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Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors.
Silaidos, CV, Reutzel, M, Wachter, L, Dieter, F, Ludin, N, Blum, WF, Wudy, SA, Matura, S, Pilatus, U, Hattingen, E, et al
GeroScience. 2024;(1):981-998
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Abstract
Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (- 15%) and ATP levels (- 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (- 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (- 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant.
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Unraveling the Mystery of Multi-Oocyte Follicles: An Observational Study.
Sahni, C, Seth, S, Nayak, AK, Singh, R
La Clinica terapeutica. 2024;(1):42-46
Abstract
INTRODUCTION Significant progress has been made in understanding oocyte fertilization and early developmental stages through in vitro fertilization (IVF) techniques. However, irregularities such as conjoined oocytes and binucleate giant oocytes, which are exceptions to the normal rule of one diploid female gamete per follicle, can potentially lead to chromosomal disorders in embryos and are recommended to be excluded from IVF attempts. The formation of primordial follicles during ovarian development, known as follicle assembly, is a critical process that establishes the ovarian follicle reserve. Multi-oocyte follicles (MOFs) containing two or more oocytes have been observed in various species, including humans, and their clinical significance on fertility and reproductive health remains unclear. Genetic and environmental factors, such as gene knockout and exposure to endocrine disruptors, have been implicated in MOF formation, but the mechanisms are not fully understood and require further investigation. MATERIAL & METHOD In this Observational study, 350 slides of ovarian tissues were scanned using an AI-based automated microscope, Grundium Ocus 20, and the TIFF images were stored in cloud storage. The slides were examined using third-party software, Pathcore Seeden Viewer, for morphometry of binovular follicles. RESULTS In our observational study, we examined 350 ovarian tissue slides in detail by using an AI-based microscope, uncovering 22 slides from seven different tissues with binovular and multinovular oocytes. These rare multi-oocyte follicles (MOFs) challenge the conventional one-oocyte-per-follicle paradigm. MOFs are likely formed when oocytes fail to separate during cortical sex cord proliferation, regulated by factors several molecular factorsas well as environmental factors. DISCUSSION Multiple Ovarian Follicles (MOFs) are rare phenomena where two or more oocytes exist in one follicle. They arise when oocytes fail to separate during ovarian development, which is governed by hormones such as follicle-stimulating hormone (FSH), inhibin, BMP-15, GDF-9, and GCNF. MOFs can be caused by dysregulation and exposure to chemicals such as diethylstilbestrol (DES) and isoflavones. Binovular oocytes, which occur when two oocytes are released during ovulation and are fertilised by different sperm, can result in non-identical twins, which are influenced by genetic and environmen-tal factors such as maternal age, heredity, hormonal imbalances, and assisted reproductive techniques such as in vitro fertilisation (IVF). Polynuclear oocytes with many nuclei can develop as a result of meiotic spindle defects and environmental influences. Identifying these oocyte types may aid in improving ART results by improving knowledge of the reasons of infertility and devising appropriate interventions.
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Probiotic supplementation modifies the gut microbiota profile of very low birth weight preterm infants during hospitalization.
