Search

Objective: The aim was to adapt an instrument that evaluates the relationship between young individuals and health professionals to the Brazilian population, which will be called the Escala de Avaliação de Vínculo entre Jovens e Profissionais de Saúde (Youth Connectedness to Provider scale). Method: The questionnaire known as the Youth Connectedness to Provider scale consists of seven Likert-like questions. The translation, back-translation, evaluation by ten specialists, and pre-test with 43 adolescents and young adults aged between 10 and 24 years were performed to assess the clarity and reliability of meanings. The content validity index was calculated for each question. Subsequently, the clinical validation was performed with 83 patients aged 10–24 years old and Cronbach's alpha coefficient was calculated. Results: A content validity index >0.8 (considered satisfactory) was obtained for all items analyzed by experts and adolescents. At the clinical validation, it showed a high internal consistency (Cronbach’s alpha = 0.76). The questions showed a good correlation, except for the question about judgment (Spearman’s rho = 0.03–0.19). Conclusions: The scale adaptation showed an adequate agreement rate at the translation evaluation and a good reliability index in the questions. This instrument provides information on strengths and topics that require more attention from professionals to improve the relationship with their patients; it can be a valuable parameter in assessing the medical consultation quality.

Abstract Background In recent years there has been a progressive rise in the number of asylum seekers and refugees displaced from their country of origin, with significant social, economic, public health and mental health implications. The aim of this study is to (1) describe the level of psychological distress and frequency of psychiatric disorders in a sample of male asylum seekers and refugees across different ethnic groups resettled in Italy; (2) establish whether the number of traumatic events experienced before, during and after the migration process is associated with level of psychological distress and depressive symptoms. Methods In two large Italian catchment areas, over a period of 1 year a consecutive series of male asylum seekers and refugees, aged 18 or above and included in the Italian protection system, were screened for psychological distress and psychiatric disorders using validated questionnaires. Results During the study period, 252 male asylum seekers or refugees were recruited. More than one-third of the participants (34.5%) showed clinically relevant psychological distress, and one-fourth (22.2%), met the criteria for a psychiatric diagnosis, mainly Post Traumatic Stress Disorder and depressive disorders. The number of traumatic events turned out to be a risk factor for both clinically relevant psychological distress and depressive disorders. Receiving good social support emerged as a protective factor, while migrants with unclear status were at higher risk of psychological distress than those holding or awaiting a permission. Discussion In an unselected sample of male asylum seekers and refugees, after around 1 year of resettlement in Italy, the frequency of psychological distress and psychiatric disorders was substantial and clinically relevant. The association between traumatic events, especially post-migration problems, and mental health conditions suggests the need of developing services to assist refugees and asylum seekers to address the multi-faceted problems they experience, such as social support in host country, legal problems concerning permit status and asylum procedure, and family reunification, as well as addressing trauma and mental health issues.

Abstract Background HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in first-line, and 74 and 10 months in 194 pertuzumab-naïve patients (p = 0.0006 and 0.03 for OS and PFS2, respectively). Conclusions Our data support the hypothesis that the addition of pertuzumab to trastuzumab reduces the amount of available plasma membrane HER2 receptor, limiting the binding of T-DM1 in cancer cells. This may help interpret the less favorable outcomes of second-line T-DM1 in trastuzumab/pertuzumab pre-treated patients compared to their pertuzumab-naïve counterpart.

The biological activities of dietary bioactive polysaccharides have been largely explored. Studies on the immunomodulating effects of oligosaccharides and polysaccharides have shown that they are able to modulate innate immunity. Prebiotics are a class of poorly digested carbohydrates that are mainly produced from dietary fibers, which are carbohydrate polymers with ten or more monomeric units as defined by the Codex Alimentarius Commission in 2009. Considering the capacity of prebiotics in reducing gut inflammation, the aim of this study was to investigate the anti-inflammatory activity of galactooligosaccharide (Bimuno® GOS) in an in vitro model of ulcerative colitis (UC)-like inflamed intestinal cells. Differentiated Caco-2 cells were exposed to 2 % dextran-sulfate-sodium salt (DSS) to induce inflammation, and then with different concentrations of Bimuno GOS (1–1,000 μg/ml). Cell monolayer permeability, tight- and adherent junction protein distribution, pro-inflammatory cytokine secretion, and NF-kB cascade were assessed. Bimuno GOS at different concentrations, while not affecting cell monolayer permeability, was shown to counteract UC-like intestinal inflammatory responses and damages induced by DSS. Indeed, Bimuno GOS was able to counteract the detrimental effects of DSS on cell permeability, determined by transepithelial electrical resistance, phenol red apparent permeability, and tight- and adherent junction protein distribution. Furthermore, Bimuno GOS inhibited the DSS-induced NF-kB nuclear translocation and pro-inflammatory cytokine secretion. Further analyses showed that Bimuno GOS was able to revert the expression levels of most of the proteins involved in the NF-kB cascade to control levels. Thus, the prebiotic Bimuno GOS can be a safe and effective way to modulate the gut inflammatory state through NF-kB pathway modulation, and could possibly further improve efficacy in inducing remission of UC.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two highly prevalent human diseases caused by excessive fat deposition in the liver. Although multiple approaches have been suggested, NAFLD/NASH remains an unmet clinical need. Here, we report the discovery of a novel class of hybrid molecules designed to function as cysteinyl leukotriene receptor 1 (CysLT1R) antagonists and G protein bile acid receptor 1 (GPBAR1/TGR5) agonists for the treatment of NAFLD/NASH. The most potent of these compounds generated by harnessing the scaffold of the previously described CystLT1R antagonists showed efficacy in reversing liver histopathology features in a preclinical model of NASH, reshaping the liver transcriptome and the lipid and energy metabolism in the liver and adipose tissues. In summary, the present study described a novel orally active dual CysLT1R antagonist/GPBAR1 agonist that effectively protects against the development of NAFLD/NASH, showing promise for further development.

