Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial.

PURPOSE: According to preclinical evidence, GLP-1 receptor may be an actionable target in neurodegenerative disorders, including Alzheimer's disease (AD). Previous clinical trials of GLP-1 receptor agonists were conducted in patients with early AD, yielding mixed results. The aim was to assess in a proof-of-concept study whether slow-release exenatide, a long-acting GLP-1 agonist, can benefit the cognitive performance of people with mild cognitive impairment (MCI). METHODS: Thirty-two (16 females) patients were randomized to either slow-release exenatide (n = 17; 2 mg s.c. once a week) or no treatment (n = 15) for 32 weeks. The primary endpoint was the change in ADAS-Cog11 cognitive test score at 32 weeks vs baseline. Secondary endpoints herein reported included additional cognitive tests and plasma readouts of GLP-1 receptor engagement. Statistical analysis was conducted by intention to treat. RESULTS: No significant between-group effects of exenatide on ADAS-Cog11 score (p = 0.17) were detected. A gender interaction with treatment was observed (p = 0.04), due to worsening of the ADAS-Cog11 score in women randomized to exenatide (p = 0.018), after correction for age, scholar level, dysglycemia, and ADAS-Cog score baseline value. Fasting plasma glucose (p = 0.02) and body weight (p = 0.03) decreased in patients randomized to exenatide. CONCLUSION: In patients with MCI, a 32-week trial with slow-release exenatide had no beneficial effect on cognitive performance. TRIAL REGISTRATION NUMBER: NCT03881371, registered on 21 July, 2016.

Can a validated website help improve university students' e-health literacy?

Background: The fight against fake news, mainly spread through Internet, is a major public health issue, even among undergraduate students. This study aims to evaluate the effectiveness of a website promoted by the Italian Federation of the Provincial Orders of the Medical Doctors as a first aid communication kit for health topics. Study design: Pre-post study using a web-based survey, conducted in April-May 2019 on Medical students and October-November 2020 on Communication Sciences students at the University of Florence (Italy). Methods. Undergraduate students of both schools were exposed to the use of the "dottoremaeveroche" website. Primary and secondary outcomes measures: the Italian-electronic Health Literacy Scale self-assessment tool was used to examine subjects' electronic Health literacy, and source quality. All responses were rated on a 5-point Likert scale. Changing in perception of abilities were examined using the Wilcoxon test. Results: The 362 participants felt moderately confident in electronic Health Literacy, with an initial Italian-electronic Health Literacy Scale overall mean score of 3.6±0.7 for medical and 3.2±0.8 for communication students. Medical students had a good idea of how to find helpful sources (3.9±0.8) and communication students felt confident in recognizing their quality (3.5±1.0). In contrast, their confidence in using Web information to make health decisions was low (medical: 2.9±1.1; communication: 2.8±1.1). All items improved significantly after "dottoremaeveroche" use (p<.001), with the overall mean score of Italian-electronic Health Literacy Scale increasing to 4.3±0.6 for medical and 4.1±0.8 for communication students. Conclusions: Low electronic health literacy levels can affect public health efforts, as seen during the COVID-19 pandemic. The effectiveness of "dottoremaeveroche" among students showed the usefulness of online educational interventions that, if further implemented, could help combat the spread of infodemic.

Toward stomatal-flux based forest protection against ozone: The MOTTLES approach.

