Association of PICK1 and BDNF variations with increased risk of methamphetamine dependence among Iranian population : a case–control study

Funding Information: This study was financially supported by the Mashhad University of Medical Sciences (Grant Number: 931681).Peer reviewedPublisher PD

Association of rs4784227-CASC16 (LOC643714 locus) and rs4782447-ACSF3 polymorphisms and their association with breast cancer risk among Iranian population

TOX3 and FOXA1 proteins are believed to be involved in the susceptibility of breast cancer. rs4782447 and rs4784227, as single nucleotide polymorphisms (SNPs), located at the 16q may affect the FOXA1 DNA binding sequence change and therefore may enhance the FOXA1-binding affinity to the promoter of TOX3 gene. This study aimed to investigate the association of these SNPs/haplotypes with breast cancer susceptibility in Iranian population. We conducted a case-control study of 1072 blood samples (505 breast cancer patients and 567 controls). Genotyping of rs4784227 and rs4782447 SNPs was carried out by ARMS PCR. Moreover, statistical analysis was done by SPSS 20.0 (IBM Inc., Chicago, IL, USA) and SNP analyser 2.0. There was a strongly significant statistical association between alleles and genotypes of rs4784227 with breast cancer susceptibility in a group of Iranian women (p<0.05). Moreover, a significant association was demonstrated between TA haplotype and breast cancer risk (OR=0.78; 95% CI (0.62-0.96); P-value=0.025). In this respect, although we did not observe a statistically significant association between rs4782447 with breast cancer susceptibility, the combination of the alleles of rs4784227 and rs4782447 SNPs may also affect the risk. This is in line with other studies where they suggest these SNPs as risk-associated polymorphisms by which lead to disruption of as a distal enhancer, FOXA1, binding and following that change in TOX3 expression that can eventually affect the risk of breast cancer

A method for improving the efficiency of DNA extraction from clotted blood samples

Funding information: This study was supported by a grant from the Research Council of the Mashhad University of Medical Sciences (Grant No: 931680). The authors would like to thank Dr. Hossein Eshghi at Department of Chemistry, Faculty of Science, the Ferdowsi University of Mashhad for his assistance in the experiment and Mohammad Sadegh Khorami who contributed to this study. We are also particularly grateful to the Research Council of the Mashhad University of Medical Sciences (MUMS) for the financial support of this studyPeer reviewedPublisher PD

Age-related Variation in Expression of Breast Cancer Tumour Markers in Iranian Patients

Background: There are believed to be several risk factors affecting the prognosis of breast cancer through their effect on the growth rate of tumour. In the present study, we investigated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and tumor protein P53 (TP53) as well-known biomarkers, particularly in breast cancer prognosis, associated with age. Method: In a case-control study, 406 breast cancer patients were considered retrospectively. In order to extract the clinical and pathologic data, we employed the patients’ records. The extracted information was compared between two groups: for patients under 40 (group I) and above 40 years of age (group II). Herein, the researchers performed statistical analysis using SPSS Ver16. Results: The most prevalent type of cancer in both groups was found to be invasive ductal carcinoma. The major method of treatment was modified radical mastectomy. According to our observations, grade 3 breast cancer was more common in group I. Lymph node involvement significantly increased in group I, while oestrogen and progesterone receptor expressions were less in this group. HER2, TP53, and Ki-67 oncogenes were overexpressed in group I compared with group II. Conclusion: Expression of HER2, TP53, and Ki-67 biomarkers and a reduction in the number of hormonal receptors in younger patients (<40YO) indicated that breast cancer might be more invasive in younger women with breast cancer and therefore, they might have poorer prognosis and less favourable outcomes

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

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

Understanding the prion-like behavior of mutant p53 proteins in triple-negative breast cancer pathogenesis: The current therapeutic strategies and future directions