ObjectiveSutureless aortic valves are an effective option for aortic valve replacement (AVR) showing non-inferiority to standard stented aortic valves for major cardiovascular and cerebral events at 1-year. We report the 1-year hemodynamic performance of the sutureless prostheses compared with standard aortic valves, assessed by a dedicated echocardiographic core lab.MethodsPerceval Sutureless Implant vs. Standard Aortic Valve Replacement (PERSIST-AVR) is a prospective, randomized, adaptive, open-label trial. Patients undergoing AVR, as an isolated or combined procedure, were randomized to receive a sutureless [sutureless aortic valve replacement (Su-AVR)] (n = 407) or a stented sutured [surgical AVR (SAVR)] (n = 412) bioprostheses. Site-reported echocardiographic examinations were collected at 1 year. In addition, a subgroup of the trial population (Su-AVR n = 71, SAVR = 82) had a complete echocardiographic examination independently assessed by a Core Lab (MedStar Health Research Institute, Washington D.C., USA) for the evaluation of the hemodynamic performance.ResultsThe site-reported hemodynamic data of stented valves and sutureless valves are stable and comparable during follow-up, showing stable reduction of mean and peak pressure gradients through one-year follow-up (mean: 12.1 ± 6.2 vs. 11.5 ± 4.6 mmHg; peak: 21.3 ± 11.4 vs. 22.0 ± 8.9 mmHg). These results at 1-year are confirmed in the subgroup by the core-lab assessed echocardiogram with an average mean and peak gradient of 12.8 ± 5.7 and 21.5 ± 9.1 mmHg for Su-AVR, and 13.4 ± 7.7 and 23.0 ± 13.0 mmHg for SAVR. The valve effective orifice area was 1.3 ± 0.4 and 1.4 ± 0.4 cm2 at 1-year for Su-AVR and SAVR. These improvements are observed across all valve sizes. At 1-year evaluation, 91.3% (n = 42) of patients in Su-AVR and 82.3% in SAVR (n = 51) groups were free from paravalvular leak (PVL). The rate of mild PVL was 4.3% (n = 2) in Su-AVR and 12.9% (n = 8) in the SAVR group. A similar trend is observed for central leak occurrence in both core-lab assessed echo groups.ConclusionAt 1-year of follow-up of a PERSIST-AVR patient sub-group, the study showed comparable hemodynamic performance in the sutureless and the stented-valve groups, confirmed by independent echo core lab. Perceval sutureless prosthesis provides optimal sealing at the annulus with equivalent PVL and central regurgitation extent rates compared to sutured valves. Sutureless valves are therefore a reliable and essential technology within the modern therapeutic possibilities to treat aortic valve disease.

The consequences of systemic inflammation are a significant burden after traumatic brain injury (TBI), with almost all organs affected. This response consists of inflammation and concurrent immunosuppression after injury. One of the main immune regulatory organs, the spleen, is highly interactive with the brain. Along this brain–spleen axis, both nerve fibers as well as brain-derived circulating mediators have been shown to interact directly with splenic immune cells. One of the most significant comorbidities in TBI is acute ethanol intoxication (EI), with almost 40% of patients showing a positive blood alcohol level (BAL) upon injury. EI by itself has been shown to reduce proinflammatory mediators dose-dependently and enhance anti-inflammatory mediators in the spleen. However, how the splenic immune modulatory effect reacts to EI in TBI remains unclear. Therefore, we investigated early splenic immune responses after TBI with and without EI, using gene expression screening of cytokines and chemokines and fluorescence staining of thin spleen sections to investigate cellular mechanisms in immune cells. We found a strong FLT3/FLT3L induction 3 h after TBI, which was enhanced by EI. The FLT3L induction resulted in phosphorylation of FLT3 in CD11c+ dendritic cells, which enhanced protein synthesis, maturation process, and the immunity of dendritic cells, shown by pS6, peIF2A, MHC-II, LAMP1, and CD68 by immunostaining and TNF-α expression by in-situ hybridization. In conclusion, these data indicate that TBI induces a fast maturation and immunity of dendritic cells which is associated with FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.

