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A core tenet of medical education is the expectation that senior residents will teach junior residents and medical students. However, many general surgery residency programs lack a formalized curriculum to equip trainees with necessary teaching skills. We evaluated the impact of resident-led residents-as-teachers (RAT) workshops (RATW) and assessed adaptability from in-person to virtual delivery. We hypothesized these courses would improve trainees' confidence in their roles as resident-teachers.Pre-COVID-19, an in-person workshop for residents (PGY1-5) was conducted over two days. During the COVID-19 pandemic, a virtual RATW for incoming interns (PGY1) was conducted during intern boot camp. Topic fidelity was preserved between the two RATWs. Resident-educators were responsible for content and delivery; the program director and associate program directors served as facilitators only. Surveys were used to evaluate residents' confidence in four core topics. A Wilcoxon test was used to compare quantitative data.There was significant improvement in confidence in all areas following RATW attendance, except for "Teaching in the OR". In sub-analysis, there was a significant improvement in this category among incoming interns post-RATW (P0.001). The majority of interns agreed that the RATW helped them transition into their new teaching role and agreed that the resident-led RATW was effective.A resident-designed and resident-led RAT curriculum in general surgery effectively improves residents' confidence in teaching and is well received by residents. We recommend the implementation of a RAT curriculum in general surgery residency and intern boot camp. The RATW was well adapted to distance-learning format.

A patient with known obstructive hypertrophic cardiomyopathy developed worsening left ventricular outflow tract obstruction, severe mitral regurgitation, and apical ballooning leading to cardiogenic shock, a combination in which treatment of each component could worsen the others. Emergency veno-arterial extracorporeal membrane oxygenation, levosimendan, and noradrenaline transiently restored adequate systemic perfusion and gas exchange. Surgical myectomy offered a more definitive solution. (Level of Difficulty: Intermediate.), Graphical abstract

Objectives The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents. Background The role of abbreviated DAPT followed by an oral P2Y12 inhibitor after PCI remains uncertain. Methods Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO ( CRD42019143120 ). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale. Results Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p Conclusions Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.

Dynamic simulation of first-principles distillation models is a very time-consuming task, yet it is necessary for monitoring, control and optimization of such processes. In this sense, this work proposes a discretized Adomian decomposition method coupled with the Local Thermodynamic Model technique in order to speed up the integration of dynamic responses for distillation columns with acceptable accuracy loss. Results show that the combination of both approximation methods can lead to at least 150x faster simulations with respect to a reference solution with equivalent model characteristics.

Despite numerous studies assessing the natural history of patients with hypertrophic cardiomyopathy (HCM), there is lack of data regarding the burden of hospitalization. Aim of this study was to describe prevalence, causes and predictors of cardiovascular hospitalization in patients with HCM.We retrospectively included 253 patients with HCM undergoing first evaluation at our center. Enrolment criteria included cardiac magnetic resonance imaging (CMRI) at baseline and 1-year follow-up. All hospital admissions were recorded during follow-up and adjudicated as acute vs elective and cardiovascular (CV) vs non-cardiovascular (non-CV).During 6.4 ± 4.0 years there were 187 hospitalizations in 92 patients (36%, at a rate of 5.7%/year). Most were CV-related (158/187,84.5%; 4.8%/year) while non-CV admissions were 29/187 (15.5%, 0.88%/year). There was a slight predominance of elective (n = 96, 58%, 2.8%/year) vs acute (n = 62, 41.8%, 2.0%/year) CV hospitalizations. Independent predictors of CV hospitalization were baseline symptoms (NYHA class II vs I: HR 2.06; 95% CI 1.24-3.43, NYHA III-IV vs I: HR 3.05; 95% CI 1.40-6.65, p = .004), indexed left atrial (LA) volume (HR 1.03; 95% CI 1.01-1.04, p .001), and lower indexed right ventricular end-diastolic volume iRVEDV) at cardiac magnetic resonance (HR 0.99; 95% CI 0.97-0.99, p = .03).In little over 6 years, CV hospitalization was required in over one-in-three of our HCM patients, often unplanned and due to acute disease-related complications. Symptomatic status, larger LA volume and reduced iRVEDV at baseline were independently associated with CV admissions. Strategies aimed at preventing hospitalizations are an important target to reduce the burden of disease in HCM patients.

