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Abstract Kindlin-2 is a cytoskeletal adapter protein that is present in many different cell types. By virtue of its interaction with multiple binding partners, Kindlin-2 intercalates into numerous signaling pathways and cytoskeletal nodes. A specific interaction of Kindlin-2 that is of paramount importance in many cellular responses is its direct binding to the cytoplasmic tails of integrins, an interaction that controls many of the adhesive, migratory and signaling responses mediated by members of the integrin family of cell-surface heterodimers. Kindlin-2 is highly expressed in many cancers and is particularly prominent in prostate cancer cells. CRISPR/cas9 was used as a primary approach to knockout expression of Kindlin-2 in both androgen-independent and dependent prostate cancer cell lines, and the effects of Kindlin-2 suppression on oncogenic properties of these prostate cancer cell lines was examined. Adhesion to extracellular matrix proteins was markedly blunted, consistent with the control of integrin function by Kindlin-2. Migration across matrices was also affected. Anchorage independent growth was markedly suppressed. These observations indicate that Kindlin-2 regulates hallmark features of prostate cancer cells. In androgen expressing cells, testosterone-stimulated adhesion was Kindlin-2-dependent. Furthermore, tumor growth of a prostate cancer cell line lacking Kindlin-2 and implanted into the prostate gland of immunocompromised mice was markedly blunted and was associated with suppression of angiogenesis in the developing tumor. These results establish a key role of Kindlin-2 in prostate cancer progression and suggest that Kindlin-2 represents an interesting therapeutic target for treatment of prostate cancer.

Summary: Background: Globally, fall-related injuries are a substantial problem, and 80% of fatal falls occur in low-income and middle-income countries. We aimed to measure time from injury to hip-fracture surgery in people aged 50 years or older living in low-income and middle-income regions, as well as to measure the proportion of patients with surgical stabilisation of their hip fracture within 72 h of admission to hospital and to identify risk factors associated with surgical delay. Methods: For this secondary analysis, we analysed data collected from Africa, Latin America, China, India, and Asia (excluding China and India) for the International Orthopaedic Multicentre Study in Fracture Care (INORMUS) between March 29, 2014, and June 15, 2022. Patients from INORMUS were included in this analysis if they were aged 50 years or older and had an isolated, primary hip fracture sustained from a ground-level fall. Staff at participating hospitals identified patients with musculoskeletal injury and referred them for assessment of eligibility. We report time from injury to surgery as three distinct time periods: time from injury to hospital admission, time from admission to surgery, and a total time from injury to surgery. Date and time of injury were self-reported by patients at the time of study recruitment. If time to hospital admission after injury exceeded 24 h, patients reported the primary reason for delayed admission. Reasons for surgery, no surgery, and surgical delay were reported by the treating team. For patients undergoing surgery, multivariable regression analyses were used to identify risk factors for surgical delay. Findings: 4486 adults aged 50 years or older with an isolated, primary hip fracture were enrolled in INORMUS from 55 hospitals in 24 countries. Countries were grouped into five regions: Africa (418 [9·3%] of 4486), Latin America (558 [12·4%]), China (1680 [37·4%]), India (1059 [23·6%]) and Asia (excluding China and India; 771 [17·2%]). Of 4486 patients, 3805 (84·8%) received surgery. The rate of surgery was similar in all regions except in Africa, where only 193 (46·3%) of 418 patients had surgery. Overall, 2791 (62·2%) of 4486 patients were admitted to hospital within 24 h of injury. However, 1019 (22·7%) of 4486 patients had delayed hospital admission of 72 h or more from injury. The two most common reasons for delayed admission of more than 24 h were transfer from another hospital (522 [36·2%] of 1441) and delayed care-seeking because patients thought the injury would heal on its own (480 [33·3%]). Once admitted to hospital, 1451 (38·1%) of 3805 patients who received surgery did so within 72 h (median 4·0 days [IQR 1·7–6·0]). Regional variation was seen in the proportion of patients receiving surgery within 72 h of hospital admission (92 [17·9%] of 514 in Latin America, 53 [27·5%] of 193 in Africa, 454 [30·9%] of 1471 in China, 318 [44·4%] of 716 in Asia [excluding China and India], and 534 [58·6%] of 911 in India). Of all 3805 patients who received operative treatment, 2353 (61·8%) waited 72 h or more from hospital admission. From time of injury, the proportion of patients who were surgically stabilised within 72 h was 889 (23·4%) of 3805 (50 [9·7%] of 517 in Latin America, 31 [16·1%] of 193 in Africa, 277 [18·8%] of 1471 in China, 189 [26·4%] of 716 in Asia [excluding China and India], and 342 [37·5%] of 911 in India). Interpretation: Access to surgery within 72 h of hospital admission was poor, with factors that affected time to surgery varying by region. Data are necessary to understand existing pathways of hip-fracture care to inform the local development of quality-improvement initiatives. Funding: The National Health and Medical Research Council of Australia, the Canadian Institutes of Health Research, McMaster Surgical Associates, Hamilton Health Sciences, and the US National Institutes of Health.

