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Francesco Pesce,1 Giacomo Matteo Bruno,2 Giorgio Lorenzo Colombo,2 Sergio Di Matteo,3 Anna Rita Maurizi,4 Valentina Mongelli,4 Silvia Mele,5 Lavinia Narici,5 Stefano Bianchi,6 Mario Bonomini,7 Giuseppe Castellano,8 Luca De Nicola,9 Giovanni Gambaro,10 Giuseppe Grandaliano,11 Gaetano La Manna,12 Antonello Pani,13 Andrea Ranghino,14 Loreto Gesualdo15 1Division of Renal Medicine, “Fatebenefratelli Isola Tiberina—Gemelli Isola”, Rome, 00186, Italy; 2Department of Drug Sciences, University of Pavia, Pavia, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 4Cardiovascular, Renal and Metabolism Medical Affairs, AstraZeneca, Milan, Italy; 5Value & Access, AstraZeneca, Milan, Italy; 6Nephrology and Dialysis Unit, Department of Internal Medicine, ASL Toscana Nordovest, Regione Toscana, Livorno, Italy; 7Department of Medicine, Section of Nephrology and Dialysis, G. D’Annunzio University, Chieti, 66013, Italy; 8UOC of Nephrology, Dialysis, and Kidney Transplant, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Department of Advanced Medical and Surgical Sciences, Nephrology and Dialysis Unit, University Vanvitelli, Naples, Italy; 10Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy; 11Department of Translational Medicine and Surgery, Università Cattolica Sacro Cuore, Rome, Italy; 12Nephrology Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 13Department of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy; 14Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti Ancona, Ancona, Italy; 15Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (Dimepre-J), University of Bari “aldo Moro”, Bari, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email colombog@unipv.itIntroduction: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis.Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases.Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention’s impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure.Discussion: A budget impact analysis projected cumulative five-year savings of € 1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at € 106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression.Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale. Keywords: eGFR, uACR, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosis

Lensing of the cosmic microwave background (CMB) is now a well-developed probe of the clustering of the large-scale mass distribution over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission will allow production of a clean map of the lensing deflections over nearly the full-sky. The number of high-S/N modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that will follow from its power spectrum and the cross-correlation with other clustering data. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous measurements of the baryon acoustic oscillation feature in the clustering of galaxies, three times smaller than the minimum total mass allowed by neutrino oscillation measurements. Lensing has applications across many other science goals of CORE, including the search for B-mode polarization from primordial gravitational waves. Here, lens-induced B-modes will dominate over instrument noise, limiting constraints on the power spectrum amplitude of primordial gravitational waves. With lensing reconstructed by CORE, one can "delens" the observed polarization internally, reducing the lensing B-mode power by 60 %. This can be improved to 70 % by combining lensing and measurements of the cosmic infrared background from CORE, leading to an improvement of a factor of 2.5 in the error on the amplitude of primordial gravitational waves compared to no delensing (in the null hypothesis of no primordial B-modes). Lensing measurements from CORE will allow calibration of the halo masses of the tens of thousands of galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. The 19 frequency channels proposed for CORE will allow accurate removal of Galactic emission from CMB maps. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE.

Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology, including: what physical process gave birth to the Universe we see today? What are the dark matter and dark energy that seem to constitute 95% of the energy density of the Universe? Do we need extensions to the standard model of particle physics and fundamental interactions? Is the ΛCDM cosmological scenario correct, or are we missing an essential piece of the puzzle? In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the COREmfive space mission proposed to ESA in answer to the "M5" call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. COREmfive has 19 frequency channels, distributed over a broad frequency range, spanning the 60-600 GHz interval, to control astrophysical foreground emission. The angular resolution ranges from 2′ to 18′, and the aggregate CMB sensitivity is about 2 μKċarcmin. The observations are made with a single integrated focal-plane instrument, consisting of an array of 2100 cryogenically-cooled, linearly-polarised detectors at the focus of a 1.2-m aperture cross-Dragone telescope. The mission is designed to minimise all sources of systematic effects, which must be controlled so that no more than 10-4 of the intensity leaks into polarisation maps, and no more than about 1% of E-type polarisation leaks into B-type modes. COREmfive observes the sky from a large Lissajous orbit around the Sun-Earth L2 point on an orbit that offers stable observing conditions and avoids contamination from sidelobe pick-up of stray radiation originating from the Sun, Earth, and Moon. The entire sky is observed repeatedly during four years of continuous scanning, with a combination of three rotations of the spacecraft over different timescales. With about 50% of the sky covered every few days, this scan strategy provides the mitigation of systematic effects and the internal redundancy that are needed to convincingly extract the primordial B-mode signal on large angular scales, and check with adequate sensitivity the consistency of the observations in several independent data subsets. COREmfive is designed as a "near-ultimate" CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation science and cannot be obtained by any other means than a dedicated space mission. It will provide well-characterised, highly-redundant multi-frequency observations of polarisation at all the scales where foreground emission and cosmic variance dominate the final uncertainty for obtaining precision CMB science, as well as 2′ angular resolution maps of high-frequency foreground emission in the 300-600 GHz frequency range, essential for complementarity with future ground-based observations with large telescopes that can observe the CMB with the same beamsize.

We demonstrate that, for the baseline design of the CORE satellite mission, the polarized foregrounds can be controlled at the level required to allow the detection of the primordial cosmic microwave background (CMB) B-mode polarization with the desired accuracy at both reionization and recombination scales, for tensor-to-scalar ratio values of r 5× 10-3. We consider detailed sky simulations based on state-of-the-art CMB observations that consist of CMB polarization with τ=0.055 and tensor-to-scalar values ranging from r=10-2 to 10-3, Galactic synchrotron, and thermal dust polarization with variable spectral indices over the sky, polarized anomalous microwave emission, polarized infrared and radio sources, and gravitational lensing effects. Using both parametric and blind approaches, we perform full component separation and likelihood analysis of the simulations, allowing us to quantify both uncertainties and biases on the reconstructed primordial B-modes. Under the assumption of perfect control of lensing effects, CORE would measure an unbiased estimate of r=(5 ± 0.4)× 10-3 after foreground cleaning. In the presence of both gravitational lensing effects and astrophysical foregrounds, the significance of the detection is lowered, with CORE achieving a 4σ-measurement of r=5× 10-3 after foreground cleaning and 60% delensing. For lower tensor-to-scalar ratios (r=10-3) the overall uncertainty on r is dominated by foreground residuals, not by the 40% residual of lensing cosmic variance. Moreover, the residual contribution of unprocessed polarized point-sources can be the dominant foreground contamination to primordial B-modes at this r level, even on relatively large angular scales, ℓ ∼ 50. Finally, we report two sources of potential bias for the detection of the primordial B-modes by future CMB experiments: (i) the use of incorrect foreground models, e.g. a modelling error of Δβs = 0.02 on the synchrotron spectral indices may result in an excess in the recovered reionization peak corresponding to an effective Δ r > 10-3; (ii) the average of the foreground line-of-sight spectral indices by the combined effects of pixelization and beam convolution, which adds an effective curvature to the foreground spectral energy distribution and may cause spectral degeneracies with the CMB in the frequency range probed by the experiment.

