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The research had the purpose of demonstrating that the use of virtual playful tools and mathematical logical thinking in EGB students of the "Bachillero" Educational Unit. In this sense, a quantitative approach was proposed in order to generate statistics through the results obtained with respect to the declared variables. At the level of results, it is evident that there is significant learning when using the PhET simulator because the student can visualize the exercise three-dimensionally. The opposite occurs when the teacher explains the same exercise on the blackboard. Finally, it is proposed as conclusions that, contrary to the control group, these students achieved significant learning, since the images provided by the PhTE simulator allowed them to visualize the proposed fractional numbers in a three-dimensional way. It is worth mentioning that, with the use of this type of simulator, students also show greater motivation and interest in learning.

We estimate the benefits of the saturated thickness (water-bearing porous material) of the alluvial aquifer in Arkansas through an application of the hedonic price model to the sale of agricultural land. There is evidence from the first-stage analysis of diminishing returns from increasing saturated thickness. Using a survey of farmer operators’ preferences and socioeconomic characteristics, we recover the underlying demand function for saturated thickness in a second-stage analysis. Shifts in the demand function reveal that produced/social capital can be a substitute or a complement to saturated thickness, and human capital is a substitute for saturated thickness.

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients had persistent infections before transplant. Nineteen of them (34%) were 6/6 matched, and 36 (66%) were 5/6 human leukocyte antigen–matched. The OS at 2 years was 91% (95% cumulative incidence, 79-96), with a median follow-up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range, 5-39 days) and 37 days (range, 20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of acute GVHD grades 2-4 on day 100 was 16% (n = 9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients underwent correction of their immune or metabolic defects. We conclude that in the absence of MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with nonmalignant disorders. This trial has been registered at www.clinicaltrials.gov as NCT00950846.

The pioneering design of chimeric antigen receptor (CAR) T-cell therapy demonstrated the potential of reprogramming the immune system. Nonetheless, T-cell exhaustion, toxicity, and suppressive microenvironments limit their efficacy in solid tumors. We previously characterized a subset of tumor-infiltrating CD4+ T cells expressing the FcγRI receptor. Herein, we detail engineering of a receptor, based on the FcγRI structure, allowing T cells to target tumor cells using antibody intermediates. These T cells showed effective and specific cytotoxicity only when an appropriate antibody was added. Only target-bound antibodies activated these cells, while free antibodies were internalized without activation. Their cytotoxic activity was correlated to target protein density, therefore targeting tumor cells with high antigen density while sparing normal cells with low or no expression. This activation mechanism prevented premature exhaustion. Furthermore, during antibody-dependent cytotoxicity these cells secreted attenuated cytokine levels compared with CAR T cells, thereby enhancing their safety profile. These cells eradicated established melanomas, infiltrated the tumor microenvironment, and facilitated host immune cell recruitment in immunocompetent mice. In NOD/SCID gamma mice the cells infiltrate, persist, and eradicate tumors. As opposed to CAR T-cell therapies, which require changing the receptor across different types of cancer, our engineered T cells remain the same across tumor types, while only the injected antibody changes. Overall, we generated a highly flexible T-cell therapy capable of binding a wide range of tumor cells with high affinity, while preserving the cytotoxic specificity only to cells expressing high density of tumor-associated antigens and using a single manufacturing process.

Background: Lesions that involve humeral avulsions of the glenohumeral ligament (HAGLs), although less common, are primary contributors to recurrent events of dislocation and subluxation of the glenohumeral joint. Purpose: To describe the clinical presentation, examination, and surgical outcomes of patients presenting with HAGL lesions who underwent repair using an arthroscopic or open technique. Study Design: Cohort study; Level of evidence, 3. Methods: A multicenter retrospective review of prospectively collected data was performed of skeletally mature patients without glenohumeral arthritis who presented with HAGL lesions and subsequently underwent arthroscopic or open repair between 2005 and 2017. Independent variables included patient characteristics, clinical presentation, physical examination findings, and arthroscopic findings. Dependent variables included pre- and postoperative Single Assessment Numeric Evaluation (SANE) score, Western Ontario Shoulder Instability Index (WOSI) score, and range of motion outcomes. Results: Eighteen patients diagnosed with a HAGL lesion who underwent primary arthroscopic repair (n = 7) or open repair (n = 11) were included. There were 17 male patients and 1 female patient with a mean age of 24.9 years (range, 16-38 years). Mean follow-up duration was 50.9 months (range, 24-160 months). Seventeen patients (94.4%) reported pain as the most common symptom, and 7 (38.9%) reported sensation of instability. Scores significantly improved from pre- to postoperative for the arthroscopic and open groups ( P < .001): SANE (mean ± SD; arthroscopic, 30.7 ± 15.7 to 92.1 ± 12.2; open, 45.5 ± 8.50 to 90.7 ± 5.24) and WOSI (arthroscopic, 51.4 ± 11.4 to 2.49 ± 3.70; open, 45.5 ± 7.37 to 11.5 ± 5.76). The magnitude of improvement in SANE scores was significantly higher for patients treated arthroscopically (Δ60.0; open, Δ46.5; P = .012). Postoperative WOSI scores were also significantly better in the arthroscopic cohort (2.49 ± 3.70; open, 11.5 ± 5.76; P = .00094). Conclusion: Symptomatic HAGL tears present primarily with pain as opposed to instability, necessitating a high index of suspicion for injury. The tears may be treated successfully with an arthroscopic or open technique with significant improvements in patient-reported outcomes and stability.

