Urine Proteome Analysis May Allow Noninvasive Differential Diagnosis of Diabetic Nephropathy

AbstractObjective: Chronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy (DN) in over one third of cases. We interrogated urine proteomic profiles generated by SELDI-TOF/MS with the aim to isolate a set of biomarkers able to reliably identify biopsy-proven DN and to establish a stringent correlation with the different patterns of renal injury. Research design and methods: Ten mug urine proteins from 190 subjects [20 healthy subjects (HS), 20 normoalbuminuric (NAD) and 18 microalbuminuric (MICRO) diabetic patients, and 132 patients with biopsy-proven nephropathy (65 DN, 10 diabetics with non-diabetic CKD (nd-CKD) and 57 non-diabetic patients with CKD)] were run by CM10 ProteinChip array and analysed by supervised learning methods (CART analysis). Results: The classification model correctly identified 75% NAD, 87.5% MICRO and 87.5% DN when applied to a blinded testing set. Most importantly, it was able to reliably differentiate DN from nd-CKD in both diabetic and non-diabetic patients. Among the best predictors of the classification model, we identified and validated 2 proteins, ubiquitin and ss2-microglobulin. Conclusions: Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis

Serra da Estrela cheeses free amino acids profiles by UPLC-DAD-MS/MS and their application for cheese origin assessment

Serra da Estrela cheese is a high-value Portuguese Protected Designation of Origin cheese, produced with raw ewe milk. Thus, information regarding its composition is of utmost relevance for both consumers and certified producers. In this work, the chromatographic profiles of free amino acids in cheeses (45 days of maturation, 6 producers located in 5 municipalities and produced from November 2017 to March 2018) were established by UPLC-DAD-MS/MS. The proposed method allowed detecting 19 free amino acids and cystine with overall limits of detection and quantification lower than 44 mol/L (1.4 mg/100 g cheese, wet matter) and then 134 mol/L (4.2 mg/100 g cheese, wet matter), respectively. In all cheeses, 17 free amino acids were quantified including 8 essential amino acids (histidine, leucine-isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine) and 9 non-essential amino acids (arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, proline, serine and tyrosine). The amounts of the free amino acids, essential free amino acids, branched chain free amino acids (leucine, isoleucine and valine) plus the free amino acids ratios (mg/g protein) were further used to identify the producer of Serra da Estrela cheeses. Linear discriminant analysis coupled with the simulated annealing variable selection algorithm was used allowing the correct classification of 96% and 90±8% of the samples, for leave-one-out and repeated K-fold cross-validation procedures, respectively. The satisfactory predictive performance pointed out the possibility of using cheeses amino acids profiles as origin biomarkers for authenticity control, warranting the correctness identification of the cheese producer/brand, which is quite relevant for ensuring the consumer confidence and satisfaction when purchasing this high-value dairy food.This work was financially supported by Associate Laboratory LSRELCM – UID/EQU/50020/2019, strategic funding UID/BIO/04469/2019-CEB and BioTecNorte operation (NORTE-01-0145-FEDER000004), and strategic project PEst-OE/AGR/UI0690/2014–CIMO funded by – funded by national funds through FCT/MCTES (PIDDAC). The authors would also like to acknowledge the funding provided by the approved Project, with reference 02/SAICT/ 2016/23290, entitled Characterization and Valorization of QSE PDO and its ability for health promotion (QCLASSE), financed by FCT. S. I. Falcão thanks National funding by FCT- Foundation for Science and Technology, P.I., through the institutional scientific employment program-contract.info:eu-repo/semantics/publishedVersio

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

First measurement of R(Xτ/ℓ)R(X_{\tau/\ell}) as an inclusive test of the b→cτνb \to c \tau \nu anomaly

We measure the tau-to-light-lepton ratio of inclusive $B$-meson branching fractions $R(X_{\tau/\ell}) \equiv \mathcal{B}(B\to X \tau \nu)/\mathcal{B}(B \to X \ell \nu)$, where $\ell$ indicates an electron or muon, and thereby test the universality of charged-current weak interactions. We select events that have one fully reconstructed $B$ meson and a charged lepton candidate from $189~\mathrm{fb}^{-1}$ of electron-positron collision data collected with the Belle II detector. We find $R(X_{\tau/\ell}) = 0.228 \pm 0.016~(\mathrm{stat}) \pm 0.036~(\mathrm{syst})$, in agreement with standard-model expectations. This is the first direct measurement of $R(X_{\tau/\ell})$

Observation of B→D(∗)K−KS0{B\to D^{(*)} K^- K^{0}_S} decays using the 2019-2022 Belle II data sample