Since the Framingham study in 1974 reported a 2 to 5 fold increase in the risk of developing heart failure (HF) in patients with diabetes mellitus (DM), other observational studies confirmed this association that has gained great visibility in recent years from of the results of cardiovascular safety studies of antidiabetic drugs. HF is defined as a clinical syndrome that results from functional or structural deterioration of ventricular filling or blood ejection. It can be classified according to the ejection fraction, the presence of symptoms and the limitation to physical activity. There are different factors associated with HF in people with DM such as age, duration of the disease, insulin use, coronary heart disease, high blood pressure, peripheral arterial disease, increased creatinine, poor glycemic control, albuminuria and obesity. In turn, HF is associated with insulin resistance and dysglycemic states that are considered of risk for the development of DM.

Abstract Background Preliminary studies have tested nicotine as a novel treatment for OCD patients who respond partially/incompletely or not at all to first and second-line treatment strategies, with the former represented by SSRIs or clomipramine, and the latter by switching to another SSRI, or augmentation with atypical antipsychotics, and/or combination with/switching to cognitive–behavioural therapy. Some studies found nicotine-induced reduction of obsessive thoughts and/or compulsive behaviour in OCD patients. We aimed to evaluate the efficacy of nicotine administration in OCD patients. Methods We searched the PubMed, ScienceDirect Scopus, CINHAL, Cochrane, PsycINFO/PsycARTICLES, and EMBASE databases from inception to the present for relevant papers. The ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) standards were used. We included all studies focusing on the effects of nicotine administration on OCD patients’ obsessions or compulsions. Studies could be open-label, cross-sectional, randomized controlled trials, case series or case reports. Results A total of five studies could be included. Nicotine administration may ameliorate behavioural features and recurrent thoughts of severe, treatment-resistant OCD patients; however, in one study it was not associated with OC symptom improvement or cognitive enhancement across various executive function subdomains. Conclusions Although encouraging, the initial positive response from the use of nicotine in OCD needs testing in large controlled studies. This, however, raises ethical issues related to nicotine administration, due to its addiction potential, which were not addressed in the limited literature we examined. As an alternative, novel treatments with drugs able to mimic only the positive effects of nicotine could be implemented.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Abstract Background Partial lesions of the anterior cruciate ligament (ACL) are more common than is generally thought, accounting for about 10–12% of ACL injuries. Selective reconstruction may be considered as an option in isolated bundle rupture. The purpose of this study is to evaluate both subjective and objective clinical results, as well as functional recovery time, after selective arthroscopic single-bundle reconstruction in a consecutive series of patients affected by partial ACL rupture. Materials and methods Thirty-six patients undergoing selective reconstruction of a single ACL bundle were retrospectively evaluated from a series of 354 ACL reconstructions performed over a 3-year period. Although the suspicion of partial lesions was present at clinical and magnetic resonance imaging (MRI) evaluation, final diagnosis was obtained during arthroscopy. All patients were operated using the same technique and type of fixation, and undergoing the same functional recovery protocol. Results Mean follow-up was 64 months (48–84 months). All patients but one achieved good functional recovery and returned to their sports within a mean period of 6.1 months. A single patient complained of postoperative instability 1 year after the index operation and needed further surgery. No complications were recorded. Conclusions Selective reconstruction of partial ACL injury is a method to bear in mind because it offers quick functional recovery. Specific technical and diagnostic steps should be performed and discussed with patients preoperatively. Level of evidence Level 4, retrospective study.

We determined prevalence of Rickettsia spp. in 172 ticks of the Amblyomma maculatum group collected from 16 urban sites in Oklahoma City, Oklahoma, USA, during 2017 and 2018. Most ticks (59.3%) were collected from 1 site; 4 (2.3%) were infected with Rickettsia parkeri and 118 (68.6%) with Candidatus Rickettsia andeanae.

This study aimed to evaluate the microbiological quality of water and tissue samples of Mytella guyanensis (Mollusk: Bivalve), a species of relevant commercial interest and is a direct part of the income and food of traditional communities in coastal regions. This study was carried out in two communities in the Cananeia Estuary known as Retiro and Itanhoapina. During the period of 2017, where the species is collected for human consumption, water and bivalve samples were collected in the localities in order to determine the concentrations of total and thermotolerant coliforms. The samples of water and M. guyanensis were analyzed to determine the Most Probable Number (MPN) of Coliforms, based on the Multiple Tube Technique. The results of the analyses showed low concentrations of coliforms in the water samples, with a similar result for the tissue samples of the individuals collected. The water analysis showed a geometric mean of 34.81 total coliforms and 20.70 MPN 100 mL-1 of thermotolerant coliforms. The averages of coliforms in the soft tissues of M. guyanensis were 190 MPN g -1 for total coliforms and 174 MPN g -1 for thermotolerant coliforms. The concentrations of coliforms in the tissue of the collected specimens showed a positive correlation with temperature and a negative correlation with salinity. There were significant differences between seasonality in relation to the concentration of total and thermotolerant coliforms in the tissue. The summer rainy season showed the highest seasonal average of coliforms in M. guyanensis. All values obtained for MPN of coliforms were below the limit established by the legislation.