Chang, HY, Lin, CY, Chiang Chiau, JS, Chang, JH, Hsu, CH, Ko, MH, Lee, HC
Pediatrics and neonatology. 2024;(1):55-63
Abstract
BACKGROUND Probiotic supplementation is increasingly being given to very low birth weight (VLBW) preterm infants. This preliminary observational study aimed to investigate the effects of multiple-strain probiotics on the gut microbiota of VLBW preterm infants. METHODS We collected meconium and stool samples on days 14, 30, and 60 after birth from 49 VLBW infants with a gestational age of <32 weeks. The infants were divided into the probiotics (n = 24) and control (n = 25) groups. The microbial composition and diversity in the gut of the two groups were analyzed using 16 S rRNA gene sequencing. RESULTS The relative abundance of Bifidobacterium and Lactobacillus was significantly higher in the probiotics group than in the control group on days 14, 30, and 60 (Bifidobacterium: p = 0.002, p < 0.0001, and p < 0.0001, respectively; Lactobacillus: p = 0.012, p < 0.0001, and p < 0.0001, respectively). The control group exhibited a significantly higher proportion of participants with a low abundance (<1%) of Bifidobacterium or Lactobacillus on days 14, 30, and 60 than those in the probiotic group. Moreover, the probiotics group exhibited a significantly lower abundance of Klebsiella on days 14 and 30 (2.4% vs. 11.6%, p = 0.037; and 7.9% vs. 16.6%, p = 0.032, respectively) and of Escherichia-Shigella on day 60 than the control group (6.1% vs. 12.3%, p = 0.013). Beta diversity analysis revealed that the microbiota profile was clearly divided into two groups on days 30 and 60 (p = 0.001). CONCLUSION Probiotic supplementation significantly increased the relative abundance of Bifidobacterium and Lactobacillus and inhibited the growth of potential pathogens. Furthermore, probiotic supplementation led to a distinct gut microbiota profile. Further research is needed to identify probiotic strains that exert significant influence on the gut microbiome and their long-term health implications in preterm infants.
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Favorable combinations of antiseizure medication with vagus nerve stimulation to improve health-related quality of life in patients with epilepsy.
Sauer, V, Glaser, M, Ellwardt, E, Saryyeva, A, Krauss, JK, Ringel, F, Groppa, S, Winter, Y
Epilepsy & behavior : E&B. 2024;:109562
Abstract
BACKGROUND Vagus nerve stimulation (VNS) is a non-pharmacological treatment of refractory epilepsy, which also has an antidepressive effect. The favorable combinations of VNS with specific mechanisms of action of antiseizure medication (ASM) on mood and health-related quality of life (HrQol) have not yet been studied. The objective was to identify favourable combinations of specific ASMs with VNS for the HrQoL and depression in refractory epilepsy. METHODS We performed an observational study including patients with refractory epilepsy and an implanted VNS (N = 151). In the first 24 months after VNS implantation, all patients were on stable ASM therapy. We used the standardized questionnaires QOLIE10, EQVAS and EQ5D to evaluate HrQoL as well as the Beck Depression Inventory (BDI). Multiple regression analysis was performed to evaluate the synergistic combinations of ASM with VNS for HrQoL. RESULTS At the year-two follow-up (N = 151, age 45.2 ± 17.0 years), significant improvement (p < 0.05) in BDI scores was found for combination of VNS with SV2A modulators (58.4 %) or AMPA antagonists (44.4 %). A significant increase of HrQoL by at least 30 % (p < 0.05) was measured for a combination of VNS with SV2A modulators (brivaracetam, levetiracetam) or slow sodium channel inhibitors (eslicarbazepine, lacosamide). CONCLUSION The results of our study suggests a favorable effect of the combination of SV2A modulators or slow sodium channel inhibitors with VNS on the HrQoL in comparison to other ASMs. Besides the possible synergistic effects on the seizure frequency, the amelioration of behavioral side effects of SV2A modulators by VNS is an important factor of HrQoL-improvement in these combinations.
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Orthostatic hypotension, orthostatic hypertension, and ambulatory blood pressure in patients with chronic kidney disease in CRIC.
Ghazi, L, Cohen, JB, Townsend, RR, Drawz, PE, Rahman, M, Pradhan, N, Cohen, DL, Weir, MR, Rincon-Choles, H, Juraschek, SP
Journal of hypertension. 2024;(2):329-336
Abstract
BACKGROUND Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown. METHODS CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP. RESULTS Of the 1386 participants (age: 58 ± 10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (β = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (β = -4 [-7.2, -0.5]) and diastolic WCE (β = -6 [-8.1, -4.2]). CONCLUSION Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes.