The growing uptake of electric vehicles (EVs) will likely require management schemes to enable their connection into distribution systems. While most of the existing approaches are developed from the operator's perspective considering EV aggregated demands at the medium-voltage (MV) level, individual users' comfort and the particularities associated with low-voltage (LV) networks need to be considered to holistically assess the EV effects in an integrated MV/LV network. This article proposes a two-level hierarchical optimization framework for the EV charging coordination (EVCC) that maximizes users' satisfaction, while avoiding operational grid issues in the whole distribution system. The framework is tailored for unbalanced distribution systems with high penetration of EVs and introduces a novel index to measure charging priority-based EV user satisfaction. To reduce the computational burden, the EVCC problem is disaggregated into an upper level for MV network operation, and a lower level for LV network and individual EV scheduling, using mixed-integer linear programming models. This framework is later embedded in a dynamic scheduling approach that copes with unexpected EV arrivals. Benefits (increased overall user satisfaction and reduced strain over distribution assets) are demonstrated via case studies in a 459-node three-phase network in which solutions were achieved under a 60-s threshold.

OBJECTIVE The objective of this study was to evaluate spinopelvic sagittal alignment and spinal compensatory changes in adult cervical kyphotic deformity. METHODS A database composed of 13 US spine centers was retrospectively reviewed for adult patients who underwent cervical reconstruction with radiographic evidence of cervical kyphotic deformity: C2–7 sagittal vertical axis > 4 cm, chin-brow vertical angle > 25°, or cervical kyphosis (T1 slope [T1S] cervical lordosis [CL] > 15°) (n = 129). Sagittal parameters were evaluated preoperatively and in the early postoperative window (6 weeks to 6 months postoperatively) and compared with asymptomatic control patients. Adult cervical deformity patients were further stratified by degree of cervical kyphosis (severe kyphosis, C2–T3 Cobb angle ≤ −30°; moderate kyphosis, ≤ 0°; and minimal kyphosis, > 0°) and severity of sagittal malalignment (severe malalignment, sagittal vertical axis T3–S1 ≤ −60 mm; moderate malalignment, ≤ 20 mm; and minimal malalignment > 20 mm). RESULTS Compared with asymptomatic control patients, cervical deformity was associated with increased C0–2 lordosis (32.9° vs 23.6°), T1S (33.5° vs 28.0°), thoracolumbar junction kyphosis (T10–L2 Cobb angle −7.0° vs −1.7°), and pelvic tilt (PT) (19.7° vs 15.9°) (p < 0.01). Cervicothoracic kyphosis was correlated with C0–2 lordosis (R = −0.57, p < 0.01) and lumbar lordosis (LL) (R = −0.20, p = 0.03). Cervical reconstruction resulted in decreased C0–2 lordosis, increased T1S, and increased thoracic and thoracolumbar junction kyphosis (p < 0.01). Patients with severe cervical kyphosis (n = 34) had greater C0–2 lordosis (p < 0.01) and postoperative reduction of C0–2 lordosis (p = 0.02) but no difference in PT. Severe cervical kyphosis was also associated with a greater increase in thoracic and thoracolumbar junction kyphosis postoperatively (p = 0.01). Patients with severe sagittal malalignment (n = 52) had decreased PT (p = 0.01) and increased LL (p < 0.01), as well as a greater postoperative reduction in LL (p < 0.01). CONCLUSIONS Adult cervical deformity is associated with upper cervical hyperlordotic compensation and thoracic hypokyphosis. In the setting of increased kyphotic deformity and sagittal malalignment, thoracolumbar junction kyphosis and lumbar hyperlordosis develop to restore normal center of gravity. There was no consistent compensatory pelvic retroversion or anteversion among the adult cervical deformity patients in this cohort.