Breast cancer (BC) is viewed as a significant public health issue and is the primary cause of cancer-related deaths among women worldwide. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype that predominantly affects young premenopausal women. The tumor suppressor p53 playsa vital role in the cellular response to DNA damage, and its loss or mutations are commonly present in many cancers, including BC. Recent evidence suggests that mutant p53 proteins can aggregate and form prion-like structures, which may contribute to the pathogenesis of different types of malignancies, such as BC. This review provides an overview of BC molecular subtypes, the epidemiology of TNBC, and the role of p53 in BC development. We also discuss the potential implications of prion-like aggregation in BC and highlight future research directions. Moreover, a comprehensive analysis of the current therapeutic approaches targeting p53 aggregates in BC treatment is presented. Strategies including small molecules, chaperone inhibitors, immunotherapy, CRISPR-Cas9, and siRNA are discussed, along with their potential benefits and drawbacks. The use of these approaches to inhibit p53 aggregation and degradation represents a promising target for cancer therapy. Future investigations into the efficacy of these approaches against various p53 mutations or binding to non-p53 proteins should be conducted to develop more effective and personalized therapies for BC treatment

PCR detection of leptospira in stray cats, probable reservoir

Leptospirosis is an important spirochetal disease in terms of public health worldwide. Numerous wild and domestic animal species are major reservoirs of Leptospira, and sources of infection for humans. Transmission to humans occurs by direct contact with infected animals, or by contact with soil or water contaminated with the urine of an infected animal, generally asymptomatic. The objective of this study was to determine the frequency of Leptospira by PCR in stray cats in Isfahan province, Iran. Amplicons of 793 bp were detected in the blood (buffy coat) of 28 out of the 132 stray cats examined (21.2%), as all of them showed no clinical signs of leptospirosis. Stray cats seem to constitute a non-negligible reservoir of Leptospira spp. for humans.Détection de la leptospirose par PCR chez le chat errant, probable réservoir La leptospirose est une infection bactérienne à spirochètes importante en santé publique dans le monde entier. De nombreuses espèces d’animaux sauvages et domestiques constituent d’importants réservoirs de leptospires et sont des sources d’infection pour l’homme. La transmission à l’homme s’effectue par contact direct avec un animal infecté ou par contact avec le sol ou l’eau, contaminé par l’urine d’un animal infecté, le plus souvent asymptomatique. Cette étude avait pour objectif, de préciser la fréquence de leptospira par PCR chez les chats errants dans la province d’Ispahan, en Iran. Des amplicons de 793 bp ont été détectés dans le sang (couche leucocytaire) de 28 chats errants sur les 132 examinés (21,2%), alors qu’aucun d’eux ne présentait de signes cliniques de la leptospirose. Ces résultats suggèrent que le chat errant peut constituer un réservoir non négligeable de Leptospira spp. pour l’homme.Azizi Shahrzad, Momtaz Hassan, Mohammad Goodarzi Amir, Tajbakhsh Elahe. PCR detection of leptospira in stray cats, probable reservoir. In: Bulletin de l'Académie Vétérinaire de France tome 166 n°1, 2013. pp. 67-70

The cross‐talk between soluble “Find me” and “Keep out” signals as an initial step in regulating efferocytosis

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage-associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross-talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process

Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis

Endometriosis is a gynecological inflammatory disorder characterized by the development of endometrial-like cells outside the uterine cavity. This disease is associated with a wide range of clinical presentations, such as debilitating pelvic pain and infertility issues. Endometriosis diagnosis is not easily discovered by ultrasound or clinical examination. Indeed, difficulties in noninvasive endometriosis diagnosis delay the confirmation and management of the disorder, increase symptoms, and place a significant medical and financial burden on patients. So, identifying specific and sensitive biomarkers for this disease should therefore be a top goal. Exosomes are extracellular vesicles secreted by most cell types. They transport between cells’ bioactive molecules such as noncoding RNAs and proteins. MicroRNAs and long noncoding RNAs which are key molecules transferred by exosomes have recently been identified to have a significant role in endometriosis by modulating different proteins and their related genes. As a result, the current review focuses on exosomal micro-and-long noncoding RNAs that are involved in endometriosis disease. Furthermore, major molecular mechanisms linking corresponding RNA molecules to endometriosis development will be briefly discussed to better clarify the potential functions of exosomal noncoding RNAs in the therapy and diagnosis of endometriosis