This paper proposes a Ka-band receiver front-end for future CubeSats Low-Earth Orbit (LEO) to Geostationary (GEO) inter-satellite links. The receiver is able to support very high data rates (up to 100 Mbit/s) in Quadrature Phase-Shift Keying (QPSK) when in the line of sight of a GEO satellite that is equipped with a steerable 70-cm antenna and transmitting a 25-W signal. The originality of the proposed approach is twofold. First we will demonstrate the receiver feasibility based on a class of miniaturized and low-cost microwave integrated circuits, currently available on the market. In particular, our receiver is based on a novel combination of integrated Low-Noise Amplifiers (LNA) with an image rejection filter, the latter exploiting the Substrate Integrated Waveguide (SIW) technology. An optimization of the via placement proved to be able to reduce the need for shielding apparatuses, thus simplifying the mechanics and reducing mass, volume and hardware costs. Secondly, we will propose a noise injection circuit capable of measuring and calibrating the receiver gain, also during in-orbit operation. Self testing capabilities are particularly relevant for CubeSats because the usage of commercial components poses serious reliability issues.

Currently digital educational applications are employed in education, since technological tools are very interesting and engaging for pupils. Augmented Reality (AR) is one of the most explored and successfully used technology. Thanks to the AR, the situated learning can occur; it suggests that people easily acquire new knowledge if learning occurs in a specific context and is embedded in a physical environment. This paper presents an AR application, called Geo+, for supporting primary school students in the acquisition of knowledge on the solid geometry. Geo+ has been developed by following a Human-Centered Design approach, thus several formative evaluation studies were performed to enhance the quality of the resulting application. A user study involving 96 pupils of the 3rd grade of primary school was performed in order to investigate the learning effectiveness, the engagement and the perceived workload of Geo+ at school. The results showed that Geo+ is effective in terms of student learning gain. In addition, pupils really appreciated the ease of use of the game; they were satisfied and felt engaging and comfortable during the interaction, none of them ask for help during the execution of the learning activities.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

Objetivo. Analizar la integración entre comprensión individual y diádica de una tabla de frecuencias en estudiantes de primaria, cuyo foco estuvo en la calidad y cualidad del producto cognitivo. Método. Participaron 90 estudiantes de 6º y 7º grado (edad: . = 12.3; DE = 0.5), seleccionados no probabilísticamente. Primero, los sujetos resolvieron de forma individual la tarea de comprensión de una tabla de doble entrada. Luego fueron agrupados en díadas que resolvieron la tarea colaborativamente. Se utilizó un cuestionario para evaluar niveles de complejidad de dicha comprensión y centrar el análisis en: (a) la comparación de desempeños individual y diádico generales, (b) las modalidades de integración entre producción individual y diádica, y (c) las modalidades según complejidad del ítem y composición sociocognitiva diádica. Resultados. Se encontró: (a) superioridad del desempeño diádico sobre el individual, (b) se identificaron diferentes modalidades de integración entre comprensión individual y diádica, y (c) la influencia del nivel de complejidad del ítem y la composición sociocognitiva sobre modalidades específicas de respuesta construidas por la díada. Conclusión. Se corrobora la hipótesis de la superioridad de las actuaciones interindividuales sobre las intraindividuales, aunque con variaciones generadas por las variables mediadoras. Los hallazgos se discutieron según la diferenciación conceptual entre producto y proceso.

La enfermedad glomerular comprende un grupo heterogéneo de entidades que se caracterizanpor la pérdida de la arquitectura o función del glomérulo secundario a proceso inflamatorio del mismo de etiología autoinmune, infecciosa, paraneoplásica, que puede ser identificada conestudios de histopatología. Su reconocimiento durante la gestación representa un reto diagnóstico por la sobreposición de cambios fisiológicos, el debut de enfermedades autoinmunitariaso de enfermedades genéticas, entre otros. La presentación clínica suele encajar en grupossindromáticos específicos, sin embargo, es frecuente que sean clínicamente indistinguibles osobrepuestos. El debut de la enfermedad renal con curso clínico de rápida instauración y deevolución desfavorable con respecto a la función renal, hace mandatorio un estudio completodesde el abordaje clínico hasta la interpretación de los hallazgos histopatológicos, encaminadoen la distinción de causas primarias y secundarias. Si bien las glomerulonefritis primarias noson las más frecuentes en la gestación, la identificación certera del diagnóstico y su adecuada clasificación permite el manejo dirigido y óptimo de las mismas. Se presentan los casos clínicosde dos gestantes con enfermedad glomerular primaria, con discrepancia en su diagnóstico,enfatizando en sus manifestaciones durante el curso de la gestación, el algoritmo diagnósticoutilizado, el tratamiento inicial y de mantenimiento utilizado. Se resalta la utilidad de la biopsiarenal, específicamente la inmunofluorencia para aclarar el mismo.