Purpose The purpose of this study is to describe the development of the 14-item reflective fostering fidelity rating (RFFR), an observational rating system to evaluate model fidelity of group facilitators in the Reflective Fostering Programme (RFP), a mentalisation-based psychoeducation programme to support foster carers. The authors assess usability, dimensionality, inter-rater reliability and discriminative ability of the RFFR. Design/methodology/approach Eighty video clip extracts documenting 20 RFP sessions were independently rated by four raters using the RFFR. The dimensionality of the RFFR was assessed using principal components analysis. Inter-rater agreement was assessed using the intra-class correlation coefficient. Findings The proportion of missing ratings was low at 2.8%. A single principal component summarised over 90% of the variation in ratings for each rater. The inter-rater reliability of individual item ratings was poor-to-moderate, but a summary score had acceptable inter-rater reliability. The authors present evidence that the RFFR can distinguish RFP sessions that differ in treatment fidelity. Originality/value To the best of the authors’ knowledge, this is the first investigation and report of the RFFR’s validity in assessing the programme fidelity of the RFP. The paper concludes that the RFFR is an appropriate rating measure for treatment fidelity of the RFP and useful for the purposes of both quality control and supervision.

ZusammenfassungDie Verwendung von pflanzlichen Heilmitteln und Nahrungsergänzungsmitteln ist weit verbreitet. In vielen Ländern der Welt weisen die Verkaufszahlen auf eine steigende Beliebtheit dieser Produkte hin. Daher ist die Gewährleistung der Sicherheit von pflanzlichen Produkten eine Priorität der öffentlichen Gesundheit. Dieser Artikel beschreibt die Aufgaben und Ziele des Botanical Safety Consortiums (BSC) – einer öffentlich-privaten Partnerschaft. Diese Partnerschaft ist das Ergebnis einer Absichtserklärung zwischen der Gesundheitsbehörde der USA (FDA), dem National Institute of Environmental Health Sciences (NIEHS, eine Unterabteilung des Ministeriums für Gesundheitspflege und Soziale Dienste der Vereinigten Staaten) und einer gemeinnützigen Organisation, dem Health and Environmental Sciences Institute (HESI). Das BSC dient als globales Forum für Wissenschaftler aus Regierungen, Hochschulen, Gesundheitsfürsorgegruppen, Industrie und gemeinnützigen Organisationen, um gemeinsam an der Anpassung und Integration neuer Ansatzmethoden (NAM) für routinemäßige Sicherheitsbewertungen von Pflanzenstoffen zu arbeiten.Die Ziele des BSC sind: 1) eine weltweite Zusammenarbeit, um existierende Sicherheitstests besser zu nutzen; 2) geeignete Methoden der chemischen Charakterisierung von Pflanzenstoffen festzusetzen; 3) pragmatische, zweckmäßige NAM zu identifizieren, um die Sicherheit von pflanzlichen Inhaltsstoffen und Fertigpräparaten zu bewerten; 4) eine Bewertung dieser Methoden mittels Vergleich mit derzeit verfügbaren Informationen zur Sicherheit von ausgewählten Pflanzenstoffen; 5) und die Integration dieser NAM in ein System, das die Bewertung von Pflanzenstoffen erleichtern kann. Der Schwerpunkt des BSC liegt zunächst auf Phytopharmaka und Nahrungsergänzungsmitteln, welche oral verabreicht werden, jedoch kann dieser Ansatz in zukünftigen Arbeitsphasen erweitert werden. Dieser Artikel beinhaltet einen Überblick über die Struktur, Ziele und Strategien dieser Initiative und erläutert die ersten Ziele, nämlich die Auswahl der Test-Pflanzenstoffe, basierend auf publizierten toxikologischen Daten.

Purpose of Review Myocardial metabolism is intricately linked to cardiac function. Perturbations of cardiac energy metabolism result in an energy-starved heart and the development of contractile dysfunction. In this review, we discuss alterations in myocardial energy supply, transcriptional changes in response to different energy demands, and mitochondrial function in the development of heart failure. Recent Findings Recent studies on substrate modulation through modifying energy substrate supply have shown cardioprotective properties. In addition, large cardiovascular outcome trials of anti-diabetic agents have demonstrated prognostic benefit, suggesting the importance of myocardial metabolism in cardiac function. Summary Understanding molecular and transcriptional controls of cardiac metabolism promises new research avenues for metabolic treatment targets. Future studies assessing the impact of substrate modulation on cardiac energetic status and function will better inform development of metabolic therapies.

We compared rates of sport and physical activity (PA) of transgender and gender diverse adolescents and adolescents questioning their gender (TGDQ) with those of cisgender adolescents. Additionally, we tested for differences in sport and PA among TGDQ youth.We used 2019 Minnesota Student Survey data (N = 125,375). We calculated descriptive statistics, then used chi-squares and one-way analyses of variance to test for differences in involvement in sports, PA lessons, and PA between TGDQ and cisgender adolescents. Then, we used the same tests to compare participation among all TGDQ adolescents, considering their gender identity and sex assigned at birth.Overall, TGDQ adolescents participated in sport and PA less than cisgender adolescents; TGD youth participated less than questioning youth. Within sex assigned at birth, participation varied by gender identity.TGDQ adolescents need support to participate in sport and PA. Adults should remain cognizant that sport restrictions could impair TGDQ adolescents' health.

