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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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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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Dairy product consumption, eating habits, sedentary behaviour and physical activity association with bone mineral density among adolescent boys: a cross-sectional observational study.
Kopiczko, A, Czapla, M, Juárez-Vela, R, Ross, C, Uchmanowicz, B
BMC pediatrics. 2024;(1):53
Abstract
BACKGROUND During childhood and adolescence, skeletal microarchitecture and bone mineral density (BMD) undergo significant changes. Peak bone mass is built and its level significantly affects the condition of bones in later years of life. Understanding the modifiable factors that improve bone parameters at an early age is necessary to early prevent osteoporosis. To identify these modifiable factors we analysed the relationship between dairy product consumption, eating habits, sedentary behaviour, and level of physical activity with BMD in 115 young boys (14-17 years). METHODS Bone parameters were measured by dual energy x-ray absorptiometry using paediatric specific software to compile the data. Dairy product consumption and eating habits were assessed by means of a dietary interview. Sedentary behaviour and physical activity was assessed in a face-to-face interview conducted using the International Physical Activity Questionnaire. Data collection on total physical activity level was performed by collecting information on the number of days and the duration of vigorous and moderate intensity (MVPA) and average daily time spent in sitting (SIT time). RESULTS The strongest relationships with BMD in distal part of forearm were found for moderate plus vigorous activity, sit time, and intake of dairy products, intake of calcium, protein, vitamin D, phosphorus from diet. Relationships between BMD, bone mineral content (BMC) in the distal and proximal part of the forearm and PA, sit time and eating parameters were evaluated using the multiple forward stepwise regression. The presented model explained 48-67% (adjusted R2 = 0.48-0.67; p < 0.001) of the variance in bone parameters. The predictor of interactions of three variables: protein intake (g/person/day), vitamin D intake (µg/day) and phosphorus intake (mg/day) was significant for BMD dis (adjusted R2 = 0.59; p < 0.001). The predictor of interactions of two variables: SIT time (h/day) and dairy products (n/day) was significant for BMD prox (adjusted R2 = 0.48; p < 0.001). Furthermore, the predictor of interactions dairy products (n/day), protein intake (g/person/day) and phosphorus intake (mg/day) was significant for BMC prox and dis (adjusted R2 = 0.63-0.67; p < 0.001). CONCLUSIONS High physical activity and optimal eating habits especially adequate intake of important dietary components for bone health such as calcium, protein, vitamin D and phosphorus affect the mineralization of forearm bones.
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N-Acetylcysteine combined with prednisolone treatment shows better hearing outcome than treatment with prednisolone alone for patients with idiopathic sudden sensorineural hearing loss: a retrospective observational study.
Kouka, M, Bevern, N, Bitter, J, Guntinas-Lichius, O
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2024;(1):107-116
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Abstract
OBJECTIVES Internationally, corticosteroids are still the mainstay treatment for patients with idiopathic sudden sensorineural hearing loss (ISSHL). This is a retrospective monocentric study investing the impact of adding N-acetylcysteine (NAC) to prednisolone treatment on patients with ISSHL at a tertiary university otorhinolaryngology department. METHODS 793 patients (median age 60 years; 50.9% women) with a new diagnosis of ISSHL from 2009 to 2015 were included in the study. 663 patients received NAC administration in addition to standard tapered prednisolone treatment. Univariate and multivariable analysis were performed to identify independent factors regarding negative prognosis of hearing recovery. RESULTS Mean initial ISSHL and hearing gain after treatment in 10-tone pure tone audiometry (PTA) were 54.8 ± 34.5 dB and 15.2 ± 21.2 dB, respectively. In univariate analysis, treatment with prednisolone and NAC was associated with a positive prognosis of hearing recovery in the Japan classification in 10-tone PTA. In multivariable analysis on Japan classification in 10-tone PTA including all significant factors from univariate analysis, negative prognosis of hearing recovery were age > median (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.139-2.385; p = 0.008), diseased opposite ear (OR 3.049; CI 2.157-4.310; p < 0.001), pantonal ISSHL (OR 1.891; CI 1.309-2.732; p = 0.001) and prednisolone alone without NAC treatment (OR 1.862; CI 1.200-2.887; p = 0.005). CONCLUSIONS Prednisolone treatment combined with NAC resulted in better hearing outcomes in patients with ISSHL than treatment without NAC.
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Prevalence of chronic kidney disease in Tunisian diabetics: the TUN-CKDD survey.
Labidi, J, Harzallah, A, Kaab, BB, Mami, I, Agrebi, S, Azzabi, A, Chargui, S, Hadj-Brahim, M, Hammouda, M, Azaiez, S, et al
BMC nephrology. 2024;(1):67
Abstract
BACKGROUND In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). METHODS This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. RESULTS The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. CONCLUSIONS In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices.