The sheep is a valuable model to test whether hormone mechanisms that sexually differentiate the brain underlie the expression of sexual partner preferences because as many as 8% of rams prefer same-sex partners. Epigenetic factors such as DNA methylation act as mediators in the interaction between steroid hormones and the genome. Variations in the epigenome could be important in determining morphological or behavior differences among individuals of the same species. In this study, we explored DNA methylation differences in the hypothalamus of male oriented rams (MORs) and female oriented rams (FORs). We employed reduced representation bisulfite sequencing (RRBS) to generate a genome-wide map of DNA methylation and RNA-Seq to profile the transcriptome. We found substantial DNA methylation and gene expression differences between FORs and MORs. Although none of the differentially methylated genes yielded significant functional terms directly associated with sex development, three differentially expressed genes were identified that have been associated previously with sexual behaviors. We hypothesize that these differences are involved in the phenotypic variation in ram sexual partner preferences, whereas future studies will have to find the specific mechanisms. Our results add an intriguing new dimension to sheep behavior that should be useful for further understanding epigenetic and transcriptomic involvement.

BackgroundBoth elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF.Method and resultsSeven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: 75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata.ConclusionsFor resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Breast cancer patients undergoing neoadjuvant chemotherapy with anthracyclines or trastuzumab can suffer cardiotoxic issues. Nowadays, the markers of cardiac damage are still not reliable, and extracellular volume (ECV) calculated from CT could be a promising cardiotoxic marker. Eighty-two patients, treated with two different chemotherapy regimens based on doxorubicin (DOX) or epirubicin-trastuzumab (EPI–TRAS), were retrospectively selected and the variations in extracellular volume (ECV) values were measured and analyzed. Whole Body CT (WB-CT) scans were acquired after 1 min, in the portal phase (PP), and after 5 min, in the delayed phases (DP), at the baseline (T0), after one year (T1) and after five years (T5) from the end of chemotherapies. The values measured by two radiologists with different levels of experience were evaluated in order to assess the inter-reader reproducibility assessment (ICC = 0.52 for PP and DP). Further, we performed a population-based analysis and a drug-oriented subgroup analysis in 54 DOX-treated and 28 EPI–TRAS-treated patients. In the general cohort of women treated with any of the two drugs, we observed in the lapse T0–T1 a relative increase (RI) of 25% vs. 20% (PP vs. DP, p < 0.001) as well as in the lapse T0–T5 an RI of 17% vs. 15% (PP vs. DP, p < 0.01). The DOX-treated patients reported in the lapse T0–T1 an RI of 22% (p < 0.0001) in PP and an RI of 16% (p = 0.018) in the DP, with ECV values remaining stably high at T5 both in PP (RI 14.0%, p < 0.0001) and in DP (RI 17%, p = 0.005) highlighting a possible hallmark of a persisting CTX sub-damage. On the other hand, ECV measured in EPI–TRAS-treated women showed an RI in T0–T1 of 18% (p = 0.001) and 29% (p = 0.006) in PP and DP, respectively, but the values returned to basal levels in T5 both in the PP (p = 0.12) and in DP setting (p = 0.13), suggesting damage in the first-year post-treatment and a possible recovery over time. For the 82 patients, an echocardiography was performed at T0, T1= 12 m + 3 m and T5 = 60 m + 6 m with LVEF values at T0 (64% ± 5%), T1 (54% ± 6%) and T5 (53% ± 8%). WB-CT-derived ECV values could provide a valid imaging marker for the early diagnosis of cardiotoxic damage in BC patients undergoing oncological treatments. We detected different patterns during the follow-up, with stably high values for DOX, whereas EPI–TRAS showed a peak within the first year, suggesting different mechanisms of cardiac damage.