Introduction: TNFα-inducible matrix metalloproteinases play a critical role in the process of airway remodeling in respiratory inflammatory disease including asthma. The cationic host defense peptide LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBECs). Methods: We used a slow off-rate modified aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα. Abundance of selected protein candidates and signaling intermediates was examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR. Results: Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by ≥2-fold compared to unstimulated cells, in response to TNFα. MMP9 was the topmost increased protein in response to TNFα, enhanced by ∼10-fold, and MMP13 was increased by ∼3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNFα-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNFα-mediated MMP9 and MMP13 production is controlled by SRC kinase and that LL-37 enhances related upstream negative regulators, namely, phospho-AKT (T308) and TNFα-mediated TNFAIP3 or A20. Conclusions: The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.

El diagnóstico de Cardiomiopatía Cirrótica está basado en la presencia de cirrosis hepática avanzada con alteraciones de la función cardíaca sin cardiopatía pre-existente, pero en gran parte de su evolución natural ésta es subclínica. Por ello son imprescindibles los estudios complementarios no invasivos para confirmar el diagnóstico y su rol pronóstico en pacientes con o sin trasplante hepático. En esta segunda parte revisamos los métodos de diagnóstico desde el ECG hasta las imágenes de resonancia magnética cardíaca.

Introduction As the rate of obesity increases, so does the incidence of obesity-related comorbidities. Metabolic and bariatric surgery (MBS) is the most effective treatment for obesity, yet this treatment is severely underused. MBS can improve, resolve, and prevent the development of obesity-related comorbidities; this improvement in health also results in lower healthcare costs. The studies that have examined these outcomes are often limited by small sample sizes, reliance on outdated data, inconsistent definitions of outcomes, and the use of simulated data. Using recent real-world data, we will identify characteristics of individuals who qualify for MBS but have not had MBS and address the gaps in knowledge around the impact of MBS on health outcomes and healthcare costs.Methods and analysis Using a large US employer-based retrospective claims database (Merative), we will identify all obese adults (21+) who have had a primary MBS from 2016 to 2021 and compare their characteristics and outcomes with obese adults who did not have an MBS from 2016 to 2021. Baseline demographics, health outcomes, and costs will be examined in the year before the index date, remission and new-onset comorbidities, and healthcare costs will be examined at 1 and 3 years after the index date.Ethics and dissemination As this was an observational study of deidentified patients in the Merative database, Institutional Review Board approval and consent were exempt (in accordance with the Health Insurance Portability and Accountability Act Privacy Rule). An IRB exemption was approved by the wcg IRB (#13931684). Knowledge dissemination will include presenting results at national and international conferences, sharing findings with specialty societies, and publishing results in peer-reviewed journals. All data management and analytic code will be made available publicly to enable others to leverage our methods to verify and extend our findings.