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Sex-specific association of visceral and subcutaneous adipose tissue volumes with systemic inflammation and innate immune cells in people living with obesity.
van den Munckhof, ICL, Bahrar, H, Schraa, K, Brand, T, Ter Horst, R, van der Graaf, M, Dekker, HM, Stienstra, R, de Graaf, J, Joosten, LAB, et al
International journal of obesity (2005). 2024;(4):523-532
Abstract
BACKGROUND AND AIMS Obesity predisposes to metabolic and cardiovascular diseases. Adipose tissue inflammation and systemic inflammation contribute to these complications. There are strong sex differences in adipose tissue distribution and in systemic inflammation. Women have more subcutaneous adipose tissue (SAT) and less visceral adipose tissue (VAT) than men. We explored the sex differences in the association between the different adipose compartments and inflammatory markers that are important in cardiometabolic disease pathophysiology. METHODS Single-center observational cohort study with 302 individuals with a BMI ≥ 27 kg/m2. We were unable to acquire MRI data from seven individuals and from another 18 the MRI data were not usable, resulting in 277 people (155 men, 122 women), aged 55-81 years. INTERVENTION We performed the following measurements: abdominal magnetic resonance imaging to measure VAT, and SAT (deep and superficial) volumes; circulating leukocyte counts and cytokine production capacity of peripheral blood mononuclear cells (PBMCs), circulating cytokines, adipokines, and targeted proteomics; abdominal sSAT biopsies for histology and gene expression. RESULTS Only in women, (s)SAT volume was associated with circulating leukocytes, monocytes, and neutrophils. Circulating IL-6 and IL-18BP were associated with SAT volume in women and VAT in men. Several circulating proteins, including monocyte-colony-stimulating factor 1 and hepatocyte growth factor, are associated with sSAT in women and VAT in men. Only in women, SAT volume is associated with SAT expression of inflammatory proteins, including leptin, CD68, TNFα and IL-1α. CONCLUSION In women living with obesity, abdominal SAT volume, especially sSAT, is associated with circulating leukocytes and inflammatory proteins. In men, these parameters mainly show associations with VAT volume. This could be because only in women, sSAT volume is associated with sSAT expression of inflammatory proteins. These findings underscore that future research on adipose tissue in relation to cardiometabolic and cardiovascular disease should take sex differences into account.
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Understanding the incidence, duration, and severity of symptoms through daily symptom monitoring among frail and non-frail older patients receiving metastatic prostate cancer treatments.
Parthipan, M, Feng, G, Breunis, H, Timilshina, N, Emmenegger, U, Hansen, A, Tomlinson, G, Matthew, A, Clarke, H, Santa Mina, D, et al
Journal of geriatric oncology. 2024;(3):101720
Abstract
INTRODUCTION Older adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer. MATERIALS AND METHODS Older adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly symptom questionnaires were administered and analyzed using linear mixed effect models. Symptom incidence, duration, and frailty associations were assessed using t-tests and chi-square tests. RESULTS Ninety participants completed the study (mean age=77 years [standard deviation=6.1], 42% frail [Vulnerable Elders Survey≥3]). The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), pain (37.5%), and decreased appetite (37.1%). Poor wellbeing had a higher incidence in frail participants (62.5% in frail vs. 31.4% in non-frail, p=0.039). Symptom duration varied across cohorts and between frail and non-frail participants. Among participants who reported moderate-to-severe symptoms at baseline, no more than 15% improved in any symptom. There were statistically significant improvements in weekly symptoms for fatigue, decreased appetite, and insomnia in the chemotherapy cohort only. DISCUSSION Limitations include a short follow-up duration, lack of a control group, and few radium-223 participants. Regular symptom monitoring can help clinicians understand temporal patterns and durations of symptoms and inform supportive care approaches.
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Self-Reported Nutritional Status and Breakfast Characterization in Latin American University Students.
