Chest X-ray evaluation using machine learning to support the early diagnosis of pulmonary TB.

TB is a public health problem, and its diagnosis can be challenging. Among imaging methods, chest X-ray (CXR) is the leading choice for assessing pulmonary TB (PTB). Recent advancements in the field of artificial intelligence have stimulated studies evaluating the performance of machine learning (ML) for medical diagnosis. This study validated a new original Brazilian tool, the XmarTB, applied to CXR images to support the early diagnosis of PTB.An ML model was trained on 3,800 normal images, 3,800 abnormal CXRs without PTB and 1,376 with PTB manifestations from the publicly available TBX11K database.The binary classification can distinguish between normal and abnormal CXR with a sensitivity of 99.4% and specificity of 99.4%. The XmarTB tool had a sensitivity of 98.1% and a specificity of 99.7% in detecting TB cases among CXRs with abnormal CXRs; sensitivity was 96.7% and specificity 98.7% in detecting TB cases among all samples.This diagnostic tool can accurately and automatically detect abnormal CXRs and satisfactorily differentiate PTB from other pulmonary diseases. This tool holds significant promise in aiding the proactive detection of TB cases, providing rapid and accurate support for early diagnosis..

Unequal climate impacts on global values of natural capital.

Ecosystems generate a wide range of benefits for humans, including some market goods as well as other benefits that are not directly reflected in market activity1. Climate change will alter the distribution of ecosystems around the world and change the flow of these benefits2,3. However, the specific implications of ecosystem changes for human welfare remain unclear, as they depend on the nature of these changes, the value of the affected benefits and the extent to which communities rely on natural systems for their well-being4. Here we estimate country-level changes in economic production and the value of non-market ecosystem benefits resulting from climate-change-induced shifts in terrestrial vegetation cover, as projected by dynamic global vegetation models (DGVMs) driven by general circulation climate models. Our results show that the annual population-weighted mean global flow of non-market ecosystem benefits valued in the wealth accounts of the World Bank will be reduced by 9.2% in 2100 under the Shared Socioeconomic Pathway SSP2-6.0 with respect to the baseline no climate change scenario and that the global population-weighted average change in gross domestic product (GDP) by 2100 is -1.3% of the baseline GDP. Because lower-income countries are more reliant on natural capital, these GDP effects are regressive. Approximately 90% of these damages are borne by the poorest 50% of countries and regions, whereas the wealthiest 10% experience only 2% of these losses.

The metabolic effects of intermittent versus continuous feeding in critically ill patients.

Intermittent (or bolus) feeding regimens in critically ill patients have been of increasing interest to clinicians and scientists. Changes in amino acid, fat and carbohydrate metabolites over time might yet deliver other benefits (e.g. modulation of the circadian rhythm and sleep, and impacts on ghrelin secretion, insulin resistance and autophagy). We set out to characterise these changes in metabolite concentration. The Intermittent versus Continuous Feeding in Critically Ill paitents study (NCT02358512) was an eight-centre single-blinded randomised controlled trial. Patients were randomised to received a continuous (control arm) or intermittent (6x/day, intervention arm) enteral feeding regimen. Blood samples were taken on trial days 1, 7 and 10 immediately before and 30 min after intermittent feeds, and at equivalent timepoints in the control arm. A pre-planned targeted metabolomic analysis was performend using Nuclear Resonance Spectroscopy. Five hundred and ninety four samples were analysed from 75 patients. A total of 24 amino acid-, 19 lipid based-, and 44 small molecule metabolite features. Across the main two axes of variation (40-60% and 6-8% of variance), no broad patterns distinguished between intermittent or continuous feeding arms, across intra-day sampling times or over the 10 days from initial ICU admission. Logfold decreases in abundance were seen in metabolites related to amino acids (Glutamine - 0.682; Alanine - 0.594), ketone body metabolism (Acetone - 0.64; 3-Hydroxybutyric Acid - 0.632; Acetonacetic Acid - 0.586), fatty acid (carnitine - 0.509) and carbohydrate metabolism ( Maltose - 0.510; Citric Acid - 0.485). 2-3 Butanediol, a by-product of sugar-fermenting microbial metabolism also decreased (- 0.489). No correlation was seen with change in quadriceps muscle mass for any of the 20 metabolites varying with time (all p > 0.05). Increasing severity of organ failure was related to increasing ketone body metabolism (3 Hydroxybutyric Acid-1 and - 3; p = 0.056 and p = 0.014), carnitine deficiency (p = 0.002) and alanine abundancy (p - 0.005). A 6-times a day intermittent feeding regimen did not alter metabolite patterns across time compared to continuous feeding in critically ill patients, either within a 24 h period or across 10 days of intervention. Future research on intermittent feeding regimens should focus on clinical process benefits, or extended gut rest and fasting.