European standards for the protection of forests from ozone (O3) are based on atmospheric exposure (AOT40) that is not always representative of O3 effects since it is not a proxy of gas uptake through stomata (stomatal flux). MOTTLES "MOnitoring ozone injury for seTTing new critical LEvelS" is a LIFE project aimed at establishing a permanent network of forest sites based on active O3 monitoring at remote areas at high and medium risk of O3 injury, in order to define new standards based on stomatal flux, i.e. PODY (Phytotoxic Ozone Dose above a threshold Y of uptake). Based on the first year of data collected at MOTTLES sites, we describe the MOTTLES monitoring station, together with protocols and metric calculation methods. AOT40 and PODY, computed with different methods, are then compared and correlated with forest-health indicators (radial growth, crown defoliation, visible foliar O3 injury). For the year 2017, the average AOT40 calculated according to the European Directive was even 5 times (on average 1.7 times) the European legislative standard for the protection of forests. When the metrics were calculated according to the European protocols (EU Directive 2008/50/EC or Modelling and Mapping Manual LTRAP Convention), the values were well correlated to those obtained on the basis of the real duration of the growing season (i.e. MOTTLES method) and were thus representative of the actual exposure/flux. AOT40 showed opposite direction relative to PODY. Visible foliar O3 injury appeared as the best forest-health indicator for O3 under field conditions and was more frequently detected at forest edge than inside the forest. The present work may help the set-up of further long-term forest monitoring sites dedicated to O3 assessment in forests, especially because flux-based assessments are recommended as part of monitoring air pollution impacts on ecosystems in the revised EU National Emissions Ceilings Directive.

Monola oil versus canola oil as a fish oil replacer in rainbow trout feeds: effects on growth, fatty acid metabolism and final eating quality.

Monola oil, a high oleic acid canola cultivar, and canola oil were evaluated as replacers of fish oil at three levels of inclusion (60%, 75% and 90%) in rainbow trout diets. After a 27-week grow-out cycle, the diet-induced effects on growth, fatty acid metabolism and final eating quality were assessed. Overall, no effects were noted for growth, feed utilisation or fish biometry, and the fatty acid composition of fish fillets mirrored that of the diets. Dietary treatments affected fillet lipid oxidation (free malondialdehyde), pigmentation and flavour volatile compounds, but only minor effects on sensorial attributes were detected. Ultimately, both oils were demonstrated to possess, to differing extents, suitable qualities to adequately replace fish oil from the perspective of fish performance and final product quality. However, further research is required to alleviate on-going issues associated with the loss of health promoting attributes (n-3 long chain polyunsaturated fatty acids) of final farmed products.

[Gallbladder polypoid lesions. Three clinical cases with difficult diagnosis and literature review]. / Lesioni polipoidi della colecisti. Presentazione di tre casi clinici di "difficile" diagnosi e revisione della letteratura.

INTRODUCTION: Gallbladder polypoid lesions occur in 1.3%-6.9% of cases. The preoperative diagnosis between benign, malignant and potentially malignant lesions is difficult. Therefore it is not possible any. PATIENTS AND METHODS: The Authors describe three cases. The case 1 was a gallbladder diffuse adenomyomatosis; the ultrasound and the CT were of little help in defining preoperatively the nature and the gravity of the thickening. Case 2 was an adenomyomatosis of the fundus: the ultrasound examinations were not able to establish preoperatively lesion's nature, site and dimensions. In the case 3, ultrasounds showed polypoid lesions and calculi concrections not found in colecistectomy. DISCUSSION: The ultrasound is the most widely used diagnostic tool in the evaluation of gallbladder polypoid lesions; its accuracy is only 66%. CT, which has an accuracy level of 75%, must be carried out there is any possibility of malignant degeneration of the polyp. If doubts persist, a MR, 93% accuracy, is indicated. In selected cases, PET can be of further help. CONCLUSIONS: The preoperative diagnosis of the nature of gallbladder polypoid lesions is "difficult" and this justifies the lack of consensus on treatment. However, the adenoma-carcinoma sequence, widely discussed in literature, can justifies to the use of CT, MR, PET and surgical treatment after an ultrasound examination.

Determination of astaxanthin stereoisomers and colour attributes in flesh of rainbow trout (Oncorhynchus mykiss) as a tool to distinguish the dietary pigmentation source.

