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Developing cost-effective monitoring protocols is a priority for wildlife conservation agencies worldwide. In particular, developing protocols that cover a wide range of species is highly desirable. Here we applied the ‘umbrella species’ concept to the context of ecological monitoring; specifically testing the hypothesis that protocols developed for the American marten would contextually allow detecting occupancy trends for 13 other mammalian species (i.e., an umbrella effect). We conducted a large-scale four-year camera trapping survey across a gradient of forest disturbance in Maine, USA. We sampled 197 sites using a total of 591 cameras and collected over 800,000 photographs to generate detection histories for the most common terrestrial species. By combining multi-season occupancy modelling and power analyses, we estimated the required sampling effort to detect 10%, 25% and 50% declines in the fourteen species. By conducting a spatially explicit comparison of sampling effort, we found evidence that monitoring protocols for American marten would provide an umbrella effect for up to 11 other mammal species. The capacity of the umbrella effect varied among species, with fisher, snowshoe hare, red squirrel, and black bear consistently covered under several scenarios. Our results support the application of the umbrella species concept to monitoring (here defined as ‘umbrella monitoring species’), providing empirical evidence for its use by management agencies.

Early recanalization of the infarct-related artery to achieve myocardial reperfusion is the primary therapeutic goal in patients with ST-elevation myocardial infarction (STEMI). To decrease the duration of ischaemia, continuous efforts have been made to improve pre-hospital treatment and to target the early period after symptom onset. In this period the platelet content of the fresh coronary thrombus is maximal and the thrombi are dynamic, and thus more susceptible to powerful antiplatelet agents. There have been substantial advances in antiplatelet therapy in the last three decades with several classes of oral and intravenous antiplatelet agents with different therapeutic targets, pharmacokinetics, and pharmacodynamic properties. New parenteral drugs achieve immediate inhibition of platelet aggregation, and fast and easy methods of administration may create the opportunity to bridge the initial gap in platelet inhibition observed with oral P2Y12 inhibitors. Moreover, potential future management of STEMI could directly involve patients in the process of care with self-administered antiplatelet agents designed to achieve rapid reperfusion. However, the potential anti-ischaemic benefits of potent antiplatelet agents will need to be balanced against their risk of increased bleeding. This study presents a comprehensive and updated review of pre-hospital antiplatelet therapy among STEMI patients undergoing primary percutaneous intervention and explores new therapies under development.

This study aimed to investigate whether early surgical decompression was associated with favorable neurological recovery in patients with traumatic spinal cord injury (tSCI). We searched PubMed and Embase from the database inception through December 2020 and selected studies comparing the impact of early versus late surgical decompression on neurological recovery as assessed by American Spinal Injury Association Impairment Scale (AIS) for adult patients sustaining tSCI. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the

The detection of allergenic proteins and the influence of processing on the structure and antigenicity of these proteins are relevant topics. Using commercial enzyme-linked immunosorbent assay kits, this study aimed to evaluate the degradation profiles of milk, egg and soy proteins during the processing of semisweet biscuits. The formulations were baked under different conditions according to a complete factorial experiment that included a three-level temperature factor and a six-level time factor. β-lactoglobulin and egg white proteins were severely degraded, the degradation of casein was intermediate, and soy proteins were the most stable. Complete allergen protein degradation was found under only the extreme baking conditions, which resulted in products that were not sensorily acceptable. Residual levels of the proteins were detected after baking, indicating that this thermal processing reduced but did not eliminate the antigenicity of these proteins; thus, baking cannot be considered a strategy to protect allergic consumers.

Background: Persistent type II endoleaks (ELIIp) occur in 8–23% of patients submitted to endovascular aneurysm repair (EVAR) and may lead to aneurysm progression and rupture. Intraoperative embolization of the abdominal aortic aneurysm (AAA) sac is effective to prevent their occurrence, however a method to achieve complete sac thrombosis has not been standardized yet. Aim of our study was to identify factors associated with prevention of ELIIp after intraoperative embolization, in order to optimize technical details. Methods: Patients at high risk for ELIIp, who underwent EVAR with AAA - sac coil embolization were prospectively collected into a dedicated database from January 2012 to March 2015. The endoluminal residual sac volume (ERV), not occupied by the endograft [ERV= AAA total volume (TV) – (AAA-thrombus volume (THV) + endograft volume (EgV)] was calculated on preoperative computed tomography and the concentration of coils implanted (CCoil= n coils implanted/ERV) for each patient was evaluated. AAA volumetric evaluation was conducted by dedicated vessels analysis software (3Mensio). ELIIp presence was evaluated by contrast-enhanced ultrasound at 6 and 12-month. Patients with ELIIp at 12 months (Group 1) were clustered and compared to patients without ELIIp (Group 2), in order to evaluate the incidence of ELIIp in patients undergone to preventive AAA-sac embolization, and identify the predictors of ELIIp prevention. Morphological potential risk factors for ELIIp such as TV, THV, VR% and EgV were also considered in all patients. Statistical correlation was assessed by Fisher Exact Test. Results: Among 326 patients undergone to standard EVAR, 61 (19% - M: 96.7%, median age: 72 [IQR: 8] years, median AAA diameter: 57 [IQR: 7] mm) were considered at high risk for ELIIp and were submitted to coil embolization. The median AAA total volume (TV) and median ERV were 156 (IQR: 59) cc and 46 (IQR: 26) cc, respectively. The median number and concentration of coils (IMWCE-38-16-45 Cook M-Ray) positioned in AAA-sac were 5 (IQR: 1) coils and 0.17 coil/cm3 (range 0.02-1.20). Among this high-risk population, the incidence of ELIIp was 29.5% and 23% at 6 and 12-month, respectively. Fourteen patients (23%) were clustered in Group1 and 47 (77%) in Group 2. Both groups were homogeneous for clinical characteristics and preoperative morphological risk factors. There were no differences in the preoperative median TV, AAA-thrombus volume (THV), %VR, EgV and number of implanted coils between Group1 and Group2. Patients in Group1 had a significantly higher ERV (59 [IQR: 13] cm3 vs. 42 [IQR: 27] cm3, P = 0.002) and lower CCoil (0.09 [IQR: 0.03] vs. 0.18 [IQR: 0.21], P = 0.006) than patients of Group2. ELIIp was significantly related to the presence of ERV > 49 cm3 (86 % vs. 42 %, Group1 and Group2 respectively, P = 0.006) and CCoil < 0.17coil/ cm3 (100% vs. 68%, Group1 e Group2 respectively, P = 0.014). Conclusion: According with our results, Coil concentration and endoluminal residual volume can affect the efficacy of the AAA – sac embolization in the prevention of ELIIp, moreover CCoil ≥0.17coil/ cm3 maight be considered to determine the tailored number of coils.

BackgroundThe World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population.ObjectivesTo estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated.MethodsPerson-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood.ResultsThe analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002–2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002–2006) and late (2007–2015) periods.ConclusionsRisk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted.

