Age-realted dementia in Kazahstan: adaptation of the 10/66 dementia research group population -based study protocol

Background. The prevalence of dementia is increasing worldwide as the population ages and affects 10 % of the population over 65 years old and 40 % of people over the age of 80.[1] In Kazakhstan, as well as in other countries around the world, the population of aged people has been increasing over the past decades. According to available statistics, by the end of 2013, the percentage of people aged 65 and older in Kazakhstan was 6.7% [2]. Given the fact that Kazakhstan's current population is about 17,221 million people [2], and based on data from the global statistics, it can be assumed that at least 115,000 elderly people could be suffering from age-related dementia. Nevertheless, such pathology is currently may not being diagnosed in Kazakhstan; consequently giving no accurate statistical data on the number of people suffering from this age-related pathology. Thus, the aim of this study is to estimate true prevalence of dementia and assess the risk factors associated with the disease

Age-realted dementia in Kazahstan: adaptation of the 10/66 dementia research group population -based study protocol

Background. The prevalence of dementia is increasing worldwide as the population ages and affects 10 % of the population over 65 years old and 40 % of people over the age of 80.[1] In Kazakhstan, as well as in other countries around the world, the population of aged people has been increasing over the past decades. According to available statistics, by the end of 2013, the percentage of people aged 65 and older in Kazakhstan was 6.7% [2]. Given the fact that Kazakhstan's current population is about 17,221 million people [2], and based on data from the global statistics, it can be assumed that at least 115,000 elderly people could be suffering from age-related dementia. Nevertheless, such pathology is currently may not being diagnosed in Kazakhstan; consequently giving no accurate statistical data on the number of people suffering from this age-related pathology. Thus, the aim of this study is to estimate true prevalence of dementia and assess the risk factors associated with the disease

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells

Mesenchymal stem cells (MSCs) represent a promising cell source for cellular therapy and tissue engineering and are currently being tested in a number of clinical trials for various diseases. However, like other somatic cells, MSCs age, and this senescence is accompanied by a progressive decline in stem cell function. Several lines of evidence suggest a role for the Rho family GTPase Cdc42 activity in cellular senescence processes. In the present study, we have examined aging-associated Cdc42 activity in rat adipose-derived mesenchymal stem cells (ADMSCs) and the consequences of pharmacological inhibition of Cdc42 in ADMSCs from aged rats. We demonstrate that ADMSCs show a decreased rate of cell growth and a decreased ability to differentiate into chrodrogenic, osteogenic and adipogenic cell lineages as a function of rat age. This is accompanied with an increased staining for SA-β-Gal activity and increased levels of Cdc42 bound to GTP. Treatment of ADMSCs from 24-month old rats with three Cdc42 inhibitors significantly increased proliferation rates, decreased SA-β-Gal staining, and reduced Cdc42-GTP. The Cdc42 inhibitor CASIN increased adipogenic and osteogenic differentiation potential in ADMSCs from 24-month old rats, and decreased the levels of radical oxygen species (ROS), p16INK4a levels, F-actin, and the activity of the ERK1/2 and JNK signaling pathways that were all elevated in these cells. These data suggest that ADMSCs show increased rates of senescence as rats age that appear to be due to elevated Cdc42 activity. Thus, Cdc42 plays important roles in MSC senescence and differentiation potential, and pharmacological reduction of Cdc42 activity can, at least partially, rejuvenate aged MSCs

Endometrium characteristics in morbidly obese bariatric surgery candidates: an explanatory analysis

