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Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease
Get PDFInsulin resistance and metabolic dysfunction in the brain are considered to be the pathophysiological core of sporadic Alzheimer's disease (sAD). In line with that fact, nutrients that could have therapeutic effects at this level have been investigated as possible targets in AD therapy. Galactose, an epimer of glucose, may serve as an alternative source of energy, and given orally may stimulate secretion of the incretin hormone glucagon-like peptide-1 (GLP-1). Our preliminary research indicated that oral galactose might prevent development of memory impairment in a rat model of sAD generated by intracerebroventricular administration of streptozotocin (STZ-icv). Here, we explored whether chronic oral galactose treatment could have beneficial effects on cognitive deficits already manifested at the time of initiation of galactose treatment in adult STZ-icv rats (treatment initiated 1 month after STZ-icv injection). The results clearly show that a 2-month exposure to oral galactose (200 mg/kg/day administered in a drink ad libitum) normalises impaired learning and memory functions. Memory improvement was accompanied by an improvement in brain glucose hypometabolism measured by 18fluorodeoxyglucose-positron emission tomography neuroimaging and by increments in active GLP-1 plasma levels as well as by an increased expression of GLP-1 receptors in the hippocampus and hypothalamus. Our findings provide strong evidence of beneficial effects of oral galactose treatment in the STZ-icv rat model of sAD and present possible underlying mechanisms including both direct effects of galactose within the brain and indirect GLP-1-induced neuroprotective effects that might open a new, dietary-based strategy in sAD treatment
Assessing serum albumin concentration, lymphocyte count and prognostic nutritional index might improve prognostication in patients with myelofibrosis
Get PDFBACKGROUND:
Primary and secondary myelofibrosis (PMF and SMF) are malignant diseases of hematopoietic stem cell characterized by the neoplastic myeloproliferation and a strong inflammatory milieu. The prognostic nutritional index (PNI) integrates information on albumin and absolute lymphocyte count (ALC) and reflects the inflammatory, nutritional and immune status of a patient. The clinical and prognostic significance of albumin, ALC and PNI in patients with myelofibrosis has not been previously investigated. ----- METHODS:
We retrospectively analyzed a cohort of 83 myelofibrosis patients treated in our institution from 2006 to 2017. Albumin, ALC and PNI were assessed in addition to other disease specific markers. ----- RESULTS:
The PMF and SMF patients had significantly lower ALC and PNI but similar albumin compared to controls. Lower albumin was significantly associated with older age and parameters reflecting more aggressive disease biology (e.g. anemia, lower platelet levels, higher lactate dehydrogenase (LDH), circulatory blasts, transfusion dependency, blast phase disease), inflammation (higher C reactive protein (CRP), constitutional symptoms) and higher degree of bone marrow fibrosis. Lower ALC was significantly associated with lower white blood cells (WBC) and lower circulatory blasts. Low PNI was associated with lower albumin, lower ALC, anemia, lower WBCs, lower serum iron and lower transferrin saturation. There was no difference in albumin, ALC and PNI regarding the driver mutations. In multivariate analysis adjusted for age and gender, low albumin (hazard ratio [HR] = 4.61, P = 0.001), low ALC (HR = 3.54, P = 0.004) and Dynamic International Prognostic Scoring System (DIPSS) (HR = 2.45, P = 0.001) were able to predict inferior survival independently of each other. Accordingly, low PNI (HR = 4.32, P < 0.001) predicted poor survival independently of DIPSS (HR = 3.31, P < 0.001). ----- CONCLUSION:
Assessing albumin, ALC and PNI might improve prognostication in patients with myelofibrosis and could assist in recognition of patients under increased risk of death
Increased arterial stiffness – similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well-controlled hypertension
Get PDFPURPOSE:
Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. ----- MATERIALS AND METHODS:
A total of 89 inflammatory bowel disease patients (60 patients with Crohn's disease and 29 patients with ulcerative colitis, age range 20-64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25-69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. ----- RESULTS:
Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL-cholesterol, and higher AIx (17.4% vs. 9.8%) (all p < .05). Higher PWV was associated with age and duration of inflammatory bowel disease in the linear regression model. PWV values were higher in hypertensive patients in the first two age quartiles while interestingly, in the last two quartiles, PWV was lower than in inflammatory bowel disease group of patients. ----- CONCLUSIONS:
Chronic subclinical inflammation is responsible for dyslipidemia and accelerated atherosclerosis which consequently alterates arterial elasticity. Inflammatory bowel disease and its duration should also be considered a risk factor for subclinical organ damage, as well as hypertension
Continuous remote monitoring of COPD patients—justification and explanation of the requirements and a survey of the available technologies
Get PDFRemote patient monitoring should reduce mortality rates, improve care, and reduce costs. We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers. Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field. We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain. Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO2) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients. We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise. We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters. The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems
The impact of hyperosmolarity on long-term outcome in patients presenting with severe hyperglycemic crisis: a population based study
Get PDFAIMS:
We compared characteristics of patients with hyperglycemic hyperosmolar state (HHS) and patients with severe hyperglycemia without the signs of hyperosmolarity and ketoacidosis; analyzed long-term all-cause mortality and potential prognostic factors. ----- METHODS:
The studied population included 261 749 adults. HHS was diagnosed in patients with plasma glucose >33.0 mmol/L, ketonuria 320 mmol/L. Patients with plasma glucose >33.0 mmol/L, ketonuria <1+ and serum osmolarity <320 mmol/L were considered as controls (nHHS). ----- RESULTS:
During the 5-year period, we observed 68 episodes of HHS in 66 patients and 51 patients with nHHS. Patients with HHS were significantly older, had lower BMI, higher serum C-reactive protein and used diuretics and benzodiazepines more frequently. Mortality rates one, three and 12 months after admission were 19.0, 32.1 and 35.7% in the HHS group, and 4.8, 6.3 and 9.4% in the nHHS group (P<0.001). However, after adjustment for patient age, these differences were not statistically significant. In multivariate Cox regression in HHS group, mortality was positively associated with age, male gender, leukocyte count, amylase, presence of dyspnea and altered mental status, and the use of benzodiazepines, ACE inhibitors and sulphonylureas, while it was inversely associated with plasma glucose, bicarbonate, and the use of thiazides and statins. A nomogram derived from these variables had an accuracy of 89% in predicting lethal outcome. ----- CONCLUSIONS:
Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes
Arterial stiffness: a helpful guide to prognosis and therapy in populations with a high baseline cardiovascular risk
Get PDFEULAR ‘points to consider’ for the conduction of workforce requirement studies in rheumatology
Get PDFObjective: Current methods used for forecasting workforce requirements in rheumatology are disparate, as are the parameters incorporated into workforce projection studies. The objective of these European League Against Rheumatism (EULAR points to consider (PTC) is to guide future workforce studies in adult rheumatology in order to produce valid and reliable manpower estimates.
