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The huge development that advanced therapy medicinal products (AMTPs) have experienced in recent years, both commercial and research, represent a challenge for hospital pharmacy at all levels. The aim of this article is to describe the implementation of an advanced therapies unit (AUT) and the process of preparation of the AMTPs according to the “good manufacturing practices” (GMP), as well as the results obtained in a tertiary hospital, as an example of the challenges posed by MTA's academic production.

El enorme desarrollo que están experimentado en los últimos años los medicamentos de terapias avanzadas (MTA), tanto industriales como en investigación, suponen un reto para la farmacia hospitalaria a todos los niveles. El objetivo del trabajo es describir la puesta en marcha de una unidad de terapias avanzadas (UTA) y el proceso de elaboración de los MTA según las «normas de correcta fabricación» (NCF), así como los resultados obtenidos en un hospital terciario, como ejemplo de los retos que supone la producción académica de los MTA.

Aim: Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. Methods: We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. Results: The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m2and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of − 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of − 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. Conclusion: This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting.

Purpose: In the present short report, we encompass the radiobiological and dosimetric advantages of particle beam radiotherapy and we illustrate the oncological pathway for patients eligible for hadrontherapy being used at the National Center for Oncological Hadrontherapy (CNAO). Methods: With a narrative approach, we examined the clinical and practical aspects of hadrontherapy compared to traditional photon beam radiotherapy. We described the need to select patients considering the intrinsic characteristics both of the tumour and the patient. Moreover, we described the decisional oncological tree and the patient pathway by our facility. Results: Considering the dosimetric and radiobiological characteristics of particle beam radiotherapy, the selection of patients can not be done regardless of the intrinsic tumour and patient hallmarks. In particular, the tumour radioresistance, the patient radiosensitivity and the need to avoid post-actinic toxicities in long-term survivors should guide the clinical indication. The finite range of particles should be considered to avoid treatment uncertainties. Multidisciplinary national and international collaboration is crucial to better manage patients to treat with hadrontherapy and to create robust clinical evidence. Conclusion: Hadrontherapy, with its distinctive physical and biological advantages, heralds a promising era in the field of precision radiotherapy. Patients’ radiosensitivity, tumour radioresistance, and treatment uncertainties should be considered to enhance the efficacy and to ameliorate the selection of patients.

The increasing interest in Additive Manufacturing (AM) technologies is mainly driven by their high design flexibility and on-demand production. As these processes expand, there is a critical need to explore the material properties of resulting products under diverse loading conditions. This work investigates the impact response of the as-built aluminum alloy AlSi10Mg, additively manufactured employing a laser powder bed fusion (L-PBF) process. Taylor-cylinder impact tests have been performed with a light gas gun at different impact velocities to probe material deformation and damage behavior under high-rate loadings and complex stress paths. Three building orientations were systematically investigated– horizontal, vertical, and at 45°. At lower striking velocities (between 180 and 200 m/s), observable mushrooming deformation occurred with no apparent damage. The shape of the impact faces and deformed profiles were recorded to assess deformation differences across the tested printing directions. In the intermediate range of velocities (240–260 m/s), shear cracking emerged as the principal damage mechanism, resulting in the formation of 45°/135° oriented cracks on the samples’ lateral surface. Increasing the impact velocity promoted these cracks’ growth, ultimately leading to the samples’ fragmentation. The vertically printed sample exhibited a slightly lower onset fragmentation velocity than the other two building directions.

Purpose: To review experience and indications for head and neck (HN) tumors at our center in relation to the published literature. Methods: HN cancer patients treated at our center either with protons (PT) or carbon ions (CIRT) were extracted from our institutional retrospective and longitudinal Registry (NCT05203250 REGAL), including all the patients treated since the beginning of our clinical activity. A literature search was conducted with selection of most representative published studies for adenoid cystic carcinoma (ACC), mucosal melanoma (MM), sinonasal cancers (SNCs) and reirradiations. Results: Since the beginning of the clinical activity in 2011, 1311 HN tumors have been treated a tour center. Majority of treated patients were ACC (52%), non-ACC salivary gland tumors (18%), paranasal sinuses tumors (9%), MM (7%), and reirradiation of recurrent tumors after previous RT (14%). Oncological outcome in terms of safety and efficacy has been published on the series of 184 ACC and 40 MM, both treated with CIRT in the years 2013–2020. Reviewed reirradiation published series included a cohort of 52 recurrent salivary gland tumors retreated with CIRT from 2013 to 2016, and the experience of 2013–2020 of retreatment of 15 SNCs (13 with CIRT and 2 with PT). Conclusion: HN tumors are major indications for particle treatment around the world and at our center. Particle treatment might be personalized for each patient, with CIRT indicated for radioresistant tumors such as ACC and MM. Data on oncologic outcomes of CIRT at our center are consistent with published series.

