scholarly journals CLINICO-MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL ASPECTS OF ENDOMETRIAL POLYP PATHOGENESIS IN POSTMENOPAUSE

2019 ◽  
Vol 16 (32) ◽  
pp. 724-731
Author(s):  
T. R. SALIKHOVA ◽  
N. S-M. OMAROV ◽  
A. U. CHERKESOVA ◽  
S. M. GADJIMURADOVA ◽  
E. R. ASKERKHANOVA
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Infiltrate ◽  
Significant Risk ◽  
High Rate ◽  
Endocrine Disorders ◽  
Endometrial Polyps ◽  
Fibrous Stroma ◽  
Age Related ◽  
Proliferation And Apoptosis ◽  
And Control

To study hypoxia-inducible transcription factor HIF-1α expression in endometrial polyps (EP) considering their clinical-morphological and immunological features during postmenopause. A complex clinical and laboratory examination of 120 postmenopausal patients was carried out. 90 of them developed EP, whereas 30 had morphologically unchanged endometrium. Immune histochemical (ICH) testing was used to evaluate HIF-1α expression in epithelial and stromal cells of polyps in adjacent and control endometrium. A complex of the most significant risk factors in EP genesis such as high rate of inflammatory disorders of genital organs (IDGO), extragenital, metabolic and endocrine disorders and intrauterine contraception (IUC) was found. High expression of HIF-1α in epithelial cells and in the area of inflammatory infiltrate of glandular fibrous EP stroma was established as compared with control endometrium. HIF-1α expression in epithelial cells and in the area of inflammatory infiltrate of EP glandular fibrous stroma against the background of inflammatory, metabolic and endocrine, immunological changes and age-related involutional processes indicated local hypoxia. Epigenetic changes can develop in the processes of proliferation and apoptosis and in the processes that control neoplastic transformation. The obtained data can provide grounds for patient-tailored EP therapy in postmenopausal patients.

scholarly journals Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty

2019 ◽  
Author(s):  
Gurmannat Kalra ◽  
Beatrice Milon ◽  
Alex M. Casella ◽  
Yang Song ◽  
Brian R. Herb ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Meta Analysis ◽  
Significant Risk ◽  
Sensory Epithelium ◽  
Open Chromatin ◽  
Specific Expression ◽  
Risk Genes ◽  
Age Related ◽  
Genome Wide ◽  
Hearing Difficulty

ABSTRACTAge-related hearing impairment (ARHI), one of the most common medical conditions, is strongly heritable, yet its genetic causes remain largely unknown. We conducted a meta-analysis of GWAS summary statistics from multiple hearing-related traits in the UK Biobank (n = up to 323,978) and identified 31 genome-wide significant risk loci for self-reported hearing difficulty (p < 5e-8), of which 30 have not been reported previously in the peer-reviewed literature at genome-wide significance. We investigated the regulatory and cell specific expression for these loci by generating mRNA-seq, ATAC-seq, and single-cell RNA-seq from cells in the mouse cochlea. Risk-associated genes were most strongly enriched for expression in cochlear epithelial cells, as well as for genes related to sensory perception and known Mendelian deafness genes, supporting their relevance to auditory function. Regions of the human genome homologous to open chromatin in sensory epithelial cells from the mouse were strongly enriched for heritable risk for hearing difficulty, even after adjusting for baseline effects of evolutionary conservation and cell-type nonspecific regulatory regions. Epigenomic and statistical fine-mapping most strongly supported 50 putative risk genes. Of these, at least 39 were expressed robustly in mouse cochlea and 16 were enriched specifically in sensory hair cells. These results reveal new risk loci and risk genes for hearing difficulty and suggest an important role for altered gene regulation in the cochlear sensory epithelium.

scholarly journals Mortality and Conversion Rate to Below Knee or Above Knee Amputation Following Transmetatarsal Amputation

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0011
Author(s):  
D. Anthony Barcel ◽  
Susan M. Odum ◽  
Taylor Rowe ◽  
Jefferson B. Sabatini ◽  
Samuel E. Ford ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conversion Rate ◽  
Significant Risk ◽  
High Rate ◽  
Administrative Database ◽  
Categorical Variables ◽  
Diabetic Patients ◽  
Knee Amputation ◽  
History Of ◽  
Transmetatarsal Amputation

