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Accumulation of amyloid in breast cancer is a well‐known phenomenon, but only immunoglobulin light‐chain amyloidosis (AL) or transthyretin (TTR) amyloid had been detected in human breast tumor samples previously. We recently reported that another amyloidogenic peptide, amyloid beta (Aβ), is present in an aggregated form in animal and human high‐grade gliomas and suggested that it originates systemically from the blood, possibly generated by platelets. To study whether breast cancers are also associated with these Aβ peptides and in what form, we used a nude mouse model inoculated with triple‐negative inflammatory breast cancer cell (SUM‐149) xenografts, which develop noticeable tumors. Immunostaining with two types of specific antibodies for Aβ identified the clear presence of Aβ peptides associated with (a) carcinoma cells and (b) extracellular aggregated amyloid (also revealed by Congo red and thioflavin S staining). Aβ peptides, in both cells and in aggregated amyloid, were distributed in clear gradients, with maximum levels near blood vessels. We detected significant presence of amyloid precursor protein (APP) in the walls of blood vessels of tumor samples, as well as in carcinoma cells. Finally, we used ELISA to confirm the presence of elevated levels of mouse‐generated Aβ40 in tumors. We conclude that Aβ in inflammatory breast cancer tumors, at least in a mouse model, is always present and is concentrated near blood vessels. We also discuss here the possible pathways of Aβ accumulation in tumors and whether this phenomenon could represent the specific signature of high‐grade cancers., Aβ (amyloid beta) and it's precursor APP can be observed in tumors formed by mouse xenograft model of human inflammatory breast cancer (IBC). Aβ is present in and around carcinoma cells and is concentrated near blood vessels. We suggest that systemic Aβ from mouse blood and/or vessels (containing amyloid precursor APP) may be, jointly with other amyloidogenic peptides, forming aggregated amyloid in these tumors.

Background The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known. Research Question What diagnostic and staging strategies are most cost-effective for lung cancer? Study Design and Methods A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes. Results For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay. Interpretation The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

The thiopurine prodrugs 6-mercaptopurine and azathioprine are among the world's essential medications for acute lymphoblastic leukemia, immunosuppression and several autoimmune conditions. Thiopurine prodrugs are efficient UVA absorbers and singlet oxygen generators and the long-term treatment with these prodrugs correlates with a high incidence of sunlight-induced skin cancer in patients. In this contribution, we show that the electronic relaxation mechanisms and photochemical properties of azathioprine are remarkably different from those of 6-mercaptopurine upon absorption of UVA radiation. UVA excitation of 6-mercaptopurine results in nearly 100% triplet yield and up to 30% singlet oxygen generation, whereas excitation of azathioprine with UVA leads to triplet yields of 15-3% depending on pH of the aqueous solution and

Background Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. Research Question Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? Study Design and Methods Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell’s C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors’ performances. Results The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P Interpretation EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

Background Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. Research Question Are the HAL and HOMER models valid across multiple centers? Study Design and Methods This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. Results Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was −0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. Interpretation HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.

The purpose of this review is to describe the Southeastern Kidney Transplant Coalition’s mission, vision, goals, and Early Transplant Access Registry as an example of a community/academic collaboration dedicated to improving access to transplantation and reducing inequities in transplant access. The barriers and facilitators to referral and evaluation for kidney transplantation are not necessarily the same as for waitlisting and transplantation. Recent findings suggest that inequities in transplant access are multilevel and multifactorial and require continued community engagement to improve access to kidney transplantation across patients, health systems, and populations. Community-engaged approaches are critical to ensuring that inequities in transplant access — which may vary across regions — are not only described but are addressed in practice in a sustainable manner.

Intraoral fixed appliances remain in the potentially corrosive environment of the mouth for an average of two years. Over time, corrosion causes the release of metal ions, such as nickel and chromium. These metals can become allergenic and cytotoxic, causing different conditions in the human body. The aim of this study therefore is to carry out a systematic review of the available scientific evidence on the accumulation of metal ions, and the genotoxic and cytotoxic effects in oral mucosa cells deriving from short- and long-term exposure to them. The systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome (quantification of metal ion deposits and assessment of their genotoxic and/or cytotoxic effects) and secondary outcome (complementary analysis of cytotoxic and genotoxic effects) were examined. The Cochrane Collaboration tool and Toxicological data Reliability Assessment Tool (ToxRTool) were used for quality assessment. Once the search was performed, a total of seven articles met the inclusion criteria and were included in this study. Two main techniques were used to assess genotoxic effects: alkaline comet assay (6/7) and micronucleus method (1/7). Cytotoxicity was evaluated (4/7) using the trypan blue dye test. Accumulations of nickel (7/7), chromium (5/7), and other metals (zinc, cobalt, iron, manganese, molybdenum, titanium) were also quantified. The results allowed us to conclude that release of metal ions and acute cell and DNA damage in oral mucosa cells takes place in the early stages of treatment. However, more long-term studies are needed to evaluate chronic exposure to metals and DNA damage, as well as cellular capacity to recover DNA integrity.