A visual inspection, which entails field surveying, such as photodocumentation and footage, is the first step of a multi-level approach to bridge health assessment. Furthermore, the use of surface models, CAD drawings, and orthophotos, guarantees complete and accurate documentation, thus allowing for a better understanding of the environment, the anthropic structures, and their relationships. All the georeferenced surveys’ outputs are especially advisable within a prespective of periodical monitoring, as forseen by national legislation. The work is aimed to study two adjacent bridges over the Arno River in Lastra a Signa, Italy. One of the bridges, Ponte nuovo sull’Arno, is an overpass for motor vehicles. The other one, which is called Passarella sull’Arno, is a pedestrian viaduct. A topographic reference network has been settled using the GNSS survey technique. 3D point clouds of the bridges have been acquired by performing a Laser Scanning survey. A bathymetric survey has been carried out to acquire a 3D point cloud of submerged bridges’ parts and the riverbed. Through a Photogrammetric survey from RPAS, an orthophoto of the area has been built. Finally, evidence of historical submerged bridge structures has been identified thanks to the multi beam survey. The work’s objective is to integrate surveying geomatics techniques to create a reliable survey of the bridges, the surrounding area, and the riverbed, as support to the most common structural health assessment methods.

Purpose: In mice, adipose tissue-derived stem cells (ASCs) reach the systemic circulation and establish ectopic adipose depots fostering insulin resistance, but whether this occurs in humans is unknown. We examined circulating ASCs in individuals with various combination of metabolic syndrome traits. Methods: We enrolled patients attending a routine metabolic evaluation or scheduled for bariatric surgery. We quantified ASCs as CD34+CD45−CD31−(CD36+) cells in the stromal vascular fraction of subcutaneous and visceral adipose tissue samples and examined the presence and frequency of putative ASCs in peripheral blood. Results: We included 111 patients (mean age 59 years, 55% males), 40 of whom were scheduled for bariatric surgery. The population of CD34+CD45−CD31−ASCs was significantly more frequent in visceral than subcutaneous adipose depots (10.4 vs 4.1% of the stromal vascular fraction; p < 0.001), but not correlated with BMI or metabolic syndrome traits. The same phenotype of ASCs was detectable in peripheral blood of 58.6% of patients. Those with detectable circulating ASCs had significantly higher BMI (37.8 vs 33.3 kg/m2; p = 0.003) and waist (111.2 vs 105.4 cm; p = 0.001), but no difference in other metabolic syndrome traits (p = 0.84). After bariatric surgery, patients with detectable circulating ASCs had greater BMI reductions at 6 months (− 10.4 vs − 7.8 kg/m2; p = 0.014). Conclusion: Presence of putative circulating ASCs, antigenically similar to those observed in the adipose tissue, is associated with greater adiposity and larger BMI reduction after surgery, but not with clinical signs of metabolic impairment. The role of circulating ASCs in adipose tissue biology and systemic metabolism deserves further investigation.

Aim: To compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D). Methods: This was a multicentre retrospective study on patients aged 70–80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015–2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM). Results: Patients initiating dapagliflozin (n= 445) differed from those initiating DPP-4i (n= 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p< 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors. Conclusions: Elderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints.

