TT, TC, and CC genotypes in control group was 31.4%, 38.6%, and 30% and in patients 25.4%, 55.4%, and 19.2%, respectively. There was no significant difference in polymorphism AluI between patients and control group and no significant association was found between this gene and bone density rate (P > 0.05). All patients and the individuals in the control group exhibited tt genotype for TaqI calcitonin gene and no significant association was found between these participants and osteoporosis. Conclusion: There was no association between two polymorphisms and osteoporosis, and between polymorphism of these two genes and osteoporosis development rate in the participants. © 2016 Morteza Dehghan, Razieh Pourahmad-Jaktaji, and Zarghampoor Farzaneh

Investigation of the presence of G354A (Cys87Tyr) mutation in osteoprotegerin gene in women with osteoporosis in Chaharmahal and Bakhtiari province

Background and aims: Osteoprotegerin (OPG) is a competitive inhibitor of the differentiation and activity of osteoclasts, which inhibits the final stages of osteoclast formation and induces its apoptosis. In addition, OPG is considered as one of the most important candidate genes in the pathogenesis of bone diseases such as osteoporosis and idiopathic hyperphosphatasia. The G354A (Cys87Tyr) mutation in the OPG gene leads to idiopathic hyperphosphatasia. This mutation is probably related to osteoporosis. The purpose of this study was to investigate the presence of G354A (Cys87Tyr) in women with osteoporosis in Chaharmahal and Bakhtiari province. Methods: In this descriptive-analytical study, the bone mineral density (BMD) of the femoral neck and lumbar spine of women referring to Shahrekord bone densitometry centers was measured by the X-ray absorptiometry technique in 2013-2014. Based on T-scores, people with osteoporosis were identified and 70 patients were enrolled in the study after receiving their consent. Finally, DNA was extracted from blood samples, amplified by polymerase chain reaction (PCR) technique, and sequenced by DNA sequencing method. Results: After DNA extraction from the blood, the quality and quantity were determined by gel electrophoresis and spectrophotometry, respectively. Then, the gene was amplified by the PCR method and the product was detected by gel electrophoresis, followed by sequencing the samples to investigate the presence of the mutation. Eventually, genotypes associated with Cys87Tyr mutation were not observed in the studied population. Conclusion: In the present study, the G354A (Cys87Tyr) mutation associated with idiopathic hyperphosphatasia was not found in women with osteoporosis. Keywords: G354A mutation, OPG gene, Osteoporosi

Association of Taq1 restriction site of Calcitonine gene and Alu1 (rs1801197) polymorphism of Calcitonin receptor gene with bone mineral density in 200 women over 45 years in Shahrekord city

زمینه و هدف: پوکی استخوان، شایع ترین اختلال در متابولیسم مواد معدنی استخوان است. جایگاه برشی Taq1 در ژن کلسیتونین و پلی مورفیسم AluI در ژن گیرنده ی کلسیتونین به عنوان عوامل ژنتیکی می توانند در ارتباط با میزان تراکم استخوان باشند. هدف از این مطالعه تعیین ارتباط بین جایگاه برش Taq1 و پلی مورفیسم AluI با میزان تراکم استخوان بود. روش بررسی: در این مطالعه توصیفی- تحلیلی، 200 خانم بالای 45 سال مراجعه کننده به مراکز سنجش تراکم استخوان شهرکرد در سال‌های 92-1391 وارد شدند. تراکم استخوان گردن ران و مهره های کمر با استفاده از روش جذب سنجی اشعه X با انرژی دوگانه (DEXA) اندازه گیری و براساس ضریب تی (T- Score) به دو گروه بیمار یا دارای پوکی استخوان (130) و سالم یا شاهد) 70 نفر) تقسیم شدند. ژنوتیپ های مختلفTaq1 (TT/Tt/tt) و AluI (TT/TC/CC) با استفاده از روشPCR RFLP تعیین شدند. یافته ها: توزیع ژنوتیپی پلی مورفیسم AluI برای ژنوتیپ های TT، TC و CC در گروه شاهد به ترتیب 4/31، 7/35 و 9/32 و در گروه بیمار به ترتیب 54/31، 08/63 و 38/5 بود. در گروه شاهد و بیمار برای جایگاه برش Taq1 فقط ژنوتیپ tt مشاهده شد. نتیجه گیری: ارتباط معنی داری بین جایگاه برش Taq1 و پلی مورفیسم AluI با میزان تراکم استخوان وجود نداشت و احتمال دارد عوامل ژنتیکی دیگری بر روی تراکم استخوان تأثیرگذار باشند

Association of ApaI and Taq1 polymorphic site of vitamin D receptor gene with bone mineral density in women aged 45 years and older