Is there a role for AMPK in the control of hepatic gluconeogenesis and could targeting AMPK in liver be a viable strategy for treating type 2 diabetes? These are frequently asked questions this review tries to answer. After describing properties of AMPK and different small-molecule AMPK activators, we briefly review the various mechanisms for controlling hepatic glucose production, mainly via gluconeogenesis. The different experimental and genetic models that have been used to draw conclusions about the role of AMPK in the control of liver gluconeogenesis are critically discussed. The effects of several anti-diabetic drugs, particularly metformin, on hepatic gluconeogenesis are also considered. We conclude that the main effect of AMPK activation pertinent to the control of hepatic gluconeogenesis is to antagonize glucagon signalling in the short-term and, in the long-term, to improve insulin sensitivity by reducing hepatic lipid content.

Residents in the Southeast region of the United States are frequently threatened by tornadoes. Previous research indicates that it is important to study the experience of tornado victims to better understand individual risk perception, preparedness, protective action, response, and recovery strategies that contribute to overall community resilience. In this study, we employ an oral-history approach and analyze the lived experience of survivors of an EF3 (on the enhanced Fujita scale) tornado in Jacksonville, Alabama. Using snowball sampling, we conducted in-depth interviews of 25 residents of Jacksonville, Alabama, who experienced the EF3 tornado on 19 March 2018. The recorded interviews were analyzed using qualitative software. Most of the participants described the support system and the range of resources accessible through the network of relations as the critical factors that facilitated recovery and contributed to resilience. The majority also emphasized the importance of being prepared and proactive when addressing future storms, but some of their actions revealed that they were also used to being reactive. The participants were either long-term residents (homeowners) or transient college students (renters), and the data gave insight into different recovery paths and challenges. Further, findings revealed ongoing trauma and recovery challenges due to the extensive, unexpected damage and the lack of temporary housing and contractor availability often associated with small, rural towns. This research aims to provide a scientific basis for improved efforts in preparedness and protective actions as well as in response and recovery strategies in tornado events and for identifying factors of community resilience in tornado-prone areas. Significance Statement Grounded in the narratives and reflections of the participants on their tornado experiences, the oral-history interviews generated important insights into psychological–behavioral responses to a disaster, as well as key building blocks of resilience, adding to the body of research surrounding disaster impact and vulnerability, especially for small, rural towns. The preserved voices, stories, and social memory are expected to benefit current and future generations of the community facing similar threats. The findings of this study will further help to inform better practice of local emergency managers and government officials for promoting public awareness of tornadoes and other weather-related risks so as to be more prepared for future extreme weather events.

Introduction. In patients with drug-resistant temporal lobe epilepsy (TLE), surgical treatment is aimed to resect an epileptogenic zone (EZ) followed by seizure control. Despite complicated EZ location, surgical resection should be considered as a treatment of choice in bilateral TLE. Objective: to evaluate surgical outcomes and factors contributing to outcomes in patients with drug-resistant bilateral TLE confirmed via magnetic resonance imaging. Materials and methods. The study included patients with unilateral (n = 50) and bilateral (n = 50) temporal lobe involvement. The results of surgical treatment were evaluated according to the classification of J. Engel (1993). Results. Favorable outcomes of surgical treatment (Engel I and Engel II) in the group with unilateral temporal lobe involvement were found in 98% of patients after 12 months, in 88% after 24 months, and in 100% after 48 and 60 months after surgery. In the group with bilateral temporal lobe involvement outcomes of surgical treatment were favorable in 41% of patients after 12 months, in 50% after 24 months, in 39% after 48 months, and in 50% of patients after 60 months post-surgery. Conclusion. Early onset, burdened perinatal history, and MRI-confirmed left temporal lobe involvement contribute to the poor outcome (Engel III and Engel IV) in the bilateral TLE group. Engel I outcomes were more common in the patients with unilateral TLE while Engel IIIV outcomes were more common in the patients with bilateral TLE.

This paper analyzes university students' academic performance between the periods before the COVID-19 pandemic and the period of the pandemic. Different scientific materials from the Scopus database are analyzed to recognize the possible factors that could alter school motivation and, consequently, the grade point average. The grades of students in eight subjects are also analyzed. The main results show that it is impossible to establish a single criterion to recognize the reasons that make young people lower their grades. In addition, it was observed that teaching methodologies are essential for improvements in the learning process.

