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 STATEMENTWhat 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.

Pipelle endometrial biopsy for abnormal uterine bleeding: do patient's pain and anxiety really impact on sampling success rate?

BACKGROUND: Pipelle endometrial biopsy is vital for the early diagnostics of endometrial pathology and is performed in outpatient setting in minimally invasive manner. One of the reported disadvantages of sampling with Pipelle curette is failure to collect enough tissue for histological analysis. The role of psychological factors such as anxiety and pain sensitivity in obtaining adequate samples is not well known. The study's objective was to explore whether there is relationship between severe pain, anxiety, and the rate of Pipelle failure. METHODS: Study included 158 women with median age of 42 who underwent Pipelle endometrial biopsy at Clinical Academic Department of Women's Health of the University Medical Center (UMC), Nur-Sultan City, Kazakhstan with an abnormal uterine bleeding from June 2019 to April 2021. Women were asked to fill survey on pain, anxiety before, during and after the procedure. RESULTS: 3.8%, 15.19% and 4.43% of women reported severe pain and 39.24%, 34.18% and 14.56% of women reported severe anxiety prior, during and after procedure, respectively. Women who experienced severe pain during procedure tend to be more anxious during procedure (p = 0.0001) and have higher number of sampling attempts (p = 0.0040). Pain level was higher among patients sampled by the junior OB/GYN specialist (p < 0.0001). We found no differences in Pipelle biopsy success rates in relationship to baseline, during and postprocedural pain and anxiety scores. CONCLUSION: Anxiety during procedure performance was significantly associated with severe pain during the procedure but did not represent a key element for the success of Pipelle biopsy.

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-ß-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-ß-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.

Inflammatory Manifestations Associated With Gut Dysbiosis in Alzheimer's Disease.

Recent studies strongly suggest that gut microbiome can influence brain functions and contribute to the development of Alzheimer's disease (AD). However, reported changes in the gut microbiomes in AD patients from different countries are not similar, and more research is needed to reveal the relationships between human microbiomes and AD in diverse ethnic populations. There is also an assumption that microbiome-associated peripheral inflammation might drive the development of sporadic AD. This cross-sectional study is aimed at analyzing the gut microbial profile and exploring potential associations with blood cytokines and some clinical parameters among individuals diagnosed with Alzheimer's in Kazakhstan. Consistent with previous studies, we have found that the microbial landscape in AD reveals specific alterations in the gut microbiome. Specifically, the AD patient group showed a decreased Firmicutes/Bacteroidetes ratio. The differential abundance analysis highlighted a dysbiosis in the gut microbiota of AD patients, marked by a reduced presence of Bifidobacterium, particularly B. breve. In our study, AD patients' altered gut microbiota composition notably features an increased presence of Pseudomonadota like Phyllobacterium and inflammatory bacteria such as Synergistetes and the Christensenellaceae family. The metabolic profiling of the AD microbiome reveals a predominant presence of pathways related to sugar, carrier molecules, tetrapyrrole, pyrimidine biosynthesis, and nucleic acid processing. This analysis also highlighted a marked reduction in SCFA, carbohydrate, polysaccharide, polyamine, and myo-inositol degradation pathways. The increases in the proinflammatory cytokines IL-1a, IL-8, IL-17A, IL-12p40, TNF-ß, MCP-1, IL-2, and IL-12p70 and the anti-inflammatory cytokines IL-10 and IL-13 were observed in AD patients. Key variables driving the separation of AD and controls include inflammatory markers (IL-1a and IL-8), growth factors (EGF), lipids (LDL), BMI, and gut microbes, like genus Tyzzerella and Turicibacter and species Parabacteroides distasonis and Bacteroides eggerthii. We have also demonstrated that almost all cytokines strongly correlate with serum adiponectin levels and specific microbial taxa in AD patients. Thus, our findings identify potential microbial and inflammatory signatures in an ethnically distinct cohort of AD patients. These could serve as AD biomarkers and microbiota-based therapeutic targets for treating AD.

