Changes in characteristics of hospitalized heart failure patients in ten years: a single-center study

SummaryBackgroundProgress in therapy and the ageing patients hospitalized with heart failure may have impacted the characteristics of this patients.AimsWe compared epidemiological data of patients admitted with heart failure during two periods separated by a 10 year interval.MethodsCharacteristics of 353 heart failure patients recruited between 2002 and 2004 with those of 304 heart failure patients recruited between 1992 and 1994 were compared retrospectively.ResultsThere is now a majority of male patients (56.4%) not found ten years ago. The average age is unchanged (75.1±11 then 76.4±11 years) even though the proportion of patients aged over 70 years has increased (75% versus 70%). Hospital length of stay has fallen from 14±9 to 10±7 days. Hospital mortality (8%) are identical. The two main etiologies remain coronary and hypertensive heart disease at 29 and 24% respectively but these proportions are lower than ten years ago (42 and 28% respectively). The ejection fraction is more often preserved (56%) than before (44%). Increased prescription of inhibitors of the renin-angiotensin system and beta-blockers is confirmed. Post-hospital and total mortality has fallen by 50 and 30% from 30 to 16% and 35 to 24% respectively at the expense of a 25% increase in the frequency of hospital readmissions from 29 to 38%.ConclusionEven if mortality has declined, heart failure remains a major public health burden with a significant number of hospital readmissions. Other approaches such as therapeutic education must therefore be developed

γ-Secretase modulators show selectivity for γ-secretase–mediated amyloid precursor protein intramembrane processing

The aggregation of β-amyloid peptide 42 results in the formation of toxic oligomers and plaques, which plays a pivotal role in Alzheimer's disease pathogenesis. Aβ42 is one of several Aβ peptides, all of Aβ30 to Aβ43 that are produced as a result of γ-secretase–mediated regulated intramembrane proteolysis of the amyloid precursor protein. γ-Secretase modulators (GSMs) represent a promising class of Aβ42-lowering anti-amyloidogenic compounds for the treatment of AD. Gamma-secretase modulators change the relative proportion of secreted Aβ peptides, while sparing the γ-secretase–mediated processing event resulting in the release of the cytoplasmic APP intracellular domain. In this study, we have characterized how GSMs affect the γ-secretase cleavage of three γ-secretase substrates, E-cadherin, ephrin type A receptor 4 (EphA4) and ephrin type B receptor 2 (EphB2), which all are implicated in important contexts of cell signalling. By using a reporter gene assay, we demonstrate that the γ-secretase–dependent generation of EphA4 and EphB2 intracellular domains is unaffected by GSMs. We also show that γ-secretase processing of EphA4 and EphB2 results in the release of several Aβ-like peptides, but that only the production of Aβ-like proteins from EphA4 is modulated by GSMs, but with an order of magnitude lower potency as compared to Aβ modulation. Collectively, these results suggest that GSMs are selective for γ-secretase–mediated Aβ production

Risk-Stratified Screening for Colorectal Cancer Using Genetic and Environmental Risk Factors:A Cost-Effectiveness Analysis Based on Real-World Data

Background &amp; Aims: Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death. Methods: Risk predictions for CRC and competing causes of death from a large community-based cohort were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40–60 years), end age (70–85 years), and screening interval (5–15 years). The outcomes included personalized screening ages and intervals and cost-effectiveness compared with uniform colonoscopy screening (ages 45–75, every 10 years). Key assumptions were varied in sensitivity analyses. Results: Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every 5 years from ages 40 to 85 for high-risk individuals. Nevertheless, on a population level, risk-stratified screening would increase net quality-adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening or reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test. Conclusions: Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small.</p

Epilepsie du sujet âgé : expérience du service de Neurologie du CHU Gabriel Touré de Bamako, Mali