Antibody-drug conjugates (ADCs) delivering pyrrolobenzodiazepine (PBD) DNA crosslinkers are currently being evaluated in clinical trials with encouraging results in Hodgkin and non-Hodgkin lymphomas. The first example of an ADC delivering a PBD DNA crosslinker (loncastuximab tesirine) has been recently approved by the U.S. Food and Drug Administration for the treatment of relapsed and refractory diffuse large B-cell lymphoma. There has also been considerable interest in mono-alkylating PBD analogues. We conducted a head-to-head comparison of a conventional PBD bis-imine and a novel PBD mono-imine. Key Mitsunobu chemistry allowed clean and convenient access to the mono-imine class. Extensive DNA binding studies revealed that the mono-imine mediated a type of DNA interaction that is described as "pseudo-crosslinking," as well as alkylation. The PBD mono-imine ADC demonstrated robust antitumor activity in mice bearing human tumor xenografts at doses threefold higher than those that were efficacious for the PBD bis-imine ADC. A single-dose toxicology study in rats demonstrated that the maximum tolerated dose of the PBD mono-alkylator ADC was approximately threefold higher than that of the ADC bearing a bis-imine payload, suggesting a comparable therapeutic index for this molecule. However, although both ADCs caused myelosuppression, renal toxicity was observed only for the bis-imine after repeated dosing, indicating possible differences in toxicological profiles that could influence tolerability and therapeutic index. These data show that mono-amine PBDs have physicochemical and pharmaco-toxicological properties distinct from their crosslinking analogues and support their potential utility as a novel class of ADC payload.

Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS). Proton MRS allows the assessment of myocardial triglyceride content and creatine concentration. Phosphorous MRS allows noninvasive in vivo quantification of the phosphocreatine-to-adenosine triphosphate ratio, a measure of cardiac energy status that is reduced in patients with severe AS. This review summarizes the changes to cardiac substrate and high-energy phosphorous metabolism and how they affect cardiac function in AS. The authors focus on the role of MRS to assess these metabolic changes, and potentially guide future (cellular) metabolic therapy in AS.

To evaluate 1-year outcomes in active-duty servicemembers who underwent patellar tendon rupture repair and to identify baseline variables associated with return to activity.We performed a retrospective review of all active-duty servicemembers undergoing primary patellar tendon rupture repair between 2009 and 2014. All patients had a minimum 12-month follow-up. Demographic variables were recorded, as well as ability to return to impact activities and remain on active-duty status. Rates of recurrent rupture and revision surgery were identified. Univariate analysis was performed to assess relations between outcomes and baseline variables.A total of 123 patients met the inclusion criteria (average age, 33.5 ± 6.6 years; 99% male patients) with a mean follow-up period of 4.3 ± 2.2 years. Whereas 67.4% of patients returned to running at an average of 8.3 months from index surgery, only 42.4% of patients resumed unrestricted occupational function. Higher rates of return to running were observed among patients with senior military rank (At 1-year follow-up, approximately two-thirds of military servicemembers undergoing primary patellar tendon repair had returned to running after surgery, whereas fewer than one-half returned to full military duty. Younger age and more senior military rank were associated with higher rates of return to running. Additionally, servicemembers of higher rank, particularly officers, had statistically higher rates of return to unrestricted activity.Level IV, therapeutic case series.

Background: Given the popularity of thigh-worn accelerometers, it is important to understand their reliability and validity. Purpose: Our study evaluated laboratory validity and free-living intermonitor reliability of the Fibion monitor and free-living intermonitor reliability of the activPAL monitor. Free-living comparability of the Fibion and activPAL monitors was also assessed. Methods: Nineteen adult participants wore Fibion monitors on both thighs while performing 11 activities in a laboratory setting. Then, participants wore Fibion and activPAL monitors on both thighs for 3 days during waking hours. Accuracy of the Fibion monitor was determined for recognizing lying/sitting, standing, slow walking, fast walking, jogging, and cycling. For the 3-day free-living wear, outputs from the Fibion monitors were compared, with similar analyses conducted for the activPAL monitors. Finally, free-living comparability of the Fibion and activPAL monitors was determined for nonwear, sitting, standing, stepping, and cycling. Results: The Fibion monitor had an overall accuracy of 85%–89%, with high accuracy (94%–100%) for detecting prone and supine lying, sitting, and standing but some misclassification among ambulatory activities and for left-/right-side lying with standing. Intermonitor reliability was similar for the Fibion and activPAL monitors, with best reliability for sitting but poorer reliability for activities performed least often (e.g., cycling). The Fibion and activPAL monitors were not equivalent for most tested metrics. Conclusion: The Fibion monitor appears suitable for assessment of sedentary and nonsedentary waking postures, and the Fibion and activPAL monitors have comparable intermonitor reliability. However, studies using thigh-worn monitors should use the same monitor brand worn on the same leg to optimize reliability.