Current U.S. immigration policies disproportionately impact Mexican-origin mixed-status families, yet few studies examine the consequences of immigration enforcement (e.g., immigration-related arrest and detention) and deportation on sibling dynamics. Given this gap, this study focuses on the experiences and changes within sibling relationships in the aftermath of parental detention and deportation. We analyzed a subsample of 20 citizen children interviews (7 sibling dyads; 2 sibling triads) from a multi-site binational study that examined the psychosocial functioning of U.S. citizen children with undocumented Mexican parents. Using inductive thematic analysis, we explored the roles and functional importance of sibling relationships before and after experiences of parents' detention and deportation. Our findings suggest that prior to detention or deportation experiences, sibling relationships were described as "normal." After these experiences, however, sibling relationships changed and developed protective adaptations, including more open communication about their experiences and the assumption of caregiving roles. In cases where deportation did not occur, there still existed the threat of future immigration-related action, which contributed to fear and an inability to share feelings and experiences among siblings. Our findings suggest that sibling relationships might serve as an important locus of stability and protection. Yet, adaptive communication may not emerge as long as the threat of apprehension, detention, and deportation exists.Las políticas migratorias actuales de los Estados Unidos afectan de manera desproporcionada a las familias de condición migratoria mixta de origen mexicano, sin embargo, pocos estudios analizan las consecuencias de la aplicación de las leyes de inmigración (por ej.: el arresto y la detención relacionados con la inmigración) y la deportación en la dinámica fraternal. Teniendo en cuenta esta falta de datos, el presente estudio se centra en las experiencias y los cambios dentro de las relaciones fraternales después de la detención y la deportación de los padres. Analizamos una submuestra de 20 entrevistas a niños ciudadanos (7 díadas de hermanos; 2 tríadas de hermanos) de un estudio binacional realizado en varios sitios que analizó el funcionamiento psicosocial de niños ciudadanos de los Estados Unidos con padres mexicanos indocumentados. Utilizando el análisis temático inductivo, analizamos los roles y la importancia funcional de las relaciones fraternales antes y después de las experiencias de detención y deportación de los padres. Nuestros resultados indican que, antes de las experiencias de detención o deportación, las relaciones fraternales se describieron como “normales”. Sin embargo, después de estas experiencias, las relaciones fraternales cambiaron y surgieron adaptaciones protectoras, por ejemplo, una comunicación más abierta acerca de sus experiencias y la asunción de roles de cuidado. En los casos donde no hubo deportación, igualmente existió la amenaza de una futura acción relacionada con la inmigración, la cual generó miedo e incapacidad de compartir sentimientos y experiencias entre hermanos. Nuestros resultados sugieren que las relaciones fraternales podrían servir como lugar importante de estabilidad y protección. Sin embargo, es posible que la comunicación adaptativa no surja mientras exista la amenaza de arresto, detención y deportación.