AbstractObjectives Patients often search for health-related information on the internet allthough this trend may have some benefits, it also has some risks, such as misinformation. The aim of this study is to evaluate how Internet information seeking affect the level of anxiety in patients with endometriosis.Materials and methods This prospective observational study was conducted at our outpatient clinic between March 2019 and December 2020. We enrolled We enrolled all patients with a confirmed sonographic diagnosis of endometriosis who had sought information about the disease prior to our visit. We divided them into two groups based on the source of information (Internet only vs multiple sources). Before the visit, we asked women to fill-in validated questionnaires about anxiety, such as the Generalized Anxiety Disorder-7 (GAD) and the Spielberg State Trait Anxiety Inventory (STAI- Y6) and the Endometriosis Health Profile (EHP) − 5. After the visit, the STAI-Y6 was resubmitted to each woman.Results We enrolled 200 women who filled-in the questionnaires: 46 reported the Internet as the only source of information, 52 sought information also from medically qualified sources, 74 consulted only healthcare professionals, and 28 resorted to medical journals. Women who used the Internet as their exclusive source of information were younger on average and their STAI-Y6 score after the visit was significantly lower compared to other group (34.1 ± 11.5 vs 42.1 ± 14.7, p = .001). Moreover, the difference between the STAI-Y6 scores before and after our assessment was higher in these women (-18.3 ± 14.7 vs −10.3 ± 16.5, p = .003).Conclusions Women who sought information online were younger, had lower levels of state trait anxiety after our medical evaluation, and a had a greater reduction in anxiety levels after our examination compared to women who consulted other sources to learn more about endometriosis.KEY MESSAGESWomen using only Internet are younger than those who use other sources of information.Women who researched symptoms online showed higher pre-examination anxiety levels.Patients with severe pain symptoms consulted both the internet and professionals.

Abstract Background The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC beta-lactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed. Findings Klebsiella pneumoniae carbapenemase (KPC) was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test. Conclusions This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.

Abstract This study aims to develop poly lactic-co-glycolic acid (PLGA) nanoparticles with an innovative imaging-guided approach based on Boron Neutron Capture Therapy for the treatment of mesothelioma. The herein-reported results demonstrate that PLGA nanoparticles incorporating oligo-histidine chains and the dual Gd/B theranostic agent AT101 can successfully be exploited to deliver a therapeutic dose of boron to mesothelioma cells, significantly higher than in healthy mesothelial cells as assessed by ICP-MS and MRI. The selective release is pH responsive taking advantage of the slightly acidic pH of the tumour extracellular environment and triggered by the protonation of imidazole groups of histidine. After irradiation with thermal neutrons, tumoral and healthy cells survival and clonogenic ability were evaluated. Obtained results appear very promising, providing patients affected by this rare disease with an improved therapeutic option, exploiting PLGA nanoparticles.

Enteric fistulas are a common problem in gastrointestinal tract surgery and remain associated with significant mortality rates, due to complications such as sepsis, malnutrition, and electrolyte imbalance. The increasingly widespread use of open abdomen techniques for the initial treatment of abdominal sepsis and trauma has led to the observation of so-called entero-atmospheric fistulas. Because of their clinical complexity, the proper management of enteric fistula requires a multidisciplinary team. The main goal of the treatment is the closure of enteric fistula, but also mortality reduction and improvement of patients’ quality of life are fundamental. Successful management of patients with enteric fistula requires the establishment of controlled drainage, management of sepsis, prevention of fluid and electrolyte depletion, protection of the skin, and provision of adequate nutrition. Many of these fistulas will heal spontaneously within 4 to 6 weeks of conservative management. If closure is not accomplished after this time point, surgery is indicated. Despite advances in perioperative care and nutritional support, the mortality remains in the range of 15 to 30%. In more recent years, the use of negative pressure wound therapy for the resolution of enteric fistulas improved the outcomes, so patients can be successfully treated with a non-operative approach. In this review, our intent is to highlight the most important aspects of negative pressure wound therapy in the treatment of patients with enterocutaneous or entero-atmospheric fistulas.