We present a measurement of the branching fractions of four $B^{0,-}\to D^{(*)+,0} K^- K^{0}_S$ decay modes. The measurement is based on data from SuperKEKB electron-positron collisions at the $\Upsilon(4S)$ resonance collected with the Belle II detector and corresponding to an integrated luminosity of ${362~\text{fb}^{-1}}$. The event yields are extracted from fits to the distributions of the difference between expected and observed $B$ meson energy to separate signal and background, and are efficiency-corrected as a function of the invariant mass of the $K^-K_S^0$ system. We find the branching fractions to be: $$\text{B}(B^-\to D^0K^-K_S^0)=(1.89\pm 0.16\pm 0.10)\times 10^{-4},$$ $$\text{B}(\overline B{}^0\to D^+K^-K_S^0)=(0.85\pm 0.11\pm 0.05)\times 10^{-4},$$ $$\text{B}(B^-\to D^{*0}K^-K_S^0)=(1.57\pm 0.27\pm 0.12)\times 10^{-4},$$ $$\text{B}(\overline B{}^0\to D^{*+}K^-K_S^0)=(0.96\pm 0.18\pm 0.06)\times 10^{-4},$$ where the first uncertainty is statistical and the second systematic. These results include the first observation of $\overline B{}^0\to D^+K^-K_S^0$, $B^-\to D^{*0}K^-K_S^0$, and $\overline B{}^0\to D^{*+}K^-K_S^0$ decays and a significant improvement in the precision of $\text{B}(B^-\to D^0K^-K_S^0)$ compared to previous measurements

Control and prevention measures for legionellosis in hospitals: A cross-sectional survey in Italy

Risk assessment, environmental monitoring, and the disinfection of water systems are the key elements in preventing legionellosis risk. The Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine, and Public Health and the Italian Multidisciplinary Society for the Prevention of Health Care-Associated Infections carried out a national cross-sectional survey to investigate the measures taken to prevent and control legionellosis in Italian hospitals. A multiple-choice questionnaire was developed, comprising 71 questions regarding hospital location, general characteristics, clinical and environmental surveillance, and control and preventive measures for legionellosis in 2015. Overall, 739 hospitals were enrolled from February to June 2017, and 178 anonymous questionnaires were correctly completed and evaluated (response rate: 24.1%). The survey was conducted using the SurveyMonkey (R) platform, and the data were analyzed using Stata 12 software. Of the participating hospitals, 63.2% reported at least one case of legionellosis, of which 28.2% were of proven nosocomial origin. The highest case numbers were reported in the Northern Italy, in hospitals with a pavilion structure or cooling towers, and in hospitals with higher numbers of beds, wards and operating theaters. Laboratory diagnosis was performed using urinary antigen testing alone (31.9%), both urinary antigen testing and single antibody titer (17.8%), or with seroconversion also added (21.5%). Culture-based or molecular investigations were performed in 28.8% and 22.1% of the clinical specimens, respectively. The water systems were routinely tested for Legionella in 97.4% of the hospitals, 62% of which detected a positive result (> 1000 cfu/L). Legionella pneumophila serogroup 2-15 was the most frequently isolated species (58.4%). The most common control measures were the disinfection of the water system (73.7%), mostly through thermal shock (37.4%) and chlorine dioxide (34.4%), and the replacement (69.7%) or cleaning (70.4%) of faucets and showerheads. A dedicated multidisciplinary team was present in 52.8% of the hospitals, and 73% of the hospitals performed risk assessment. Targeted training courses were organized in 36.5% of the hospitals, involving nurses (30.7%), physicians (28.8%), biologists (21.5%), technicians (26.4%), and cleaners (11%). Control and prevention measures for legionellosis are present in Italian hospitals, but some critical aspects should be improved. More appropriate risk assessment is necessary, especially in large facilities with a high number of hospitalizations. Moreover, more sensitive diagnostic tests should be used, and dedicated training courses should be implemented

A Next-Generation Liquid Xenon Observatory for Dark Matter and Neutrino Physics

The nature of dark matter and properties of neutrinos are among the mostpressing issues in contemporary particle physics. The dual-phase xenontime-projection chamber is the leading technology to cover the availableparameter space for Weakly Interacting Massive Particles (WIMPs), whilefeaturing extensive sensitivity to many alternative dark matter candidates.These detectors can also study neutrinos through neutrinoless double-beta decayand through a variety of astrophysical sources. A next-generation xenon-baseddetector will therefore be a true multi-purpose observatory to significantlyadvance particle physics, nuclear physics, astrophysics, solar physics, andcosmology. This review article presents the science cases for such a detector.<br