The role of the deep cervical extensor muscles in multi-directional isometric neck strength.

Clinical management of whiplash-associated disorders is challenging and often unsuccessful, with over a third of whiplash injuries progressing to chronic neck pain. Previous imaging studies have identified muscle fat infiltration, indicative of muscle weakness, in the deep cervical extensor muscles (multifidus and semispinalis cervicis). Yet, kinematic and muscle redundancy prevent the direct assessment of individual neck muscle strength, making it difficult to determine the role of these muscles in motor dysfunction. The purpose of this study was to determine the effects of deep cervical extensor muscle weakness on multi-directional neck strength and muscle activation patterns. Maximum isometric forces and associated muscle activation patterns were computed in 25 test directions using a 3-joint, 24-muscle musculoskeletal model of the head and neck. The computational approach accounts for differential torques about the upper and lower cervical spine. To facilitate clinical translation, the test directions were selected based on locations where resistance could realistically be applied to the head during clinical strength assessments. Simulation results reveal that the deep cervical extensor muscles are active and contribute to neck strength in directions with an extension component. Weakness of this muscle group leads to complex compensatory muscle activation patterns characterized primarily by increased activation of the superficial extensors and deep upper cervical flexors, and decreased activation of the deep upper cervical extensors. These results provide a biomechanistic explanation for movement dysfunction that can be used to develop targeted diagnostics and treatments for chronic neck pain in whiplash-associated disorders.

Survival in a pediatric patient with cerebral aspergillosis: A case report.

Aspergillosis is an infrequent infection in the Central Nervous System with a mortality rate higher than 95 %. Early diagnosis is challenging and crucial. In this report, we present the case of a six-year-old female with an intense headache accompanied by left hemiparesis, gaze deviation, horizontal nystagmus, and vomiting of mucous content on five occasions. After several approaches, a cerebrospinal fluid PCR resulted positive for Aspergillus spp., and then management started with amphotericin B at 2.6 mg/kg/day and was managed to have voriconazole. She survived, and two years after her first hospital admission, she suffered from cerebral aspergillosis sequelae. An area of improvement is the coordination between the request and delivery of studies outside the institution. In this case, the patient´s mother did not report the analysis results on time, delaying the diagnosis.

Germline Testing identifies Pathogenic/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors.

10% of pancreatic neuroendocrine tumors (pNETs) are related to inherited syndromes (MEN1, MEN4, VHL, NF1, TSC). Growing evidence suggests that clinically sporadic pNETs can also harbor germline pathogenic variants. In this study, we report the prevalence of pathological/likely pathological germline variants (P/LP) in a high-risk cohort and an unselected cohort. We collected clinical data of patients with pNETs seen at MD Anderson Cancer Center (MDACC) and Johns Hopkins Hospital (JHH). High-risk cohort included (n=132) patients seen at MDACC who underwent germline testing for high-risk criteria (early onset, personal or family history of cancer and syndromic features) between 2013-2019. Unselected cohort (n=106) patients seen at JHH who underwent germline testing following their diagnosis of pNETs between 2020 to 2022. In the high-risk cohort (n=132), 33% (n=44) had P/LP variants. The majority of the patients had P/LP variants in MEN1 56% (n=25), followed by DNA repair pathways 18% (n=8), and 7 %(n=3) in MSH2 (Lynch Syndrome). Patients with P/LP were younger (45 years vs 50 years; p=0.002). In the unselected cohort (n=106), 21% (n=22) had P/LP. The majority were noted in DNA repair pathways 40% (n=9) and MEN1 36% (n=8). Multifocal tumors correlated with the presence of P/LP (p=0.0035). MEN1 germline P/LP variants correlated with younger age (40 vs 56 years) (p=0.0012). presence of multifocal tumors (p<0.0001), and WHO grade 1 histology (p=0.0078). P/LP variants are prevalent in patients with clinically sporadic pNET irrespective of high-risk features. The findings support upfront universal germline testing in all pNET patients.

Dysfunctional latent transforming growth factor ß activation after corneal injury in a classical Ehlers-Danlos model.

