In western countries, the proportion of people over age 60 is increasing faster than any other group. This is linked to higher rates of obesity. Older age, co-morbidities and obesity are all ...associated with frailty syndrome. In the core of both frailty and sarcopenia there are dysfunction and deterioration of the muscle and the fat tissues. This overview interlinks the phenotypes presented in older adults such as sarcopenia and frailty—alone and with relation to obesity, muscle function and fat tissue accumulation.
Observational studies have well described the loss of muscle mass and strength through the years of adult life, both components of frailty and sarcopenia. They have shown that these changes are associated with dysmetabolism and functional deterioration, independent of common explanatory variables. In the metabolic mechanism core of this link, insulin resistance and higher ectopic fat accumulation may play a role. Basic experiments have partially validated this hypothesis. Whether there is a synergistic effect of obesity and frailty phenotype on morbidity risk is still questionable and currently under investigation; however, few cohort studies have shown that the frail–obese or sarcopenic–obese group have higher probability for metabolic complications.
Muscle mass loss and fat accumulation in the muscle in the elderly, with or without the presence of obesity, may explain some of the functional and metabolic defects shown in the frail, sarcopenic population.
•Sarcopenia and frailty are interlinked via muscle tissue dynamics.•The loss of muscle strength is a major factor, in addition to the loss of its mass.•Obesity and frailty/sarcopenia may interact with respect to metabolic risk.•Mechanism of interaction involves hormonal dysregulation and inflammatory pathways.
5-hydroxymethylcytosine (5hmC) is an epigenetic DNA modification. Tissue-specific reduction in global 5hmC levels has been associated with various types of cancer. One of the challenges associated ...with detecting 5hmC levels is its extremely low content, especially in blood. The gold-standard for reliable global 5hmC quantitation is liquid chromatography-tandem mass spectroscopy (LC-MS/MS) operating in a multiple reaction monitoring (MRM) mode. Difficulties associated with 5hmC detection by LC-MS/MS include its low abundance, low ionization efficiency and possible ion suppression from co-eluted compounds. Hence, detecting 5hmC levels in blood samples for diagnosis of leukemia and other blood malignancies presents a unique challenge. To overcome these difficulties we introduce a simple chemoenzymatic method for specifically tagging 5hmC, resulting in an eight-fold increase in detection sensitivity. We demonstrate that we could quantitatively detect 5hmC levels in various human tissues, including blood samples from healthy individuals and leukemia patients, using the most basic quadrupole mass-analyzer instrument and only 200 ng of DNA. The limit of detection (LOD) of our technique is 0.001% 5hmC from 300 ng DNA, sufficient for future mass-spectroscopy based diagnostics of diseases associated with low 5hmC levels such as leukemia.
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•Specific chemoenzymatic tagging of 5hmC results in eight folds signal enhancement in LC-MS/MS measurements.•A detection limit of 0.001% 5hmC from only 300 ng (9 fmol) DNA achieved with a basic LC-MS/MS device.•A reduction in %5hmC in leukemia patients was detected relative to healthy individuals, from only 200 ng DNA.•Proven reproducibility and accuracy of %5hmC levels in blood, solid tissues and synthetic DNA samples.•A potential for routine 5hmC% detection in clinical laboratories, using cost-effective LC/MS-MS devices.
•Minimally supervised home-based resistance training (MSHBRT): ≤15% of sessions.•In elderly, MSHBRT is effective in enhancing muscle strength.•The effect on muscle strength of MSHBRT may be inferior ...to resistance-training.
In an attempt to define feasible means to improve compliance with current recommendations on resistance training in older subjects, published evidence on the efficacy and safety of minimally supervised home-based resistance training (MSHBRT) on muscle strength and functionality was systematically evaluated in this population segment for the first time. We performed a meta-analysis using the following data sources: MEDLINE (Ovid), EMBASE and Cochrane, with a total of 1160 subjects with a mean age of 72 ± 6.3 years. MSHBRT modestly increased lower body strength (MD 0.6 Kg, 95% CI, 0.16–1.04) in a diverse population of older adults including subjects with significant age-related diseases. Although earlier evidence indicates that larger increments in muscle performance and function can be attained through more intense and directly supervised resistance training, MSHBRT may comprise a useful and inexpensive method to preserve and even enhance lower body muscle strength in older adults.