Aim: The aim of the present study was to analyze retrospectively the results of patients who underwent early-staged, i.e., within 24–48 h, carotid artery stenting (e-s CAS) before coronary artery bypass grafting (CABG). Methods: Between December 2014 and December 2022, 1046 consecutive patients underwent CABG; 31 of these patients (3%) were subjected to e-s CAS prior to CABG (e-s CAS + CABG group). Preoperative and intraoperative variables and early and mid-term results of the e-s CAS + CABG group were compared with those of patients who underwent isolated CABG (CABG group). Results: As compared with the CABG group, the e-s CAS + CABG group showed a worse clinical risk profile due to higher Euroscore-2 values and incidence of obstructive pulmonary disease and bilateral carotid artery and peripheral artery diseases (p < 0.05, for all comparisons). The combined end point of operative mortality, periprocedural myocardial infarction, and stroke was 3.2% (0%/0%/3.2%) in the e-s CAS + CABG group vs. 5.9% (2.2%/2.8%/0.9%) in the CABG group (p > 0.5, for all measurements). At 5 years, actuarial survival was 74% ± 16% in the e-s CAS + CABG group vs. 93% ± 4.0% in the CABG group, freedom from cardiac death was 100% vs. 98% ± 1.0% (p = 0.6), and freedom from MACCEs was 85% ± 15% vs. 97% ± 2.5% (p > 0.1, for all comparisons). Independent predictors of all-causes death were advanced age at the operation (p < 0.0001), a lower value for left ventricular ejection fraction (p = 0.05), and a high Euroscore-2 (p = 0.04). Conclusions: CABG preceded by e-s CAS appears to be associated with satisfactory early outcomes while limiting the risk of myocardial infarction to a very short time interval between the two procedures. Freedom from late all-causes death, cardiac death, and MACCEs were comparable and equally satisfactory, underscoring the positive protective effects of CAS and CABG on the carotid and coronary territories over time.

El objetivo de esta reflexión es destacar el papel estratégico de la agroecológica para guiar al mundo hacia una transición de agricultura resiliente, biodiversa y productiva, capaz de producir local y regionalmente suficiente cantidad de alimentos sanos y accesibles para toda la humanidad a pesar de las múltiples crisis que afectan al planeta. Incluso antes del conflicto armado entre Rusia y Ucrania, la economía mundial sufría las repercusiones de varias crisis: climática, COVID-19 y el aumento de los costos de insumos y alimentos, con consecuencias devastadoras para las personas pobres de los países de bajos ingresos. La guerra en Ucrania, un país "granero" para el mundo, está profundizando estos desafíos en una escala sin precedentes. No hay duda de que el sistema alimentario mundial actual necesita una reforma profunda masiva. Está siendo desgarrado por la desigualdad, el hambre, la destrucción ambiental, la crisis climática, los abusos a los derechos humanos y de los trabajadores. La agroecología presenta una alternativa viable, incluyendo una verdadera reforma agraria que asegure que los derechos de uso y manejo de las tierras, los territorios, el agua, las semillas, y la agrobiodiversidad estén en manos de los y las campesinas quienes producen los alimentos y no del sector empresarial. Como alternativa viable al sistema alimentario industrial, la agroecología provee principios y prácticas para apoyar a los pequeños agricultores producir alimentos para sus comunidades y alimentar al mundo de manera sostenible y saludable.

Abstract Biological sex impacts disease prevalence, severity and response to therapy in asthma, however preclinical studies often use only one sex in murine models. Here, we detail sex-related differences in immune responses using a house dust mite (HDM)-challenge model of acute airway inflammation, in adult mice of two different strains (BALB/c and C57BL/6NJ). Female and male mice were challenged (intranasally) with HDM extract (~ 25 μg) for 2 weeks (N = 10 per group). Increase in serum HDM-specific IgE showed a female bias, which was statistically significant in BALB/c mice. We compared naïve and HDM-challenged mice to define immune responses in the lungs by assessing leukocyte accumulation in the bronchoalveolar lavage fluid (BALF), and profiling the abundance of 29 different cytokines in BALF and lung tissue lysates. Our results demonstrate specific sex-related and strain-dependent differences in airway inflammation. For example, HDM-driven accumulation of neutrophils, eosinophils and macrophages were significantly higher in females compared to males, in BALB/c mice. In contrast, HDM-mediated eosinophil accumulation was higher in males compared to females, in C57BL/6NJ mice. Differences in lung cytokine profiles indicated that HDM drives a T-helper (Th)17-biased response with higher IL-17 levels in female BALB/c mice compared to males, whereas female C57BL/6NJ mice elicit a mixed Th1/Th2-skewed response. Male mice of both strains showed higher levels of specific Th2-skewed cytokines, such as IL-21, IL-25 and IL-9, in response to HDM. Overall, this study details sex dimorphism in HDM-mediated airway inflammation in mice, which will be a valuable resource for preclinical studies in allergic airway inflammation and asthma.

