Beneficial Effect of Phenytoin and Carbamazepine on GFAP Gene Expression and Mutant GFAP Folding in a Cellular Model of Alexander's Disease

Alexander's disease (AxD) is a rare, usually relentlessly progressive disorder of astroglial cells in the central nervous system related to mutations in the gene encoding the type III intermediate filament protein, glial fibrillary acidic protein (GFAP). The pathophysiology of AxD is only partially understood. Available data indicate that an excessive GFAP gene expression may play a role. In particular, a "threshold hypothesis" has been reported, suggesting that mutant GFAP representing about 20% of the total cellular GFAP should be sufficient to cause disease. Thus, strategies based on reducing cellular mutant GFAP protein levels and/or activating biological processes involved in the correct protein folding could be effective in counteracting the toxic effect of misfolded GFAP. Considering that clomipramine (CLM), which has been selected by a wide small molecules screening as the greatest inhibitory potential drug against GFAP expression, is contraindicated because of its proconvulsant activity in the infantile form of AxD, which is also characterized by the occurrence of epileptic seizures, two powerful antiepileptic agents, carbamazepine (CBZ) and phenytoin (PHT), which share specific stereochemical features in common with CLM, were taken into consideration in a reliable in vitro model of AxD. In the present work, we document for the first time that CBZ and PHT have a definite inhibitory effect on pathological GFAP cellular expression and folding. Moreover, we confirm previous results of a similar beneficial effect of CLM. In addition, we have demonstrated that CBZ and CLM play a refolding effect on mutant GFAP proteins, likely ascribed at the induction of CRYAB expression, resulting in the decrease of mutant GFAP aggregates formation. As CBZ and PHT are currently approved for use in humans, their documented effects on pathological GFAP cellular expression and folding may indicate a potential therapeutic role as disease-modifying agents of these drugs in the clinical management of AxD, particularly in AxD patients with focal epilepsy with and without secondary generalization

Inhibition of Listeria monocytogenes by a formulation of selected dairy starter cultures and probiotics in an in vitro model

Three strains of lactic acid bacteria (LAB) and a commercial probiotic were selected to evaluate their in vitro activity towards Listeria monocytogenes. The strains Lactococcus lactis ssp. lactis, strain 340, L. lactis ssp. lactis, strain 16; Lactobacillus casei ssp. casei, strain 208 and Enterococcus faecium UBEF-41 were inoculated into skim milk and brain heart infusion broth (BHI) to get an initial Lactococcus: Lactobacillus: E. faecium UBEF-41 ratio of 2:1:1 and a concentration of approximately 7 log cfu mL−1 until challenge vs. pathogen. L. monocytogenes ATCC 7644 was also inoculated in same media to get approximately 4 log cfu mL−1. Growth curves in skim milk and BHI at 4, 10 and 30 °C, respectively were studied for: (i) LAB formulation; (ii) L. monocytogenes and (iii) LAB vs. L. monocytogenes. When challenged with LAB, at 30 °C in milk, L. monocytogenes was not detectable after day-3 and in BHI it decreased below log cfu mL−1 after day-5. At 10 and 4 °C, in both media, L. monocytogenes counts were always significantly lower (p < .001) than the counts of L. monocytogenes alone from day-2 for milk at 4 °C and BHI at 10 °C and from day-7 for BHI at 4 °C and milk at 10 °C. In conclusion, the proposed formulation was able to limit L. monocytogenes in vitro growth, even at refrigeration temperature

Indici per la valutazione della qualit? ecologica dei laghi

Collection of methods to evaluate lake quality using biological element

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Emergency Department and Out-of-Hospital Emergency System (112-AREU 118) integrated response to Coronavirus Disease 2019 in a Northern Italy centre

Since December 2019, the world has been facing the life-threatening disease, named Coronavirus disease-19 (COVID-19), recognized as a pandemic by the World Health Organization. The response of the Emergency Medicine network, integrating "out-of-hospital" and "hospital" activation, is crucial whenever the health system has to face a medical emergency, being caused by natural or human-derived disasters as well as by a rapidly spreading epidemic outbreak. We here report the Pavia Emergency Medicine network response to the COVID-19 outbreak. The "out-of-hospital" response was analysed in terms of calls, rescues and missions, whereas the "hospital" response was detailed as number of admitted patients and subsequent hospitalisation or discharge. The data in the first 5&nbsp;weeks of the Covid-19 outbreak (February 21-March 26, 2020) were compared with a reference time window referring to the previous 5&nbsp;weeks (January 17-February 20, 2020) and with the corresponding historical average data from the previous 5&nbsp;years (February 21-March 26). Since February 21, 2020, a sudden and sustained increase in the calls to the AREU 112 system was noted (+\u2009440%). After 5&nbsp;weeks, the number of calls and missions was still higher as compared to both the reference pre-Covid-19 period (+\u200948% and\u2009+\u200910%, respectively) and the historical control (+\u200953% and\u2009+\u200922%, respectively). Owing to the overflow from the neighbouring hospitals, which rapidly became overwhelmed and had to temporarily close patient access, the population served by the Pavia system more than doubled (from 547.251 to 1.135.977 inhabitants,\u2009+\u2009108%). To minimize the possibility of intra-hospital spreading of the infection, a separate "Emergency Department-Infective Disease" was created, which evaluated 1241 patients with suspected infection (38% of total ED admissions). Out of these 1241 patients, 58.0% (n\u2009=\u2009720) were admitted in general wards (n\u2009=\u2009629) or intensive care unit (n\u2009=\u200991). To allow this massive number of admissions, the hospital reshaped many general ward Units, which became Covid-19 Units (up to 270 beds) and increased the intensive care unit beds from 32 to 60. In the setting of a long-standing continuing emergency like the present Covid-19 outbreak, the integration, interaction and team work of the "out-of-hospital" and "in-hospital" systems have a pivotal role. The present study reports how the rapid and coordinated reorganization of both might help in facing such a disaster. AREU-112 and the Emergency Department should be ready to finely tune their usual cooperation to respond to a sudden and overwhelming increase in the healthcare needs brought about by a pandemia like the current one. This lesson should shape and reinforce the future