Among adolescents, Latinas are at an increased risk of experiencing suicidal ideation and attempts compared to non-Hispanic, White youth. Previous research indicates that family dynamics are influential as both protective and risk factors. Although significant research has been conducted over the past several decades examining the mother-daughter relationship, few studies have examined the father-daughter relationship among Latina adolescent suicide attempters. The relationship dynamics between fathers and daughters of Latina descent are both similar and unique compared to mother-daughter relationships. Given this, an in-depth analysis is warranted. To address this gap, the present study utilized dyadic thematic analysis to describe father-daughter relationships (N = 10 dyads, 20 individual interviews) and fathers' reactions to their Latina daughters' suicide attempt(s). Three themes emerged from the results (a) dynamic proximity, which describes the variation in emotional and physical closeness between fathers and daughters; (b) father as protector, which describes fathers' roles in protecting or failing to protect their daughters; (c) responses to the suicide attempt, which describes the various ways fathers responded to daughters' suicide attempts, ranging from helpful action to apathy. Themes gleaned from in-depth interviews informed a deeper understanding of these complex, multifaceted relationships, and how they may be linked to fathers' responses to daughters' suicide attempts. Implications for future research and clinical practice with youth at risk for suicidal ideations and behaviors, along with the impact of such experiences on families, are discussed.Entre las adolescentes, las latinas corren un mayor riesgo de tener ideación e intentos suicidas en comparación con las jóvenes blancas no hispanas. Hay investigaciones previas que indican que la dinámica familiar influye tanto como factor protector como de riesgo. Aunque se ha investigado bastante durante las últimas décadas sobre la relación entre madre e hija, en pocos estudios se ha examinado la relación entre padre e hija en adolescentes latinas que han intentado suicidarse. La dinámica de la relación entre padres e hijas de ascendencia latina es tanto similar como única en comparación con la de la relación entre madres e hijas. En virtud de esto, es necesario un análisis profundo. Para subsanar esta carencia, en el presente estudio se utilizó el análisis temático diádico para describir las relaciones entre padres e hijas (N = 10 díadas, 20 entrevistas individuales) y las reacciones de los padres a los intentos de suicidio de sus hijas latinas. De los resultados surgieron tres temas: (a) la proximidad dinámica, que describe la variación en la cercanía emocional y física ente los padres y las hijas; (b) el padre como protector, que describe los roles de los padres a la hora de proteger o no proteger a sus hijas; (c) las respuestas al intento de suicidio, que describe las diversas maneras en las que los padres respondieron a los intentos de suicidio de las hijas, las cuales variaron desde medidas de ayuda hasta apatía. Los temas obtenidos de entrevistas detalladas informaron una mayor comprensión de estas relaciones complejas y multifacéticas, y de cómo pueden vincularse con las respuestas de los padres a los intentos de suicidio de las hijas. Se debaten las consecuencias para futuras investigaciones y para la práctica clínica con las jóvenes en riesgo de ideaciones y conductas suicidas, así como el efecto de dichas experiencias en las familias.在青少年中，与非西班牙裔的白人青年相比，拉美裔青少年的自杀意念和有自杀企图的风险更高。以前的研究表明，家庭动态既是保护因素也是风险因素。尽管在过去的几十年里，对母女关系进行了大量的研究，但很少有研究对拉丁裔青少年中有自杀企图的人群的父女关系进行研究。与母女关系相比，拉丁裔的父亲和女儿之间的关系动态既相似又有独特性。鉴于此，有必要进行深入分析。为了解决这个研究的空白问题，本研究使用了二元主题分析来描述父女关系（N = 10对，20个单独访谈）和父亲对他们的拉丁裔女儿自杀企图的反应。研究结果分析得出了三个主题（a）动态接近，描述了父亲和女儿之间在情感和身体上的亲近程度的变化；（b）作为保护人的父亲，描述了父亲在保护或未能保护女儿方面的角色；（c）对自杀企图的反应，描述了父亲对女儿自杀企图的各种反应，从帮助行动到毫不关心。从深入访谈中收集到的主题使我们对这些复杂的、多方面的关系有了更深入的了解，以及它们如何与父亲对女儿自杀企图的反应相联系。讨论了对未来研究和临床实践的影响，以及对有自杀意念和行为风险的青少年的影响，还有这种经历对家庭的影响。.

Background A multi-user competitive game within the virtual world Second Life for undergraduate radiology learning was adapted for team participation. This study aimed to assess student perception, impact on learning, and eventual correlation of game results with post-exposure tests and course grades. Methods The game consisted of six weekly stages, dedicated to thoracic, abdominal, and musculoskeletal radiological anatomy and semiology. Participants had several days a week to review self-guided radiology educational content and then complete individual multiple-choice tests and solve team tasks to progress through the game's ranking. Additionally, they completed a cognitive load test, a questionnaire about the experience and a post-exposure knowledge test. Results Fifty-two students organised into 13 teams participated in the game and assessed different aspects of the experience with a mean score ≥ 7.8 on a 10-point scale, highlighting the participation of the teacher (9.3 ± 1.1), the educational contents (8.8 ± 1.4) and the usefulness for their education (8.7 ± 1.4). Participants obtained better post-exposure test results (p p Conclusion A multi-user game adapted to team competition to learn radiology in Second Life was very positively perceived by third-year medical students, who highly valued its content, organisation, and usefulness for their training. Most of the participants agreed that they had collaborated as a team and that playing in competitive environments helps them learn better. The best post-exposure and academic results compared to non-participating students indicate the potential impact of the game on learning.