Abstract Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, to which it associates; we also show that it promotes NED and anchorage-independent growth, as well as a motile phenotype of PrCa cells. Given our observations that high levels of αVβ3 and, as shown here, of NgR2 are detected in human and mouse NEPrCa, our findings appear to be highly relevant to this aggressive and metastatic subtype of PrCa. This study is novel because NgR2 role has only minimally been investigated in cancer and has instead predominantly been analyzed in neurons. These data thus pave new avenues toward a comprehensive mechanistic understanding of integrin-directed signaling during PrCa progression toward a NE phenotype.

The origin of breast cancer, whether primary or recurrent, is unknown. Here, we show that invasive breast cancer cells exposed to hypoxia release small extracellular vesicles (sEVs) that disrupt the differentiation of normal mammary epithelia, expand stem and luminal progenitor cells, and induce atypical ductal hyperplasia and intraepithelial neoplasia. This was accompanied by systemic immunosuppression with increased myeloid cell release of the alarmin S100A9 and oncogenic traits of epithelial-mesenchymal transition, angiogenesis, and local and disseminated luminal cell invasion in vivo. In the presence of a mammary gland driver oncogene (MMTV-PyMT), hypoxic sEVs accelerated bilateral breast cancer onset and progression. Mechanistically, genetic or pharmacologic targeting of hypoxia-inducible factor-1α (HIF1α) packaged in hypoxic sEVs or homozygous deletion of S100A9 normalized mammary gland differentiation, restored T cell function, and prevented atypical hyperplasia. The transcriptome of sEV-induced mammary gland lesions resembled luminal breast cancer, and detection of HIF1α in plasma circulating sEVs from luminal breast cancer patients correlated with disease recurrence. Therefore, sEV-HIF1α signaling drives both local and systemic mechanisms of mammary gland transformation at high risk for evolution to multifocal breast cancer. This pathway may provide a readily accessible biomarker of luminal breast cancer progression.

Objective To explore the behavioural drivers of fear of litigation among healthcare providers influencing caesarean section (CS) rates.Design Scoping review.Data sources We searched MEDLINE, Scopus and WHO Global Index (1 January 2001 to 9 March 2022).Data extraction and synthesis Data were extracted using a form specifically designed for this review and we conducted content analysis using textual coding for relevant themes. We used the WHO principles for the adoption of a behavioural science perspective in public health developed by the WHO Technical Advisory Group for Behavioural Sciences and Insights to organise and analyse the findings. We used a narrative approach to summarise the findings.Results We screened 2968 citations and 56 were included. Reviewed articles did not use a standard measure of influence of fear of litigation on provider’s behaviour. None of the studies used a clear theoretical framework to discuss the behavioural drivers of fear of litigation. We identified 12 drivers under the three domains of the WHO principles: (1) cognitive drivers: availability bias, ambiguity aversion, relative risk bias, commission bias and loss aversion bias; (2) social and cultural drivers: patient pressure, social norms and blame culture and (3) environmental drivers: legal, insurance, medical and professional, and media. Cognitive biases were the most discussed drivers of fear of litigation, followed by legal environment and patient pressure.Conclusions Despite the lack of consensus on a definition or measurement, we found that fear of litigation as a driver for rising CS rates results from a complex interaction between cognitive, social and environmental drivers. Many of our findings were transferable across geographical and practice settings. Behavioural interventions that consider these drivers are crucial to address the fear of litigation as part of strategies to reduce CS.

(1) Objective: Twenty years’ experience of Bentall–De Bono operations by one surgeon. (2) Methods: From January 2003 to September 2023, four-hundred-and-two patients aged 65.9 ± 15 years underwent a Bentall operation. The EuroScore-2 was 5.0% ± 3.8%. Associated procedures were performed on 113 patients (28.1%). Results: Operative mortality was 1.2% (n = 5), in particular 0.69% (n = 2/289) for isolated Bentall operation, 2.65% (n = 3/113) for combined procedures (p < 0.05). Postoperative acute heart failure occurred in 38 patients (9.45%). Preoperative pulmonary hypertension (44 ± 14 vs. 33 ± 7 mmHg), cardiopulmonary bypass time (169 ± 61 min. vs. 124 ± 42 min.) and aortic cross-clamp time (133 ± 45 min. vs. 107 ± 34 min.) have been recognized as independent predictors of mortality and cardiac complications (p < 0.05). Conclusions: In our experience, the Bentall operation was associated with low operative mortality and low rate of complications. For this reason, in agreement with the patients, we have modified surgical indication for ascending aortic aneurysms and now we think that it is time to change surgical guidelines.

