Free-of-charge hepatitis C virus antibody (HCV Ab) screening in some key populations and in 1969-1989 birth cohorts have been funded in Italy as the first step in confirming diagnosis in individuals who may be unaware of their infection. The purpose of this study is to leverage existing in-hospital routine screening data to better understand the distribution of HCV. A retrospective study of hospitalized patients (PTs) tested for HCV Ab for 5 years (from January 2017 to December 2022) in San Raffaele hospital was conducted according to age categories: birth year group before 1947 (patients older than 76 years old), birth year group 1947-1968, birth year group 1969-1989, and two other groups with birth year groups 1990-2000 and 2001-2022 (with patients younger than 33 years old) using the TriNetX platform. Among the 42,805 in-hospital PTs tested, 1297 (3.03%) were HCV Ab positive. The prevalence of HCV Ab was greater in PTs over the age of 76 (5.3%), whereas it was lower in the youngest birth year cohort (2000-2022, 0.16%). Among 1297 HCV Ab positive PTs, only 198 (15.3%) were tested for the presence of HCV RNA. The birth cohort 1969-1989 had a modest seroprevalence (1.5%), yet they were the most affected age group, with 44.4% being HCV RNA positive. The in-hospital HCV screening including birth year cohort 1947-1989 could be a more valuable option compared to the screening for birth year group 1969-1989 in the general population.

Nowadays, hospitals are facing the need for an accurate prediction of rehospitalizations. Rehospitalizations, indeed, represent both a high financial burden for the hospital and a proxy measure of care quality. The current work aims to address such a problem with an innovative approach, by building a Process Mining-Deep Learning model for the prediction of 6-months rehospitalization of patients hospitalized in a Cardiology specialty at San Raffaele Hospital, starting from their medical history contained in the Patients Hospital Records, with the double purpose of supporting resource planning and identifying at-risk patients.

Free-of-charge HCV screening in some key populations and in 1969–1989 birth cohorts have been funded in Italy as the first step to diagnosing individuals unaware of their infection. The aim of this study is to use available in-hospital routine screening data to understand the inpatients HCV screening in a region of North Italy. A retrospective search of in-hospital patients tested for HCV-antibody (HCV-Ab) from January 2017 to the end of December 2022, was conducted according to age categories (older than 76 years, birth group 1947-1968; birth group1969-1989 and two other categories with patients younger than 33 years) using the TriNetX network. Of 42,805 in-hospital patients tested, 1,297 (3.03%) resulted HCV-Ab positive. The proportion decreased from 2017 to 2022 (from 2.03% to 0.36%) years). The higher prevalence of HCV-Ab was in patients older than 76 years (5.3%) while, the lowest was in the younger birth cohort (2000-2022, 0.16%). Of 1,297 patients found HCV-Ab positive, only 198 (15.3%) were tested for the presence of HCV RNA. Although the birth cohort 1969-1989 had a lower seroprevalence (1.5%), they represented the most affected age group with 44.4% of HCV RNA positivity. The in-hospital HCV screening including birth cohort 1947-1989 could be a valuable option respect to the screening for birth group 1969-1989 in the general population. Since a high proportion of patients were not tested for HCV RNA during hospitalization, reflex testing promptly ascertaining an active infection could facilitate linkage to care to stop the burden of HCV.

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.

Neuromodulators adapt sensory circuits to changes in the external world or the animal's internal state and synapses are key control sites for such plasticity. Less clear is how neuromodulation alters the amount of information transmitted through the circuit. We investigated this question in the context of the diurnal regulation of visual processing in the retina of zebrafish, focusing on ribbon synapses of bipolar cells. We demonstrate that contrast-sensitivity peaks in the afternoon accompanied by a four-fold increase in the average Shannon information transmitted from an active zone. This increase reflects higher synaptic gain, lower spontaneous "noise" and reduced variability of evoked responses. Simultaneously, an increase in the probability of multivesicular events with larger information content increases the efficiency of transmission (bits per vesicle) by factors of 1.5-2.7. This study demonstrates the multiplicity of mechanisms by which a neuromodulator can adjust the synaptic transfer of sensory information.