Background and aims To investigate diabetes treatment initiation and continuation in the next sixth months in newly diagnosed Italian subjects. Methods and results We analyzed administrative claims of 11,300,750 Italian residents. Subjects with incident diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes occurring in 2018 but not in 2017. Incident cases were 65,932 of whom 91.4% received the prescription of a glucose lowering drug. Among the latter, those receiving a prescription of a noninsulin medication but no insulin were 84.8%, those receiving a prescription of insulin only were 9.4%, and those receiving prescriptions of both insulin and noninsulin drugs were 5.8%. Metformin was the most frequently drug initially prescribed in noninsulin treated subjects (~85%) and sulphonylurea receptor (SUR) agonists collectively ranked as second (~13%). Lispro (35%) and glargine (34%) were the most frequently prescribed molecules in subjects who were insulin treated. Differences in prescriptions were found in age categories, with increased use of SUR agonists across decades. In the first six months, as many as 50% of noninsulin treated patients continued with the initial drug, ~15% added a second agent, ~5% switched to another medication, and ~30% discontinued any glucose lowering treatment. Conclusions These data document that current guidelines are often neglected because prescriptions of SUR agonists as first agent are still quite common and insulin is prescribed more than expected. They point out the urgent need to improve the dissemination and implementations of guidelines in diabetes care.

Objective : Pulptomy and pulpectomy usually are the most common techniques used in pulp therapy for primary teeth and despite the relative ease of performing this techniques iatrogenic errors may. furcal perforation of common errors can be occurred during performing pulp therapy in primary molars. two types of furcal perforation were selected according to time factor elapsed since their occurrence ( recent and long standing) and these types of perforation treated with MTA. This study was directed to evaluate the ability of MTA to treat furacal perforation in primary molars regarding the time factor Subjects and Methods: thirty patients were selected 15 with accidently recently ( group A) furcally perforated molars and 15 with long standing old perforation (group B), and the two types sealed with MTA and then completed by conventional pulp therapy treatment either by pulptomy or pulpectomy for group A , and pulpectomy for group B, then they followed up clinically and radiographically for 12 months. Result: there was statistically significant difference in success incidence between the two groups (p=0.014); being higher in recent perforation. For long standing perforation; 10 patients out of 15 patients (66.7%) showed success; while in recent perforation; 15 patients (100%) showed success. Conclusion : recent type of perforation which repaired at the same visit has a higher success rate and better prognosis than old type or long standing in primary molars

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

Background: To date, no prospective study has been conducted to investigate the role of socioeconomic status (SES) on clinical outcome of glioblastoma (GBM) in Italy, where there is a National Health Service that provides universal coverage regardless of the patient's economic status. Methods: We performed a prospective observational study investigating the association between SES and survival in GBM patients at our institution, a hub centre for brain cancer research and treatment. We included GBM patients who underwent medical treatment or chemo-radiation between April 2017 and December 2017. The SES was measured using the income-brackets, attributed by the Italian Ministry of Finance on the basis of the income of the fiscal family unit, referring to the previous year. Results: One hundred and six patients were included in the study. In multivariate analysis, overall survival (OS) correlated significantly with higher-income (HR = 0.623.95% CI 0.467–0.832; p = 0.001) and MGMT methylation status (HR = 0.158.95% CI 0.082–0.304; P < 0.001). When adjusted for age, performance status and extension of surgery, survival benefit remained superior for higher-income HR = 0.641 (95% CI 0.478–0.858; p = 0.003) and MGMT methylated tumours HR = 0.167 (95% CI 0.084–0.331; p < 0.001). Conclusions: SES is an important determinant of prognosis in GBM even in the Italian National Health Service, which provides universal, largely free and relatively comprehensive healthcare. Despite aspirations to achieve equality in healthcare, socioeconomic differences exist and may impact the clinical outcome.

Introduction The number of citations is considered as an indirect indicator of the merit of an article, journal or researcher, although it is not an infallible method to determine scientific quality. Our goal is to determine the characteristics of the articles most cited about pancreas and laparoscopy. Methods We performed a search of all articles published in any journal about pancreas and laparoscopy until September 2019 and selected the 100 most cited papers. We recorded number of citations, journal, year of publication, quartil, impact factor, institution, country, authors type of paper, type of surgery, topic and area. Results The top 100 citations account 10,970 citations in total. The journal with the most articles is Surgical Endoscopy and 2007 is the year with the highest number of articles in the top 100 citations. The percentage of publications from America and Europe are similar. Case series is the most frequently paper, outcomes/morbidity is the most frequently discussed topic, and distal pancreatectomy is the most frequently type of surgery. Conclusions This bibliometric study on pancreas and laparoscopy is conditioned by the time factor, since laparoscopy has arrived later at pancreatic surgery, probably due to the morbidity and mortality associated with pancreatic surgery and the need for a high specialization in this field. The literature is recent and scarce. More and better-quality studies are needed in this field.

Introduction: The aim of this study was to assess whether antibiotic prophylaxis or therapy is sufficient for laparoscopic or vaginal prolapse surgery with mesh. Methods: This is a single-center prospective study. The study was divided into 3 groups. Protocol A: metronidazole (15 mg/kg) and piperacillin-tazobactam (2 g) 1 h before surgery and, for postoperative treatment, gentamycin (160 mg) 1 h before surgery in a single dose. Metronidazole and piperacillin-tazobactam were administered until hospital discharge. Protocol B: gentamycin and piperacillin-tazobactam in the same manner as group A. Protocol C: clindamycin (600 mg) and gentamicin (160 mg) 1 h before surgery in a single dose. Results: We included 87 consecutive patients who underwent prolapse surgery involving mesh prostheses: 57 by the laparoscopic approach and 30 by the vaginal route. Of these, 30 patients were included in protocol A, 30 in protocol B, and 27 in protocol C. There were no statistically significant differences among the 3 protocols regarding any postoperative complications, except for urinary tract infections that were more in the vaginal approach than in the laparoscopic route, in protocol A (p = 0.002). Conclusions: One-shot prophylaxis can be successfully used in prolapse surgery regardless of the surgical approach.

The study found out the dependence of the manifestation of symptoms of chronic non-communicable diseases of the digestive system on the duration of a person’s own unit of time. It was identified that individual age points of exacerbations of chronic non-communicable diseases of the gastrointestinal tract are consistent with the duration of the individual’s own biological cycle. Method. In each patient examined by the chronometric test method the “ τ type” was determined, for which the classical method of reproducing intervals with a duration of tQ = 2, 3, 4, 5 c was used, which were set by the experimenter and reproduced by the surveyed using an electronic chronoscope with an accuracy of 0.001 c. Results. It was identified that individual age points of exacerbations of chronic non-communicable diseases of the gastrointestinal tract are consistent with the duration of the individual’s own biological cycle.