We examined caregiver’s knowledge, attitudes, and concerns about their child’s psychotropic medication regimen and the potential side effects, describe how they seek information regarding treatment, and ascertain their perspectives toward deprescribing. We surveyed 48 caregivers of children 6–17 years old treated with two or more psychotropic medications or an antipsychotic medication, analyzing outcomes using descriptive statistics. Almost all (N = 44, 92%) participants reported feeling very knowledgeable about why medications were prescribed, but only one-third (N = 16, 33%) reported feeling very knowledgeable about potential problems with long-term use or polypharmacy. Half of respondents (N = 24, 50%) reported asking their provider about reducing/stopping medications due to concerns about harmful effects, and nearly half (N = 20, 42%) reported stopping medications earlier than recommended. Interventions to engage caregivers in shared decision-making about complex medication regimens and to support prescribers to safely deprescribe psychotropic medications are needed to address caregivers’ concerns regarding psychotropic medication use.

Background HPV and C.trachomatis are the most prevalent, viral and bacterial STI worldwide. Both commonly have an asymptomatic development and can evolve into a persistent infection which, added to coinfections, may be important cofactors for the oncogenic transformation. Objective Evaluate the prevalence of oral and genital HPV and C.trachomatis infection in women with normal and abnormal cervical cytology. Study design The cross-sectional study included 200 swabs, 100 oral and 100 cervical from 50 women with normal and 50 with abnormal cervical cytology. HPV and C.trachomatis infections were detected using PCR with specific primers. Results HPV DNA was detected in 27% (n = 27/100) of women with normal and abnormal cytology. Out of 100 genital samples we detected HPV DNA in 18% (n = 18/100) and 14% (n = 14/100) out of 100 oral samples. HPV genotypes detected were genotype 6 of low-risk and 16, 31, 52, 58 and 16–31 coinfection of high-risk. C.trachomatis DNA was detected in 49% (n = 49/100) of patients. Out of 100 genital samples we detected C.trachomatis in 35% (n = 35/100) and 31% (n = 31) out of 100 oral samples. There is statistically significant (p C.trachomatis infection but there is no statistically significant between cytology and the other characteristics. Conclusions Since the histology of oral mucosa resembles that of the uterine cervix, we can anticipate the presence of HPV and other STI which are detected in different lesions of genital areas and the oral mucosa. Therefore, is important C.trachomatis detection and specific treatment in asymptomatic women because this infection may increase the risk of HPV persistence and coinfection induces a pro-inflammatory environment that may promote the carcinogenesis.

Background Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. Research Question What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? Study Design and Methods This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%. Results Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P Interpretation When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.

Although there are no convincing evidences of detrimental effect of SARS-CoV2 infection on the cerebellum, the COVID-19 pandemic could impact the life quality of patients with cerebellar ataxias, but few studies have addressed this concern. To assess the motor and mental health changes caused by the COVID-19 pandemics in Cuban patients with cerebellar ataxias, three hundred four patients with cerebellar ataxias and 167 healthy controls were interviewed for risks of exposure to COVID-19, and the self-perception of the pandemics’ impact on the disease progression and on the mental health. All subjects underwent the Hospital Anxiety and Depression Scale. The patients reported low exposition to SARS-CoV2 infection, but one case was confirmed with a mild COVID-19. Overall, depressive and anxiety symptoms were significantly and marginally increased in patients, respectively, with higher scores in cases with severe and moderate ataxia. Positive patient’s impression of psychopathological changes was associated to increased age, age at onset, and anxiety. Sixty-seven patients had a positive self-perception of ataxia progression, which was mainly influenced by higher anxiety scores but not by the adherence to at-home exercise programs. However, the practice of physical exercise was related with lower depression and anxiety scores, but this therapeutical effect was not significantly influenced by the disease stage. We demonstrated the negative effect of the COVID-19 pandemic on the mental and motor deficits in Cuban patients with cerebellar ataxias and the positive effect of the at-home physical exercise programs on their mental well-being. These findings give rationales to develop tele-medicine approaches to minimize these health impacts and to study the long-term effects of such sequelae and accordingly define their treatments.

A strain of Alcaligenes faecalis A12C (A. faecalis A12C) isolated from Argyrosomus regius is a probiotic in fish. Previous experiments showed that A. faecalis A12C had inhibitory effects on the growth of multidrug-resistant bacteria. We aimed to confirm whether A. faecalis A12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis. We used 30 male rats, randomly divided into 6 groups (n = 5): three groups (HA7, HA15, HA30) received A. faecalis A12C in drinking water (6 × 108 CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival after A. faecalis A12C administration was 100% in all groups. Mild eosinophilia (1.5%, p p E. coli decline in faeces, parallel to an increase in A. faecalis A12C at 7 days. E. coli had a tendency to recover initial values, while A. faecalis A12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated with A. faecalis A12C before E. coli intra-abdominal inoculation, and IC group inoculated with no A. faecalis A12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest that A. faecalis A12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.