Objective To synthesise the evidence from studies that implemented interventions to increase/reintroduce the use of assisted vaginal births (AVB).Design Systematic review.Eligibility criteria We included experimental, semi-experimental and observational studies that reported any intervention to reintroduce/increase AVB use.Data sources We searched PubMed, EMBASE, CINAHL, LILACS, Scopus, Cochrane, WHO Library, Web of Science, ClinicalTrials.gov and WHO.int/ictrp through September 2021.Risk of bias For trials, we used the Cochrane Effective Practice and Organisation of Care tool; for other designs we used Risk of Bias for Non-Randomised Studies of Interventions.Data extraction and synthesis Due to heterogeneity in interventions, we did not conduct meta-analyses. We present data descriptively, grouping studies according to settings: high-income countries (HICs) or low/middle-income countries (LMICs). We classified direction of intervention effects as (a) statistically significant increase or decrease, (b) no statistically significant change or (c) statistical significance not reported in primary study. We provide qualitative syntheses of the main barriers and enablers for success of the intervention.Results We included 16 studies (10 from LMICs), mostly of low or moderate methodological quality, which described interventions with various components (eg, didactic sessions, simulation, hands-on training, guidelines, audit/feedback). All HICs studies described isolated initiatives to increase AVB use; 9/10 LMIC studies tested initiatives to increase AVB use as part of larger multicomponent interventions to improve maternal/perinatal healthcare. No study assessed women’s views or designed interventions using behavioural theories. Overall, interventions were less successful in LMICs than in HICs. Increase in AVB use was not associated with significant increase in adverse maternal or perinatal outcomes. The main barriers to the successful implementation of the initiatives were related to staff and hospital environment.Conclusions There is insufficient evidence to indicate which intervention, or combination of interventions, is more effective to safely increase AVB use. More research is needed, especially in LMICs, including studies that design interventions taking into account theories of behaviour change.PROSPERO registration number CRD42020215224.

El objetivo de esta reflexión es mostrar cómo se puede utilizar la agroecología en el desarrollo de un nuevo sistema agrícola post-COVID-19 como alternativa de desarrollo sostenible, revitalizando la agricultura campesina creando sistemas alternativos de producción animal y potencializando la agricultura urbana. Un sistema agrícola basado en la agroecología, es capaz de minimizar las futuras interrupciones generalizadas del suministro de alimentos debido a las pandemias y el cambio climático al mejorar los vínculos entre la producción de alimentos a pequeña escala, el consumo local y proporcionar pautas para la reconstrucción de un sistema agrícola posterior a la COVID-19. La agroecología es una estrategia que se centra en lograr la autonomía y la resiliencia, que puede transformar rápidamente las formas en que los pequeños agricultores producen y consumen alimentos al mismo tiempo que abordan los desafíos globales, incluido el cambio climático, la pérdida de biodiversidad, la inseguridad alimentaria, la pobreza y el deterioro de la salud.

Mobile electrocardiogram (ECG) devices are valuable tools for teaching ECG interpretation. The primary purpose of this follow-up study was to determine if an ECG active learning session could be safely and effectively performed during the coronavirus disease 2019 (COVID-19) pandemic using a newly developed mobile 6-lead ECG device. Additionally, we examined the educational impact of these active learning sessions on student knowledge of cardiovascular physiology and the utility of the mobile 6-lead ECG device in a classroom setting. In this study, first-year medical students (MS1) performed four active learning activities using the new mobile 6-lead ECG device. Data were collected from 42 MS1s through a quantitative survey administered in September 2020. Overall, students felt the activity enhanced their understanding of the course material and that the activity was performed safely and in compliance with local COVID-19 guidelines. These results emphasize student preference for hands-on, small group learning activities in spite of the pandemic.

Background: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. Methods: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. Results: 39 patients (M:F = 26:13), with a median age of 64 years (44–83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4–169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46–12.07, p = 0.008 and HR = 13.56, 95%CI 2.45–74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23–38.83, p = 0.002 and HR = 11.88, 95%CI 2.28–61.84, p = 0.003, respectively). Conclusion: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.