Background: Improved therapy in CF has led to an overall improvement in nutritional status. The objectives of our study are: to cross-sectionally assess nutritional status and serum levels of fat-soluble vitamins; to retrospectively evaluate the efficacy of modulators on nutritional status and fat-soluble vitamin levels. Methods: In patients younger than 2 years of age, we evaluated growth, in patients aged 2–18 years, we assessed BMI z-scores, and in adults, we assessed absolute BMI values. Levels of 25(OH)D, vitamins A, and E were measured. Results: A cross-sectional analysis was conducted on 318 patients, 109 (34.3%) with pancreatic sufficiency. Only three patients were under 2 years old. In 135 patients aged 2–18 years, the median BMI z-score was 0.11, and 5 (3.7%) patients had malnutrition (z-score ≤ 2SD). In 180 adults, the median BMI was 21.8 kg/m2. Overall, 15 (13.7%) males (M) and 18 (25.3%) females (F) were underweight (18 < BMI > 20); 3 (2.7%) M and 5 (7.0%) F had a BMI < 18. Suboptimal 25(OH)D levels were found in patients with pancreatic insufficiency. The prevalence of deficiency of vitamins A and E is low. After one year of treatment with modulators, the increase in BMI was more consistent (M: 1.58 ± 1.25 kg/m2 F: 1.77 ± 1.21 kg/m2) in elexacaftor/tezacaftor/ivacaftor (ETI)-treated patients compared with other modulators, with a significant increase in levels of all fat-soluble vitamins. Conclusions: Malnutrition is present in a limited number of subjects. The prevalence of subjects with suboptimal 25(OH)D levels is high. ETI showed a beneficial effect on nutritional status and circulating levels of fat-soluble vitamins.

The COVID-19 pandemic has brought health systems to the brink of collapse in several regions around the world, as the demand for health care has outstripped the capacity of their services, especially regarding intensive care. In this context, health system managers have faced a difficult question: who should be admitted to an intensive care unit (ICU), and who should not? This paper addresses this decision problem using Expected Utility Theory and Bayesian decision analysis. In order to estimate the chances of survival for patients, a structured protocol has been proposed conjointly with physicians, based on the Sequential Organ Failure Assessment (SOFA) score. A portfolio selection approach is proposed to support tackling the ICU allocation problem. A simulation study shows that the proposed approach is more advantageous than other approaches already presented in the literature, with respect to the number of lives saved. The patients’ probabilities of survival inside and outside the ICU are important parameters of the model. However, assessing such probabilities can be a difficult task for health professionals. In order to give due treatment to the imprecise information regarding these probabilities, a Monte Carlo simulation is used to estimate the probabilities of recommending a patient be admitted to the ICU is the most appropriate decision, given the conditions presented. The methodology was implemented in an Information and Decision System called SIDTriagem, which is available online for free. With regards to managerial implications, SIDTriagem has a great potential to help in the response to public health emergencies systems as it facilitates rational decision-making regarding allocating ICU beds when resources are scarce.

This study illustrates the sensing and wound healing properties of silk fibroin in combination with peptide patterns, with an emphasis on the printability of multilayered grids, and envisions possible applications of these next-generation silk-based materials. Functionalized silk fibers covalently linked to an arginine–glycine–aspartic acid (RGD) peptide create a platform for preparing a biomaterial ink for 3D printing of grid-like piezoresistors with wound-healing and sensing properties. The culture medium obtained from 3D-printed silk fibroin enriched with RGD peptide improves cell adhesion, accelerating skin repair. Specifically, RGD peptide-modified silk fibroin demonstrated biocompatibility, enhanced cell adhesion, and higher wound closure rates at lower concentration than the neat peptide. It was also shown that the printing of peptide-modified silk fibroin produces a piezoresistive transducer that is the active component of a sensor based on a Schottky diode harmonic transponder encoding information about pressure. We discovered that such biomaterial ink printed in a multilayered grid can be used as a humidity sensor. Furthermore, humidity activates a transition between low and high conductivity states in this medium that is retained unless a negative voltage is applied, paving the way for utilization in non-volatile organic memory devices. Globally, these results pave the way for promising applications, such as monitoring parameters such as human wound care and being integrated in bio-implantable processors.

Objetivos: se analizaron los efectos de la simetría-asimetría de competencia y de la afinidad socioafectiva sobre la interacción colaborativa, en la comprensión de una tabla de frecuencias. Método: se distribuyeron en díadas simétricas y asimétricas, según igualdad-diferencia entre las competencias específicas de sus integrantes, y, a su vez, con y sin afinidad socioafectiva recíproca. Participaron 90 estudiantes (45 díadas) de sexto y séptimo grado de escolaridad primaria (edad, M = 12.3, DE = .5), seleccionados de manera no probabilística. Cada díada resolvió 12 ítems de elección múltiple; cada uno de estos evaluaba un aspecto de la comprensión de la tabla. La interacción colaborativa fue analizada desde un sistema de categorías de tres niveles jerárquicos. Resultados: sugirieron una influencia de la afinidad socioafectiva al interior de la asimetría cognitiva, en tanto la presencia de la primera se asoció con un menor desequilibrio de los aportes entre los compañeros, relativos a la resolución de la tarea. En cambio, en la simetría de competencia, la afinidad socioafectiva se asoció con mínimas variaciones. Conclusiones: los hallazgos se discuten desde una perspectiva situada o contextualizante del hecho sociocognitivo, que pretende superar la concepción clásica epistémica.