Oral Microbiome Stamp in Alzheimer's Disease.

Recent studies have suggested that periodontal disease and alterations in the oral microbiome may be associated with cognitive decline and Alzheimer's disease (AD) development. Here, we report a case-control study of oral microbiota diversity in AD patients compared to healthy seniors from Central Asia. We have characterized the bacterial taxonomic composition of the oral microbiome from AD patients (n = 64) compared to the healthy group (n = 71) using 16S ribosomal RNA sequencing. According to our results, the oral microbiome of AD has a higher microbial diversity, with an increase in Firmicutes and a decrease in Bacteroidetes in the AD group. LEfSe analysis showed specific differences at the genus level in both study groups. A region-based analysis of the oral microbiome compartment in AD was also performed, and specific differences were identified, along with the absence of differences in bacterial richness and on the functional side. Noteworthy findings demonstrated the decrease in periodontitis-associated bacteria in the AD group. Distinct differences were revealed in the distribution of metabolic pathways between the two study groups. Our study confirms that the oral microbiome is altered in AD. However, a comprehensive picture of the complete composition of the oral microbiome in patients with AD requires further investigation.

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 1−6­mild 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 < 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.

Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan.

We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.

Circulating adiponectin levels, expression of adiponectin receptors, and methylation of adiponectin gene promoter in relation to Alzheimer's disease.

BACKGROUND: The role of adiponectin (ADIPOQ) in Alzheimer's disease (AD) has been documented, however, demonstrating controversial results. In this study, we investigated blood serum ADIPOQ levels, methylation of the adiponectin gene promoter, and adiponectin receptors (AdipoR1 and AdipoR2) expression in blood samples isolated from AD patients and healthy controls. METHODS: We performed a case-control study including 248 subjects (98 AD patients and 150 healthy controls); ADIPOQ serum levels, AdipoR1, and AdipoR2 levels in PBMC were measured by ELISA Kits, and ADIPOQ gene methylation was analyzed using methyl-specific PCR. RESULTS: Serum adiponectin levels were threefold higher in the AD group compared to the controls. We have also found a positive correlation between adiponectin and MMSE scores and high-density lipoprotein cholesterol (HDL-C) in AD patients. A significant difference in the proportion of methylation of the CpG sites at - 74 nt of the ADIPOQ gene promoter was detected in AD cases, and the levels of adiponectin in blood serum were significantly higher in methylated samples in the AD group compared to controls. The amount of AdipoR1 was significantly higher among AD subjects, while the expression of AdipoR2 did not vary between AD patients and controls. CONCLUSION: These findings may contribute to a deeper understanding of the etiological factors leading to the development of dementia and may serve as a basis for the development of predictive biomarkers of AD.

Pipelle Endometrial Biopsy for Abnormal Uterine Bleeding in Daily Clinical Practice: Why the Approach to Patients Should Be Personalized?

BACKGROUND: Abnormal uterine bleeding (AUB) is a common gynecologic condition, and proper management is based on the histological evaluation of an adequate endometrial sample obtained via biopsy. The aims of this study were to evaluate factors influencing the reliability and success rate of Pipelle endometrial sampling for histopathological diagnosis. METHODS: One hundred and eighty patients with AUB underwent endometrial sampling using both Pipelle and dilatation and curettage (D&C) procedures at the Clinical Academic Department of Women's Health, University Medical Center between January 2019 and April 2021. We analyzed the effects of age, menopausal status, ethnicity, body mass index (BMI), provider experience, and procedure indication on the success and reliability of each procedure. RESULTS: Pipelle sampling was successful in 144 (80.56%) women, while D&C was successful in 164 (91.11%) women. Analysis using Fisher's exact test showed that age, menopausal status, and biopsy indication were factors affecting the success rate of both methods, while ethnicity, BMI, and physician experience had no influence. Overall concordance in the histopathological results between Pipelle and D&C was 91.72%. CONCLUSION: Pipelle sampling was found to be reliable for the detection of endometrial carcinoma and endometrial hyperplasia, while its reliability was low in cases of endometrial polyps. The endometrial sampling approach should be personalized in daily clinical practice for women with AUB, and Pipelle sampling is not suitable for all patients. If an endometrial polyp is suspected, the physician should consider other diagnostic tools, bearing in mind all of the factors influencing endometrial sampling success and reliability rates.