Apoptotic volume decrease (AVD) in A549 cells exposed to water-soluble fraction of particulate matter (PM10).

Exposure to atmospheric particulate matter (PM) is recognized as a human health risk factor of great concern. The present work aimed to study the cellular mechanisms underlying cytotoxic effects of airborne particulate matter <10 µm in size (PM10), sampled in an urban background site from January to May 2020, on A549 cells. In particular, the study addressed if PM10 exposure can be a main factor in the induction of the Apoptotic Volume Decrease (AVD), which is one of the first events of apoptosis, and if the generation of intracellular oxidative stress can be involved in the PM10 induction of apoptosis in A549 cells. The cytotoxicity of PM10 samples was measured by MTT test on cells exposed for 24 h to the PM10 aqueous extracts, cell volume changes were monitored by morphometric analysis of the cells, apoptosis appearance was detected by annexin V and the induction of intracellular oxidative stress was evaluated by the ROS sensitive CM-H2DCFDA fluorescent probe. The results showed cytotoxic effects ascribable to apoptotic death in A549 cells exposed for 24 h to aqueous extracts of airborne winter PM10 samples characterized by high PM10 value and organic carbon content. The detected reduced cell viability in winter samples ranged from 55% to 100%. Normotonic cell volume reduction (ranging from about 60% to 30% cell volume decrease) after PM10 exposure was already detectable after the first 30 min clearly indicating the ability of PM10, mainly arising from biomass burning, to induce Apoptotic Volume Decrease (AVD) in A549 cells. AVD was prevented by the pre-treatment with 0.5 mM SITS indicating the activation of Cl- efflux presumably through the activation of VRAC channels. The exposure of A549 cells to PM10 aqueous extracts was able to induce intracellular oxidative stress detected by using the ROS-sensitive probe CM-H2DCFDA. The PM10-induced oxidative stress was statistically significantly correlated with cell viability inhibition and with apoptotic cell shrinkage. It was already evident after 15 min exposure representing one of the first cellular effects caused by PM exposure. This result suggests the role of oxidative stress in the PM10 induction of AVD as one of the first steps in cytotoxicity.

Evaluation and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens using a new multiplex assay: a real-life experience on an Italian population.

Summary: Background. House dust mites (HDM) are among the most important allergen sources worldwide, representing a major cause of perennial allergic rhinitis and asthma. Aim. To evaluate the prevalence of IgE responses towards a comprehensive panel of HDM allergens and to evaluate the implications of molecular sensitization profiles on respiratory symptoms. Methods. 155 consecutive HDM-allergic patients (mean age: 27.5 years; range: 1-62; female: 63), 86 affected by rhinitis and 68 by asthma, were enrolled. Specific IgE reactivity to Der f 1, Der p 1, Der f 2, Der p 2, Der p 5, Der p 7, Der p 10, Der p 11, Der p 20, Der p 21 and Der p 23 was tested in patients' sera using the last version of the multiparametric assay Allergy Explorer (ALEX). Results. In all, major and minor allergens were positive, respectively, in 96.8% and 50.9% of the patients. Prevalence and IgE levels of Der f 1, Der f 2, Der p 1 and Der p 20 were significantly higher in asthmatic patients (p less than 0.05), whereas subjects negative for minor allergens resulted more frequently suffering from rhinitis (p = 0.0001). Asthmatic patients had IgE reactivity to a larger number of HDM allergens (mean 5.4; SD ± 2.3) than patients with only rhinitis (mean 4.2; SD ± 2.5) (p = 0.003), whereas no differences in the number of HDM positive molecules and in the specific IgE levels were found among different ages. Conclusions. This study confirms that the assessment of IgE to a comprehensive panel of HDM allergens defines different serological reactivity profiles that seem associated with different clinical presentations.