During childhood, neuronal modifications occur so that typical childhood communicative development occurs. This work aims to contribute to the understanding of differences in the speech encoding of infants and school-age children by assessing the effects of child development, in different phases of early childhood, on the encoding of speech sounds. There were 98 subjects of both sexes, aged from 1 day to 8 years and 9 months who participated in the study. All subjects underwent a Frequency Following Response (FFR) assessment. A regression and linear correlation showed the effects of age in the FFR components, i.e., significant decrease in the latency and increased amplitude of all FFR waves with age. An increase in the slope measure was also observed. Younger infants require more time and show less robust responses when encoding speech than their older counterparts, which were shown to have more stable and well-organized FFR responses.

Marine ecosystems are structured by coexisting species occurring in adjacent or nested assemblages. Mangroves and corals are typically observed in adjacent assemblages (i.e., mangrove forests and coral reefs) but are increasingly reported in nested mangrove-coral assemblages with corals living within mangrove habitats. Here we define these nested assemblages as "coexisting mangrove-coral" (CMC) habitats and review the scientific literature to date to formalize a baseline understanding of these ecosystems and create a foundation for future studies. We identify 130 species of corals living within mangrove habitats across 12 locations spanning the Caribbean Sea, Red Sea, Indian Ocean, and South Pacific. We then provide the first description, to our knowledge, of a canopy CMC habitat type located in Bocas del Toro, Panama. This canopy CMC habitat is one of the most coral rich CMC habitats reported in the world, with 34 species of corals growing on and/or among submerged red mangrove aerial roots. Based on our literature review and field data, we identify biotic and abiotic characteristics common to CMC systems to create a classification framework of CMC habitat categories: (1) Lagoon, (2) Inlet, (3) Edge, and (4) Canopy. We then use the compiled data to create a GIS model to suggest where additional CMC habitats may occur globally. In a time where many ecosystems are at risk of disappearing, discovery and description of alternative habitats for species of critical concern are of utmost importance for their conservation and management.

NAPRT, the rate-limiting enzyme of the Preiss–Handler NAD biosynthetic pathway, has emerged as a key biomarker for the clinical success of NAMPT inhibitors in cancer treatment. Previous studies found that high protein levels of NAPRT conferred resistance to NAMPT inhibition in several tumor types whereas the simultaneous blockade of NAMPT and NAPRT results in marked anti-tumor effects. While research has mainly focused on NAMPT inhibitors, the few available NAPRT inhibitors (NAPRTi) have a low affinity for the enzyme and have been scarcely characterized. In this work, a collection of diverse compounds was screened in silico against the NAPRT structure, and the selected hits were tested through cell-based assays in the NAPRT-proficient OVCAR-5 ovarian cell line and on the recombinant hNAPRT. We found different chemotypes that efficiently inhibit the enzyme in the micromolar range concentration and for which direct engagement with the target was verified by differential scanning fluorimetry. Of note, the therapeutic potential of these compounds was evidenced by a synergistic interaction between the NAMPT inhibitor FK866 and the new NAPRTi in terms of decreasing OVCAR-5 intracellular NAD levels and cell viability. For example, compound IM29 can potentiate the effect of FK866 of more than two-fold in reducing intracellular NAD levels. These results pave the way for the development of a new generation of human NAPRTi with anticancer activity.

OBJECTIVES/GOALS: The purpose of this report is to describe the role of Periodontal Disease (PD) in Coronary Artery Disease (CAD) in a Hispanic country. METHODS/STUDY POPULATION: Literature and Puerto Rican experience was reviewed and will be discussed. RESULTS/ANTICIPATED RESULTS: PD produces inflammatory disease by bacterial infection in the gingiva. This factor PD activates an inflammatory process affecting the CAD cascade inducing myocites, endothelial cells activation and cytokines. The incidence of gingival disease in the Puerto Rican population (P) is around 50%; of this group 80% will develop periodontal disease. Including this factor and diabetes mellitus Type 2, still the incidence of CAD is 20-30% less than the U.S.A. DISCUSSION/SIGNIFICANCE OF IMPACT : CAD is a systemic disease related to genetic factors and inflammation. PD is related to an inflammatory process, which will activate the CAD process, producing tissue infarcts. The daily use of resolving or liquid Omega 3 in the gingival tissue is useful in the prevention of gingival and periodontal disease. CONFLICT OF INTEREST DESCRIPTION: All authors have no relationship with any industry or financial associations in connection with the submitted abstract.