Background: Epilepsy is a common condition in the elderly, although it is poorly documented in our context. This work aims at determine the epidemiological and clinical characteristics of epilepsy in elderly people. Patients and Methods: This was a prospective study over a period of one year in the Department of Neurology of Gabriel Toure Teaching Hospital (CHU) in Mali. Were eligible, all subjects aged 50 years or older that had at least two documented seizures, recorded and reported by the patient or his family. For the diagnosis of the seizure, we used validated form of Limoges Institute. Results: During the study period, 1753 patients were admitted to the neurology department of CHU Gabriel Touré, 39 cases of epilepsy in the elderly have been diagnosed, i.e. 2.2% of patients in the department. The average age was 63 years, ranging from 50 to 84 years. Partial seizures were the most represented with 43.6% of cases. Symptomatic epilepsy was found in 82.1% of patients, 18% of patients had no definite etiology. The causes were dominated by vascular epilepsyin 25 cases (64.1%). Treatment was started in all patients with a success after 6 months. Sodium valproate was the most prescribed as first-line therapy 51.3% (20 patients), followed by carbamazepine (41%). Conclusion: This prospective study of epilepsy in the elderly confirms the high prevalence of this  disease in this age group. With the multiple illnesses in the elderly, this condition will require a multidisciplinary management.Introduction : La prévalence élevée de l’épilepsie chez le sujet âgé est bien documentée. L’épilepsie chez la personne âgée reste très peu rapportée dans notre contexte. Ce travail a pour objectif de déterminer les caractéristiques épidémiologiques et cliniques de cette pathologie chez le sujet âgé. Patients et Méthodes : Il s’agissait d’une étude prospective réalisée sur une période d’un an dans le service de Neurologie du Centre Hospitalier Universitaire (CHU) Gabriel Touré au Mali. Ont été éligibles, tous les sujets âgés de 50 ans ou plus qui ont présenté au moins deux crises épileptiques documentées, constatées et rapportées par le patient et /ou son entourage. Pour le diagnostic de la crise, nous avons utilisé le questionnaire validé de L’Institut de Neurologie et Epidémiologie Tropicale de Limoges. Résultats : Durant la période d’étude, 1753 patients ont été admis dans le service de Neurologie du CHU Gabriel Touré ; 39 cas d’épilepsie du sujet âgé ont été diagnostiqués, soit 2,2% des malades dans le service. L’âge moyen était de 63 ans avec des extrêmes de 50 à 84 ans. Les crises partielles étaient les plus représentées, soit 69,2% des cas. Une épilepsie symptomatique a été retrouvée chez 82,1% des patients ; 18% des patients n’avaient pas d’étiologie bien déterminée. Les étiologies étaient dominées par les causes vasculaires, soit 64,1% (25) des cas. Un traitement a été mis en route chez tous nos patients avec un succès après 6 mois. Le Valproate de sodium (VPA) a été la molécule la plus prescrite en première intention soit 51,3% (20) des patients, suivi de la Carbamazépine (41%). Conclusion : Au vu de la poly pathologie, l’épilepsie du sujet âgé nécessite une prise en charge pluridisciplinaire

Isothermal folding of G-quadruplexes

Thermodynamic studies of G-quadruplex stability are an essential complement to structures obtained by NMR or x-ray crystallography. An understanding of the energetics of quadruplex folding provides a necessary foundation for the physical interpretation of quadruplex formation and reactivity. While thermal denaturation methods are most commonly used to evaluate quadruplex stability, it is also possible to study folding using isothermal titration methods. G-quadruplex folding is tightly coupled to specific cation binding. We describe here protocols for monitoring the cation-driven quadruplex folding transition using circular dichroism or absorbance, and for determination of the distribution of free and bound cation using a fluorescence indicator. Together these approaches provide insight into quadruplex folding at constant temperature, and characterize the linkage between cation binding and folding

Cryptococcose extra-neuroméningée au cours du sida à Bamako, Mali (à propos de 2 observations)

Non-neuromeningeal cryptococcosis forms resulting from disseminated infection are rarely reported in African literature and are non-documented in Malian medical ward. We report two clinical observations. Case 1: a 26-year-old patient, carrying the HIV-1 infection, in which the clinical examination revealed skin lesions simulating molluscum contagiosum and functional impairment of the lower limbs. Radiography of the lumbar spine showed vertebral osteolysis on L4–L5. Cryptococcal research remained negative in the CSF but positive at histological examination of the skin lesions and in pathological products of lumbosacral drainage. The treatment with fluconazole and ARV led to a favorable outcome. Case 2: a 42-year-old patient, admitted for fever cough, known for his non-compliance to ARVs and in which the examination found a syndrome of pleural condensation and a painful swelling of the outer third of the right clavicle (around the acromio-clavicular joint). Paraclinical investigations concluded in osteolysis of the acromial end of the right clavicle and an image of the right lung with abundant effusion. Cryptococcal research was positive in the pleural effusion and in the product of aspiration of acromio-clavicular tumefaction, negative in CSF. It seems important to think of a cryptococcal etiology even in the absence of clinical meningeal signs in front of any cutaneous sign and any fluctuating swelling in HIV+ patient