Non-functioning pituitary adenomas Greenman, Yona, MD; Stern, Naftali, MD
Best Practice & Research Clinical Endocrinology & Metabolism,
10/2009, Letnik:
23, Številka:
5
Journal Article
Recenzirano
Non-functioning pituitary tumours are mostly of gonadotroph cell origin and are devoid of humoral hypersecretory syndromes. They are usually large at the time of diagnosis, commonly presenting with ...headaches, visual field defects and hypopituitarism. Trans-sphenoidal surgery remains the treatment of choice for rapid decompression of neighbouring structures, often bringing to normalisation or improvement of visual and pituitary function. The management of patients with postoperative residual tumours is still a matter of debate and may include observation alone, the use of dopamine agonists or radiation therapy. There are no controlled or comparative studies of the available therapeutic options; therefore, recommendations are not evidence based. Patients need long-term follow-up for the detection and treatment of hypopituitarism, visual dysfunction and tumour growth that may develop over time.
Background
Increased oxidative stress in diabetes increases nitric oxide (NO) oxidation and low l‐arginine (Arg) could further reduce NO and impair vascular function, thereby accelerating, in the ...long run, vascular complications. We therefore measured Arg and asymmetric dimethylarginine (ADMA) levels in patients with type 2 diabetes mellitus (T2DM) and healthy controls. Additionally, we observed the diabetic individuals over time to see if Arg and asymmetric dimethylarginine predicted T2DM complications.
Methods
We examined baseline serum Arg and ADMA levels in a cohort of 105 participants with type 2 diabetes and compared them with an age‐ and weight‐matched nondiabetic group of 137 individuals who served as a reference population. Additionally, we assessed whether Arg and/or ADMA predicted macrovascular and microvascular complications over 6 years of follow‐up.
Results
Serum Arg was lower in individuals with T2DM than in controls (64 ± 28 vs 75 ± 31 μmol/L; P = .009) and inversely related to hemoglobin A1c (r = −0.2; P = .002). Over follow‐up, we observed that participants with T2DM in the lowest quartile of Arg had increased risk for the subsequent evolution of nephropathy, peripheral neuropathy, and composite microvascular complications (odds ratio OR = 5.5; 95% confidence interval CI −1.9 to 16; P = .002). The highest ADMA quartile was associated with increased risk for both microvascular (OR = 4.5; 95% CI −1.4 to 14.1; P = .009) and 6.5‐year incident macrovascular complications (OR = 8.3; 95% CI 1.9‐35.5; P = .004).
Conclusion
l‐Arginine levels are lower in individuals with T2DM than in matched controls. Both low Arg and high ADMA, independent of each other and adjusted for classical risk factors, predict the incidence of microvascular complications.
There is recent concern regarding the documented mismatch between demand and supply, vis-à-vis the growing need for trained endocrinologists unmet by parallel rise in the world workforce of ...endocrinologist. Due to the increasing complexity of disease in inpatients, in recent years we have experienced a growing demand for inpatient endocrine consults. Surprisingly, the need for the endocrinology subspecialty in the overall care of inpatients in the current setting of general hospitals has received little attention.
A retrospective analysis of endocrine consult service based on solicited consults carried out during 3 consecutive months.