The presence of carotenoids in animal tissue reflects their sources along the food chain. Astaxanthin, the main carotenoid used for salmonid pigmentation, is usually included in the feed as a synthetic product. However, other dietary sources of astaxanthin such as shrimp or krill wastes, algae meal or yeasts are also available on the market. Astaxanthin possesses two identical asymmetric atoms at C-3 and C-3' making possible three optical isomers with all-trans configuration of the chain: 3S,3'S, 3R,3'S, and 3R,3'R. The distribution of the isomers in natural astaxanthin differs from that of the synthetic product. This latter is a racemic mixture, with a typical ratio of 1:2:1 (3S,3'S:3R,3'S:3R,3'R), while astaxanthin from natural sources has a variable distribution of the isomers deriving from the different biological organism that synthesized it. The high-performance liquid chromatographic (HPLC) analysis of all-trans isomers of astaxanthin was performed in different pigment sources, such as red yeast Phaffia rhodozyma, alga meal Haematococcus pluvialis, krill meal and oil, and shrimp meal. With the aim to investigate astaxanthin isomer ratios in flesh of fish fed different carotenoid sources, three groups of rainbow trout were fed for 60 days diets containing astaxanthin from synthetic source, H. pluvialis algae meal and P. rhodozyma red yeast. Moreover, the distribution of optical isomers of astaxanthin in trout purchased on the Italian market was investigated. A characteristic distribution of astaxanthin stereoisomers was detected for each pigment sources and such distribution was reproduced in the flesh of trout fed with that source. Colour values measured in different sites of fillet of rainbow trout fed with different pigment sources showed no significant differences. Similarly, different sources of pigment (natural or synthetic) produced colour values of fresh fillet with no relevant or significant differences. The coefficient of distance computed amongst the feed ingredient and the trout fillet astaxanthin stereoisomers was a useful tool to identify the origin of the pigment used on farm.

What do Italians at high risk of stroke know about ischaemic stroke? A survey among a group of subjects undergoing neuro-sonographic examination.

The objective was to assess the knowledge about ischaemic stroke among selected groups of persons at high risk for stroke. Outpatients referred to 3 hospital ultrasound departments in the Marche Region (Italy) were asked to answer a questionnaire. Data were collected on: (1) demographic characteristics; (2) risk profile determined using Coppola et al.'s scoring system; (3) knowledge about symptoms, risk factors, part of the body injured and best referral option for stroke. Of the 352 respondents, around 52% were unable to report even one warning symptom of stroke, while 58.4% of participants at increased risk did not know any risk factors. Only 64.5% identified the brain as the part of the body injured by stroke. Only 59.4% considered the Emergency Department as the best referral option in the event of stroke. This study confirms poor knowledge about stroke in our study population, particularly in subjects with increased stroke risk.

Comparison of the performances of Nero Siciliano pigs reared indoors and outdoors: 2. Joints composition, meat and fat traits.

A study on the effect of rearing system on tissue composition of principal joints and chemical-physical traits of meat and subcutaneous fat, was carried out on a local pig breed. A total of 78 Nero Siciliano pigs was used; 41 pigs were reared in woods, 37 pigs were reared in pens and fed a commercial diet. Weight at slaughter was 101.9 and 88.2 kg for indoor and outdoor pigs, respectively. Means were estimated at 77 kg of live weight. At ham dissection outdoor-pigs showed higher percentages of lean (58% vs. 55%) and lower subcutaneous fat (31% vs. 34%). In Longissimus lumborum outdoor-pigs showed a higher intramuscular fat percentage (4.3% vs. 3.3%), a lower protein content (22.2% vs. 23.4%), and higher free water (9.6 vs. 7.9 cm(2)). Outdoor pigs produced more light (L(*)=50 vs. 46.7) and more yellow (b(*)=5.84 vs. 4.88) meat. Subcutaneous fat of outdoor pigs showed higher percentages of MUFA (53.3% vs. 47.2%) and lower percentages of PUFA (10.85% vs. 14.45%), no differences were found for n-3 PUFA. Outdoor-pigs had lower atherogenicity (0.48 vs. 0.53) and thrombogenicity (1.03 vs. 1.21) indices.

Identification of species in animal feedstuffs by polymerase chain reaction--restriction fragment length polymorphism analysis of mitochondrial DNA.