زمینه و هدف: پوکی استخوان یک بیماری خاموش است که مسبب کاهش در استحکام و تراکم بافت استخوانی بوده و منجر به افزایش شکستگی استخوان‌ها می‌شود. اهمیت پلی‌مورفیسم‌های ApaI و TaqI ژن گیرنده ویتامین D (VDR) در متابولیسم و تراکم استخوان در نقاط دیگر جهان نشان داده شده است. هدف از این مطالعه بررسی ارتباط بین این پلی مورفیسم ها با میزان تراکم استخوان در زنان 45 سال و بالاتر در استان چهارمحال و بختیاری بود. روش بررسی: در این مطالعه توصیفی- تحلیلی، 200 خانم 45 سال و بالاتر مراجعه کننده به مراکز سنجش تراکم استخوان شهرکرد در سال های 92-1391 شرکت کردند. تراکم استخوان گردن ران و مهره های کمر با استفاده از روش DEXA اندازه گیری و براساس درجه T-Score آن ها به دو گروه بیمار (130) و سالم (70) تقسیم شدند. ژنوتیپ های مختلف (ApaI (AA/Aa/aa وTaq1 (TT/Tt/tt) با روش PCR RFLP تعیین و فراوانی آن ها در گروه بیمار محاسبه شد. یافته ها: بین پلی مورفیسم ApaI و میزان تراکم استخوان ارتباط معنی داری مشاهده نشد. پلی مورفیسم TaqI و میزان تراکم استخوان گردن ران ارتباط معنی داری داشت؛ ولی با تراکم استخوان مهره های کمری ارتباط معنی داری نداشت. بیماران دارای ژنوتیپ هموزیگوت غالب (TT) در مقایسه با ژنوتیپ های دیگر، کمترین میزان تراکم استخوان گردن ران را داشتند و میزان تراکم استخوان مهره‌های کمر در سه ژنوتیپ TaqI یکسان بود. نتیجه گیری: پلی مورفیسم TaqI ممکن است یک نشانگر خوب در تشخیص زنان مستعد پوکی استخوان در استان چهارمحال و بختیاری و حتی در ایران باشد. اگرچه باید جمعیت های دیگر و بزرگتری برای تأیید این نتایج مطالعه شوند

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Sp1 binding site polymorphism of a collagen gene (rs 1800012) in women aged 45 and over and its association with bone density

Background/aim: Sp1 polymorphism of type I collagen genes is accompanied with bone collagen disorders and severe clinical phenotypes such as osteogenesis imperfecta. The aim of this study was to study the association between COLIA1 Sp1 polymorphism and bone density rate. Materials and methods: In this descriptive, analytical study conducted in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenolchloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. Results: The genotype distribution of Sp1 polymorphism for the SS, Ss, and ss genotypes was 57.1%, 31.4%, and 11.4%, respectively, in the control group and 9.2%, 75.4%, and 15.4%, respectively, in the patients. Statistically, Sp1 polymorphism in patients had a significant deviation (P = 0.001, chi(2) = 34.25) and there was no Hardy-Weinberg equilibrium. In the control group, there was no significant deviation for Sp1 polymorphism (P = 0.226, chi(2) = 2.97). Sp1 polymorphism was significantly associated with bone density. Women with the SS genotype had the highest bone density. Conclusion: Sp1 gene polymorphism is associated with bone density rate in women aged 45 and over, and is more commonly observed in homozygosity. Determining this genotype's polymorphism is valuable to identify the women at risk of developing osteoporosis

The Combination of Zerumbone and 5-FU: A Significant Therapeutic Strategy in Sensitizing Colorectal Cancer Cells to Treatment

Objectives. Chemotherapy is considered to be essential in the treatment of patients with colorectal cancer (CRC), but drug resistance reduces its efficacy. Many patients with advanced CRC eventually show resistance to 5-fluorouracil (5-FU) therapy. Synergistic and potentiating effects of combination therapy, using herbal and chemical drugs, can improve patients’ response. Zerumbone (ZER), which is derived from ginger, has been studied for its growth inhibitory function in various types of cancer. Methods. The cytotoxic effects of ZER and 5-FU alone and their combination, on the SW48 and HCT-116 cells, were examined, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The mRNA and protein levels of β-catenin, survivin, and vimentin were measured in treated CRC cells, using qRT-PCR and western blot. Colony formation assay, scratch test, and flow cytometry were performed to detect the changes of proliferation, migration, and apoptosis. Key Findings. In HCT-116- and SW48-treated cells, the proliferation, the gene and protein expression levels of the markers, the migration, the colony formation, and the survival rates were all significantly reduced compared to the control groups, and the sharpest decline was observed in the 5-FU+ZER treatment groups. Conclusions. Combination therapy has shown promising results in CRC cells, especially in drug-resistant cells

Intra-rater reliability of sonographic measurement of the supraspinatus muscle thickness in Empty can, Full can and Hug up tests

Background: Sonography is used for measuring the muscle morphology including length, depth, cross-sectional area, bulk and pennation angle. The supraspinatus is the most common affected muscle among the rotator cuff muscles. There is no study about the reliability of sonographic measurement of supraspinatus thickness in the positions of empty can (EC), full can (FC) and hug up (HU) tests. The present study aims to investigate the intra-rater reliability of the measurement of sonographic thickness of supraspinatus muscle in the rest and positions of the EC, FC and HU tests. Methods: The present study was a descriptive-analytic study which was carried out in a cross-sectional method on ten healthy women aged: 22.10±2.76 years without any tendon pathology. The study was carried out during four weeks (January to March in 2017). The supraspinatus thickness was scanned during rest and contracted states. The positions of measuring ultrasonic thickness of supraspinatus were as follow: position of EC test: the arm in 90-degree elevation in the scaption plane with the thumb-down, position of FC test: the arm in 90-degree elevation in the scaption plane with the thumb-up, position of HU test: the palm of hand was placed on the opposite shoulder with the elbow flexed using a 0.5-kg weight cuff. Intra-rater reliability of ultrasonic muscle thickness measurements were examined in one day. Results: All intra-rater reliability values were equal or more than 0.90: the value was 0.90 (95%CI: 0.65-0.97) in the rest position, while for the measurement of ultrasonic thickness of the supraspinatus was 0.96 (95%CI: 0.87-0.99) in the position of EC test, 0.97 (95%CI: 0.90-0.99) and 0.96 (95%CI: 0.86-0.99) in the positions of FC and HU tests, respectively. Conclusion: Measurement of ultrasonic thickness of supraspinatus muscle is a reliable method in the rest and positions of EC, FC and HU tests. This method can be used to compare the muscle thickness changes in the positions of the above tests. &nbsp