From the psychological approach known as “Distributed Cognition” it is possible to postulate three ways of cognitive distribution in the activity systems: physical, social-communicational and symbolic-instrumental. This communication broaches the configuration of said systems, in terms of the institutional practices prevailing in the National University of Rosario (Universidad Nacional de Rosario-UNR), Argentina. These institutional practices vary in compliance with the type of knowledge given in the teaching action: social and non-social. The research involved the naturalistic observation of 28 university classes belonging to three social courses and three exact-natural courses (14 classes per epistemic course type). The observation focused on three distribution cognition systems. Gathered results suggest a meaning relationship between the mentioned epistemic-institutional types and the configuration of the physical and symbolic systems.

We performed a cross-sectional parasitological survey to assess the prevalence of protozoa and helminth infection among 275 school-age children (SAC) living in rural and peri-urban areas located in different ecological zones of the Department of La Paz, Bolivia. Public health activities for the control of STH, based on the biannual administration of mebendazole to preschool and school children are implemented at national level since 1986.We found an overall prevalence of 82.2% for intestinal parasites, including protozoa (80%) and helminths (23.3%). Blastocystis and Entamoeba coli were the most prevalent protozoa (found in 44% and 20.7% of the SAC enrolled); as for helminths, Ascaris lumbricoides and Hymenolepis nana were diagnosed in 14.5% and 3.3% of the children, respectively, followed by Trichuris trichiura 1.4%, Enterobius vermicularis 1.4%, Strongyloides stercoralis 0.7% and hookworms 0.7%.Molecular characterization of Blastocystis positive samples evidenced three different subtypes (ST1, ST2, ST3) highlighting the risk of transmission also from animal reservoir. We found a significant difference in the distribution of intestinal parasitic infection (IPIs) by ecological zone (44/74. 59% in Andean highlands, 94/170, 88% in tropical lowlands and 88/94, 94% in the Yungas, p

Information about the early growth of infectious outbreaks is indispensable to estimate the epidemic spreading. A large number of mathematical tools have been developed to this end, facing as much large number of different dynamic evolutions, ranging from sub-linear to super-exponential growth. Of course, the crucial point is that we do not have enough data during the initial outbreak phase to make reliable inferences. Here we propose a straightforward methodology to estimate the epidemic growth dynamic from the cumulative infected data of just a week, provided a surveillance system is available over the whole territory. The methodology, based on the Newcomb-Benford Law, is applied to the Italian covid 19 case-study. Results show that it is possible to discriminate the epidemic dynamics using the first seven data points collected in fifty Italian cities. Moreover, the most probable approximating function of the growth within a six-week epidemic scenario is identified.

Objective: To compare perioperative outcomes of the elderly versus non-elderly patients on ERPs undergoing laparotomy for gynecologic surgery. Methods: From January 2016 to June 2017, patients undergoing elective laparotomies for gynecologic surgery were enrolled in a perioperative ERP protocol. Outcomes were compared between the elderly (age ≥ 70 years) and the non-elderly (age ≤ 69 years). Primary outcomes were length of stay and perioperative complication rates. Comparisons were performed using chi-squared tests or Fisher’s exact tests for categorical data and Student’s t-test or Wilcoxon rank-sum tests for continuous variables, with p

In recent years, the ENEA has introduced a novel methodology based on motion magnification (MM) into the Italian cultural heritage protection and monitoring field. It consists of a digital video signal processing technique able to amplify enormously the tiny movements recorded in conventional videos, while preserving the general topology of the acquired frames. Though the idea of such a methodology is not new, it has recently been provided with an efficient algorithm that makes possible a viable and low-cost magnification. Applications are extremely varied in almost every field of science and technology; however, we are interested in its application to the safeguarding of architectural heritage, a sector of the utmost importance for Italy. As ancient buildings can be extremely sensitive to even minimally invasive instrumentation, most common monitoring sensors can be replaced by contactless tools and methods, such as video-based techniques like MM. It offers many advantages: easy to use, contactless devices, virtual sensors, reusability of the videos, practicality, intuitive graphical results, quantitative analyses capability and low costs. These characteristics are well suited to the monitoring of large ancient monuments; on the other hand, historical sites have peculiarities of their own, requiring careful approaches, proper tools and trained personnel. Moreover, outdoor applications of MM present quite notable difficulties from a practical point of view, e.g., the dimensions of the studied objects, uncontrolled environmental conditions, spurious vibrations, lighting change/instability, etc. Here we give a general idea of the potential of MM and related issues, using some relevant in-the-field case studies in Italian heritage protection.

Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in leukemic blasts relative to the control. In pediatric patients treated with conventional chemotherapy, comprising cytarabine, daunorubicin and etoposide (ADE), ex vivo drug sensitivity results correlated with minimal residual disease (r = 0.63) and one year relapse-free survival (r = 0.70; AUROC = 0.94). In the de novo ADE analysis cohort of 13 patients, AML cells showed greater sensitivity to bortezomib/panobinostat compared with ADE, and comparable sensitivity between venetoclax/azacitidine and ADE ex vivo. Two patients showed a differential response between ADE and bortezomib/panobinostat, thus supporting the incorporation of ex vivo drug sensitivity testing in clinical trials to further evaluate the predictive utility of this platform in children with AML.