----- Methods: The EULAR Standardised Operating Procedures were followed. A multidisciplinary task force with experts including patients with rheumatic diseases from 11 EULAR countries and the USA was assembled. A systematic literature review (SLR) was conducted to retrieve workforce models in rheumatology and other medical fields. PTC were based on expert opinion informed by the SLR, followed by group discussions with consensus obtained through informal voting. The level of agreement with the PTC was voted anonymously.
----- Results: A total of 10 PTC were formulated. The task force recommends models integrating supply (=workforce available in rheumatology), demand (=health services requested by the population) and need (=health services that are considered appropriate to serve the population). In general, projections of workforce requirements should consider all factors relevant for current and future workload in rheumatology inside and outside of direct patient care. Forecasts of workforce supply should consider demography and attrition of rheumatologists, as well as the effects of new developments in healthcare. Predictions of future need/demand should take demographic, sociocultural and epidemiological development of the population into account.
----- Conclusion: These EULAR-endorsed PTC will provide guidance on the methodology and the parameters to be applied in future national and international workforce requirement studies in rheumatology
Variability analysis and inter-genotype comparison of human respiratory syncytial virus small hydrophobic gene
Get PDFBACKGROUND: Small hydrophobic (SH) gene is one of the mostly diverse genomic regions of human respiratory
syncytial virus (HRSV). Its coding region constitutes less than 50% of the complete gene length, enabling SH gene
to be highly variable and the SH protein highly conserved. In standard HRSV molecular epidemiology studies, solely
sequences of the second hypervariable region of the glycoprotein gene (HVR2) are analyzed. To what extent do the
strains identical in HVR2 differ elsewhere in genomes is rarely investigated. Our goal was to investigate whether
diversity and inter-genotype differences observed for HVR2 are also present in the SH gene. ----- METHODS: We sequenced 198 clinical samples collected within a limited area and time frame. In this HRSV
collection, rapid and significant changes in HVR2 occurred.
Results: Over 20% of strains from this pool (containing HRSV genotypes NA1, ON1, GA5, BA9 and BA10) would be
incorrectly assumed to be identical to another strain if only the HVR2 region was analysed. The majority of
differences found in SH gene were located in the 5′ untranslated region (UTR). Seven indels were detected, one
was genotype GA5 specific. An in-frame deletion of 9 nucleotides (coding for amino acids 49–51) was observed in
one of group A strains. Fifteen different SH protein sequences were detected; 68% of strains possessed the
consensus sequence and most of others differed from the consensus in only one amino acid (only 4 strains differed
in 2 amino acids). The majority of differing amino acids in group A viruses had the same identity as the
corresponding amino acids in group B strains. When analysis was restricted to strains with identical HVR2
nucleotide sequences and differing SH protein sequences, 75% of differences observed in the SH ectodomain were
located within region coding for amino acids 49–51. -----
CONCLUSIONS: Basing HRSV molecular epidemiology studies solely on HVR2 largely underestimates the complexity of
circulating virus populations. In strain identification, broadening of the genomic target sequence to SH gene would
provide a more comprehensive insight into viral pool versatility and its evolutionary processes
Intramedullary spinal cord lipoma mimicking a late subacute hematoma
Get PDFSpinal cord lipomas are rare and benign tumors which may cause progressive neurological deficits due to their local expansion. We present the case of a 59-year-old male patient with severe lumbosacral pain and slowly progressive paresis of the right leg, misdiagnosed with degenerative spine disease. Repeated magnetic resonance (MR) T1-weighted images of the thoracic spine suggested a subacute intramedullary hematoma. Due to progression of the neurological deficit, the patient was referred to a neurosurgeon, who indicated surgical evacuation of the hematoma. The intraoperative finding revealed an intramedullary spinal cord lipoma, which was later confirmed by histological analysis. Since subacute intramedullary hematomas and intramedullary spinal cord lipomas present with similar clinical and radiological features, diffusion-weighted MR imaging should be used to distinguish these entities