Aim: The study examined the effect of time on amount of voltage generated in a foot beat electricity generating system stored in a battery. Study Design: A system made of piezoelectric materials was designed such that the foot beats of dancers on a platform would cause a mechanical deformation that would lead to conversion of mechanical energy due to pressure from the foot beats to electrical energy; and can be stored in a rechargeable lead acid battery for future use. Place and Duration of Study: Awka Anambra State, Nigeria, between November 2018 and April 2020. Methodology: A sheet of plywood measuring 300 mm x 300 mm x 3 mm thick was placed on a hard wooden board of 300 mm x 300 mm x 25 mm thick where twelve piezoelectric sensors were connected in series with foam spring inserted as separators and to aid in returning after deformation. As the dancers step on the platform, multimeter was used to take the voltage and current readings, while Lead acid rechargeable battery could be connected at the output point to store energy generated in the system and or Light Emitting Diodes (LED) and Universal Serial Bus (USB) outputs. A stop clock was also used to take the time. Results: The study revealed that it would require 901 seconds for a 50kg dancer to increase a unit voltage state of charge in a battery. It also found that it would require 749 seconds for a 60 kg dancer; and 595 seconds for an 80kg dancer respectively to increase the same 1-unit voltage state of charge in a battery. The study showed that the voltage in the battery would continue to increase until the battery is fully charged at which point it is expected that there would no longer be any increase in charge in the battery irrespective of increase in the number of foot beats or time. Conclusion: The result implies that the charge in battery caused by pressure from the foot beats is subject to the maximum voltage capacity of the battery in the system. Likewise, the amount of time and number of foot beats required to add a unit voltage state of charge in a battery in the system is subject to the applied pressure from the foot beats. In view of this, the study craves for popularisation of this technology through large scale research supported by government, corporate organisations or international organisations and institutions that will support new products development in the building and construction industry as it is the case in India and other developed countries.

The work carried out by analyzes of the literature data on assessing the severity of acute pancreatitis and predicting its course and mortality. A comparison of traditional point scales for assessing the severity of AP was made.As a result of a comparative analysis, it was found that the most objective instrumental method for diagnosing acute pancreatitis and its complications was MSCT with the determination of the CT index of severity. Balthazar scale allows assessing the severity of the disease and forming a prognosis for the development of complications. However, computed or magnetic resonance imaging with intravenous contrast enhancement allows an accurate assessment of the severity of the disease not earlier than 72 hours and has some contraindications.Estimating and predictive systems Ranson, APACHE, Krasnorogov, Bozhenkov systems, Pugaeva and Achkasova, BISAP and HAPS allow identyfying the severity of the clinical course of acute pancreatitis, have a high sensitivity, but at the same time require significant time and resources for execution. Glasgow-Imrie, SAPS, MODS, and SOFA scales mainly calculate mortality and degree of multiple organ failure in critically ill patients; these severity assessment systems are not specific for patients with acute pancreatitis.The optimal scale for assessing the severity of AP should allow assessing the patient's condition and prognosis from the moment of admission to the outcome of the disease. The practicing surgeon will be interested in an affordable, inexpensive, easy-to-use system for determining the severity of acute pancreatitis. For surgeons, the time factor plays a key role in determining tactics, and, therefore, improves the prognosis of the disease.

Background and aims The most used indicator for the renal function is the glomerular filtration rate (GFR). Current used predictive GFR equations were calibrated on patients with chronic kidney disease. Thus, they are not very precise in healthy individuals. The estimation of skeletal muscle mass (SMM) allows the prediction of the daily urinary creatinine excretion (24hUCrE). This study proposes an equation for the estimation of GFR based on SMM (eGFRMuscle) and serum creatinine (SCr). Methods and results Four hundred sixty-six free-living men underwent a bioelectrical impedance analysis for the evaluation of SMM (kg), a blood withdrawal for the measurement of SCr (mg/dL), and a 24-h urinary collection for the assessment of 24hUCrE (g/24 h). The linear regression analysis between SMM and 24hUCrE and the measurement of SCr allowed developing a predictive equation of eGFRMuscle. The equation predicting eGFRMuscle (ml/min/1.73 m2) was SMM (kg) × 3.06/SCr (mg/dL). eGFRMuscle was statistically different from eGFR predicted by Cockroft–Gault, MDRD Study, and CKD-EPI equations (p = 0.017, p Conclusions The equation presented in this study results in age, weight, gender, and ethnicity independent because it arises directly from SMM estimation. Therefore, the proposed equation could allow evaluating the GFR also in healthy people with low, average, or high weight, and in older people, regardless of GFR and SCr levels.

Background and aims: Data from animals suggest that immunoglobulins G (IgG) play a mechanistic role in atherosclerosis and diabetes through endothelial dysfunction and insulin resistance. Patients with common variable immunodeficiency (CVID), who have low circulating levels of IgG and are treated with intravenous polyclonal IgG (IVIgG), may provide an ideal model to clarify whether circulating IgG modulate endothelial function and affect insulin sensitivity in humans. Methods and results: We studied 24 patients with CVID and 17 matched healthy controls (HC). Endothelial function was evaluated as flow mediated dilation (FMD) of the brachial artery at baseline and 1, 7, 14, and 21 days after IVIgG infusion in the CVID patients. We measured also plasma glucose, insulin, and calculated the HOMA-IR index. We also investigated the role of human IgG on the production of Nitric Oxide (NO) in vitro in Human Coronary Artery Endothelial Cells (HCAEC). Compared to HC, FMD of CVID patients was significantly impaired at baseline (9.4 ± 0.9 and 7.6 ± 0.6% respectively, p < 0.05) but rose above normal levels 1 and 7 days after IVIgG infusion to return at baseline at 14 and 21 days. Serum insulin concentration and HOMA-IR index dropped by 50% in CVID patients after IVIgG (p < 0.002 vs. baseline). In vitro IgG stimulated NO production in HCAEC. Conclusions: Reduced IgG levels are associated with endothelial dysfunction and IVIgG stimulates endothelial function directly while improving insulin sensitivity. The current findings may suggest an anti-atherogenic role of human IgG.

O objetivo do trabalho foi investigar o efeito agudo do óleo essencial de eucalipto (OEE) nas respostas cardiovasculares de repouso e após sessão de exercício resistido isométrico (ERI). Vinte idosos, após serem submetidos a sessões experimentais com inalação de OEE ou condição controle, permaneceram em recuperação durante 60 min (Rec-60’) para depois realizaram três séries de 1 min (1 min de recuperação entre séries) no ERI, para membro superior dominante em aparelho de preensão manual, com intensidade de 30% da contração voluntária máxima (ERI-30%). Intervalos R-R (iRR) e medidas no domínio da frequência (low frequency – LF e high frequency – HF) além da pressão arterial (PA), frequência cardíaca (FC) e duplo produto (DP) foram avaliados. Não ocorreram diferenças (p>0,05) quando comparadas as sessões (OEE vs.controle) na Rec-60’ e ERI-30%. Diferenças foram encontradas no fator tempo do repouso para Rec-60’ nas variáveis FC e iRR e do repouso para ERI-30% na PA sistólica, PA diastólica e DP. A inalação do OEE não proporcionou alterações significativas nas respostas cardiovasculares e autonômicas de idosos no repouso e após sessão de ERI-30%.