BackgroundThe regional emergency medical service (EMS) in Lombardy (Italy) developed clinical algorithms based on operator-based interviews to detect patients with COVID-19 and refer them to the most appropriate hospitals. Machine learning (ML)-based models using additional clinical and geospatial epidemiological data may improve the identification of infected patients and guide EMS in detecting COVID-19 cases before confirmation with SARS-CoV-2 reverse transcriptase PCR (rtPCR).MethodsThis was an observational, retrospective cohort study using data from October 2020 to July 2021 (training set) and October 2021 to December 2021 (validation set) from patients who underwent a SARS-CoV-2 rtPCR test within 7 days of an EMS call. The performance of an operator-based interview using close contact history and signs/symptoms of COVID-19 was assessed in the training set for its ability to determine which patients had an rtPCR in the 7 days before or after the call. The interview accuracy was compared with four supervised ML models to predict positivity for SARS-CoV-2 within 7 days using readily available prehospital data retrieved from both training and validation sets.ResultsThe training set includes 264 976 patients, median age 74 (IQR 55–84). Test characteristics for the detection of COVID-19-positive patients of the operator-based interview were: sensitivity 85.5%, specificity 58.7%, positive predictive value (PPV) 37.5% and negative predictive value (NPV) 93.3%. Contact history, fever and cough showed the highest association with SARS-CoV-2 infection. In the validation set (103 336 patients, median age 73 (IQR 50–84)), the best-performing ML model had an AUC of 0.85 (95% CI 0.84 to 0.86), sensitivity 91.4% (95 CI% 0.91 to 0.92), specificity 44.2% (95% CI 0.44 to 0.45) and accuracy 85% (95% CI 0.84 to 0.85). PPV and NPV were 13.3% (95% CI 0.13 to 0.14) and 98.2% (95% CI 0.98 to 0.98), respectively. Contact history, fever, call geographical distribution and cough were the most important variables in determining the outcome.ConclusionML-based models might help EMS identify patients with SARS-CoV-2 infection, and in guiding EMS allocation of hospital resources based on prespecified criteria.

Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28was associated with lower virological failure (p= 0.012), even after adjusting for baseline CD4 count (p= 0.048), but not when adjusted for baseline HIV-1 viral load (p= 0.082) or both (p= 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir’s characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.

In Dynamic Tensile Extrusion (DTE) test, the material is subjected to extreme conditions, such as severe plastic deformations, high pressures, and large variations of temperature and strain rate. Although the numerical simulation of this test is ideal for constitutive model validation, there are several computational features to assess before performing further analyses. This work aims to evaluate the influence of constitutive modeling and computational parameters on the predicted material jet in the simulation of DTE tests on Oxygen-Free High Conductivity Copper at different extrusion velocities. Dynamic transient analyses have been performed with implicit finite element code using a single-step Houbolt procedure. To begin with, three constitutive models (the Mechanical Threshold Stress, modified Johnson–Cook, and Zerilli-Armstrong) were selected and model parameters have been identified on available uniaxial tensile test data at different temperature and strain rates. Successively, the effect of friction, damping, remeshing, and extrusion die modeling has been investigated by performing parametric numerical simulations at 400 m/s extrusion velocity and an optimum set of computational parameters was determined. Finally, constitutive models' performance has been verified by comparing the predicted size, shape, and number of extruded fragments at different velocities with experimental data. The ability to correctly predict the size and shape of the last temporally forming fragment appears to be directly related to the ability of the constitutive model to accurately describe the material response in the viscous drag regime.

In Italia vivono circa 4 milioni di persone con il diabete e ogni anno ci sono circa 350 mila nuove diagnosi. Le persone con diabete ricevono prescrizioni di farmaci, esami di laboratorio e strumentali e richiedono ricoveri ospedalieri più spesso delle persone senza il diabete. Il diabete è gravato da aumentata mortalità e accorcia la vita, soprattutto nelle persone di media età. La qualità della cura nelle persone con diabete è subottimale, soprattutto fra chi non è assistito nei centri diabetologici (che, peraltro, rappresentano dei luoghi “salvavita”). Il diabete contribuisce fortemente alla spesa sanitaria e comporta ingenti spese, non tutte specificamente sanitarie. Nonostante tutto questo e nonostante leggi nazionali e regionali, documenti di indirizzo nazionali e regionali, PDTA regionali e locali, promesse e proponimenti di varia provenienza, la pandemia diabete non riceve le attenzioni che merita.

Eating disorder psychopathology was found to be related to a history of trauma. Nonetheless, our understanding of the mediators of the relationship between childhood trauma and eating disorders remains to be improved. The current study revealed that certain early maladaptive schemas (i.e., defectiveness, failure, and negativity) mediated the relationship between childhood trauma and eating disorder symptoms and that outpatients who experienced severe childhood trauma reported more severe eating disorder symptoms and greater severity of certain early maladaptive schemas, such as emotional deprivation, defectiveness, failure, vulnerability, insufficient self-control, and negativity. Our findings support the need to consider early maladaptive schemas in the treatment of traumatized patients with eating disorders.