During 3 months, there were 767 consults, comprised of 156 diabetes referrals and 611 endocrine/metabolic consult requests. The 611 "non-glucocentric" consult requests were related to 295 inpatients (2.1 ± 2.7 consults/patient). Mean patient age was 58.9 ± .18 years (range 21-92), with some F/M preponderance (58/42%). Requests for endocrine consults were evenly distributed (49.8%, 50.2%) between internal medicine and surgery wards. Case distribution was as follows: thyroid 45.4%, calcium & bone 11.5%, pituitary 12%, adrenal 10% and all others 8.1-0.7%. The mean response time was 4.4 ± 2.7 h. The consults had a discernible effect on the patients' disease management in 60% of the patients. Of these, the consults modified the hospital treatment in 74%, the discharge treatment recommendations in 19% and the diagnosis in 7%.
At a large medical center, endocrine consults were requested for ~ 3.3% of all admitted inpatients. The endocrine consults modified pre-consult diagnosis or treatment in ~ 60% of the cases. Contrary to its common image as an exclusively outpatient-based subspecialty, endocrinology practiced by specialists and endocrine trainees has a notable role in the daily care of inpatients admitted to a referral general hospital.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study was designed to improve blood glucose level predictability and future hypoglycemic and hyperglycemic event alerts through a novel patient‐specific supervised‐machine‐learning (SML) ...analysis of glucose level based on a continuous‐glucose‐monitoring system (CGM) that needs no human intervention, and minimises false‐positive alerts. The CGM data over 7 to 50 non‐consecutive days from 11 type‐1 diabetic patients aged 18 to 39 with a mean HbA1C of 7.5% ± 1.2% were analysed using four SML models. The algorithm was constructed to choose the best‐fit model for each patient. Several statistical parameters were calculated to aggregate the magnitudes of the prediction errors. The personalised solutions provided by the algorithm were effective in predicting glucose levels 30 minutes after the last measurement. The average root‐mean‐square‐error was 20.48 mg/dL and the average absolute‐mean‐error was 15.36 mg/dL when the best‐fit model was selected for each patient. Using the best‐fit‐model, the true‐positive‐hypoglycemia‐prediction‐rate was 64%, whereas the false‐positive‐ rate was 4.0%, and the false‐negative‐rate was 0.015%. Similar results were found even when only CGM samples below 70 were considered. The true‐positive‐hyperglycemia‐prediction‐rate was 61%. State‐of‐the‐art SML tools are effective in predicting the glucose level values of patients with type‐1diabetes and notifying these patients of future hypoglycemic and hyperglycemic events, thus improving glycemic control. The algorithm can be used to improve the calculation of the basal insulin rate and bolus insulin, and suitable for a closed loop “artificial pancreas” system. The algorithm provides a personalised medical solution that can successfully identify the best‐fit method for each patient.
Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and ...vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a 'recovery' pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies.
A balanced diet and weight loss are the first lines of treatment for the prevention of metabolic syndrome (MS). Dietary strategies may include changing the composition of macronutrients, adopting a ...particular dietary pattern as a Mediterranean diet. However, the role of micronutrients, particularly potassium, in the propensity for or treatment of the syndrome is unclear. The study aimed to examine the relationship between the presence of the MS and its risk factors and the 24-h potassium excretion as the most valid proxy for dietary intake. The analyses were performed as part of the national survey estimating sodium and other electrolytes excretion conducted between 2014–2016 in Israel. The survey included urine collection, anthropometric and blood pressure measurements, and a comprehensive medical questionnaire that included details on the intake of medications that may affect electrolyte secretion. A model was constructed to evaluate the probability for the MS. MS score and its probability were examined in relation to potassium excretion at different levels and in stratification to sex. A total of 581 participants were included in the analysis. The mean potassium excretion was 2818 ± 1417 mg. The prevalence of the MS was 18.5% among participants with above-average potassium excretion and about 10.4% among participants with lower-than-average excretion (p = 0.007). A dose–response relationship was observed between MS score and potassium: the higher the score, the lower was the excretion of potassium. Potassium excretion, rather than sodium excretion, correlated with all components of the MS and even predicted MS independently from other variables. This is the first study based on a national survey showing that potassium consumption, as represented by daily excretion in urine, is inversely related to the presence of MS components after adjustment for several leading variables and careful exclusion of participants taking drugs which may interfere in potassium excretion.
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