The acoustical properties of tetraethyl orthosilicate based granular silica aerogels.

Available data suggests that granulated aerogels can be of interest in terms of their sound absorption performance in the audio frequency range. However, there is still no thorough understanding of the complex physical phenomena which are responsible for their observed acoustical properties. This work is an attempt to address this gap through advanced material characterization methods and mathematical modelling. Aerogel samples are produced through a two-step, acid-base sol-gel process, with sol silica concentration and density being the main variables. Their pore structure is carefully characterized by nitrogen sorption analysis and scanning electron microscopy. The acoustical properties of hard-backed granular silica aerogels are measured in an impedance tube and the results predicted accurately with the adopted theoretical model. Although silica aerogels have over 90% of open interconnected pores, this was neither reflected in the measured acoustical properties nor the parameter values predicted with the model. Novel results show that only a proportion of the micro and mesopores in the direct vicinity of the grain surface influenced the acoustical properties of aerogels. Further work in the hierarchical pore structure of aerogels is required to better understand the roles of different pore scales on the measured acoustical properties of a granulated aerogel.

Efficacy and safety of methylphenidate on attention deficit hyperactivity disorder in children with Down syndrome.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common co-morbidity that affects up to 44% of children with Down syndrome (DS). There is a need for reliable, good quality research on the use of methylphenidate within this population. The objective of this study is to report our experience regarding the management of ADHD in these children using methylphenidate. METHODS: This study is a retrospective observation of 21 children with DS, followed at Jérôme Lejeune Institute between 2000 and 2018. The diagnosis of ADHD was made using the Diagnostic and Statistical Manual of Mental Disorders criteria. Efficacy was measured as response or non-response on two main symptoms: attention/concentration and hyperactivity/impulsivity. Safety was evaluated by the presence or absence of side effects. RESULTS: Sixteen out of the 21 children (76%) showed improvement with methylphenidate. The average age of treatment onset in responding children was 8 years and 10 months versus 6 years and 3 months in non-responders (P = 0.05). Average dose/weight was significantly different in responders and non-responders (0.82 vs. 0.54 mg/kg/day, respectively; P = 0.03). Twelve children out of 21 (57%) experienced side effects; only three experienced side effects severe enough to require treatment interruption. Most common side effects were loss of appetite and difficulties in falling asleep. CONCLUSION: Methylphenidate was effective and safe in treating ADHD in 76% of cases in children with DS, with few serious side effects to report. Early diagnosis of ADHD is important to improve the quality of life, learning, inclusion and socialisation of children with DS.

SARS-CoV-2 concentrations and virus-laden aerosol size distributions in outdoor air in north and south of Italy.

The COVID-19 disease spread at different rates in the different countries and in different regions of the same country, as happened in Italy. Transmission by contact or at close range due to large respiratory droplets is widely accepted, however, the role of airborne transmission due to small respiratory droplets emitted by infected individuals (also asymptomatic) is controversial. It was suggested that outdoor airborne transmission could play a role in determining the differences observed in the spread rate. Concentrations of virus-laden aerosol are still poorly known and contrasting results are reported, especially for outdoor environments. Here we investigated outdoor concentrations and size distributions of virus-laden aerosol simultaneously collected during the pandemic, in May 2020, in northern (Veneto) and southern (Apulia) regions of Italy. The two regions exhibited significantly different prevalence of COVID-19. Genetic material of SARS-CoV-2 (RNA) was determined, using both real time RT-PCR and ddPCR, in air samples collected using PM10 samplers and cascade impactors able to separate 12 size ranges from nanoparticles (diameter D < 0.056 µm) up to coarse particles (D > 18 µm). Air samples tested negative for the presence of SARS-CoV-2 at both sites, viral particles concentrations were <0.8 copies m-3 in PM10 and <0.4 copies m-3 in each size range investigated. Outdoor air in residential and urban areas was generally not infectious and safe for the public in both northern and southern Italy, with the possible exclusion of very crowded sites. Therefore, it is likely that outdoor airborne transmission does not explain the difference in the spread of COVID-19 observed in the two Italian regions.

Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2.