Introduction: Endometrial cancer (EC) is the most prevalent gynecologic malignancy in the US and is strongly associated with obesity. With the increasing number of morbidly obese women of reproductive age, endometrial health and prevention of endometrial malignancies is a pressing public health concern. Objective: To explore the rate of endometrial pathology in a small cohort of cancer free, morbidly obese, female bariatric surgery candidates and to determine the success rate of Pipelle endometrial sampling in this group. Methods: Thirty-seven bariatric surgery candidates provided informed consent for endometrial sampling in an outpatient setting. Women were eligible to participate if they were considering bariatric surgery, had an intact uterus, had no history of EC, and had not undergone endometrial ablation. Endometrial samples were obtained using a Pipelle endometrial suction curette and processed at the Pathology Department of Magee-Womens Hospital. Results: We were unable to obtain samples from five women due to anatomical anomalies, such as cervical stenosis. Of the 32 collected samples, 8 were classified as insufficient to evaluate; therefore, 24 readable biopsies were analyzed. Of these 24, 1 was diagnosed as hyperplasia without atypia, 1 hyperplasia with atypia, 3 suggestive endometrial polyps, 1 endometrial tubal metaplasia, 5 normal secretory, 8 proliferative pattern, and 2 benign atrophic endometrial tissue. Four samples revealed hormonal effect likely due to pharmacologic treatment for uterine bleeding. While histologic evidence of unopposed estrogen was prevalent, no one presented with cancer. Thus, this study found an overall rate of subclinical pathology of 20% among women who could be sampled and an overall 35% Pipelle failure rate, including the 5 technically impossible biopsies suggesting morbidly obese patients may be difficult to evaluate with Pipelle biopsy. Conclusion: Morbidly obese women are at a higher risk of having undiagnosed endometrial pathology, at rates greater than previously reported. Results suggest the importance of additional research to more thoroughly examine relationships between levels of obesity and endometrial pathology, as well as to explore underlying mechanisms. This line of research may open new avenues for endometrial cancer prevention and control, and possibly revert this major public health problem

GUT MICROBIOME ALTERATIONS IN SENIORS SUFFERING FROM ALZHEIMER’S DISEASE

Introduction: One of the important factors influencing human health and attracting increasing attention of scientists during the last two decades is gut microbiome. It has been demonstrated that the links exist between gut microbiome density and composition and a number of pathological conditions including diabetes, obesity and cardiovascular diseases. These diseases, in turn, are the established risk factors for the development of Alzheimer’s disease (AD). Moreover, there is data indicating that gut microbiome can directly affect brain functions. However, only few studies have characterized the human gut microbiome communities associated with AD. Therefore, more research is needed in order to reveal the relationships existing between gut microbiome and brain functions and their influence on the development and progression of AD. Material and methods: Stool samples were obtained from patients with AD (n =11) and cognitively normal age- and sex-matched participants (n =13). The composition of gut microbiome was characterized by 16S ribosomal RNA MiSeq sequencing. Data analysis was performed using an independent computational pipeline, less OTUs scripts (LotuS) [Hildebrand, F., 2013], SILVA reference database were used as reference for 16S rRNA alignment. Statistical analyses were performed using R version 3.0.2. Results: Our preliminary results demonstrated that gut microbiota of AD individuals had overall higher α-diversity compared to healthy controls, although this difference was not significant, while β-diversity analysis has revealed statistical significance (R-squared: 0.075975; p-value <0.033). Among bacterial genera, microbiome of AD participants was characterized by a preponderance of Eubacterium copros, Lachnospiraceae NK, Rikenellaceae RC9, Christensenellacea, Prevotella, Ruminococcus torgue, Parabacterides, Coprococcus and Corynebacterium (LDA score [log10] > 3), whereas the healthy microbiome was characterized by a preponderance of Lactobacillus, Holdemania, Holdemanella, Granucatella (LDA score [log10] > 3). The relative abundances of Lachnospiraceae, Lactobacillus, Eubacterium, and Odoribacter were significantly different in AD patients compared to healthy participants (p < 0.01). Our data are consistent with the results of Vogt et al. (2017) showing that in patients with AD the dominant families were Lachnospiraceae and Ruminococcaceae. Conclusion: Distinct microbial communities were associated with patients with AD when compared with cognitively healthy seniors. However, more data is needed to ascertain our findings

Pipelle endometrial sampling success rates in Kazakhstani settings: results from a prospective cohort analysis