Aspirin is the most commonly used medication worldwide. Beside its well-known anti-inflammatory effects, a role has emerged in the prevention of cardiovascular events. However, a significant benefit has been demonstrated in secondary cardiovascular prevention only, while there is limited evidence supporting a role in primary prevention. This discrepancy might depend on the that so far, the high-risk populations that will achieve the greatest benefits yet experiencing minimal harmful side effects have not been identified. Patients with autoimmune systemic rheumatic diseases have an increased risk of cardiovascular complications compared with the general population, which makes aspirin of potential value in these subjects. Moving from general aspects of aspirin pharmacology and specific issues in general population, the aim of this study is to review the evidence about the role of low-dose aspirin in primary cardiovascular prevention in autoimmune systemic rheumatic diseases.

Background The aim of this study was to compare early and long-term outcomes of endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in patients aged ≤ 65 years. Methods Data of patients aged ≤65 years undergoing infrarenal abdominal aortic aneurysm repair, between 2005 and 2013, were retrospectively reviewed. All EVAR procedures were performed according to the instruction for use, and only OSR procedures with an infrarenal aortic cross-clamping were included in the study. Results In this group of 115 patients (EVAR: 58 patients, 51% and OSR: 57 patients, 49%), EVAR and OSR patients had similar comorbidities, except for obesity (EVAR: 38% vs. OSR: 19%; P = 0.03). A stay in the intensive care unit (ICU) was necessary in 19% of patients with EVAR versus 79% with OSR (P = 0.001), and the amount of blood transfusion was 236 ± 31 mL for EVAR versus 744 ± 98 mL for OSR (P = 0.001). The hospital stay was 4 ± 2 days for EVAR versus 9 ± 6 days for OSR (P = 0.03). The overall 30-day mortality was 1% (EVAR: 0% vs. OSR: 2%; P = 0.30). Five patients (4%) required reinterventions within 30 days (EVAR: 0% vs. OSR: 8%, P = 0.001). The mean follow-up was 86 ± 38 months. Freedom from reintervention at 10 years after EVAR was 81% versus OSR 74%; (P = 0.77). Late reinterventions were reported in 13 patients (23%) with OSR and in 10 patients (17%) with EVAR. Postoperative retrograde ejaculation occurred more often in patients with OSR (31%) versus EVAR (2%) (P = 0.001). During the follow-up, cancer was found in 19 (17%) patients with no difference between EVAR and OSR (P = 0.83). The global survival at 10 years was 72% (EVAR: 79% vs. OSR: 70%; P = 0.94). Conclusions In this study, EVAR was associated with a shorter hospital stay, less need for the ICU, and less early reinterventions than OSR. Survival and reinterventions during the follow-up were not significantly different between EVAR and OSR. According to these results, EVAR may be considered for patients aged ≤65 years with a favorable anatomy.

Supplemental Digital Content is Available in the Text., Background: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials. Methods: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25). Results: The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline. Conclusion: The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss.

Background: Fenestrated and branched endovascular aneurysm repair endograft (f/bEVAR) allows the endovascular repair of thoracoabdominal and juxtarenal and pararenal abdominal aortic aneurysms (T-J-P-AAAs); however, given their high cost and complexity, their use should be limited to patients with life expectancy >2 years. Nevertheless, the number of patients older than 80 years treated by f/bEVAR is growing, with no hard evidence of the real efficacy in this context. The aim of the present study is to analyze the survival of ≥80-year-old patients treated with f/bEVAR, and to identify possible predictors of late mortality. Methods: An analysis of clinical, anatomical, and technical characteristics of patients treated with f/bEVAR for J-, P-, and T-AAA from 2010 to 2019 in a single academic center was performed. Follow-up data were collected prospectively with clinical visit and computed tomography angiography at discharge, after 6 months, and yearly thereafter. Survival after 2 years was evaluated by Kaplan–Meier analysis. Possible predictors of mortality were evaluated by univariable/multivariable analysis. Results: In the study period, a total of 243 f/bEVARs were considered: 83 for TAAA (34%) and 160 for J/PAAA (66%). Mean age was 73 ± 6 years, with 35 (14%) patients ≥80 years old; 209 patients (86%) were male and 78 (39%) had an American Society of Anesthesiology score IV. The 30-day and 2-year survival were 96% and 80 ± 3%, respectively. At a mean follow-up of 36 ± 25 months, independent predictors of late mortality by Cox regression analysis were chronic obstructive pulmonary disease (COPD), chronic renal failure (CRF), and ≥80 years old (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.02–3.2, P = 0.05; HR 1.7, 95% CI 1.01–3.4, P = 0.04; HR 3.1, 95% CI 1.5–6.3, P = 0.002, respectively). Preoperative clinical characteristics were similar in ≥80 years old versus younger patients, except for the prevalence of TAAA (14% vs. 38%, P = 0.04). The technical success and 30-day mortality were similar in ≥80 vs.

BACKGROUND: Cardiac magnetic resonance (CMR) is the standard of reference for myocardial fibrosis detection by late gadolinium enhancement. Cardiac computed tomography (CCT) is emerging as a promising alternative. The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the feasibility and diagnostic accuracy of a comprehensive functional and anatomical cardiac evaluation with CCT as compared with CMR and invasive coronary angiography as standard of reference. METHODS: Consecutive patients with a newly diagnosed left ventricle (LV) dysfunction (left ventricular ejection fraction

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has an impact also on neurosurgical training and education, especially in most affected countries. We surveyed Italian neurosurgical residents, asking them to provide a brief description and analyze the situation they are experiencing and how the educational system reacted to the pandemic in one of the most affected countries all over the world. Methods An 18-question, web-based survey was administered to Italian neurosurgical residents from May 3 to May 11, 2020, by web-link or e-mail invitation. Closed-ended, multiple choice questions were focused on the experience of neurosurgical residents in the last 2 months (from March to May 2020) concerning both clinical and educational aspects. Results Among 331 Italian neurosurgical residents invited to participate, 192 responded to the survey (58%). According to the participants’ responses, in the whole country, only 29.7% of residents were directly involved in the clinical management of COVID-19 patients. Time spent in the clinic and surgical activity was significantly reduced in most of the cases. Educational activities as well as scientific activity and time spent for studying, on the other hand, were reported to be significantly increased by the majority of respondents. Conclusions Most Italian neurosurgical residents reported significant changes on both training and education, highlighting a prompt reaction of the educational system in the whole country, regardless the local and regional diffusion of the pandemic. Electronic supplementary material The online version of this article (10.1007/s00701-020-04460-0) contains supplementary material, which is available to authorized users.