We forecast the main cosmological parameter constraints achievable with the CORE space mission which is dedicated to mapping the polarisation of the Cosmic Microwave Background (CMB). CORE was recently submitted in response to ESA's fifth call for medium-sized mission proposals (M5). Here we report the results from our pre-submission study of the impact of various instrumental options, in particular the telescope size and sensitivity level, and review the great, transformative potential of the mission as proposed. Specifically, we assess the impact on a broad range of fundamental parameters of our Universe as a function of the expected CMB characteristics, with other papers in the series focusing on controlling astrophysical and instrumental residual systematics. In this paper, we assume that only a few central CORE frequency channels are usable for our purpose, all others being devoted to the cleaning of astrophysical contaminants. On the theoretical side, we assume ΛCDM as our general framework and quantify the improvement provided by CORE over the current constraints from the Planck 2015 release. We also study the joint sensitivity of CORE and of future Baryon Acoustic Oscillation and Large Scale Structure experiments like DESI and Euclid. Specific constraints on the physics of inflation are presented in another paper of the series. In addition to the six parameters of the base ΛCDM, which describe the matter content of a spatially flat universe with adiabatic and scalar primordial fluctuations from inflation, we derive the precision achievable on parameters like those describing curvature, neutrino physics, extra light relics, primordial helium abundance, dark matter annihilation, recombination physics, variation of fundamental constants, dark energy, modified gravity, reionization and cosmic birefringence. In addition to assessing the improvement on the precision of individual parameters, we also forecast the post-CORE overall reduction of the allowed parameter space with figures of merit for various models increasing by as much as ∼ 107 as compared to Planck 2015, and 105 with respect to Planck 2015 + future BAO measurements.

We forecast the scientific capabilities to improve our understanding of cosmic inflation of CORE, a proposed CMB space satellite submitted in response to the ESA fifth call for a medium-size mission opportunity. The CORE satellite will map the CMB anisotropies in temperature and polarization in 19 frequency channels spanning the range 60-600 GHz. CORE will have an aggregate noise sensitivity of 1.7 μKċ arcmin and an angular resolution of 5' at 200 GHz. We explore the impact of telescope size and noise sensitivity on the inflation science return by making forecasts for several instrumental configurations. This study assumes that the lower and higher frequency channels suffice to remove foreground contaminations and complements other related studies of component separation and systematic effects, which will be reported in other papers of the series "Exploring Cosmic Origins with CORE." We forecast the capability to determine key inflationary parameters, to lower the detection limit for the tensor-to-scalar ratio down to the 10-3 level, to chart the landscape of single field slow-roll inflationary models, to constrain the epoch of reheating, thus connecting inflation to the standard radiation-matter dominated Big Bang era, to reconstruct the primordial power spectrum, to constrain the contribution from isocurvature perturbations to the 10-3 level, to improve constraints on the cosmic string tension to a level below the presumptive GUT scale, and to improve the current measurements of primordial non-Gaussianities down to the fNLlocal < 1 level. For all the models explored, CORE alone will improve significantly on the present constraints on the physics of inflation. Its capabilities will be further enhanced by combining with complementary future cosmological observations.

Abstract: Urinary infection is common in diabetic patients. The objective of this research was to determine the frequency, etiology, antimicrobial susceptibility and risk factors associated with urinary tract infection in patients with type 2 diabetes. 108 outpatients with a presumptive diagnosis of urinary tract infection during May 2016-May 2017, in the city of Jipijapa, Ecuador, were studied. For the uroculture the calibrated loop technique was used. The susceptibility to antibiotics was determined by the Kirby & Bauer method. The qualitative variables were compared with chi-squared or Fisher's exact test. The Odd radio (OR) and its 95% confidence intervals (CI) were calculated. Values of p ≤ 0.05 were considered significant. A frequency of 73.15% of urinary infection was found. The microorganism most frequently isolated was Escherichia coli (78.48%). The highest percentages of resistance were observed for amoxicillin (78.87%) and cephalexin (71.83%). Bad hygiene habits, the presence of kidney stones and an active sex life were risk factors for urinary tract infections. Nitrofurantoin, fosfomycin, fluoroquinolones and some beta-lactams still represent a useful alternative in the chemotherapy of uncomplicated urinary tract infections in diabetic patients. Resumen: Las infecciones urinarias son comunes en pacientes diabéticos. El objetivo de esta investigación fue: determinar la frecuencia, etiología, susceptibilidad antimicrobiana y factores de riesgo asociados a infección urinaria en pacientes con diabetes tipo 2. Se estudiaron 108 pacientes ambulatorios, con diagnóstico presuntivo de infección de vías urinarias, durante el periodo mayo 2016 - mayo 2017, en la ciudad de Jipijapa, Ecuador. Para el urocultivo se utilizó la técnica del asa calibrada. La susceptibilidad a los antibióticos se determinó mediante el método de Kirby & Bauer. Las variables cualitativas se compararon con ji cuadrado o la prueba exacta de Fisher. Se calculó el Odd radio (OR) y sus intervalos de confianza (IC) del 95%. Valores de p ≤ 0,05 fueron considerados significativos. La frecuencia de infección urinaria fue de 73,15%. El microorganismo más frecuentemente aislado fue Escherichia coli (78,48%). Los mayores porcentajes de resistencia se observaron para amoxicilina (78,87%) y cefalexina (71,83%). Los malos hábitos de higiene, la presencia de cálculos renales y una vida sexual activa resultaron factores de riesgo para las infecciones urinarias. La nitrofurantoina, fosfomicina, fluoroquinolonas y algunos betalactámicos, todavía representan una alternativa de utilidad en la quimioterapia de las infecciones urinarias no complicadas en pacientes diabéticos.