Neuromodulators adjust sensory circuits to changes in the external world or the animal’s internal state and synapses are key control sites for such plasticity. Less clear is how neuromodulation alters the amount of information transmitted through the circuit. We investigated this question in the context of the diurnal regulation of visual processing in zebrafish, focusing on synapses of retinal bipolar cells. We demonstrate that contrast-sensitivity peaks in the afternoon accompanied by an average four-fold increase in the Shannon information transmitted at individual active zones. This increase reflects higher synaptic gain, lower spontaneous “ noise” and reduced variability of evoked responses. Simultaneously, an increase in the probability of multivesicular events with larger information content increases the efficiency of transmission (bits per vesicle) by factors of 2-3. This study demonstrates how the potentiation of multivesicular release by neuromodulators can increase the synaptic transfer of information and the efficiency of the vesicle code.

After SARS-CoV-2 vaccines development came at an unprecedented speed, ensuring safe and efficient mass immunization, vaccine delivery became the major public health mandate. Although mass-vaccination sites have been identified as essential to curb COVID-19, their organization and functioning is challenging. In this paper we present the planning, implementation and evaluation of a massive vaccination center in Lombardy - the largest Region in Italy and the most heavily hit by the pandemic. The massive hub of Novegro (Milan), managed by the Gruppo Ospedaliero San Donato, opened in April 2021. The Novegro mass-immunization model was developed building a layout based on the available scientific evidence, on comparative analysis with other existing models and on the experience of COVID- 19 immunization delivery of Gruppo Ospedaliero San Donato. We propose a "vaccine islands" mass-immunization model, where 4 physicians and 2 nurses operate in each island, with up to 10 islands functioning at the same time, with the capacity of providing up to 6,000 vaccinations per day. During the first week of activity a total of 37,900 doses were administered (2,700/day), most of them with Pfizer vaccine (85.8%) and first doses (70.9%). The productivity was 10.5 vaccines/hour/vaccine station. Quality, efficiency and safety were boosted by ad-hoc personnel training, quality technical infrastructure and the presence of a shock room. Constant process monitoring allowed to identify and promptly tackle process pitfalls, including vaccine refusals (0.36%, below expectations) and post-vaccinations adverse reactions (0.4%). Our innovative "vaccine islands" mass-immunization model might be scaled-up or adapted to other settings. The Authors consider that sharing best practices in immunization delivery is fundamental to achieve population health during health emergencies.

Over the last year, health systems across Europe have encountered the most difficult times for a generation. Throughout the world, health services buckled under the strain of COVID-19, confronting enormous challenges around hospital capacity and workforce planning during a pandemic. As managers are pondering whether there will be a return to a ‘new normal‘, important questions will be asked about how to increase the resilience and readiness of health systems whilst also providing high-quality routine care catching up on the backlog of many months of missed operations. Health management will be at the centre of providing solutions for these unprecedented difficulties. Bringing practitioners, researchers and academics together to share solutions has never been more important than today. The EHMA Annual Conference 2021 organised by EHMA in collaboration with the Associação Portuguesa de Administradores Hospitalares (APAH) and its academic partners, the Escola Nacional de Saúde Pública and the Universidade Nova: Nova School of Business and Economics brought together experts from across the world to discuss solutions to managing services in the post-COVID future. With a rich and diverse programme, the conference offered a unique opportunity to share experiences and find answers to some of the most difficult problems in leading and managing the health services of tomorrow. The EHMA Annual Conference is widely considered the preeminent place to share experiences, skills and competencies in the field of health management. With a strong focus on innovative practices in governing, planning and delivering services, the EHMA 2021 Annual Conference allowed getting in touch with European and international colleagues to discuss the latest developments in governance and leadership, digital transformation, integrated care, and creating sustainable person-centred services.

Value-Based Medicine (VBM) is imposing itself as 'a new paradigm in healthcare management and medical practice. In this perspective paper, we discuss the role of VBM in dealing with the large productivity issue of the healthcare industry and examine some of the worldwide industrial and technological trends linked with VBM introduction. To clarify the points, we discuss examples of VBM management of stroke patients. In our conclusions, we support the idea of VBM as a strategic aid to manage rising costs in healthcare, and we explore the idea that VBM, by establishing value-generating networks among different healthcare stakeholders, can serve as the long sought-after redistributive mechanism that compensate patients for the industrial exploitation of their personal medical records.

Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

BACKGROUND: No clinical standardized methods exist to identify the early stage of the development of pump thrombosis in the setting of HVAD (Medtronic Inc., USA) implantation. We aimed at developing a clinically relevant tool to evaluate HVAD operation during long-term support and at identifying a new reliable marker for the early diagnosis of pump thrombosis reflecting altered patient-pump physiological interplay. METHODS: We developed a novel algorithm based on time-frequency analysis of the HVAD log files allowing the detection of the intrinsic circadian rhythmicity of the pump power consumption. With this tool, we retrospectively evaluated (1) post-operative restoration of circadian rhythm (n = 14 patients), (2) long-term stability of circadian rhythmicity in patients with no reported adverse events (n = 12), and (3) alteration of circadian fluctuations in patients who suffered from pump thrombosis (n = 19). RESULTS: We demonstrate (1) progressive development of circadian rhythm following post-operative recovery (93% of the patients, 23 +/- 15 days after implantation), (2) long-term stability of circadian rhythmicity in patients with no thrombotic complications (92% of the patients; 962 (445-1447) days of support), and (3) severe instability and loss of circadian fluctuations before the thrombotic event (89% of the patients, 12 +/- 6 days ahead of the clinical manifestation of overt pump thrombosis). Furthermore, we provide the first clinical evidence of recovery of circadian rhythmicity following non-surgical resolution of pump thrombosis. CONCLUSIONS: Time-frequency analysis of the HVAD log files provides a new tool for the early diagnosis of pump thrombosis. Loss of circadian rhythmicity might trigger medical evaluation, improving the results of medical management of pump thrombosis, and decreasing the need for pump exchange. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.

Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.

The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties.

Neurons in the visual system vary widely in the spatiotemporal properties of their receptive fields (RFs), and understanding these variations is key to elucidating how visual information is processed. We present a new approach for mapping RFs based on the filtered back projection (FBP), an algorithm used for tomographic reconstructions. To estimate RFs, a series of bars were flashed across the retina at pseudo-random positions and at a minimum of five orientations. We apply this method to retinal neurons and show that it can accurately recover the spatial RF and impulse response of ganglion cells recorded on a multi-electrode array. We also demonstrate its utility for in vivo imaging by mapping the RFs of an array of bipolar cell synapses expressing a genetically encoded Ca2+ indicator. We find that FBP offers several advantages over the commonly used spike-triggered average (STA): (i) ON and OFF components of a RF can be separated; (ii) the impulse response can be reconstructed at sample rates of 125 Hz, rather than the refresh rate of a monitor; (iii) FBP reveals the response properties of neurons that are not evident using STA, including those that display orientation selectivity, or fire at low mean spike rates; and (iv) the FBP method is fast, allowing the RFs of all the bipolar cell synaptic terminals in a field of view to be reconstructed in under 4 min. Use of the FBP will benefit investigations of the visual system that employ electrophysiology or optical reporters to measure activity across populations of neurons.

Cross-modal regulation of visual performance by olfactory stimuli begins in the retina, where dopaminergic interneurons receive projections from the olfactory bulb. However, we do not understand how olfactory stimuli alter the processing of visual signals within the retina. We investigated this question by in vivo imaging activity in transgenic zebrafish expressing SyGCaMP2 in bipolar cell terminals and GCaMP3.5 in ganglion cells. The food-related amino acid methionine reduced the gain and increased sensitivity of responses to luminance and contrast transmitted through OFF bipolar cells but not ON. The effects of olfactory stimulus were blocked by inhibiting dopamine uptake and release. Activation of dopamine receptors increased the gain of synaptic transmission in vivo and potentiated synaptic calcium currents in isolated bipolar cells. These results indicate that olfactory stimuli alter the sensitivity of the retina through the dopaminergic regulation of presynaptic calcium channels that control the gain of synaptic transmission through OFF bipolar cells.