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Pedal medial arterial calcification in diabetic foot ulcers: A significant risk factor of amputation and mortality.
Chen, L, Chen, D, Gong, H, Wang, C, Gao, Y, Li, Y, Tang, W, Zha, P, Ran, X
Journal of diabetes. 2024;(4):e13527
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Abstract
AIMS: Pedal medial arterial calcification (MAC) is frequently observed in individuals with diabetic foot ulcers (DFUs). However, the impact of pedal MAC on individuals with DFUs remains uncertain. The main aim of this study was to evaluate the association between pedal MAC with amputation and mortality outcomes. METHODS A prospective, observational cohort study was conducted at West China Hospital from January 2012 to December 2021. Logistic regression analyses, Kaplan-Meier survival method, and Cox proportional hazards models were employed to evaluate the relationship between pedal MAC and amputation as well as mortality. RESULTS A total of 979 patients were enrolled in the study. Peripheral artery disease (PAD) was observed in 53% of patients with DFUs, and pedal MAC was found in 8%. Over a median follow-up of 46 (23-72) months, foot amputation was performed on 190 patients, and mortality occurred in 246 patients. Pedal MAC showed a significant association with amputation both in unadjusted analysis (odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.86-4.76, p < .001) and after adjusting sex, age, albumin levels, hemoglobin levels, and diabetic retinopathy status (OR 2.29, 95% CI 1.33-3.93, p = .003). The risk of amputation was found to be twofold higher in individuals with PAD and pedal MAC compared to those with PAD alone (OR 2.05, 95% CI 1.10-3.82, p = .024). Furthermore, the presence of pedal MAC was significantly associated with an increased risk of mortality (p = .005), particularly among individuals with DFUs but without PAD (HR 4.26, 95% CI 1.90-9.52, p < .001), rather than in individuals presenting with both DFUs and PAD. CONCLUSION The presence of pedal MAC is significantly associated with both amputation and mortality in individuals with DFUs. Moreover, pedal MAC could provide additional value to predict amputation other than PAD.
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Perioperative point-of-care-testing of plasmacholinesterases identifies older patients at risk for postoperative delirium: an observational prospective cohort study.
Gruendel, MS, Brenneisen, W, Wollborn, J, Haaker, G, Meersch, M, Gurlit, S, Goebel, U
BMC geriatrics. 2024;(1):136
Abstract
BACKGROUND Postoperative delirium (POD) is a severe perioperative complication that may increase mortality and length-of-stay in older patients. Moreover, POD is a major economic burden to any healthcare system. An altered expression of Acetylcholine- and Butyrylcholinesterases (AChE, BuChE) due to an unbalanced neuroinflammatory response to trauma or an operative stimulus has been reported to play an essential role in the development of POD. We investigated if perioperative measurement of cholinesterases (ChEs) can help identifying patients at risk for the occurrence of POD in both, scheduled and emergency surgery patients. METHODS This monocentric prospective observational cohort study was performed in a tertiary hospital (departments of orthopaedic surgery and traumatology). One hundred and fifty-one patients aged above 75 years were enrolled for scheduled (n = 76) or trauma-related surgery (n = 75). Exclusion criteria were diagnosed dementia and anticholinergic medication. Plasma samples taken pre- and postoperatively were analysed regarding AChE and BuChE activity. Furthermore, perioperative assessment using different cognitive tests was performed. The type of anaesthesia (general vs. spinal anaesthesia) was analysed. Primary outcome was the incidence of POD assessed by the approved Confusion Assessment Method (CAM) in combination with the expression of AChE and BuChE. RESULTS Of 151 patients included, 38 (25.2%) suffered from POD; 11 (14%) in scheduled and 27 (36%) in emergency patients. AChE levels showed no difference throughout groups or time course. Trauma patients had lower BuChE levels prior to surgery than scheduled patients (p < 0.001). Decline in BuChE levels correlated positively with the incidence of POD (1669 vs. 1175 U/l; p < 0.001). Emergency patients with BuChE levels below 1556 U/L were at highest risk for POD. There were no differences regarding length of stay between groups or incidence of POD. The type of anaesthesia had no influence regarding the incidence of POD. Only Charlson Comorbidity Index and Mini Nutrition Assessment demonstrated reliable strength in respect of POD. CONCLUSIONS Perioperative measurement of BuChE activity can be used as a tool to identify patients at risk of POD. As a point-of-care test, quick results may alter the patients' course prior to the development of POD. TRIAL REGISTRATION https://drks.de/search/de/trial/DRKS00017178 .