Relevance. Road traffic injuries, having the nature of a global epidemic, pose an urgent medical and social problem. Among victims of road traffic accidents, mortality is many times higher than that of victims who were injured under other circumstances. The survival of victims in road accidents depends on the timeliness, quality and capacity of emergency medical care, on the competence of care providers and on the effectiveness of the organization of this type of medical care at the prehospital stage.Intention – to estimate the time of providing emergency medical care for victims on the federal highway M-8 “Kholmogory” on the territory of the Arkhangelsk region.Methodology. The material of the study was a sample of 906 medical records (form 003/y) for victims of the road accidents, who were admitted to hospitals of Arkhangelsk region in the period from 01.01.2012 to 31.12.2018. Registered forms were selected according to the criteria of retrospective full-design documentary observation. Differences between the observation groups were considered statistically significant at level of p < 0.05 as adjusted for multiple comparisons (Bonferroni correction).Results and Discussion. Time factor of emergency medical care on the federal highway M-8 “Kholmogory” in 3 medical districts of the Arkhangelsk region was characterized. The ambulance teams arrived at the place of accident within 20 minutes in 30 (3.3 %) cases, from 21 to 40 minutes – in 345 (38.1 %) cases, from 41 to 60 minutes – in 299 (33 %) cases and over a period of more than 1 hour – in 232 (25.6 %) cases. There was no statistically significant difference in time of providing emergency medical care for victims with isolated, multiple and concomitant traumas.Conclusion. It was shown that in 74.4 % of cases (p < 0.001) ambulance arrived at the site of a road accident earlier than 60 minutes. The largest number of cases of providing emergency medical care exceeding 60 minutes was noted in the Arkhangelsk Medical District – 28.4 % (p < 0.013), and the lowest –in the Severodvinsk Medical District – 18.3 %. In more than a quarter (26 %) of cases the emergency medical care was provided for victims with polytrauma beyond the 60 minutes period, with most of them in the Arkhangelsk Medical District (p = 0.004).

Introducción: El objetivo de este estudio fue comparar dos herramientas de cribado nutricional, Nutritional Risk Screening 2002 (NRS-2002) y Fase de Filtro Nutricional Analítico (FILNUT), sobre una muestra de pacientes al ingreso hospitalario, analizar la prevalencia de riesgo nutricional, evaluar la concordancia entre ambos y su validez para identificar pacientes en riesgo.Material y métodos: Estudio descriptivo, transversal, donde se evaluaron 271 pacientes admitidos dentro de las primeras 72 horas, con el método NRS-2002 utilizado como gold standard y la herramienta FILNUT. Se utilizó el Test de Chi2 para la asociación estadística entre los distintos métodos y la concordancia fue estudiada a través del índice kappa. La precisión se evaluó mediante sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo, y razón de verosimilitud. La validez de los test de cribado nutricional para identificar pacientes en riesgo, se analizó mediante la comparación de curvas ROC con cálculo del área bajo la curva (AUC).Resultados: La prevalencia de pacientes en riesgo nutricional fue 61% con FILNUT y 31% con NRS-2002. El método FILNUT con una alta sensibilidad (92,8%), deja un gran número de falso positivos por su baja especificidad (53,3%). La concordancia entre ambos métodos fue aceptable (Kappa=0,37). Mediante la curva ROC, se comprobó que los test de cribado fueron válidos para identificar pacientes en riesgo: FILNUT AUC = 0,999 (IC 95% 0,963-0,100); NRS-2002 AUC = 0,708 (IC 95% 0,643-0,767).Conclusiones: El método FILNUT es una herramienta de cribado válida que reveló mayor prevalencia de riesgo nutricional y con alta sensibilidad descartó apropiadamente a aquellos pacientes sin riesgo. Al comparar ambas herramientas, FILNUT incorpora el uso de prealbúmina, cuyos bajos valores deberían considerarse como potencial riesgo nutricional. Por otra parte, su escaso factor tiempo y costos directos en su realización, lo avalan como herramienta eficiente. La simplicidad y facilidad requerida para su realización contrastan con el NRS-2002 que requiere de personal capacitado.

Background and aims Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. Methods and results Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. Conclusion NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

This qualitative action research study aimed to examine teachers’ perceptions about peer observation as an instrument for their Continuous Professional Development (CPD). For this purpose, the experiences of 12 purposefully selected secondary school teachers were captured through peer observation tool followed by focus group interviews to answers two research questions i.e. do teachers perceive peer observation as an effective instrument for their continuous professional development; and what are the merits and demerits in seeking sound professional development through peer observations? The conclusion reveals that peer observation was viewed by teachers as a valuable tool for their professional growth. Teachers reported that peer observation allowed them less anxiety, hesitation and pressure during teaching making the process more reliable and authentic. However, participants also reported time factor and less experience in observation on the part of teachers as obstacles to peer observation. The study includes some suggested recommendations for a more improved peer observation program.

Objective: The aim of this study was to evaluate aortic remodelling and associated complications in patients treated by thoracic endovascular aneurysm repair (TEVAR) for blunt traumatic aortic injuries (BTAI). Methods: This was a retrospective, observational, multicentre study. Remodelling was considered as aortic diameter variations of >2 mm and distal graft and aortic axis angle modification measured by computed tomography angiography (CTA). The predefined levels of measurement were the proximal end of the graft (D1: landing in zone [LZ] 2; D2: LZ 3); distal end (D3); and control measurement (D4) 15 mm beyond D3. Survival, procedure, graft, and/or radiation exposure related complications were registered. CTA was required within three months and at one, six, and 10 years post-operatively. Results: Between 2004 and 2017 52 patients were treated; 47 were included for remodelling analysis (five immediate deaths were excluded); median age was 47 years (range 20–80 years). Mean TEVAR oversizing was 19.6% ± 9.7% (range 5%–35%). Following a median follow up of 67.4 ± 56.1 months (range 14–153 months) survival at one, three, six, and 10 years was 90.4% (standard error [SE] 4.1%), 88.3% (SE 4.5%) 84.8% (SE 5.5%), and 84.8% (SE 5.5%), respectively. There were no procedure/graft related complications except for one late intramural haematoma that required re-intervention. Freedom from aortic remodelling at one, six, and 10 years was 85.1% (SE 5.2%), 30.9% (SE 8.6%), and 24.7% (SE 8.8%), respectively. The increase in D1/D2 and D3 diameters were influenced by time from intervention (both p

SummaryAim: to analyze the mechanism, nature of injuries, including localization andconcomitant injuries, in patients with injuries of the large vessels during the Joint Forceoperation (JFO) in eastern Ukraine for the period 2014–2020.Materials and methods. We analyzed 234 cases of gunshot wounds of the largevessels during the JFO in the East of Ukraine in the period from February 2014 toFebruary 2020, who were treated at the Military Medical Clinical Centers of Ukraine atthe stages of medical evacuation.Results and conclusions: 1. The most cases of injuries of large vessels wererecorded in 2014, which is 24.8% of all identified such cases, the least – in 2020, whichis 3.5%. 2. When studying the mechanism of trauma, the greatest number of injuries ofthe large vessels was registered with shrapnel wounds, accounting for 37.6%, and withmine-explosive injury – 25.6%. 3. When studying the frequency of vascular lesions, thegreatest number of injuries of the large vessels was recorded in trauma of the vessels ofthe lower extremities, namely, the femoral-popliteal segment – in 68.4% as well asvessels of the upper extremities – in 27.8%, of which the largest proportion was forartery damage – 47% of the total structure of such injury. 4. 70.5% studied cases areassociated with damage of bones and nerves. In 38.5%, the wounds are multiple andcover wounds of other anatomical sites. 5. The success of the treatment of injuries of thelarge vessels depends on the time factor. The best results were recorded in patients withthe shortest time from injury to specialized medical care.