Alessandro Picelli,1,2 Davide Lobba,1 Patrizia Vendramin,3 Giuseppe Castellano,3 Elena Chemello,1 Vittorio Schweiger,4,5 Alvise Martini,4,5 Massimo Parolini,4,5 Marialuisa Gandolfi,1,2 Enrico Polati,4,5 Nicola Smania1,2 1Neuromotor and Cognitive Rehabilitation Research Center, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; 2Neurorehabilitation Unit, Department of Neurosciences, Hospital Trust of Verona, Verona, Italy; 3Anesthesia, Intensive Care and Pain Therapy Unit, “Girolamo Fracastoro” Hospital, San Bonifacio, Italy; 4Anesthesia and Intensive Care Section, Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, Verona, Italy; 5Pain Therapy Center, Department of Emergency and Intensive Care, Hospital Trust of Verona, Verona, Italy Purpose: Hemiplegic shoulder pain (HSP) is the most common pain condition after stroke. Pulsed radiofrequency (PRF) treatment of the suprascapular nerve (SSN) effectively relieves shoulder pain conditions. To date, there is no study about the effects of PRF treatment for HSP. Thus, our aim was to report on a case series about its use in chronic stroke. Patients and methods: Six chronic stroke patients with HSP (visual analog scale [VAS] score for pain ≥30 mm) underwent ultrasound-guided SSN PRF treatment. All were evaluated before treatment and at 4 and 16 weeks of follow-up. The main outcome was VAS score. Secondary outcomes were Modified Ashworth Scale, shoulder passive range of motion (PROM), Disability Assessment Scale (DAS), Fugl-Meyer Assessment, and EuroQol-5 dimension questionnaire (EuroQol-5D) scores. Results: As compared with baseline, improvement was observed in the following parameters: VAS for pain (at 4 weeks, P=0.023; at 16 weeks, P=0.023); shoulder PROM for abduction (at 4 weeks, P=0.023; at 16 weeks, P=0.024), flexion (at 4 and 16 weeks, P=0.024), extension (at 4 and 16 weeks, P=0.02), and external rotation (4 and 16 weeks, P=0.02); DAS for hygiene (at 4 and 16 weeks, P=0.024), dressing (at 4 weeks, P=0.02; at 16 weeks, P=0.024), and pain (at 4 weeks, P=0.024; at 16 weeks, P=0.023); and EuroQol-5D (at 4 and 16 weeks, P=0.024). Conclusion: Our observations support the use of ultrasound-guided SSN PRF treatment for HSP in chronic stroke patients. Keywords: chronic pain, pain management, rehabilitation