Background and Objectives: Hemolysis is reported to be present in up to 10% of blood gas specimens in the central lab; however, few data on the incidence of hemolysis using a point-of-care testing (POCT) blood gas analysis are available in the setting of the emergency department. The aims of this study were: (1) to analyze the prevalence of hemolysis in blood gas samples collected in the ED using a POCT device; and (2) to evaluate the impact of hemolysis on blood sample results and its clinical consequences. Materials and Methods: We collected 525 consecutive POCT arterial blood gas samples using syringes with electrolyte-balanced heparin within 3 different EDs in the metropolitan area of Rome. Immediately after the collection, the blood samples were checked for the presence of hemolysis with a POCT instrument (i.e., HEMCHECK, H-10 ®). The samples were then subsequently processed for blood gasses, and an electrolytes analysis by a second operator blinded for the hemolysis results. A venous blood sample was simultaneously collected, analyzed for it’s potassium value, and used as a reference. Results: Of the samples, 472 were considered for the statistics, while 53 were excluded due to the high percentage of hemolysis due to operator fault in carrying out the measurement. The final mean hemolysis per operator was 12% (±13% SD), and the total final hemolysis was 14.4%.Potassium (K+) was significantly higher in the hemolyzed group compared with the non-hemolyzed sample (4.60 ± 0.11 vs. 3.99 ± 0.03 mEq/L; p < 0.001), and there were differences between arterial potassium versus venous potassium (D(a-v) K+, 0.29 ± 0.06 vs.−0.19 ± 0.02 mEq/L, p < 0.01). A Bland–Altman analysis confirmed that hemolysis significantly overestimated blood potassium level. Conclusion: Almost 12% of POCT blood gas analysis samples performed in the ED could be hemolyzed, and the presence of this hemolysis is not routinely detected. This could cause an error in the interpretation of the results, leading to the consideration of potassium concentrations being below the lower limit within the normal limits and also leading to the diagnosis of false hyperkalemia, which would have potential clinical consequences in therapeutic decision-making in the ED. The routine use of a POCT hemolysis detector could help prevent any misdiagnoses.

Pancreatic cancer is a leading cause of cancer mortality and is projected to become the second-most common cause of cancer mortality in the next decade. While gene-wide association studies and next generation sequencing analyses have identified molecular patterns and transcriptome profiles with prognostic relevance, therapeutic opportunities remain limited. Among the genes that are upregulated in pancreatic ductal adenocarcinomas (PDAC), the leukaemia inhibitory factor (LIF), a cytokine belonging to IL-6 family, has emerged as potential therapeutic candidate. LIF is aberrantly secreted by tumour cells and promotes tumour progression in pancreatic and other solid tumours through aberrant activation of the LIF receptor (LIFR) and downstream signalling that involves the JAK1/STAT3 pathway. Since there are no LIFR antagonists available for clinical use, we developed an in silico strategy to identify potential LIFR antagonists and drug repositioning with regard to LIFR antagonists. The results of these studies allowed the identification of mifepristone, a progesterone/glucocorticoid antagonist, clinically used in medical abortion, as a potent LIFR antagonist. Computational studies revealed that mifepristone binding partially overlapped the LIFR binding site. LIF and LIFR are expressed by human PDAC tissues and PDAC cell lines, including MIA-PaCa-2 and PANC-1 cells. Exposure of these cell lines to mifepristone reverses cell proliferation, migration and epithelial mesenchymal transition induced by LIF in a concentration-dependent manner. Mifepristone inhibits LIFR signalling and reverses STAT3 phosphorylation induced by LIF. Together, these data support the repositioning of mifepristone as a potential therapeutic agent in the treatment of PDAC.

The approval of larotrectinib and entrectinib for cancer patients harboring an NTRK gene fusion has represented a milestone in the era of “histology-agnostic” drugs. Among the clinical trials that led to the approval of these two drugs, most of the enrolled patients were affected by soft tissue sarcomas, lung, and salivary gland cancer. However, as next-generation sequencing assays are increasingly available in the clinical setting, health care professionals may be able to detect NTRK gene fusions in patients affected by tumor types under or not represented in the clinical trials. To this aim, we systematically reviewed MEDLINE from its inception to 31 August 2022 for case reports and case series on patients with NTRK gene fusion-positive tumors treated with TRK inhibitors. A virtual cohort of 43 patients was created, excluding those enrolled in the above-mentioned clinical trials. Although our results align with those existing in the literature, various cases of central nervous system tumors were registered in our cohort, confirming the benefit of these agents in this subgroup of patients. Large, multi-institutional registries are needed to provide more information about the efficacy of TRK inhibitors in cancer patients affected by tumor types under or not represented in the clinical trials.