The acute otitis media (AOM) is a frequent bacterial infection in Pediatrics. Despite the advance of antibiotic therapy in the treatment of this infection, there is the possibility of a rare complication, Gradenigo Syndrome (GS). This is a serious complication that should be suspected in a patient with abducens nerve paralysis, pain in the trigeminal innervation area and AOM. The objective of this work was to describe a case report in pediatric regarding to Gradenigo’s Syndrome and reinforce the importance of early diagnosis in the treatment. In addition, a literature review of articles in journals indexed in the following databases was carried out: Pubmed, Lilacs and Scielo. The case report presented is a 7-year-old girl, presenting a typical clinical of GS that evolved satisfactorily with the management based on broad-spectrum antibiotic therapy, without the need for a subsequent surgical approach. Thus, it is clear that the identification of the classic triad of GS, in addition to performing imaging tests, allows for an early diagnosis of the disease, favoring a conservative approach with antibiotic therapy.

Genetic mutations in breast cancer susceptibility gene 1 or 2 (BRCA1/2) confer a high risk for developing breast cancer; however, at least 50% of women with BRCA1/2 mutations go undiagnosed. This study evaluated differences in patient demographics, clinical characteristics, and BRCA1/2 mutation testing in the USA, European Union (EU4), and Israel in a real-world population of patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC).This study was a retrospective analysis of data from the Adelphi Real World ABC Disease Specific Programme in the USA, EU4, and Israel. Medical oncologists completed a patient record form, which included detailed questions on demographics, clinical assessments and outcomes, and treatment history. Eligible patients were at least 18 years of age and receiving therapy for stage IIIb-IV ABC.Among the 2527 study patients, 407 were from the USA, 1926 were from the EU4, and 194 were from Israel; 86% had hormone receptor-positive (HR+)/HER2- ABC and 14% had triple-negative breast cancer (TNBC). Israeli patients had a higher rate of family history of BRCA-related cancer (69%) compared with patients in the EU4 (18%; p 0.0001) and USA (18%; p 0.0001). Among patients with HR+/HER2- ABC, the BRCA1/2 testing rate was 99% in Israel, 37% in the EU4, and 68% in the USA (p 0.0001 vs Israel and the EU4). The age of tested patients was significantly younger in Israel (56 years) compared with the EU4 (59 years; p = 0.016 vs Israel) and USA (64 years; p 0.0001 vs Israel and the EU4). Among patients with TNBC, the BRCA1/2 testing rate was 100% in Israel, 78% in the EU4 (p 0.0001 vs Israel), and 93% in the USA (p 0.002 vs the EU4). Among tested patients, genetic counseling rates were also higher in Israel (98%) compared with the EU4 (40%; p 0.0001) and USA (38%; p 0.0001).Testing and genetic counseling rates for BRCA1/2 mutations were very high in Israel, potentially due to the high rate of family history of BRCA-related cancer in this population and higher general awareness of genetic testing. In the EU4 and USA, overall rates of testing for BRCA1/2 mutations and genetic counseling were significantly lower compared with Israel. Given the high risk of breast cancer in BRCA1/2 mutation carriers and the efficacy of new therapies in treating ABC with a BRCA1/2 mutation, efforts should be made to improve BRCA1/2 testing rates in Europe and the USA.

En este trabajo de investigación tuvo como objetivo general analizar la normativa penal, en relación con el delito de abigeato y su afectación al sector ganadero de la parroquia Borbón en el periodo 2020.Para realizar lo antes planteado la metodología fue descriptivo y de campo. La población estuvo conformada por diez dueños de fincas de la parroquia antes mencionada. La técnica de recolección de datos fue la observación directa, la encuesta y la revisión documental, el instrumento el cuestionario con preguntas mixtas. Se validó a través del juicio de expertos y el coeficiente de Alfa de Cronbach. Para el análisis de la data se empleó la estadística descriptiva Resultados: la mayoría de los dueños dedican su finca a labores de agricultura y ganadería (70%); un 50% de los dueños de fincas les extrajeron entre una y dos reses por último, el 80% de los entrevistados consideran que las penas en el Código Penal ecuatoriano no corresponden o no están acordes entre el delito y la tipificación, para quienes roben, hurten y trafiquen. Conclusiones: Esta conducta típica, antijurídica y culpable que atenta contra un bien jurídico protegido, siendo este; el derecho a la propiedad y se determinará si la normativa penal vigente en relación con este delito, garantiza efectivamente la protección de los derechos de propiedad de las familias ganaderas.