Abstract: Staphylococcus aureus is an increasingly important pathogen, due to the arsenal of virulence factors which presents, in addition to its high capacity to generate antimicrobial resistance. The objectives of this research were: confirm methicillin resistance by amplification the mecA gene and the presence of genes that encode Panton Valentine leucocidin (PVL) virulence factor. These genes have been investigated using polymerase chain reaction (PCR). All isolates showed the mecA gene, 50% of these strains were carrying the gene for PVL. 54,17% of the samples from pediatric patients, yield positive for this leukocidin. The highest percentage of isolation was found in samples of skin and soft tissues (85.7%). Resumen: Staphylococcus aureus se presenta como un patógeno cada vez más importante, debido al arsenal de factores de virulencia que presenta, sumado a su elevada capacidad de generar resistencia a los antimicrobianos Los objetivos de esta investigación fueron: confirmar la resistencia a meticilina mediante la amplificación del gen mecA y detectar la presencia de los genes que codifican el factor de virulencia leucocidina de Panton Valentine (PVL). Se investigaron estos genes empleando la reacción en cadena de polimerasa (PCR). Todos los aislamientos presentaron el gen mecA, el 50% de estas cepas resultó portador del gen para PVL. El 54,17% de las muestras de pacientes pediátricos, dio positivo para esta leucocidina. El mayor porcentaje de aislamiento se encontró en muestras de piel y tejidos blandos (85,7%).

Abstract: Some species of Aeromonas have emerged as important pathogens associated with the development of gastrointestinal and extra-intestinal infections. The objective of this study was to evaluate the potential virulence of Aeromonas strains from vegetables. Virulence factors were analyzed: DNase, lecitinasa, caseinase, gelatinase, hemolysines and hemaglutinies, in 59 strains of A. hydrophila and 61 of A. caviae, isolated from coriander, parsley and lettuce obtained in establishments in Maracaibo city. The results were analyzed through statistics c2. The virulence factors studied were expressed for more of the 80% of the strains. Four of the 6 factors were expressed in greater proportion in Aeromonas hydrophila strains, although the difference between the species only significant in for caseinase expression (94.9% vs 72.1%, p 0.05). A significant difference was evident in the number of virulence factors expressed by the two species, being higher for A. hydrophila (p 0,05). Se evidenció una diferencia significativa en el número de factores de virulencia expresado por las dos especies, siendo mayor para A. hydrophila (p < 0,05). La expresión de un número elevado de factores de virulencia por las cepas de Aeromonas analizadas, permite atribuirles un potencial de patogenicidad similar al descrito en las cepas procedentes de infecciones humanas.

Staphylococcus aureus is an increasingly important pathogen, due to the arsenal of virulence factors which presents, in addition to its high capacity to generate antimicrobial resistance. The objectives of this research were: confirm methicillin resistance by amplification the mecA gene and the presence of genes that encode Panton Valentine leucocidin (PVL) virulence factor. These genes have been investigated using polymerase chain reaction (PCR). All isolates showed the mecA gene, 50% of these strains were carrying the gene for PVL. 54,17% of the samples from pediatric patients, yield positive for this leukocidin. The highest percentage of isolation was found in samples of skin and soft tissues (85.7%).

Some species of Aeromonas have emerged as important pathogens associated with the development of gastrointestinal and extra-intestinal infections. The objective of this study was to evaluate the potential virulence of Aeromonas strains from vegetables. Virulence factors were analyzed: DNase, lecitinasa, caseinase, gelatinase, hemolysines and hemaglutinies, in 59 strains of A. hydrophila and 61 of A. caviae, isolated from coriander, parsley and lettuce obtained in establishments in Maracaibo city. The results were analyzed through statistics χ2. The virulence factors studied were expressed for more of the 80% of the strains. Four of the 6 factors were expressed in greater proportion in Aeromonas hydrophila strains, although the difference between the species only significant in for caseinase expression (94.9% vs 72.1%, p 0.05). A significant difference was evident in the number of virulence factors expressed by the two species, being higher for A. hydrophila (p