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Congenital hydrocephalus (CH), occurring in approximately 1/1,000 live births, represents an important clinical challenge due to the limited knowledge of underlying molecular mechanisms. The discovery of novel CH genes is thus essential to shed light on the intricate processes responsible for ventricular dilatation in CH. Here, we identify FLVCR1(feline leukemia virus subgroup C receptor 1) as a gene responsible for a severe form of CH in humans and mice. Mechanistically, our data reveal that the full-length isoform encoded by the FLVCR1gene, FLVCR1a, interacts with the IP3R3-VDAC complex located on mitochondria-associated membranes (MAMs) that controls mitochondrial calcium handling. Loss of Flvcr1ain mouse neural progenitor cells (NPCs) affects mitochondrial calcium levels and energy metabolism, leading to defective cortical neurogenesis and brain ventricle enlargement. These data point to defective NPCs calcium handling and metabolic activity as one of the pathogenetic mechanisms driving CH.

Mitochondrial permeability transition (mPT) is a phenomenon that abruptly causes the flux of low molecular weight solutes (molecular weight up to 1,500) across the generally impermeable inner mitochondrial membrane. The mPT is mediated by the so-called mitochondrial permeability transition pore (mPTP), a supramolecular entity assembled at the interface of the inner and outer mitochondrial membranes. In contrast to mitochondrial outer membrane permeabilization, which mostly activates apoptosis, mPT can trigger different cellular responses, from the physiological regulation of mitophagy to the activation of apoptosis or necrosis. Although there are several molecular candidates for the mPTP, its molecular nature remains contentious. This lack of molecular data was a significant setback that prevented mechanistic insight into the mPTP, pharmacological targeting and the generation of informative animal models. In recent years, experimental evidence has highlighted mitochondrial F1FoATP synthase as a participant in mPTP formation, although a molecular model for its transition to the mPTP is still lacking. Recently, the resolution of the F1FoATP synthase structure by cryogenic electron microscopy led to a model for mPTP gating. The elusive molecular nature of the mPTP is now being clarified, marking a turning point for understanding mitochondrial biology and its pathophysiological ramifications. This Review provides an up-to-date reference for the understanding of the mammalian mPTP and its cellular functions. We review current insights into the molecular mechanisms of mPT and validated observations — from studies in vivo or in artificial membranes — on mPTP activity and functions. We end with a discussion of the contribution of the mPTP to human disease. Throughout the Review, we highlight the multiple unanswered questions and, when applicable, we also provide alternative interpretations of the recent discoveries.

Purpose: Diabetes is a growing health problem. The aim of this study was to capture time trends in mortality associated with diabetes. Methods: The mortality database of the Veneto region (Italy) includes both the underlying causes of death, and all the diseases mentioned in the death certificate. The annual percent change (APC) in age-standardized rates from 2008 to 2017 was computed by the Joinpoint Regression Program. Results: Overall 453,972 deaths (56,074 with mention of diabetes) were observed among subjects aged ≥ 40 years. Mortality rates declined for diabetes as the underlying cause of death and from diabetes-related circulatory diseases. The latter declined especially in females − 4.4 (CI 95% − 5.3/− 3.4), while in males the APC was − 2.8 (CI 95% − 4.0/− 1.6). Conclusion: We observed a significant reduction in mortality during the period 2008–2017 in diabetes either as underlying cause of death or when all mentions of diabetes in the death certificate were considered.

Purpose: To evaluate the effects of the COVID-19 pandemic on the Ophthalmic Emergency Department (OED) activity of the tertiary eye centre of Verona.Methods: OED reports of patients visited during lockdown (COVID-period) and in the corresponding period of 2017, 2018 and 2019 (COVID-free period) have been retrieved to draw a comparison. Patients’ demographic and clinical data recorded and analysed are the following: age, gender, previous ocular history, aetiology, symptoms onset, type of symptoms, discharge diagnosis, urgency and severity of diagnosis.Results: OED consultations dropped from 20.6 ± 7.3 visits/day of the COVID-free period to 8.6 ± 4.6 visits/day of the COVID-period. In the COVID-period patients waited longer before physically going to the OED, lamented more vision loss and less redness and reported a higher percentage of traumatic events when compared to the COVID-free period. A significant reduction of ocular surface conditions occurred, while vitreo-retinal disorders increased. Overall, both urgency and severity of diagnosed diseases raised significantly in the COVID-period.Conclusion: The COVID-19 pandemic drove a significant reduction of the overall OED activity. People with less urgent and milder conditions preferred to wait and endure their ocular discomfort for a few days rather than leaving home and risking to contract the infection. Our analysis highlights how several times the OED is used improperly by patients diagnosed with non-urgent disorders. A more accurate use of the OED would allow a reduction of management costs and the avoidance of overcrowding, which can lead to delays in the care of patients that really need assistance.