Aim: To investigate the association of discordance in patient- and physician-reported symptoms on health-related quality of life (HRQoL) in hepatocellular carcinoma (HCC). Patients & methods: Data were drawn from a point-in-time survey of physicians and patients conducted in Germany, Italy and Spain (October 2018 – January 2019). Physicians and their consulting patients independently reported baseline characteristics, symptoms, treatment history and satisfaction, and HRQoL derived using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Results: Of 486 patients analysed, tiredness (73.3%, 73.7%), pain/aches (67.7%, 66.9%) and weight/appetite loss (54.3%, 53.7%) were the most common and concordant patient and physician-reported symptom domains, respectively. The symptom domains showing the largest discordance were reflux/indigestion (14.6%, 5.1%), neurological (11.9%, 5.6%), dermatological (9.3%, 6.2%) symptoms and jaundice (4.7%, 10.3%). Reduced HRQoL was observed with increasing symptom-reporting discordance. Conclusion: Further studies should investigate how symptom-reporting discordance influences patient satisfaction and HRQoL.

Aims We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases. Methods and results In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity–outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively. Conclusions We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity–outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.

BackgroundIdiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complementC4in IIM pathology was unknown.MethodsWe elucidated the gene copy number (GCN) variations of totalC4,C4AandC4B, longandshort genesin 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion.ResultsThe large study populations helped establish the distribution patterns of variousC4GCN groups. Low GCNs ofC4T(C4T=2+3) andC4Adeficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28–2.91), p=5.0×10−53forC4T, and 2.82 (2.48–3.21), p=7.0×10−57forC4Adeficiency. Contingency and regression analyses showed that among patients withC4Adeficiency, the presence ofHLA-DR3became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% hadHLA-DR3with an OR of 11.02 (1.44–84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies.ConclusionsC4Adeficiency is relevant in dermatomyositis,HLA-DRB1*03is important in IBM and bothC4Adeficiency andHLA-DRB1*03contribute interactively to risk of polymyositis.

Universal Design came into prominence as a successor to the Americans with Disabilities Act (ADA), contributing to broader notions of accessibility beyond baseline codes and standards. Rooted in human factors research, Universal Design primarily centers on supporting human performance through the development of accessible and usable environments (Steinfeld and Maisel 2012, 95-96). As such, Universal Design pedagogies predominantly focus on enhancing environments for people with disabilities and aging populations (O Shea 2018, 721; Steinfeld and Maisel 2012, 49). However, some believe Universal Design is on the cusp of a paradigm shift to address broader aspects of social justice (Salmen 2012; Steinfeld and Maisel 2012, 159-160). This paper synthesizes existing literature to explore how current academic and practice-facing Universal Design pedagogies support the movement’s expansion to address social justice across demographic groups. Critical audiences for this work include architectural educators, students, researchers, policymakers, and building professionals interested in advancing the theory and practice of Universal Design. Recommendations from this work reposition Universal Design pedagogies as a pathway for creating more equitable and inclusive buildings, spaces, and communities that are truly designed for all.

BACKGROUND: Research has identified persistent disparities in alcohol, e-cigarette, and marijuana use, by sexual orientation, gender identity, and race/ethnicity. Using an intersectionality framework, the present study analyzes three large datasets to identify intersecting social positions bearing the highest burden of substance use. METHODS: Data from adolescents in grades 9–12 in three samples (2019 Minnesota Student Survey, 2017–2019 California Healthy Kids Survey, and 2017 National Teen Survey) were harmonized for analysis (N=602,470). Chi-square Automatic Interaction Detection analysis compared the prevalence of four types of substance use across all combinations of four social positions (6 racial/ethnic identities, 5 sexual orientations, 3 gender identities, 2 sexes assigned at birth). For each substance, 10 intersectional groups with the highest prevalence of use were examined. RESULTS: In the full sample, 12–14% of participants reported past 30 day alcohol, e-cigarette, or marijuana use, and 7% reported past 30 day binge drinking. Several intersecting marginalized social positions were consistently found to bear a high burden of substance use. For example, transgender and gender diverse (TGD) Latina/x/o young people, particularly those assigned male at birth, were in the high prevalence groups for alcohol use, binge drinking, and marijuana use. Black TGD or gender-questioning youth were commonly in the high prevalence groups. DISCUSSION: Findings suggest that support, resources, and structural changes specifically tailored to youth with multiple marginalized identities (especially TGD) may be needed. The results argue for intersectional efforts that explicitly address racial/ethnic and cultural differences, while also integrating awareness and understanding of sexual and gender diversity.