The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease.

Gut microbiome is a community of microorganisms in the gastrointestinal tract. These bacteria have a tremendous impact on the human physiology in healthy individuals and during an illness. Intestinal microbiome can influence one's health either directly by secreting biologically active substances such as vitamins, essential amino acids, lipids et cetera or indirectly by modulating metabolic processes and the immune system. In recent years considerable information has been accumulated on the relationship between gut microbiome and brain functions. Moreover, significant quantitative and qualitative changes of gut microbiome have been reported in patients with Alzheimer's disease. On the other hand, gut microbiome is highly sensitive to negative external lifestyle aspects, such as diet, sleep deprivation, circadian rhythm disturbance, chronic noise, and sedentary behavior, which are also considered as important risk factors for the development of sporadic Alzheimer's disease. In this regard, this review is focused on analyzing the links between gut microbiome, modern lifestyle, aging, and Alzheimer's disease.

The Effects of Mobile Phone Radiofrequency Electromagnetic Fields on ß-Amyloid-Induced Oxidative Stress in Human and Rat Primary Astrocytes.

Amyloid beta peptide (Aß) is implicated in the development of pathological reactions associated with Alzheimer's disease (AD), such as oxidative stress, neuro-inflammation and death of brain cells. Current pharmacological approaches to treat AD are not able to control the deposition of Aß and suppression of Aß-induced cellular response. There is a growing body of evidence that exposure to radiofrequency electromagnetic field (RF-EMF) causes a decrease of beta-amyloid deposition in the brains and provides cognitive benefits to Alzheimer's Tg mice. Herein, we investigated the effects of mobile phone radiofrequency EMF of 918 MHz on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), activity of NADPH-oxidase, and phosphorylation of p38MAPK and ERK1/2 kinases in human and rat primary astrocytes in the presence of Aß42 and H2O2. Our data demonstrate that EMF is able to reduce Aß42- and H2O2-induced cellular ROS, abrogate Aß42-induced production of mitochondrial ROS and the co-localization between the cytosolic (p47-phox) and membrane (gp91-phox) subunits of NADPH oxidase, while increasing MMP, and inhibiting H2O2-induced phosphorylation of p38MAPK and ERK1/2 in primary astrocytes. Yet, EMF was not able to modulate alterations in the phosphorylation state of the MAPKs triggered by Aß42. Our findings provide an insight into the mechanisms of cellular and molecular responses of astrocytes on RF-EMF exposure and indicate the therapeutic potential of RF-EMF for the treatment of Alzheimer's disease.

Health challenges in Kazakhstan and Central Asia.

The Central Asian region, which encompasses Kazakhstan, Uzbekistan, Tajikistan, Turkmenistan and Kyrgyzstan, is an interesting geographic region with a rich history dating back to the Silk Road, Mongol conquests and expansion of the Russian Empire. However, from a public health viewpoint, the Central Asian region is under-investigated, and many public health challenges exist, as countries of Central Asia inherited the centralised medical systems practiced in the Soviet Union, and are currently undergoing rapid transitions. A large number of low and middle-income countries around the world, including countries of Central Asia, face a double burden of chronic and infectious disease. This essay focuses on the exploration of the most important public health challenges in the Central Asian region, including limited scientific productivity, the double burden of chronic and infectious disease, the need for healthcare reform and the reduction in care variation. Central Asia has a large number of medical schools, medical centres, and emerging research institutes that can be used to foster a change in medical and public health practice in the region.

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

BACKGROUND: Endometrial 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). METHODS: Twenty-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. RESULTS: Of 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). CONCLUSIONS: The 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.