Objectives: This study was designed to measure and compare dentin microhardness and MTA (ProRoot, Dentsply Tulsa Dental, Tulsa, OK) dislocation resistance (DR) used in regenerative endodontic treatment (RET) after application of three different intracanal medication(ICM) for 2,4 and 12 weeks’ time intervals. Material and methods: One-hundred sixty eight human maxillary central incisors were selected for the study. Teeth were cut apically 12 mm below and coronally 2 mm above the cemento-enamel junction. Canals were instrumented up to instrument F5 (ProTaper Universal, Dentsply Maillefer, Ballaigues, Switzerland), then Peeso drills (Mani, Tochigi, Japan) were used from No. 1 up to No. 6 , passing 1 mm beyond the apical foramen to obtain larger root canals. Between every 2 consecutive instruments 2 mL of 2.5% sodium hypochlorite (NaOCl) used for canals irrigation , final flush using 5 mL of 2.5% NaOCl and 5 mL of 17% ethylene-diamine-tetra-acetic acid (EDTA, Sigma) followed by 10 mL of distilled water. Samples were randomly divided according to the type of the ICM used inside the canal into 4 equal groups (n = 42); Group 1: Double antibiotic past(DAP) paste: 1:1 mixture of ciprofloxacin (Cipro 500 mg, Schering Plough, Kenilworth, NJ, USA) and metronidazole (Flagyl 500 mg, Sanofi-Aventis, Tours, France), Group 2: Bioactive glass powders (BAG S53P4) of 60 mol% SiO2, 12 mol% P2O5 and 28 mol% CaO composition were prepared through sol gel processing route, all reagents were purchased from Sigma-Aldrich(Dorset, UK). Group 3: Non-setting Calcium hydroxide (CH) (Merk, Germany) was used, and finally, Group 4(Control): where no ICM was applied. Samples were kept in saline solution for either 2, 4, and 12 weeks, randomly selected samples from each group n=14 at each interval where intracanal medication removed, half of them n=7 were subjected to dentin Vickers microhardness test, in remaining half n=7 MTA (ProRoot, Dentsply Tulsa Dental, Tulsa, OK) placed 4 mm deep into the coronal third of the roots having a 4 mm-long chamber, samples were stored for a week at 37 °C at 100 % humidity to allow the complete setting of MTA, then push-out test was used to measure the dislocation resistance DR of MTA. Collected data were analyzed using a two-way ANOVA followed by Bonferroni’s post-hoc test was used for pair-wise comparisons (P ≤ 0.05). Results: showed that both DAP, CH groups of intracanal medication and time interval had a significant decreasing effect on dentine microhardness and MTA dislocation resistance the DR of MTA (P-value

ObjectiveThe initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days).MethodsThis is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality.ResultsIn 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (pConclusionPercutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic.Trial registration numberNCT04412655.

Relevance . Whether it comes under microbial plaque to demineralization of enamel depends on the presence of cariesogenic bacteria that exhibit proteolytic activity in relation to the organic components of the interdigital spaces of enamel, easily digestible carbohydrates that enter the oral cavity when eating, the buffer capacity of saliva, capable of neutralizing the pH of plaque within an hour to neutral values after eating. On the knowledge of these factors is based the strategy of prevention of dental caries, based on nutrition management. Of all the above, the optimal factor of influence on the cariesogenic situation in the oral cavity is the time factor – the frequency of consumption of easily digestible carbohydrates during the day. Eating easily digestible carbohydrates that can be a nutrient medium for the oral microflora is recommended only during Breakfast, lunch and dinner, but not during snacks. Purpose . To determine the value of the time factor to change the qualitative composition of plaque. Materials and methods . In a series of clinical-anamnestic and clinical-laboratory studies studied the material-plaque obtained during the examination of 137 adult young people-students aged 18 to 20 years. Plaque sampling was performed immediately after the determination of its cariesogenicity by colometric method by J. L. Hardwick and E. B. Manlay, and after 60 minutes a clinical micrometer was used to determine the short-chain fatty acids in this plaque. Results. The proposed clinical micrometod for determination of short-chain fatty acids in dental plaque stated an increase in the optical density of smears in persons with high caries resistance with a decrease in the optical density in smears in the presence of a carious process in the oral cavity. The obtained data correlate well with the indicators of cariesogenicity in plaque, which increases with a decrease in the content of short-chain fatty acids. Therefore, the content of short-chain fatty acids and dental plaque caries require an individual approach to oral hygiene in different patients. Conclusion. The optimal factor of influence on the cariesogenic situation in the oral cavity is the time factor - the frequency of consumption of easily digestible carbohydrates during the day. Eating easily digestible carbohydrates that can be a nutrient medium for the oral microflora is recommended only during breakfast, lunch and dinner.

Purpose To evaluate the Covera Plus (Bard, Tempe, Arizona) covered stent as a bridging stent in branched thoraco-abdominal endovascular aneurysm repair (BEVAR). Materials and Methods Retrospective analysis of 112 self-expandable stents was performed at 2 university centers between August 2017 and March 2019. Thirty-one consecutive BEVAR procedures were studied (21 males; mean age, 75 years; 29 American Society of Anesthesiologists grade III/IV) with 119 patent target vessels (7 did not receive the studied device). Primary endpoints were technical success, branch instability, and primary/secondary clinical success. Secondary endpoints included primary/secondary patency and any adverse events. Results Technical success was 100%. Median follow-up was 12 months (interquartile range, 6–14 months). Branch instability was registered twice (2/112), due to immediate renal occlusion and type Ic endoleak; no additional events occurred during the follow-up. Primary clinical success was 84%. There were 2 immediate deaths, 1 upper limb ischemia, 1 hemorrhage from splenic artery, and 1 type Ic endoleak; these last 3 events were successfully treated, with a secondary clinical success of 100% that was maintained during the follow-up. One late death occurred. Primary patency was 99% (111/112) and 100% (105/105) within 30 days and at the end of the study period,respectively. Adverse events included 4 acute kidney injuries and 2 spinal cord ischemia. No type I/III endoleaks, occlusion, fracture, or dislodging were diagnosed after 30 days. Conclusions The stent graft seems safe and effective for bridging in BEVAR with low branch instability and high patency rate. Longer follow-up is required to confirm these promising results.