Saavedra Clarke, S, Parra-Soto, S, Murillo, G, Carpio-Arias, V, Landaeta-Díaz, L, Nava-González, EJ, Ríos-Castillo, I, Nuñez-Martínez, BE, Gómez, G, Araneda-Flores, J, et al
Journal of the American Nutrition Association. 2024;(3):252-260
Abstract
OBJECTIVE To associate breakfast consumption frequency with self-reported nutritional status and dietary patterns of Latin American university students by human development. MATERIAL AND METHODS This was a cross-sectional, multicenter observational study. University students from 11 Latin American countries (Argentina, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, Peru, Paraguay, Panama and Uruguay) were invited to participate by answering an online self-administered questionnaire on food consumption and sociodemographic indicators, associations were investigated using logistic regression. RESULTS The logistic regression analysis showed significant associations between breakfast consumption and the crude model, models 2 and 3 in countries with very high and upper-middle/high human development. However, after adjustment in the most comprehensive model, the association is no longer statistically significant. In the fully adjusted model of the variables, a significant relationship was observed between breakfast consumption and both healthy and unhealthy dietary patterns. Specifically, students who typically consume breakfast exhibit greater consumption of oatmeal and fruits, as well as healthier dinner choices. Conversely, they exhibit lower consumption of fast food, sugary drinks, and juices. In particular, in highly developed countries, along with the mentioned foods, consumption of dairy was linked to breakfast consumption in a positive way, while alcohol consumption was negatively associated. CONCLUSION University students who eat breakfast on a regular basis maintain a healthier diet in comparison to those who do not, irrespective of their country's level of human development.
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Contribution of non-socioeconomic factors to healthy quality of life in socioeconomically deprived patients with advanced gastrointestinal cancer: Measuring attributable fraction.
An, Z, Nie, J, Huang, Y, Fang, P, Meng, X, Cai, C, Yu, L
Journal of advanced nursing. 2024;(3):1154-1165
Abstract
BACKGROUND The quality of life of patients with advanced gastrointestinal cancer is seriously impaired, and socioeconomic deprivation often has a serious impact on their quality of life. However, little is known about the relative contribution of non-socioeconomic factors to the quality of life of patients with advanced gastrointestinal cancer with socioeconomic deprivation. AIM: This study aims to investigate the situation and predictors of quality of life of patients with socioeconomic deprivation and evaluate the independent effects of some non-socioeconomic factors. DESIGN A retrospective study based on cross-sectional design. METHODS Data were obtained from 1075 patients with advanced gastrointestinal cancer who received family palliative treatment in the hospice ward of Zhongnan Hospital of Wuhan University from March 2010 to October 2020, including demographic and clinical questionnaires, Karnofsky Performance Status scale and Cancer Pain and Quality of Life Questionnaire of Chinese Cancer Patients. RESULTS The quality of life of patients with advanced gastrointestinal cancer with socioeconomic deprivation is impaired and is affected by gait, self-care ability, abdominal distension, nutritional status, weight loss, constipation and posture. Improvement in six of these factors-gait, self-care ability, abdominal distension, nutritional status, weight loss and posture-has an independent positive impact on the development of a healthy quality of life for patients. CONCLUSIONS Gait, self-care ability, abdominal distension, nutritional status, weight loss and posture are important determinants of healthy quality of life in patients with advanced gastrointestinal cancer with socioeconomic deprivation, and early identification and strength management of these non-socioeconomic factors may neutralize the negative impact of socioeconomic factors on the quality of life. IMPLICATIONS FOR PRACTICE This study provides new ideas and intervention entry points for global nurses in practice innovations to improve the quality of life of socioeconomically deprived patients with advanced gastrointestinal cancer. It enables them to focus on the effectiveness of non-socioeconomic factors in the development and implementation of targeted care plans for patients with advanced gastrointestinal cancer experiencing socioeconomic deprivation globally. REPORTING METHOD This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. PATIENT OR PUBLIC CONTRIBUTION No patient or public contribution.
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Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer.
Rao, AR, Noronha, V, Ramaswamy, A, Kumar, A, Pillai, A, Gattani, S, Sehgal, A, Kumar, S, Castelino, R, Dhekale, R, et al
Clinical oncology (Royal College of Radiologists (Great Britain)). 2024;(1):e61-e71
Abstract
AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.