BackgroundThe aim of this study was to investigate the association between serum albumin levels in the ED and the severity of SARS-CoV-2 infection.MethodsThis is a retrospective observational study conducted from 15 March 2020 to 5 April 2020 at the EDs of three different hospitals in Italy. Data from 296 patients suffering from COVID-19 consecutively evaluated at EDs at which serum albumin levels were routinely measured on patients’ arrival in the ED were analysed. Albumin levels were measured, and whether these levels were associated with the presence of severe SARS-CoV-2 infection or 30-day survival was determined. Generalised estimating equation models were used to assess the relationship between albumin and study outcomes, and restricted cubic spline (RCS) regression was used to plot the adjusted dose-effect relationship for possible clinical confounding factors.ResultsThe mean albumin level recorded on entry was lower in patients with severe SARS-CoV-2 infection than in those whose infections were not severe (3.5 g/dL (SD 0.3) vs 4 g/dL (SD 0.5)) and in patients who had died at 30 days post-ED arrival compared with those who were alive at this time point (3.3 g/dL (SD 0.3) vs 3.8 g/dL (SD 0.4)). Albumin <3.5 g/dL was an independent risk factor for both severe infection and death at 30 days, with adjusted odd ratios of 2.924 (1.509–5.664) and 2.615 (1.131–6.051), respectively. RCS analysis indicated that there was an adjusted dose–response association between the albumin values recorded on ED and the risk of severe infection and death.ConclusionAlbumin levels measured on presentation to the ED may identify patients with SARS-CoV-2 infection in whom inflammatory processes are occurring and serve as a potentially useful marker of disease severity and prognosis.

Structural variants (SVs) can affect protein-coding sequences as well as gene regulatory elements. However, SVs disrupting protein-coding sequences that also function as cis-regulatory elements remain largely uncharacterized. Here, we show that craniosynostosis patients with SVs containing the histone deacetylase 9 (HDAC9) protein-coding sequence are associated with disruption of TWIST1regulatory elements that reside within the HDAC9sequence. Based on SVs within the HDAC9‐TWIST1locus, we defined the 3′-HDAC9sequence as a critical TWIST1regulatory region, encompassing craniofacial TWIST1enhancers and CTCF sites. Deletions of either Twist1enhancers (eTw5-7Δ/Δ) or CTCF site (CTCF-5Δ/Δ) within the Hdac9protein-coding sequence led to decreased Twist1expression and altered anterior/posterior limb expression patterns of SHH pathway genes. This decreased Twist1expression results in a smaller sized and asymmetric skull and polydactyly that resembles Twist1+/−mouse phenotype. Chromatin conformation analysis revealed that the Twist1promoter interacts with Hdac9sequences that encompass Twist1enhancers and a CTCF site, and that interactions depended on the presence of both regulatory regions. Finally, a large inversion of the entire Hdac9sequence (Hdac9INV/+) in mice that does not disrupt Hdac9expression but repositions Twist1regulatory elements showed decreased Twist1expression and led to a craniosynostosis-like phenotype and polydactyly. Thus, our study elucidates essential components of TWIST1transcriptional machinery that reside within the HDAC9sequence. It suggests that SVs encompassing protein-coding sequences could lead to a phenotype that is not attributed to its protein function but rather to a disruption of the transcriptional regulation of a nearby gene.

Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.

The aberrations induced by the sample and/or by the sample holder limit the resolution of optical microscopes. Wavefront correction can be achieved using a deformable mirror with wavefront sensorless optimization algorithms but, despite the complexity of these systems, the level of correction is often limited to a small area in the field of view of the microscope. In this work, we present a plug and play module for aberration measurement and correction. The wavefront correction is performed through direct wavefront reconstruction using the spinning-pupil aberration measurement and controlling a deformable lens in closed loop. The lens corrects the aberrations in the center of the field of view, leaving residual aberrations at the margins, that are removed by anisoplanatic deconvolution. We present experimental results obtained in fluorescence microscopy, with a wide field and a light sheet fluorescence microscope. These results indicate that detection and correction over the full field of view can be achieved with a compact transmissive module placed in the detection path of the fluorescence microscope.