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play an important role in the pathogenicity and transmission of SARS-CoV-2. The identification of targeted antiviral mouth rinses to reduce salivary viral load would contribute to reducing the COVID-19 pandemic. While awaiting the results of significant clinical studies, which to date do not exist, the commercial availability of mouth rinses leads us to search among them for reagents that would have specific antiviral properties with respect to SARS-CoV-2. The challenges facing this target were examined for 7 reagents found in commercially available mouth rinses and listed on the ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, and essential oils. Because SARS-CoV-2 is an enveloped virus, many reagents target the outer lipid membrane. Moreover, some of them can act on the capsid by denaturing proteins. Until now, there has been no scientific evidence to recommend mouth rinses with an anti-SARS-CoV-2 effect to control the viral load in the oral cavity. This critical review indicates that current knowledge of these reagents would likely improve trends in salivary viral load status. This finding is a strong sign to encourage clinical research for which quality protocols are already available in the literature.

Exploring Relative Preferences for HIV Service Features Using Discrete Choice Experiments: a Synthetic Review.

PURPOSE OF REVIEW: Aligning HIV treatment services with patient preferences can promote long-term engagement. A rising number of studies solicit such preferences using discrete choice experiments, but have not been systematically reviewed to seek generalizable insights. Using a systematic search, we identified eleven choice experiments evaluating preferences for HIV treatment services published between 2004 and 2020. RECENT FINDINGS: Across settings, the strongest preference was for nice, patient-centered providers, for which participants were willing to trade considerable amounts of time, money, and travel distance. In low- and middle-income countries, participants also preferred collecting antiretroviral therapy (ART) less frequently than 1 monthly, but showed no strong preference for 3-compared with 6-month refill frequency. Facility waiting times and travel distances were also important but were frequently outranked by stronger preferences. Health facility-based services were preferred to community- or home-based services, but this preference varied by setting. In high-income countries, the availability of unscheduled appointments was highly valued. Stigma was rarely explored and costs were a ubiquitous driver of preferences. While present improvement efforts have focused on designs to enhance access (reduced waiting time, travel distance, and ART refill frequency), few initiatives focus on the patient-provider interaction, which represents a promising critical area for inquiry and investment. If HIV programs hope to truly deliver patient-centered care, they will need to incorporate patient preferences into service delivery strategies. Discrete choice experiments can not only inform such strategies but also contribute to prioritization efforts for policy-making decisions.

Comparison of the impact of ships to size-segregated particle concentrations in two harbour cities of northern Adriatic Sea.

Detailed information on in-harbour shipping contribution to size segregated particles in coastal cities are scarce, especially in the busy Mediterranean basin. This poses issues for human exposure and air quality in urban harbour agglomerates, where only criteria pollutants (i.e. PM10 and/or PM2.5) are usually monitored. In this work, particle number and mass size distributions, in a large size range (0.01-31 µm), were obtained in two coastal cities of northern Adriatic Sea: Venice (Italy) and Rijeka (Croatia). Three size ranges were investigated: nanoparticles (diameter D < 0.25 µm); fine particles (0.25 1 µm). Absolute concentrations were larger in Venice for all size ranges showing, using analysis of daily trends, a large influence of local meteorology and boundary-layer dynamics. Contribution of road transport was larger (in relative terms) in Rijeka compared to Venice. The highest contributions of shipping were in Venice, mainly because of the larger ship traffic. Maximum impact was on nanoparticles 7.4% (Venice) and 1.8% (Rijeka), the minimum was on fine range 1.9% (Venice) and <0.2% (Rijeka) and intermediate values were found in the coarse fraction 1.8% (Venice) and 0.5% (Rijeka). Contribution of shipping to mass concentration was not distinguishable from uncertainty in Rijeka (<0.2% for PM1, PM2.5, and PM10) and was about 2% in Venice. Relative contributions as function of particles size show remarkable similitudes: a maximum for nanoparticles, a quick decrease and a successive secondary maximum (2-3 times lower than the first) in the fine range. For larger diameters, the relative contributions reach a minimum at 1-1.5 µm and there is a successive increase in the coarse range. Size distributions showed a not negligible contribution of harbour emissions to nanoparticle and fine particle number concentrations, compared to PM2.5 or PM10, indicating them as a better metric to monitor shipping impacts compared to mass concentrations (PM2.5 or PM10).

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study.