The aim of this study was to evaluate the feasibility of Pipelle endometrial sampling and to explore factors influencing Pipelle success rate in the clinical settings of Kazakhstan. This prospective analysis included 87 patients who had undergone Pipelle biopsy due to medical indications for endometrial sampling. We analysed physician and patient-related factors potentially influencing the success rate of this method. Pipelle endometrial biopsy overall success rate was 82.76%. The indications for the procedure and patients' age were key factors influencing Pipelle sampling success (p .001). The success rate was the highest in the group with abnormal uterine bleeding as a biopsy indication in the reproductive age group (93.19%; p .001). Pipelle biopsy was found to be an acceptable option for endometrial sampling in our clinical setting; at the same time, physicians should consider the potential influencing factors on its success rate like indications for the procedure, BMI and patients' age as well as their menopausal status. In order to provide precise future directions, there is a need to study a larger number of patients.IMPACT STATEMENT What is already known on this subject? Compared to dilation and curettage sampling conducted in the operation room, Pipelle endometrial sampling is relatively inexpensive, associated with less morbidity, safe, accurate, and can be performed in an office setting. What do the results of this study add? This is the first prospective data analysis about Pipelle endometrial sampling in Kazakhstani population. What are the implications of these findings for clinical practice and/or further research? Enabling the timely diagnosis of current endometrial pathology, Pipelle endometrial sampling approach may have an important impact on healthcare safety and efficiency, and improve overall treatment outcomes and the quality of life of Kazakhstani population if used consistently.Nazarbayev University [110119FD4540]This study was supported by the Nazarbayev University Grant [Number 110119FD4540, 2019-2022]

Endometrial histology in severely obese bariatric surgery candidates: an exploratory analysis

Abstract BackgroundEndometrial pathology risk has been linked to obesity; however, little is known of its prevalence in severely obese women not seeking care for endometrial pathology associated symptoms. This pilot study was designed to explore the frequency and risk factors associated with endometrial pathology in cancer-free, severely obese, bariatric surgery candidates using the Pipelle endometrial sampling technique (SureFlex Preferred Curette, Bioteque America, Inc, New Taipei City, Taiwan). MethodsTwenty-nine severely obese bariatric surgery candidates with intact uteruses and no history of endometrial cancer or endometrial ablation were included in this subanalysis from a larger cohort of 47. Endometrial samples were obtained using a Pipelle endometrial suction curette at a single time point before surgery. Logistic regression was used to assess the relationship between body mass index and endometrial pathology when adjusting for age and race. ResultsOf the 29 successful biopsies, 8 (27.6%) were classified as abnormal endometrium: 1 was classified as complex atypical hyperplasia, 1 was classified as hyperplasia without atypia, 4 samples were identified with endometrial polyps, and 2 samples were identified with metaplasia. None presented with cancer. Increasing body mass index was significantly associated with higher risk of abnormal endometrium (OR = 1.19, 95% CI [1.03–1.36], P = .01). ConclusionsThe findings in this sample suggest that obesity may be associated with increased risk of having undiagnosed endometrial pathology. More thorough examination of relationships between levels of obesity and endometrial pathology are needed to better characterize high cancer risk groups who may benefit from introducing new screening measures

Factors Influencing on Pain in Patients Undergoing Pipelle Endometrial Biopsy for Abnormal Uterine Bleeding: Why a Personalized Approach Should Be Applied?

Objectives. Abnormal uterine bleeding (AUB) is a common complaint of women in different age groups, and endometrial biopsy is widely used to investigate the underlying causes. The aim of this observational study was to assess factors influencing pain in patients undergoing endometrial biopsy for AUB. Methods. Pain intensity before, during, and after Pipelle sampling was evaluated using the numerical rating scale (NRS), where “0” represents no pain at all, “10”—the worst pain ever possible. Pain rating was categorized as 1–6—mild to moderate, 7 and above as severe pain. Results. The study included 160 women who underwent Pipelle biopsy. The median age in the cohort was 42 (34–48) years, 18.1% of women were postmenopausal, 56.3% were either overweight or obese, 30% were nulliparous and 80% reported urban residency. The median pain score during the procedure was 2 (0–4). Pain scores of 5 (4–7) were reported with the junior gynecologist and 2 (0–4) in the senior gynecologist (p \u3c 0.0001). Conclusion. The pain was found to have a strong association with the type of provider performing the endometrial sampling procedure. This fact suggests the need for a personalized approach and that psychological or informational interventions should be scheduled before the procedure to decrease pain and increase satisfaction