Category: Midfoot/Forefoot; Diabetes; Other Introduction/Purpose: Non-traumatic lower extremity amputations (LEA), especially those performed in dysvascular and diabetic patients, are known to have poor long-term prognosis. Perioperative mortality has been reported at between 4 and 10%, and the 1 and 5 year mortality rates range between 22-33% and 39-69%, respectively. While poor outcomes in these patients have been described, there is no consensus as to the predictors of mortality. The purpose of the study is to determine the percentage of patients who had a complication following transmetatarsal amputation (TMA) and identify associated risk factors for complications and mortality. Methods: We queried our institution’s administrative database to identify 247 TMA procedures performed in 229 patients between January, 2002 and December, 2016. Electronic health records were reviewed to document complications defined as reoperation, amputation and mortality. Mortality was also verified using the National Death Index. Additionally, we recorded risk factors including diabetes, A1c level, end stage renal disease (ESRD), cardiovascular disease (CVD), peripheral vascular disease (PVD), history of revascularization, contralateral amputation, and neuropathy. The majority of the study patients were males (157, 69%) and the average age was 57 years (range 24-91). The median BMI was 28 (range 16-58) and 29% of the study patients were obese with a BMI ≥ 30. Fishers Exact tests were used to compare categorical variables. Kruskal-Wallis and Independent T-tests were used to compare numeric data. All data were analyzed using SAS/STAT software version 9.4 (Carey, NC) and a 0.05 level of significance was defined apriori. Results: The conversion rate to below (BKA) or above knee amputation (AKA) was 26% (64 of 247). Males (p=.0274), diabetics (p=.0139), patients in ESRD (p=.019), and patients with a history of CVD (p=.0247) or perioperative revascularization (p=.022) were more likely to undergo further amputation following an index TMA. BMI was significantly higher in patients requiring BKA/AKA (p=.0305). There were no significant differences in age (p=.2723) or A1c levels (p=.4219). The overall mortality rate was 35% (84 of 229). Diabetes (p=.0272), ESRD (p=.0031), history of CVD (p<.0001) or PVD (p=.0179) were all significantly associated with mortality. Patients who died were significantly older (p=.0006) and had significantly higher A1c levels (p=.0373). BMI was not significantly associated with mortality. Twenty-two patients who had 23 further amputations subsequently died. Conclusion: In our series of patients undergoing TMA, 26% underwent further amputation and 35% of patients died. Conversion rate to BKA or AKA occurred at a high rate regardless of preoperative revascularization or the use of tendo-achilles or gastrocnemius lengthening procedures. Male sex, diabetes, ESRD, history of CVD or revascularization are significant risk factors for further amputation. ESRD, diabetes, history of CVD or PVD, older age and higher A1c levels are significant risk factors for mortality. These data provide useful insight into risk factors to be emphasized when counseling patients and their families to establish realistic postoperative expectations.

scholarly journals Autobiographical Memory in Normal Ageing and Dementia

1991 ◽  
Vol 4 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Harvey J. Sagar ◽  
Edith V. Sullivan ◽  
Suzanne Corkin
Keyword(s):  
Memory Function ◽  
Early Adulthood ◽  
Normal Subjects ◽  
Elderly Subjects ◽  
Retrieval Cues ◽  
Age Related ◽  
Normal Ageing ◽  
Severity Of Dementia ◽  
And Control ◽  
Cue Words

Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD) in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

scholarly journals Age-related skin changes

2012 ◽  
Vol 65 (5-6) ◽  
pp. 191-195 ◽  
Author(s):  
Aleksandra Levakov ◽  
Nada Vuckovic ◽  
Matilda Djolai ◽  
Mihaela Mocko-Kacanski ◽  
Snezana Bozanic
Keyword(s):  
Inflammatory Infiltrate ◽  
Subcutaneous Fat ◽  
The Sun ◽  
Intercellular Substance ◽  
Dermoepidermal Junction ◽  
Skin Changes ◽  
Age Related ◽  
Fat Reduction ◽  
Males And Females ◽  
Skin Samples

Age-related skin changes can be induced by chronological ageing, manifested in subcutaneous fat reduction, and photo-ageing eliciting increased elastotic substance in the upper dermis, destruction of its fibrilar structure, augmented intercellular substance and moderate inflammatory infiltrate. Forty-five biopsy skin samples of the sun-exposed and sun-protected skin were analyzed. The patients were both males and females, aged from 17 to 81 years. The thickness of the epidermal layers and the number of cellular living layers is greater in younger skin. The amount of keratohyaline granules is enlarged in older skin. Dermoepidermal junction is flattened and the presence of elastotic material in the dermis is pronounced with age. The amount of inflammatory infiltrate is increased, the fibrous trabeculae are thickened in older skin and the atrophy of the hypodermis is observed. Chronological ageing alters the fibroblasts metabolism by reducing their life span, capacity to divide and produce collagen. During ageing, the enlargement of collagen fibrils diminishes the skin elasticity.

Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

2021 ◽  
Vol 162 (33) ◽  
pp. 1318-1327
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Life Expectancy ◽  
Significant Risk ◽  
Low Grade ◽  
Aging Effects ◽  
Protective Function ◽  
Beneficial Effects ◽  
Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

Constipation in patients with comorbidity

2021 ◽  
Author(s):  
Е.А. Лялюкова ◽  
Е.Н. Логинова
Keyword(s):  
Gastrointestinal Tract ◽  
Neurological Diseases ◽  
The Elderly ◽  
Lifestyle Changes ◽  
Secretory Cells ◽  
Endocrine Disorders ◽  
Silver Age ◽  
Functional Changes ◽  
Slowing Down ◽  
Age Related

Пациенты пожилого и старческого возраста в силу физиологических причин и коморбидной патологии имеют высокий риск развития запора. Причиной запора чаще всего являются алиментарные факторы и возраст-ассоциированные заболевания и повреждения толстой кишки (дивертикулярная болезнь, ишемия толстой кишки, ректоцеле, геморрой и другие); метаболические, эндокринные расстройства и неврологические заболевания. Возрастные анатомические, структурные и функциональные изменения пищеварительной системы вносят свой вклад в развитие запоров у пожилых. У пациентов «серебряного возраста» отмечено увеличение длины желудочно-кишечного тракта, прогрессирование атрофических, склеротических изменений слизистой и подслизистой оболочки, снижение количества секреторных клеток, замещение мышечных волокон соединительной тканью и др. Все это способствует замедлению транзита по желудочно-кишечному тракту и нарушению акта дефекации. Образ жизни пожилых людей также может способствовать развитию запора. Низкое содержание в рационе клетчатки, употребление преимущественно термически обработанной пищи, нарушение ритма питания (прием пищи 1-2 раза в день) являются одной из причин возникновения запоров у пожилых, чему способствуют трудности при жевании вследствие стоматологических проблем. Колоноскопия показана всем пациентам пожилого и старческого возраста с запором, а выявление «симптомов тревоги» необходимо проводить при каждом визите пациента. Вне зависимости от причины вторичного запора, все пациенты должны осуществлять ряд мер немедикаментозного характера, включающих изменение образа жизни, диету с включением достаточного количества клетчатки и потребление жидкости. Физические методы лечения могут включать лечебную гимнастику, массаж толстой кишки для стимуляции моторной активности кишечника в определенное время. При неэффективности немедикаментозных мероприятий рекомендуется использование осмотических слабительных, а также средств, увеличивающих объем каловых масс. Высокая эффективность и безопасность псиллиума позволяет рекомендовать его в лечении хронического запора у пожилых пациентов. Elderly and senile patients, due to physiological reasons and comorbid pathology, have a high risk of constipation. The causes of constipation are more often nutritional factors and age-associated diseases and damage to the colon (diverticular disease, colon ischemia, rectocele, hemorrhoids, and others); metabolic, endocrine disorders and neurological diseases. Age-related anatomical, structural and functional changes in the digestive system contribute to the development of constipation in the elderly. In patients of «silver age», there was an increase in the length of the gastrointestinal tract, the progression of atrophic, sclerotic changes in the mucous and submucosa, a decrease in the number of secretory cells, replacement of muscle fibers with connective tissue, etc. All this contributes to the slowing down of transit through the gastrointestinal tract and the violation of the act of defecation. Elderly lifestyles can also contribute to constipation. The low fiber content in the diet, the use of mainly thermally processed food, the violation of the rhythm of the diet (eating 1-2 times a day) are one of the causes of constipation in the elderly, which is facilitated by difficulty in chewing due to dental problems. Colonoscopy is ordered for all elderly and senile patients with constipation, and the identification of «anxiety symptoms» should be carried out at each patient visit. Regardless of the cause of secondary constipation, all patients should take a number of non-pharmacological measures, including lifestyle changes, a diet with adequate fiber, and fluid intake. Physical therapies may include medical gymnastics, colon massage to stimulate bowel movement at specific times. If non-drug measures are ineffective, it is recommended to use osmotic laxatives, as well as agents that increase the volume of feces. Psyllium supplementation is recommended for treatment of chronic constipation in elderly patients due to its high efficacy and safety.

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