BACKGROUND: Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. METHODS: This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the "appropriate anaesthesia zone" defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45-60 and systolic arterial pressure of 80-140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. RESULTS: Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0-40) vs 5 (0-116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2-20) vs 8 (2-60) days, P=0.017). CONCLUSIONS: SmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: NCT 02556658.

Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study.

OBJECTIVE: Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. METHODS: Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. RESULTS: Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). CONCLUSIONS: We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers.

Biocatalytic Self-Assembly Using Reversible and Irreversible Enzyme Immobilization.

Biocatalytic control of molecular self-assembly provides an effective approach for developing smart biomaterials, allowing versatile enzyme-mediated tuning of material structure and properties as well as enabling biomedical applications. We functionalized surfaces with bioinspired polydopamine and polyphenol coatings to study the effects of enzyme surface localization and surface release on the self-assembly process. We show how these coatings could be conveniently used to release enzymes for bulk gelation as well as to irreversibly immobilize enzymes for localizing the self-assembly to the surface. The results provide insights to the mode of action of biocatalytic self-assembly relevant to nanofabrication and enzyme-responsive materials.

A storage ring experiment to detect a proton electric dipole moment.

A new experiment is described to detect a permanent electric dipole moment of the proton with a sensitivity of 10-29 e ⋅ cm by using polarized "magic" momentum 0.7 GeV/c protons in an all-electric storage ring. Systematic errors relevant to the experiment are discussed and techniques to address them are presented. The measurement is sensitive to new physics beyond the standard model at the scale of 3000 TeV.

Salvage total laryngectomy after conservation laryngeal surgery for recurrent laryngeal squamous cell carcinoma.

The aim of the present study was to evaluate the oncological efficacy of salvage total laryngectomy in patients who had previously undergone supracricoid partial laryngectomy or transoral laser microsurgery for treatment of laryngeal squamous cell carcinoma. We retrospectively reviewed the medical, surgical and pathological records of 35 patients who underwent salvage total laryngectomy after recurrence of laryngeal cancer (following supracricoid partial laryngectomy or transoral laser microsurgery). Kaplan-Meier survival curves as well as univariate and multivariate analyses of prognostic factors were performed. No statistically significant differences were seen comparing the supracricoid partial laryngectomy group with the transoral laser microsurgery group for overall survival and disease-specific survival at 3 years (OS = 38% vs. 52%, p = 0.16; DSS = 40% vs. 61%, p = 0.057) or locoregional control at 2 years (LRC = 40% vs. 54%, p = 0.056). A trend indicating worse survival and locoregional control for supracricoid partial laryngectomy patients emerged. Preservation of the osteocartilaginous frame in transoral laser microsurgery could hypothetically result in better salvageability of anterior recurrences with extralaryngeal spread.

Metastable hydrogels from aromatic dipeptides.

We demonstrate that the well-known self-assembling dipeptide diphenylalanine (FF) and its amidated derivative (FF-NH2) can form metastable hydrogels upon sonication of the dipeptide solutions. The hydrogels show instantaneous syneresis upon mechanical contact resulting in rapid expulsion of water and collapse into a semi-solid gel.

Antibodies directed against annexin A2 and obstetric morbidity.

Acquired and inherited thrombophilia have both been reported to be associated with an increased risk of obstetric complications in early or later stages of pregnancy. Annexin A2 (ANXA2) is strongly expressed in vascular and placental tissues and plays a crucial role in fibrinolysis. The aim of the present study was to evaluate the prevalence of antibodies directed against ANXA2 in patients with recurrent miscarriage or obstetric complications. Anti-ANXA2 antibodies (aANXA2) were detected by ELISA in the sera from 46 women with obstetric morbidity, mainly recurrent miscarriage. The cut-off value for positivity was defined as 3 standard deviations above the mean optical density (OD) obtained in the sera from 42 female blood donors. The prevalence of aANXA2 in patients and healthy individuals was 15.2% and 2.3%, respectively. A statistically significant difference was observed between the 2 groups in terms of aANXA2 IgG titers (p=0.01). The highest aANXA2 levels were observed in sera from 2 patients with recurrent miscarriage and one patient with preeclampsia. aANXA2 could play a role in thrombotic mechanisms leading to recurrent pregnancy loss and placental vascular disease. Further studies are needed to determine whether ANXA2 is critical for maintenance of placental integrity.