Fossil fuels are used as the primary energy source in most countries, negatively contributing to the environmental impact. Even though various technologies exist to exploit solar thermal energy in low-carbon processes, the use of solar thermal energy in the industry sector is currently minimal. The main obstacles are modeling an optimal integration and identifying its energy potential, economic feasibility and environmental benefits. The novelty of this study is the modeling of an integration of solar heat for an industrial process located in a topographically complex territory such as the Alps using the software Dymola – Dassault Systems®. The methodology proposed is structured in several steps: (I) industrial process characterization; (II) collection of local hourly data for radiation and climatic temperature; (III) study of the position of sun and components of incident angle; (IV) comparison among three solar technologies (CPC, LFR, PTC), in terms of efficiency, IAM and heat production; (V) focus on PTC: sizing of HTF, mass flow rate, HEX; (VI) focus on PTC: dynamic modeling with Dymola – Dassault Systems® (HTF temperature, solar heat, solar fraction); (VII) economic and environmental impact. In this paper, the case study of a pasta factory called “Felicetti”, located in the north-east of the Italian Alps, has been considered in order to investigate and evaluate the possibility of supplying solar heat for the drying process. The days of a week in June, exhibiting variable DNI, are used to demonstrate the dynamics and robust integration of the solar heat in the industrial process of pasta drying. The dynamic modelling results show that the PTC solar field can guarantee 23% of weekly energy coverage saving about 4.7 CO 2 / week . The economic analysis shows a pay-back time up to 9 years and a reduction of CO 2 emissions up to 99 t/year.

Background Chiari I malformation (CMI) and the topics concerning it have been the subject of numerous discussions and polarizing controversies over the course of the last 20 years. Methods The opinions of 63 recognized international CMI experts from 4 continents, with a collective surgical experience of >15,000 CMI cases, were gathered through a detailed questionnaire. Results Three facts emerged from the analysis of the results: 1) Most of the replies showed a high level of consensus on most CMI-related topics. 2) Several topics, which had been considered controversial as recently as 10 years ago, are now more widely accepted. 3) The so-called 5-mm rule was rejected by 88.5% of the CMI experts who responded to the questionnaire. Conclusions Sixty three recognized international CMI experts from 4 continents, with a collective surgical experience of >15,000 CMI cases were polled about a number of CMI topics. The results showed a high level of consensus, as well as a paradigm shift.

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR. METHODS: This multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport. RESULTS: In the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was -3.0 mV (-6.6; 0.6) at day 15, -4.1 mV (-7.8; -0.4, p = .04) at day 26 (end of treatment) and - 3.7 mV (-8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile. CONCLUSIONS: In F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity. ispartof: Journal Of Cystic Fibrosis vol:18 issue:4 pages:536-542 ispartof: location:Netherlands status: published

Background Drug-eluting technologies improve 12-month angiographic results of femoropopliteal (FP) interventions, but few data on the comparison between drug-coated balloons (DCBs) and drug-eluting stents (DES) are available. Objectives The aim of this study was to compare, after balloon pre-dilation, a strategy of DCB followed by provisional self-expanding nitinol bare-metal stent implantation with a strategy of systematic DES implantation in patients at high risk for FP restenosis. Methods Patients presenting with either intermittent claudication or critical limb ischemia undergoing FP intervention were randomly assigned 1:1 to DCB or DES after successful target lesion pre-dilation. The primary endpoint was 12-month target lesion binary restenosis, assessed using Doppler ultrasound. Secondary endpoints were freedom from target lesion revascularization and from major amputation. Results A total of 192 patients, 96 in the DCB group and 96 in the DES group, with 240 lesions in 225 limbs, were included. Diabetes and critical limb ischemia were present in >50% in both groups. Mean lesion length was 14 cm, and baseline target lesion occlusion reached about 60% of cases in both groups. The systematic DES strategy yielded larger post-procedural minimal luminal diameter and a lower incidence of residual dissection compared to DCB, in which nitinol stents were used in only 21% of the lesions. Twelve-month target lesion restenosis was observed in 22% of DCB-treated versus 21% of DES-treated patients (p = 0.90). Clinically driven target lesion revascularization was necessary in 14% of DCB patients versus 17% of DES patients (p = 0.50). Conclusions DCB was not superior to DES in the treatment of complex FP lesions in a high-risk population, yielding similar rate of restenosis and clinically driven target lesion revascularization. (Paclitaxel-Eluting Balloon Angioplasty With Provisional Use of Nitinol Stent Versus Systematic Implantation of Paclitaxel-Eluting Stent for the Treatment of Femoropopliteal De Novo Lesions; NCT01969630)