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors

Appropriateness of antiplatelet therapy for primary and secondary cardio- and cerebrovascular prevention in acutely hospitalized older people

Aims: Antiplatelet therapy is recommended for the secondary prevention of cardio- and cerebrovascular disease, but for primary prevention it is advised only in patients at very high risk. With this background, this study aims to assess the appropriateness of antiplatelet therapy in acutely hospitalized older people according to their risk profile. Methods: Data were obtained from the REPOSI register held in Italian and Spanish internal medicine and geriatric wards in 2012 and 2014. Hospitalized patients aged 6565 assessable at discharge were selected. Appropriateness of the antiplatelet therapy was evaluated according to their primary or secondary cardiovascular prevention profiles. Results: Of 2535 enrolled patients, 2199 were assessable at discharge. Overall 959 (43.6%, 95% CI 41.5\u201345.7) were prescribed an antiplatelet drug, aspirin being the most frequently chosen. Among patients prescribed for primary prevention, just over half were inappropriately prescribed (52.1%), being mainly overprescribed (155/209 patients, 74.2%). On the other hand, there was also a high rate of inappropriate underprescription in the context of secondary prevention (222/726 patients, 30.6%, 95% CI 27.3\u201334.0%). Conclusions: This study carried out in acutely hospitalized older people shows a high degree of inappropriate prescription among patients prescribed with antiplatelets for primary prevention, mainly due to overprescription. Further, a large proportion of patients who had had overt cardio- or cerebrovascular disease were underprescribed, in spite of the established benefits of antiplatelet drugs in the context of secondary prevention

Implementation of the Frailty Index in hospitalized older patients: Results from the REPOSI register

Background: Frailty is a state of increased vulnerability to stressors, associated to poor health outcomes. The aim of this study was to design and introduce a Frailty Index (FI; according to the age-related accumulation of deficit model) in a large cohort of hospitalized older persons, in order to benefit from its capacity to comprehensively weight the risk profile of the individual. Methods: Patients aged 65 and older enrolled in the REPOSI register from 2010 to 2016 were considered in the present analyses. Variables recorded at the hospital admission (including socio-demographic, physical, cognitive, functional and clinical factors) were used to compute the FI. The prognostic impact of the FI on in-hospital and 12-month mortality was assessed. Results: Among the 4488 patients of the REPOSI register, 3847 were considered eligible for a 34-item FI computation. The median FI in the sample was 0.27 (interquartile range 0.21\u20130.37). The FI was significantly predictive of both in-hospital (OR 1.61, 95%CI 1.38\u20131.87) and overall (HR 1.46, 95%CI 1.32\u20131.62) mortality, also after adjustment for age and sex. Conclusions: The FI confirms its strong predictive value for negative outcomes. Its implementation in cohort studies (including those conducted in the hospital setting) may provide useful information for better weighting the complexity of the older person and accordingly design personalized interventions

Prevalence and Determinants of the Use of Lipid-Lowering Agents in a Population of Older Hospitalized Patients: the Findings from the REPOSI (REgistro POliterapie Societ\ue0 Italiana di Medicina Interna) Study

Background: Older patients are prone to multimorbidity and polypharmacy, with an inherent risk of adverse events and drug interactions. To the best of our knowledge, available information on the appropriateness of lipid-lowering treatment is extremely limited. Aim: The aim of the present study was to quantify and characterize lipid-lowering drug use in a population of complex in-hospital older patients. Methods: We analyzed data from 87 units of internal medicine or geriatric medicine in the REPOSI (Registro Politerapie della Societ\ue0 Italiana di Medicina Interna) study, with reference to the 2010 and 2012 patient cohorts. Lipid-lowering drug use was closely correlated with the clinical profiles, including multimorbidity markers and polypharmacy. Results: 2171 patients aged >65\ua0years were enrolled (1057 males, 1114 females, mean age 78.6\ua0years). The patients treated with lipid-lowering drugs amounted to 508 subjects (23.4%), with no gender difference. Atorvastatin (39.3%) and simvastatin (34.0%) were the most widely used statin drugs. Likelihood of treatment was associated with polypharmacy ( 655\ua0drugs) and with higher Cumulative Illness Rating Scale (CIRS) score. At logistic regression analysis, the presence of coronary heart disease, peripheral vascular disease, and hypertension were significantly correlated with lipid-lowering drug use, whereas age showed an inverse correlation. Diabetes was not associated with drug treatment. Conclusions: In this in-hospital cohort, the use of lipid-lowering agents was mainly driven by patients\u2019 clinical history, most notably the presence of clinically overt manifestations of atherosclerosis. Increasing age seems to be associated with lower prescription rates. This might be indicative of cautious behavior towards a potentially toxic treatment regimen