OBJECTIVES Bipolar disorder (BP) is commonly researched in digital settings. As a result, standardized digital tools are needed to measure mood. We sought to validate a new survey that is brief, validated in digital form, and able to separately measure manic and depressive severity. METHODS We introduce a 6-item digital survey, called digiBP, for measuring mood in BP. It has three depressive items (depressed mood, fidgeting, fatigue), two manic items (increased energy, rapid speech), and one mixed item (irritability); and recovers two scores (m and d) to measure manic and depressive severity. In a secondary analysis of individuals with BP who monitored their symptoms over 6 weeks (n = 43), we perform a series of analyses to validate the digiBP survey internally, externally, and as a longitudinal measure. RESULTS We first verify a conceptual model for the survey in which items load onto two factors ("manic" and "depressive"). We then show weekly averages of m and d scores from digiBP can explain significant variation in weekly scores from the Young Mania Rating Scale (R2 = 0.47) and SIGH-D (R2 = 0.58). Lastly, we examine the utility of the survey as a longitudinal measure by predicting an individual's future m and d scores from their past m and d scores. CONCLUSIONS While further validation is warranted in larger, diverse populations, these validation analyses should encourage researchers to consider digiBP for their next digital study of BP.

Coronary flow reserve (CFR) is a well-validated flow-based physiological parameter that has shown value in clinical risk stratification. CFR can be invasively assessed, classically by Doppler and, more recently, by thermodilution with saline boluses (CFRthermo-bolus). Alternatively, continuous thermodilution is a novel operator-independent, highly-reproducible technique to invasively quantify maximum absolute coronary flow (AF). This study aimed to assess the feasibility of this method to quantify resting AF and to determine CFR (CFRThermo-infusion) as compared with CFRthermo-bolus. Sixty-two consecutive patients with suspicion of coronary disease and absence of significant epicardial lesions were prospectively investigated. AF at maximal hyperemia (20 mL/min) and at lower infusion rates (6-8-10-12 mL/min) were systematically measured using a dedicated catheter and a temperature/pressure guidewire. The absence of baseline Pd/Pa decrease at 6 (0.15 ± 0.2%), 8 (0.17 ± 0.18%) and 10 mL/min (0.2 ± 0.12%) demonstrated absence of hyperemia at ≤10 mL/min (all p = NS). However, at 12 mL/min hyperemia was confirmed by a significant decrease in Pd/Pa (1.3 ± 1.5%, p

Pulmonary arterial hypertension (PAH) is an uncommon but lethal and progressive disease in which prostacyclin, nitric oxide and endothelin-1 pathways are disturbed and contribute to the pathophysiology of this disease. Endothelin receptor antagonists are a class of drugs that have been approved as PAH therapy. Macitentan is a lipophilic, tissue specific, dual receptor antagonist with a higher potency than bosentan and a reduced risk of hepatic injury. Macitentan has shown a reduction in morbidity and mortality due to PAH at long-term follow-up and improvements in hemodynamics, exercise capacity and functional class at the short term. Its main adverse events are nasopharyngitis, bronchitis and an increased risk of anemia. We review the clinical data of macitentan and its use in PAH.

Physical agents are a form of energy that have the ability to interfere with matter, and are used in the process of rehabilitation, among them we can find the use of water, heat, cold, sound, electrical currents, and electromagnetic radiation. The main objective of this study is to analyze if is beneficial the use of physical agents in the intervention and interaction with pediatric patients (0 to 17 years). Material and methods: An extensive search of bibliographic material in Google Academic, Medigraphic, Physiotherapy Evidence Database (PEDro), Pubmed, was conducted between July 6 and October 30, 2020, with the limits: studies in pediatric patients, written in Spanish and English, which were of the type: systematic reviews, controlled and randomized studies, and practice guidelines. Results: Of the 1860 studies analyzed, only 45 could be added for this research since they met the inclusion criteria. The initial hypothesis could be tested: physical agents are effective in the treatment of pediatric patients, however it is considered that more research is needed in this area.