Restriction site analysis of Polymerase Chain Reaction (PCR) products of cytochrome b mitochondrial DNA was applied to identify species in meat meal and animal feedstuffs. PCR was used to amplify a variable region of cytochrome b mitochondrial DNA gene. Species differentiation was determined by digestion of the obtained 359 bp amplicon with restriction enzymes, which generated species-specific electrophoresis patterns; the sequencing of PCR products was used as confirming analysis. PCR-RFLP analysis revealed the presence of meat meal in animal feedstuffs and distinguished species of interest. The results supported the application of the method in control measures which should be adopted for meat-meal-based animal feed, as suggested by EU law. As a technical improvement, to simplify the analysis, the number of enzymes presented in this study for the detection of different species was smaller than others described in the literature; discrimination between ruminant and nonruminant species and between mammalian and poultry species was possible with few digestions.

Stroke unit: a cardio-cerebral approach.

Stroke units are special units where stroke patients receive, simultaneously, medical and physical treatment. Compared to general neurological and medical wards, stroke units show a significant reduction of short- and long-time mortality, and an improvement of long-term quality of life. Nevertheless, mortality in these units is still high (1-year mortality approximately 32%; 5-year mortality degrees 60%), and consequently, new approaches are needed to control stroke parameters during the acute phase, with the goal to reduce mortality rates. The philosophy of our stroke unit in Fermo (Italy), is to establish a strong association between heart and brain care by approaching each stroke patient as a cardiocerebral patient. In particular, we perform 12-lead Holter ECG monitoring, to prevent the vicious cycle affecting correct cerebral and cardiac functions, and to react to cardiac complications, mostly arrhythmias, that can worsen cerebral damage. Holter ECG monitoring allows a fast physiotherapeutic approach, a better evaluation of metabolic parameters, and collectively, a better global evaluation of the patient during the acute phase of disease. In two years of activity, 80 patients that were admitted to our stroke unit during 1998, and treated as cardio-cerebral patients, were followed-up. This combined treatment decreased the 1-year mortality rate by about 30%, in comparison with the 22% mortality rate reported in the literature. These results confirm the validity of stroke units, as well as of our approach based on cardio-cerebral control of each stroke patient.

Bilateral empyema caused by adult-onset Still's disease.

Empyemas are usually of infectious origin. Noninfectious causes of empyema may be a considerable diagnostic challenge, as exemplified in the present case report. A 21-year-old male presented with high fever, sore throat and myalgias of 1 week duration. In the following days, bilateral pleural effusions developed, with cellular counts in the pleural fluid up to 117 x 10(9)/liter (98% neutrophils). Despite institution of empiric antibiotic therapy, spiking fever continued. All culture studies resulted in being negative. Following the report of a serum ferritin concentration of 6,975 microg/l, adult-onset Still's disease was diagnosed and successfully treated with anti-inflammatory drugs. This case adds adult-onset Still's disease to the list of noninfectious causes of empyema and underlies the value of measuring serum ferritin as a diagnostic tool.

Racemization kinetics of aspartic acid in fish material under different conditions of moisture, pH, and oxygen pressure.

The racemization kinetics of aspartic acid in heat-treated whole herring have been studied under conditions of treatment comparable to those that may occur in processing of fish meal. D-Aspartic acid content in the samples has been measured by RP-HPLC with precolumn automatic derivatization. The major parameters affecting the rate of racemization of aspartic acid k(Asp) have been demonstrated to be temperature (elevation of temperature from 95 to 120 degrees C resulted in an increase of k(Asp) from 0.46 to 3.39x10(-3) min(-1)), moisture of the raw material (reduction of the moisture content of the raw material from 80 to 15% lowered k(Asp) measured at 95 degrees C from 0.46 to 0.06x10(-3) min(-1)), and to a lesser extent, pH (k(Asp) at 95 degrees C was lowered from 0.46 to 0.37x10(-3) min(-1) following a decrease of pH from 7.0 to 4.0). No significant effects on the racemization rate of aspartic acid was observed for reducing the oxygen pressure to 0.8%. The results from the present study show that the content of D-aspartic acid in fish material is a function of heat exposure and may be used to predict the thermal history of fish meal.

High-performance liquid chromatographic determination of polyamines in milk as their 9-fluorenylmethoxycarbonyl derivatives using a column-switching technique.