This study investigated the effect of 4 weeks of high-intensity interval training (HIIT) with specific techniques (TS-G) vs. repeated sprints (RS-G) and analyzed the inter-individual variability [classified into responders (Rs) and non-responders (NRs)] on sport-related fitness in taekwondo (TKD) athletes. Athletes of both genders (n = 12) were randomly assigned into TS-G and RS-G groups. Both groups trained 3 days/week for 4 weeks [two blocks of three rounds of 2 min of activity (4-s of all-out efforts with 28-s dynamical pauses) with 1 min of recovery in between and 5 min between blocks] during their regular training. The related sport fitness assessments included squat jump (SJ), countermovement jump (CMJ), multiple frequency speed of kick test (FSKTMULT), specifically total kicks and Kick Decrement Index (KDI), and 20-m shuttle run (20MSR). Relevant results indicate a significant effect of the time factor in both groups for SJ performance and a significant decrease for KDI in RS-G. In addition, an improvement in performance according to the effect size analysis in the TS-G in total kicks, KDI, and 20MSR. Complementarily, a higher proportion of athlete Rs was reported in TS-G vs. RS-G for SJ (50% vs. 30.3%, respectively), CMJ, and total kicks (16.6% vs. 0%). In conclusion, the addition to the regular training of a HIIT with specific-techniques and repeated-sprints associated with intervals and similar structure of the combat during 4 weeks of training can improve the concentric characteristics of lower limb performance, although they were not the sufficient stimuli in the other components of TKD-related fitness.

PURPOSE To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively ( P < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without ( P < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease–negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.

What have been the causes and consequences of technological evolution in world history? In particular, what propels innovation and diffusion of military technologies, details of which are comparatively well preserved and which are often seen as drivers of broad socio-cultural processes? Here we analyze the evolution of key military technologies in a sample of pre-industrial societies world-wide covering almost 10,000 years of history using Seshat: Global History Databank. We empirically test previously speculative theories that proposed world population size, connectivity between geographical areas of innovation and adoption, and critical enabling technological advances, such as iron metallurgy and horse riding, as central drivers of military technological evolution. We find that all of these factors are strong predictors of change in military technology, whereas state-level factors such as polity population, territorial size, or governance sophistication play no major role. We discuss how our approach can be extended to explore technological change more generally, and how our results carry important ramifications for understanding major drivers of evolution of social complexity. © 2021 Turchin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by: a John Templeton Foundation grant to the Evolution Institute, entitled "Axial-Age Religions and the Z-Curve of Human Egalitarianism" (HW, PF, PT); a Tricoastal Foundation grant to the Evolution Institute, entitled "The Deep Roots of the Modern World: The Cultural Evolution of Economic Growth and Political Stability" (PT); an Economic and Social Research Council Large Grant to the University of Oxford, entitled "Ritual, Community, and Conflict" (REF RES-060-25-0085) (HW); a grant from the European Union Horizon 2020 research and innovation programme (grant agreement No 644055 [ALIGNED, www.aligned-project.eu]) (HW, PF); a European Research Council Advanced Grant to the University of Oxford, entitled (Ritual Modes: Divergent modes of ritual, social cohesion, prosociality, and conflict" (HW, PF); a grant from the Institute of Economics and Peace to develop a Historical Peace Index (HW, PF, PT, DH); and the program (Complexity Science,) which is supported by the Austrian Research Promotion Agency FFG under grant № 873927 (PT).

The aim of the study was to evaluate the effect of training and detraining on the physical fitness components of people living with HIV/AIDS (PLHA). The study was characterized as experimental with a sample composed of 21 people divided into two groups: 11 volunteers (PLHA, 46.9 ± 8.0 years, 63.8 ± 12.7 kg, 161.7 ± 8.7 cm, 7 men, and 4 women), using antiretroviral therapy (ART) and 10 people without HIV/AIDS in the control group (CG, 43.8 ± 13.8 years, 75.2 ± 11.2 kg, 163.3 ± 7.8 cm, 3 men, and 7 women), with the same average age and level of physical activity. The intervention, applied to both groups, consisted of combined training for 15 weeks, followed by detraining for 5 weeks. Before and after the training and detraining period the following parameters were evaluated: body composition by dual energy radiological absorptiometry (DXA), cardiorespiratory fitness by ergospirometer, and strength of upper and lower limbs by isometric dynamometer. The results show the effect of the intervention moments on the strength and oxygen consumption variables (time factor), considering the two study groups. Regarding the analysis of the interaction (group vs. time), there was a significant effect on the isometric extension strength of the left (p = 0.019) and right (p = 0.030) knees, with training (left: 10.4%; right: 12.4%) and detraining (left: −10.8%; right: −12.1%) effect in PLHA, when compared with the control group (left: 8.1 and 3.9%, respectively; right: 11.5 and −0.2%, respectively). In addition, there was a significant interaction on ventilatory threshold 1 (p = 0.002), indicating a significantly greater increase with training (27.3%) and decrease with detraining (−22.7%) in the PLHA group compared with the Control group (19.9 and −6.7%, respectively). In conclusion, combined training and the subsequent period of detraining caused similar responses in body composition, isometric strength, and cardiorespiratory fitness of PLHA and CG, except for the extensor strength of the lower limbs and ventilatory threshold 1, which presented positive effects on training and negative effects on detraining for PLHA.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03075332.

BACKGROUND Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4–13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged CONCLUSIONS Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in “the perfect wave” of NHANES, including the years 2007–2010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA.

The degree of speech development is not the same as that of hearing impairment and depends on the following factors: the degree of hearing impairment; the time of onset of the hearing analyzer defect; pedagogical conditions of the child after hearing analyzer dysfunction; specific characteristics of the child. Each of the above factors plays a major role in assessing children’s speech. Hearing and speech development in children are directly related. The more a child’s hearing, the more speech is affected. If the importance of hearing is low, then the deviation of speech is not pronounced. If there is a hearing loss, the child will remain deaf until special education begins. With moderate hearing loss, there are disturbances in the phonetic, lexical, grammatical side of speech. Hearing loss can occur at different times in a child’s life. The presence or absence of a secondary appearance of the defect depends on the time factor. The faster the impairment occurs, the more it affects the formation of speech function. In a child under the age of two, the ability to hear leads to a complete lack of speech if speech is not yet formed. By the age of 3-3.5, hearing loss leads to loss of formed speech. If special preparation is not started immediately, speech will be almost completely broken by the age of 4-5 with full hearing. At the age of 6-7 years, hearing loss leads to a sharp deterioration of the child's speech, and without special pedagogical assistance, speech gradually deteriorates.