The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 °C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.

A new methodology using differential pulse voltammetry and artificial neural network (ANN) for simultaneous determination of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate (PG) and tert-butylhydroquinone (TBHQ) in biodiesel samples is proposed. A platinum ultramicroelectrode (ume) was used as working electrode and measures were taken directly in biodiesel:ethanol medium without previous preparation. On this condition, detection limits for the antioxidants separately are 20.5, 32.4, 35.5 and 26.5 mg L−1 for BHA, BHT, PG and TBHQ, respectively. The artificial neural network model allowed the quantification of the individual concentrations overcoming the strongly overlapped voltammograms obtained for the mixture of the four antioxidants. For the model construction, a variable selection step through decision trees (DT) led to a reduction of prediction errors by 17.5%. The optimized DT-ANN model presented high correlation (0.97474, 0.99995, 0.98246 and 0.98928 for BHA, BHT, PG and TBHQ, respectively) between real and predicted values. Recovery percentages found were between 82.6% and 106.7%, except for two samples whose values were 76.0% and 114.7%. From the accuracy found between nominal and estimated concentration, it is inferred that the proposed methodology is a good alternative to quantify phenolic antioxidants in biodiesel samples.

Patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) and peripheral arterial disease (PAD) present a worse prognosis compared to those without PAD. We sought to describe contemporary trends of in-hospital management and outcome of patients admitted for NSTE-ACS with associated PAD.We analyzed data from 6 Italian nationwide registries, conducted between 2001 and 2014, including consecutive NSTE-ACS patients.Out of 15,867 patients with NSTE-ACS enrolled in the 6 registries, 2226 (14.0%) had a history of PAD. As compared to non-PAD patients, those with PAD had significantly more risk factors and comorbidities (all p 0.0001) that increased over time. Patients with PAD underwent less frequently coronary angiography (72.0% vs 79.2%, p 0.0001) and percutaneous coronary intervention (PCI, 42.9% vs 51.8%, p 0.0001), compared to patients without PAD. Over the years, a progressive and similar increase occurred in the rates of invasive procedures both in patients with and without PAD (both p for trend0.0001). The crude in-hospital mortality rate did not significantly change over time (p for trend = 0.83). However, as compared to 2001, the risk of death was significantly lower in all other studies performed at different times, after adjustment for multiple comorbidities.. At multivariable analysis, PAD on admission was an independent predictor of in-hospital mortality [odds ratio (OR): 1.75; 95% confidence intervals (CI): 1.35-2.27; p 0.0001].Over the 14 years of observation, patients with PAD and NSTE-ACS exhibited worsening baseline characteristics and a progressive increase in invasive procedures. Whereas crude in-hospital mortality did not change over time, we observed a significant reduction in comorbidity-adjusted mortality, as compared to 2001.