A high-performance liquid chromatographic method for the determination of polyamines in milk is milk is described. Polyamines were extracted in perchloric acid and derivatized with 9-fluorenylmethoxycarbonyl chloride (FMOC-Cl). The excess of reagent was reacted with aspartic acid before the analysis on a column-switching system. Linearity of derivatization was calculated for each amine and the coefficient of regression ranged from 0.994 to 0.999. Chromatographic separation of FMOC-polyamines was achieved with a gradient elution programme of water-acetonitrile. The correlation coefficients of the standard curves in the concentration range from 0.5 to 5 nmol ml-1 were higher than 0.991. The repeatability of the method, expressed as R.S.D. for each polyamines ranged from 3.0 to 8.6%. The percent mean recoveries at 1 nmol ml-1 spiking level were 49 +/- 3, 58 +/- 5, 61 +/- 5 and 48 +/- 4 for putrescine, cadaverine, spermidine and spermine, respectively. The limit of detection, calculated on the basis of three times signal-to-noise ratio, was 50 pmol ml-1 for each polyamine.

[Clinical and instrumental diagnosis of Alzheimer's and multi-infarct dementia]. / Diagnosi clinico-strumentale nello studio della demenza di Alzheimer e nella demenza multinfartuale.

We investigated the possible correlation between functional and anatomical imaging techniques and clinical exams in patients with Alzheimer's and vascular dementia. We examined 24 patients affected with dementia, 16 of them with Alzheimer's disease. 7 with multiinfarct and 1 with mixed dementia. All patients were submitted to clinical, morphological (MRI, CT) and functional (SPECT, cerebral flowmetry) studies. The severity of hypoperfusion revealed by SPECT was highly correlated with cognitive impairment in Alzheimer's dementia patients. The abnormal perfusion was mostly bilateral, in the temporal-parietal region, and involved the frontal regions only in the most severe cases. CT and especially MRI showed aspecific cortical and subcortical atrophy, most evident in the medial temporal region. In the patients with multiinfarct dementia, the hypoperfused cortical regions revealed by SPECT were sometimes related to vascular lesions proved at MRI and CT. In the patients with multiinfarct dementia, MRI showed more or less apparent white matter lesions referrable to ischemic insult, besides cortical and subcortical atrophy. MRI allows a differential diagnosis between these two cerebral pathologic conditions of aging. Cerebral flowmetry by Xenon 133 inhalation showed reduced cerebral blood flow in both dementia types. In Alzheimer patients, regional flow was reduced especially in the posterior parietal regions. In multiinfarct dementia patients, flow was more diffusely reduced and asymmetrical. Brain function imaging appears to yield useful information for the differential diagnosis in the most common dementia syndromes. Since the neuropathologic data from brain biopsy are rarely available, clinical and instrumental findings must be integrated for diagnostic and pathogenetic insights of the diseases causing cognitive impairment.

High-performance liquid chromatographic determination of oxytetracycline in channel catfish (Ictalurus punctatus) muscle tissue.

A high-performance liquid chromatographic method for the determination of oxytetracycline in channel catfish muscle tissue is presented. Oxytetracycline is extracted three times from muscle tissue with an ethylenediaminetetraacetic acid disodium salt-McIlvaine buffer (pH 4.0) by using an Ultra Turrax. Analysis is carried out by using high-performance liquid chromatography and an acetonitrile-oxalic acid (0.05 mol 1(-1), pH 2.2) mixture (14 + 86, v/v) is used as mobile phase. Oxytetracycline is separated on a Lichrosorb RP-8 125 x 4.0 mm i.d. column and ultraviolet detection at 355 nm is used. The limit of quantification is 10 ng g-1 and the linearity, tested in the spiking range 20-500 ng g-1, is 0.9997. Recovery from muscle spiked at 20, 50, 100, 200 and 500 ng g-1 levels is in the range 70-80%. Precision, expressed as percentage relative standard deviation, is below 7%. The method is applied to muscle tissue from channel catfish fed on a medicated diet.