ABSTRACTSince December 2019, Coronavirus has been spreading rapidly across the world. From its early stages, while the rest of the world was still new to COVID-19, Italy was one of the first and most severely hit countries. The chronic nature of the COVID-19 outbreak and untimely treatments were translated into an unstable social and emotional environment. This study explores the societal response to the first wave of the pandemic outbreak in Italy, looking at geographic variations, social and policy perspectives, and sentiments across northern, central, and southern regions. For this study, we collected nearly three million tweets associated with the coronavirus outbreak in the Italian regions of Lombardy, Lazio, and Sicily, during the months of March-May, 2020. A sentiment analysis was developed to (i) identify the spatio-temporal distribution of the polarity patterns of anger, fear, and joy; (ii) test correlation between these sentiments and COVID-19 cases; and (iii) determine the statistical significance between the sentiments across geographies. Findings provide insights on the relationship between sentiment variations and spatio-temporal case distribution associated with regional differences. These findings align with those of the “Track IT. COVID-19 International Survey,” that investigated the societal response of Italians to the new measures enforced by local governments. Overall, the findings of this study can be weaved together into important implications for emotional wellbeing and economic perspective.

Background: The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, becoming pandemic. Several studies have shown that diabetes mellitus (DM) is an independent risk factor that increases mortality and other adverse outcomes of coronavirus disease-19 (COVID-19). Studies have suggested that SARS-CoV-2 may bind dipeptidyl peptidase-4 (DPP4) for entering cells of the respiratory tract. Besides, DPP4 takes part in immune system regulation. Thus, DPP-4 inhibitors (DPP4i) may play a role against COVID-19. Methods: We focused on the impact of DPP4i treatment on COVID-19-related outcomes in people with DM. For this purpose, we conducted a systematic review and meta-analysis to summarize the existing evidence on this topic. Results: Retrospective observational studies provide inconsistent results on the association between use of DPP4i and outcomes of COVID-19. While two studies reported significantly lower mortality rates among patients with DM who received DPP4i versus those who did not, a series of other studies showed no effect of DPP4i or even worse outcomes. A meta-analysis of 7 studies yielded a neutral estimate of the risk ratio of COVID-19-related mortality among users of DPP4i (0.81; 95% CI 0.57–1.15). Conclusion: In the absence of randomized controlled trials, observational research available so far provides inconclusive results and insufficient evidence to recommend use of DPP4i against COVID-19.

The aberrations in an optical microscope are commonly measured and corrected at one location in the field of view, within the so-called isoplanatic patch. Full-field correction is desirable for high-resolution imaging of large specimens. Here we present, to the best of our knowledge, a novel wavefront detector, based on pupil sampling with subapertures, measuring the aberrated wavefront phase at each position of the specimen. Based on this measurement, we propose a region-wise deconvolution that provides an anisoplanatic reconstruction of the sample image. Our results indicate that the measurement and correction of the aberrations can be performed in a wide-field fluorescence microscope over its entire field of view.

ABSTRACTIntroductionPeople living with HIV (PLWH) are aging and will receive life-long treatment: despite substantial improvement in drug efficacy and tolerability, side effects still occur and they can blunt antiretroviral treatment effectiveness. Since age may affect drug exposure and may be associated with side-effects we aimed at reviewing available data on the effect of age on antiretrovirals’ pharmacokinetics in adult patients.Areas coveredWe searched public databases and major conference proceedings for data on age and pharmacokinetics/pharmacodynamics in PLWH. We limited our review to currently used drugs and focused on population pharmacokinetics and physiologically-based pharmacokinetic modeling studies.Expert opinionAvailable evidence of a potential detrimental effect in elderly PLWH is limited by study design and small sample sizes. Careful consideration of undoubtful benefits and potential harms is advised when prescribing ARVs to geriatric patients and the knowledge of pharmacokinetics changes need to be included in the process. With the ‘greying’ of the pandemic we need studies with a specific focus on geriatric patients living with HIV that will consider specific phenotypes and associated changes (including sarcopenia).

The Italian Association for Stress Analysis (AIAS) was founded in 1971 by researchers from academia, research centers and industry. AIAS was intended as a community where to discuss, to share and to develop scientific knowledge related to all technical aspects of stress analysis. In the years, from an initial focus on experimental techniques, AIAS contributed considerably to the development of modern numerical methods and computational techniques for the mechanical engineering design. In 2015, AIAS turned in the Italian Scientific Society of Mechanical Engineering Design.