Although acute myeloid leukemia (AML) with NPM1 mut /FLT3-ITDneg is a low-risk entity, its relapse rate remains high. Out of 333 AML patients, 27 were NPM1 mut, and were analyzed in greater detail in order to find associations between clinical and molecular features and cumulative incidence of relapse. Next-generation sequencing (NGS) was performed on diagnosis and remission samples using two capture-based panels. The presence of the FLT3 D835 variant at diagnosis and a qPCR value of NPM1 mut ≥0.1% after induction chemotherapy were associated with an increased probability of relapse, especially if both conditions are present together. By contrast, patients in which the main clone found at diagnosis harbored NPM1 variant had a lower risk of relapse. Nineteen of the 85 variants found at diagnosis were detected by NGS in remission. AML Subgroup with NPM1 mut/FLT3-ITDneg is a heterogeneous entity, which can be further risk-stratified based on molecular biomarkers.

La biodiversidad y el binomio salud-enfermedad tienen una relación triangular. El ser humano está acabando con la estabilidad de este triángulo, que mantiene la vida como la conocemos; a causa del aumento de la población y sus actividades que modifican los ecosistemas para satisfacer las crecientes demandas de alimentos, agua dulce, fibra, madera y combustible, entre otras necesidades. Teniendo en consecuencia cambios de uso de suelo, fragmentación y perdida de hábitat, que favorecen el contacto entre personas, animales domésticos y silvestres; lo que incrementa el riesgo en la transmisión de enfermedades infecciosas, tanto emergentes como reemergentes. El mantenimiento de la biodiversidad representa una potencial solución ante la presencia de enfermedades, porque permite la regulación y amortiguamiento de las mismas. El descontrol de estas enfermedades lleva a presentar grandes pandemias, que además son zoonóticas. Entre ellas la peste negra, leptospirosis, dengue, ébola, chikungunya, COVID-19 y hasta la gripe común. Todas estas enfermedades tienen un factor común, que es la alteración del hábitat o condición ambiental ocasionado por causas antrópicas.

Automatic control of physiological variables is one of the most active areas in biomedical engineering. This paper is centered in the prediction of the analgesic variables evolution in patients undergoing surgery. The proposal is based on the use of hybrid intelligent modelling methods. The study considers the Analgesia Nociception Index (ANI) to assess the pain in the patient and remifentanil as intravenous analgesic. The model proposed is able to make a one-step-ahead prediction of the remifentanil dose corresponding to the current state of the patient. The input information is the previous remifentanil dose, the ANI variable and the electromyogram signal. Modelling techniques used are Artificial Neural Networks and Support Vector machines for Regression combined with clustering methods. Both training and validation were done with a real dataset from different patients. Results obtained show the potential of this methodology to calculate the drug dose corresponding to a given analgesic state of the patient.

Background The COVID-19 pandemic has affected medical practice in fields not related to the infection. Neurogastroenterology is a subspecialty of gastroenterology focused on motility and functional gastrointestinal disorders, including consultations, and conducting procedures (eg, endoscopies, manometries/pH-monitoring). Aim The aim of this study was to determine the impact of COVID-19 on Neurogastroenterology in Latin America. Methods Members of the Latin American Society of Neurogastroenterology were invited by e-mail and social networks to participate in an online anonymous survey. It included 24 questions on demographics, clinical practice and procedure characteristics, impact of the pandemic, Telemedicine, and involvement in COVID-19 patient care. Results Sixty-one members mainly from Colombia, Mexico, and Brazil answered the survey. All reported a negative impact on their practice (88.6%: a 61% to 100% decrease), mainly in office consultations and elective endoscopies. Interestingly, emergency endoscopies decreased by 33.3%, while only 4% stopped performing manometries/pH-monitoring. The main reasons were patients' fear for consulting, country's lockdown, and physician's decision to prevent infection spread. Telemedicine was implemented by 83% but only 64.7% were being remunerated. Almost 46% had to reduce salaries and working hours of their personnel. Fifty-nine percent had colleagues diagnosed with COVID-19, 24.6% were involved in these patients' care, and 11.5% were mobilized to COVID-19 wards. There were country differences: Colombia, lockdown (P=0.001); Mexico, COVID-19 patient-care (P=0.053); Mexico/Colombia, working in COVID-19 wards, (P=0.012); Brazil, less common elective procedures' ban (P=0.012) and Telemedicine/reimbursement (P=0.034). Conclusions The COVID-19 pandemic has negatively impacted the practice and wellness of Neurogastroenterologists in Latin America. Guidelines to resume activities and policies for Telemedicine practice and reimbursement are warranted.