Maritime transport for both passengers and freight is continuously increasing and, consequently, the global attention toward its sustainability is growing. Ships offer advantages in terms of environmental impact compared to other transportation systems but the increasing traffic volume is expected to increase pollutants. Noise produced in port areas has been neglected for too long, until the INTERREG Maritime programme Italy-France 2014-2020 has brought to light how citizen complaints are emerging for some of the main ports in the Mediterranean. However, port noise prevention and management is difficult as knowledge on specific sources is very limited in the literature. Furthermore, on field measurements are difficult to be performed given the complexity of the port area, where multiple types of sound emitters mix and confuse each other. Noise maps represent the first important step in order to align ports to the requirements set by the Environmental Noise Directive to the transportation infrastructures. Once computed, they are an excellent tool supporting port management towards the reduction of citizens' noise exposure while ensuring traffic growth. The present paper reports a guideline for the characterization of noise sources needed as inputs for the noise maps, as developed in the framework of the INTERREG Maritime programme Italy-France 2014-2020. On the basis of the current state of the art, a procedure has been elaborated for different categories of noise sources acting in port, ranging from stationary to moving ships, from mooring operations to loading/unloading operations, from industrial activities to road and railway traffic.

Introduction Sepsis is the third leading cause of morbidity and mortality in neonates. Sepsis in neonates is characterized as the systemic inflammation owing to infection within the first 28days after birth. The molecular mechanism causing the exaggerated inflammation phenotype in neonates has not been completely elucidated. Receptor interacting protein kinase 3 (RIPK3) is a protein identified as a mediator in programmed necrosis or necroptosis. We hypothesize that RIPK3 could be responsible for the inflammatory response in neonates and that deficiency in the RIPK3 protein attenuates inflammation and organ injury in neonatal sepsis. Methods Male and female C57BL6 wild-type (WT) and RIPK3 knock-out (KO) newborn mice aged 5–7days (3–4g body weight) were injected intraperitoneally with 0.9mg/g cecal slurry (CS). At 10h after injection, the newborns were euthanized and blood, the lungs and gut tissues were collected. Results At 10h after CS injection, serum cytokines IL-6 and IL-1β in the WT mice were increased by 511- and 43-fold whereas in KO mice, these levels were increased by 166-fold and 22-fold, respectively. Lung IL-1β in the WT mice increased by 7-fold after CS injection whereas only a 4-fold increase was seen in the KO mice. In the lungs of CS injected KO mice, the injury score, MIP-2 mRNA, myeloperoxidase (MPO) activity and TUNEL staining were significantly reduced by 76%, 70%, 26% and 74%, respectively compared to the CS WT mice. Gut TUNEL staining was also reduced by 80%. Conclusion The deficiency in RIPK3 attenuated serum and lung cytokines, lung injury and neutrophil infiltration and lung and gut apoptosis. These data suggest that RIPK3, in part, is responsible for the systemic inflammatory response in neonatal sepsis.

Background Pseudomonas aeruginosa is the etiological agent of systemic and skin infections that are often difficult to treat. Photodynamic therapy (PDT) and, more recently, phototherapy (PT), are emerging among antimicrobial treatments to be combined with antibiotics. Visible light, either alone or combined with a photosensitizer (PS), elicits photooxidative stress that induces microbial death. The response of bacteria to phototherapy seems to involve the antioxidant machinery. This study relies on the effects of detoxifying catalase A (KatA) in response to PDT and PT-induced photooxidative stress. Methods The photo- and photodynamic inactivation experiments have been targeted at P. aeruginosa PAO1 and its isogenic derivative katA− mutant. The microorganisms were irradiated by a wide-spectrum halogen-tungsten lamp or light-emitting diodes (LEDs). Two photosensitizers, Tetrakis-(1-methyl-4-pyridyl)-21H, 23porphine, tetra-p-tosylate (TMPyP) porphyrin and Toluidine Blue O (TBO), were applied as part of the photodynamic approach. Results P. aeruginosa katA− mutant was more sensitive than wild-type strain PAO1 to wide-spectrum light and blue LED (464 nm) treatments. The complementation of KatA, in katA− mutant, restored the light response of wild-type PAO1. Upon TBO treatment and irradiation by visible light (halogen lamp or LED), the sensitivity of katA− mutant was significant higher (p = 0.028 and p = 0.045, respectively) than that of the PAO1 strain. Conclusions This study provides the first description of KatA in the response to photooxidative stress induced by photo- and photodynamic therapy.

Background: Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy. Methods: This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of −2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301. Findings: Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and −0·6% (−1·0 to −0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p