One-year molecular survey of astrovirus infection in turkeys in Poland

The presence of turkey astrovirus (TAstV) was monitored in meat-type turkey flocks in Poland in 2008. Clinical samples (10 individual faecal swabs/flock) from 77 flocks aged 1-19 weeks were collected from different regions of the country. RT-PCR experiments were performed for detection and molecular characterization of TAstV using four sets of primers within the RdRp gene (ORF1b). The prevalence of astrovirus was 34/77 (44.15%) in the flocks tested. TAstV type 2 was associated with 30 of 77 infections (38.9%), either alone or in mixed infections; TAstV type 1 was detected in 9 of 77 flocks (11.6%), either alone or in mixed infections; ANV was detected only in one flock (1.29%) by sequence analysis during this study. Phylogenetic analysis revealed genetic variability in the TAstV strains that were isolated. Some of Polish TAstV-2 strains were genetically related to the North American isolates; however, most of them formed a distinct subgroup of “European” isolates, suggesting their separate origin or evolution. Additionally, due to the high variability of the TAstV sequences, the most suitable method for TAstV typing seems to be sequencing

Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route

Astroglial cells, due to their passive electrical properties, were long considered subservient to neurons and to merely provide the framework and metabolic support of the brain. Although astrocytes do play such structural and housekeeping roles in the brain, these glial cells also contribute to the brain's computational power and behavioural output. These more active functions are endowed by the Ca2+-based excitability displayed by astrocytes. An increase in cytosolic Ca2+ levels in astrocytes can lead to the release of signalling molecules, a process termed gliotransmission, via the process of regulated exocytosis. Dynamic components of astrocytic exocytosis include the vesicular-plasma membrane secretory machinery, as well as the vesicular traffic, which is governed not only by general cytoskeletal elements but also by astrocyte-specific IFs (intermediate filaments). Gliotransmitters released into the ECS (extracellular space) can exert their actions on neighbouring neurons, to modulate synaptic transmission and plasticity, and to affect behaviour by modulating the sleep homoeostat. Besides these novel physiological roles, astrocytic Ca2+ dynamics, Ca2+-dependent gliotransmission and astrocyte–neuron signalling have been also implicated in brain disorders, such as epilepsy. The aim of this review is to highlight the newer findings concerning Ca2+ signalling in astrocytes and exocytotic gliotransmission. For this we report on Ca2+ sources and sinks that are necessary and sufficient for regulating the exocytotic release of gliotransmitters and discuss secretory machinery, secretory vesicles and vesicle mobility regulation. Finally, we consider the exocytotic gliotransmission in the modulation of synaptic transmission and plasticity, as well as the astrocytic contribution to sleep behaviour and epilepsy

Productivity and economic feasibility of cultivated forage and food crops in the central highlands of Ethiopia

The study was conducted to evaluate the yield performance of improved forage and food crops and to estimate the profitability of fodder and food crops in Holetta and Ejere areas, central highlands of Ethiopia during 2019 and 2020 cropping seasons. The experiment was laid out in randomized complete block design with three replications and evaluated two annual forage crops, two perennial forage crops, and two cereal food crops. Data on herbage dry matter (DM) yield was collected for forage crops while straw and grain yields were measured for food crops. Partial budget analysis was made to evaluate the economic feasibility of forage and food crops production. The result revealed that the herbage DM yield varied (P&lt;0.05) at each location during each production year and combined over years and between the two locations. The straw and grain yields of food crops also varied (P&lt;0.05) between the two production years and locations. The nutritive values of herbage and straw yields of forage and food crops differed (P&lt;0.05) for all measured parameters. The crude protein and in-vitro dry matter digestibility of perennial forage crops were relatively higher than annual forage crops and straw of food crops. The partial budget analysis result indicated that the gross revenue (GR) and net return (NR) obtained from food crops were the highest followed by annual forage crops while the least was recorded from perennial forage crops during the first year of production. However, perennial forage crops produced the higher GR and NR than food crops and annual forage crops in the second year of production. In the second year of production, among the forage crops, Desho grass generated 308, 293, 287, and 232% while Rhodes grass generated 99, 92, 90, and 62% more NR than wheat, sole oat, barley, and oat/vetch mixtures, respectively. The benefit-cost ratio (BCR) of perennial forage crops was the lowest (3.0 for Desho and 1.6 for Rhodes) in the first year of production but the ratio was the highest (17.2 for Desho and 8.6 for Rhodes) in the second year of production. This confirms the better economic feasibility of perennial forage crops as they can be maintained using minimal management cost once they have been established