Como educadores a veces resulta difícil realizar adaptaciones curriculares a las asignaturas para lograr la inclusión de estudiantes con necesidades educativas especiales. En este artículo se reflexiona acerca de los fundamentos teóricos de partida a considerar para el abordaje del tema de las adaptaciones curriculares aplicadas en el aprendizaje del idioma inglés para estudiantes con discapacidad auditiva. Se asume como posición metodológica un enfoque cualitativo con un diseño no experimental y alcance de una investigación exploratoria e interpretativa, basada en la revisión documental. Los resultados más importantes demuestran la falta de capacitación de los docentes en materia de adaptaciones curriculares para atender a niños con necesidades educativas especiales auditivas en el área de inglés, lo cual se evidencia en el grado de incertidumbre frente al hecho de tener que atender a estudiantes con discapacidad auditiva en el aula y al desconocimiento de las metodología para afrontar los requerimientos educativos que demandan dichos estudiantes, es por ello que se deben promover acciones que permitan la formación de los docentes en lo atinente a la realización de modificaciones o adaptaciones curriculares que coadyuven a la promoción de una educación igualitaria e inclusiva.

This scoping review will explore existing literature related to occupational therapy interventions and delivery methods for pediatric Complex Regional Pain Syndrome.Complex Regional Pain Syndrome is a debilitating pain condition that is becoming increasingly diagnosed within the pediatric population. Untreated, it can negatively impact a child's occupational engagement and participation, social functioning, and family dynamics. A multidisciplinary treatment approach is typically recommended, including occupational therapy as an essential component. Occupational therapy interventions for pediatric Complex Regional Pain Syndrome usually promote a child's ability to participate in daily activities to prevent further impairments and disability. Despite evidence that occupational therapy practitioners treat this population, no review has been completed regarding the available literature on occupational therapy interventions for pediatric Complex Regional Pain Syndrome.This review will consider studies in English that include any form of occupational therapy interventions for participants with Complex Regional Pain Syndrome who are 18 years or younger, with no limitations on publication date. Quantitative, qualitative, and observational studies, and text and opinion papers will be considered.JBI methodology will be used to conduct this scoping review. MEDLINE (PubMed), Embase, Scopus, APA PsycINFO (EBSCO), CINAHL (EBSCO), OTDBASE, OT Search (AOTA), OTseeker, and ProQuest Dissertations and Theses Global will be searched, with no limit on publication date. Two independent reviewers will screen the titles, abstracts, and full text of the selected studies. Data collection will be performed with a tool developed by the researchers based on the standardized tool from the JBI System for Unified Meta-Analysis and Review of Information. Data will be presented in a comprehensive narrative summary.

To examine the perceptions of labor and delivery (LD) nurses and childbearing women in the postpartum period regarding a restricted visitor policy during the COVID-19 pandemic.Descriptive mixed-methods survey and open-ended questions.One hospital in the southwestern United States. There is limited evidence regarding recently imposed visitor restrictions related to COVID-19.Individuals who were pregnant and self-identified as women who gave birth during October 2020 through March 2021 (n = 674) and LD nurses (n = 47).Participants who had given birth with visitor restrictions completed an online survey, and LD nurses completed a paper survey.Childbearing women had positive and negative views; they valued a more intimate familial bonding and recovery without visitors and appreciated decreased pressure to accommodate family/friends. They were also disappointed with sibling restrictions and were sad and frustrated with visitor limitations, especially in special circumstances (e.g., NICU admission or extended stays). Nurses expressed that visitor restrictions allowed more time for higher-quality nursing care/patient teaching and decreased distractions in emergencies, leading to safer care. Women and nurses reported that visitor restrictions allowed women more rest and relaxation as well as less worry and strain from juggling family and friends who wanted to visit, but they also identified that there was decreased family support when it was needed.Women's responses were mixed, with some preferring support from many visitors, while others appreciated the intimate focus of just their partner. Most nurses preferred fewer visitors but could empathize with women.

An ideal fixation system for guided bone (GBR) regeneration in oral surgery must fulfil several criteria that includes the provision of adequate mechanical fixation, complete resorption when no longer needed, complete replacement by bone, as well as be biocompatible and have a good clinical manageability. For the first time, a biodegradable magnesium fixation screw made of the magnesium alloy WZM211 with a MgF2 coating has been designed and tested to fulfill these criteria. Adequate mechanical fixation was shown for the magnesium fixation screw in several benchtop tests that directly compared the magnesium fixation screw with an equivalent polymeric resorbable device. Results demonstrated slightly superior mechanical properties of the magnesium device in comparison to the polymeric device even after 4 weeks of degradation. Biocompatibility of the magnesium fixation screw was demonstrated in several in vitro and in vivo tests. Degradation of the magnesium screw was investigated in in vitro and in vivo tests, where it was found that the screw is resorbed slowly and completely after 52 weeks, providing adequate fixation in the early critical healing phase. Overall, the magnesium fixation screw demonstrates all of the key properties required for an ideal fixation screw of membranes used in guided bone regeneration (GBR) surgeries.

Programme de l’année 2021-2022 : Vienne 1880-1900. Histoire culturelle et sociale.