Introduction Chest pain and its clinical manifestations are the most common reasons for presentation to the emergency department (ED). Given that the prevalence of chest pain due to acute myocardial infarction (AMI) in the ED is modest, clinicians should use cardiac troponins to safely and rapidly rule out AMI, avoiding the delayed release of low risk patients. The study aims to develop and validate an algorithm to early rule-out of non-ST elevation myocardial infarction (NSTEMI) in subjects admitted to the ED with symptoms of myocardial infarction. Methods High sensitivity cardiac Troponin T (hs-cTnT) serial measurements (baseline, T0; after 1 h, T1; after 3 h, T3) were used to develop and validate the algorithm, respectively, in 6403 and 773 consecutive admissions suggestive of AMI. Results Patients were classified as having or not having NSTEMI according to clinical assessment, diagnostic imaging, and serial measurements ofhs-cTnT; ROC curve analysis allowed to find changes in consecutive hs-cTnT associated with diagnostic sensitivity close to 100%. Only patients with hs-cTnTat T0 lower than 14 ng/L resultedto be eligible for the safe rule-out of NSTEMI. Conclusions Although some points remain to be improved, the results obtained indicate that algorithms for fast NSTEMI rule-out are feasible and safe.

Background Fenestrated/branched endografts for aortic repair (FB-EVAR) are valid options to treat thoracoabdominal aortic aneurysms (TAAAs). Successful repair requires manipulation of target visceral vessels (TVVs) with possible splanchnic ischemia. The aim of the study was to evaluate the clinical impact of splanchnic ischemia occurring in FB-EVAR for TAAA. Methods Between 2010 and 2015, patients with TAAAs undergoing FB-EVAR were prospectively enrolled. Clinical, morphological, procedural, and 30-day data were evaluated. Splanchnic ischemia was defined as the presence of splanchnic ischemic lesions (SILs) visible at perioperative computed tomography angiography. Preoperative, postoperative, and 30-day hepatic/pancreatic/renal laboratory functions were analyzed. End points were incidence of SILs, laboratory splanchnic functions worsening (≥25% of baseline), and presence of related clinical/morphological and procedural risk factors. Results Thirty-six patients (male: 78%; age: 73 ± 7 years) with 27 (75%) type I-III and 9 (25%) type IV TAAA who underwent FB-EVAR for a total of 127 TVV (branches: 47–60%; fenestrations: 53–67%). Fourteen SILs occurred in 12 (33%) patients: 4 (29%) in pancreas, 3 (21%) in spleen, 2 (14%) in bowel, 5 (36%) in kidney. The cause was embolic in 79% and thrombotic in 21%. No preoperative clinical/morphological data or procedural data were correlated with SIL. Pancreatic, hepatic, or renal function worsening occurred at 24 hr in 16 (44%), 16 (44%), and 9 (25%) cases, respectively. Overall, SILs were associated with increased values of C-reactive protein (CRP) (17.9 ± 0.4 vs. 9.9 ± 9.0 mg/dL; P = 0.03) and bilirubin (1.2 ± 2.3 vs. 1.0 ± 0.5 mg/dL; P = 0.02) at 24 hr. Specifically, SIL of the celiac trunk and superior mesenteric and renal arteries' parenchyma were associated with the significant laboratory function changes 24 hr. SIL of the superior mesenteric artery was associated with increased 30-day mortality (50% vs. 7 %; P = 0.002). Pancreatic, hepatic, or renal function worsening occurred at 30 days in 2 (6%), 0 (0%), and 4 (12%) cases, with similar laboratory tests in patients with and without SIL. Conclusions SIL can be frequently detected after FB-EVAR for TAAA and appears mainly of embolic origin. No clinical, morphological, or procedural predictors could be identified in our series. Postoperative laboratory changes of CRP, bilirubin, activated partial thromboplastin time, and amylases are associated with SIL but disappear without clinical consequences within 30 days. However, SIL occurring in the superior mesenteric artery are associated with an increased 30-day mortality.

Objective The objective was to provide an exhaustive characterization of ECG features in a large cohort of dilated cardiomyopathies (DCMs) and then investigate their possible prognostic role in the long term. Background ECG is an accessible, reproducible, low-cost diagnostic and prognostic tool. However, an extensive description of ECG features and their long-term prognostic role in a large cohort of DCM is lacking. Methods All available baseline ECGs of DCM patients enrolled from 1992 to 2013 were systematically analysed. Patients underwent to a complete clinical-laboratory evaluation. The study outcome measures were death or heart transplant (D/HT) and sudden death or malignant ventricular arrhythmias (SD/MVA). Results Four hundred and fourteen DCM patients were enrolled. During a median follow-up of 125 months, 55 and 57 patients experienced D/HT and SD/MVA, respectively. At multivariate analysis, left ventricular hypertrophy (P = 0.017), heart rate (HR, P = 0.005) and anterolateral T-wave inversion (P = 0.041) predicted D/HT. Regarding SD/MVA, S wave amplitude in V2 (P = 0.008), R wave amplitude in DIII (P = 0.007), anterolateral T-wave inversion (P = 0.017) emerged as predictors. At receiver-operating curve analyses, the addition of ECG models to the clinical-laboratory evaluation significantly increased the area under the curve both for D/HT (from 0.68 to 0.74, P = 0.042) and SD/MVA (from 0.70 to 0.77, P = 0.048). Conclusion The exhaustive systematic evaluation of ECG has an incremental impact in the prognostication of a large cohort of DCM patients, also regarding the arrhythmic stratification.

Food allergy is a hot topic, considering the rise in incidence the allergic disease exhibits in children. Nevertheless, the recent medical literature does not cover the natural history and evolution particularities of this disease. The first atopic diseases are food allergies and atopic dermatitis, followed by astma and allergic rhinitis. The most frequent food allergies are cow’s milk protein, egg, wheat, soy, peanut and fish. The severity of symptoms on the onset of cow’s milk protein allergy is predictive for a negative impact on length of the disease. Egg allergy is a predictive factor for astma. Peanut and fish allergies may be persistent into adulthood. Food allergy is polimorphic, the diagnosis takes time and the course of the disease is different for different allergens and clinical forms.

Human physiology and pathophysiology of diseases have been proved to show rhythmic variation in response to temporal factors. This behavior is intertwined in field of clinical physiology in form of chronomedicine and chronotherapy for the better outcomes of treatment. Ayurveda scholars have also described rhythmic variation in biological entities like Dosha, Agni, Bala, presentation of diseases in relation to diurnal, meal intake and seasonal factors. They have well documented different domain of drug i.e. collection of drug, preparation of medicine, intervention of therapeutic procedures and administration of medicine in accordance to variation in biological entities and time. This article is aimed to summarize all these documented observations of Ayurveda regarding chronomedicine and chronotherapy and discuss in view of contemporary sciences, so that it can be utilized by the researchers of this field to generate evidence based data and may be applied by the physician for the better prognosis and management of the disease.