Patients with classical Ehlers Danlos syndrome (cEDS) suffer impaired wound healing and from scars formed after injuries that are atrophic and difficult to close surgically. Haploinsufficiency in COL5A1 creates systemic morphological and functional alterations in the entire body. We investigated mechanisms that impair wound healing from corneal lacerations (full thickness injuries) in a mouse model of cEDS (Col5a1+/-). We found that collagen V reexpression in this model is upregulated during corneal tissue repair and that wound healing is delayed, impaired, and results in large atrophic corneal scars. We noted that in a matrix with a 50 % content of collagen V, activation of latent Transforming Growth Factor (TGF) ß is dysregulated. Corneal myofibroblasts with a haploinsufficiency of collagen V failed to mechanically activate latent TGF ß. Second harmonic imaging microscopy showed a disorganized, undulated, and denser collagen matrix in our Col5a1+/- model that suggested alterations in the extracellular matrix structure and function. We hypothesize that a regenerated collagen matrix with only 50 % content of collagen V is not resistant enough mechanically to allow adequate activation of latent TGF ß by fibroblasts and myofibroblasts.

Cutaneous Mycobacterium avium-intracellulare infection masquerading as sarcoidosis.

Mycobacterium avium-intracellulare (MAC) infection may have different skin manifestations, including cutaneous granulomas. Granulomatous skin reactions have distinct morphologic and histopathologic appearances. We present the case of an adolescent male with cutaneous MAC, misdiagnosed as sarcoidosis after initial biopsy results, demonstrated preservation of reticulin fibers and absence of organisms within granulomas. Sarcoidal granulomas often stain positive for reticulin fibers, which could be used to distinguish them from the infectious kind. This case should alert clinicians to the fact that the presence or quantity of intact reticular fibers may not be a reliable tool to differentiate between a sarcoidal and an infectious granuloma. Our case also highlights the diagnostic challenge of cutaneous MAC infection.

In vitro activity of delafloxacin against anaerobic bacteria compared with other antimicrobials.

The aim of this study was to describe the in vitro activity of delafloxacin against 230 anaerobic isolates and compare it with the activity of other antimicrobials used against infections caused by anaerobic microorganisms. Minimal inhibitory concentrations (MICs) were lower for delafloxacin than for all other antibiotics tested with the exception of piperacillin-tazobactam and meropenem against Gram-positive anaerobic cocci. Only two (0.8 %) isolates of Bacteroides spp. showed a MIC ≥4 µg/mL. With some exceptions, the present results show lower MICs for delafloxacin in comparison to the other antibiotics used against anaerobes.

Eletroquimioterapia, uma nova terapia para pacientes com câncer cutâneo na América Latina: revisão da literatura / Electrochemotherapy, a new therapy for patients with skin cancer in Latin America: literature review

A eletroquimioterapia é uma tecnologia inovadora usada para tratar cânceres de pele e mucosa. Consiste na administração intravenosa de bleomicina seguida pela aplicação de pulsos de eletroporação no tumor em suas margens. Esses pulsos induzem a formação de poros na membrana celular, aumentando a eficácia citotóxica da bleomicina em mais de 1.000 vezes. Como a eletroporação é um fenômeno físico, diferentes tipos de tumores podem ser tratados, independentemente de sua histologia. Geralmente, apenas uma sessão de tratamento é necessária para obter resposta satisfatória. A eletroquimioterapia é uma boa opção para tumores recidivantes nos quais outras terapias não proporcionam resposta. Além disso, os tumores podem ser reduzidos com a terapia, permitindo cirurgias menos agressivas e melhorando os resultados. Muitas diretrizes de tratamento começaram a incluir o uso dessa técnica não ablativa como uma nova opção de tratamento quando outras terapias falharam ou foram rejeitadas pelo paciente. O tratamento é realizado em regime ambulatorial com altas taxas de resposta e poucos efeitos colaterais.

Electrochemotherapy is an innovative technology used to treat skin and mucosal cancers. It consists of intravenous administration of bleomycin followed by the application of electroporation pulses to the tumor at its margins. These pulses induce the formation of pores in the cell membrane, increasing the cytotoxic efficacy of bleomycin by more than 1,000- fold. As electroporation is a physical phenomenon, different types of tumors can be treated regardless of their histology. Generally, only one treatment session is needed to obtain a satisfactory response. Electrochemotherapy is a good option for recurrent tumors in which other therapies do not provide a response. Additionally, tumors can be shrunk with therapy, allowing for less aggressive surgeries and improving outcomes. Many treatment guidelines have begun to include the use of this non-ablative technique as a new treatment option when other therapies have failed or been rejected by the patient. Treatment is carried out on an outpatient basis with high response rates and few side effects.

Prevalencia de la arteria umbilical única en gestantes: su relación con otras malformaciones y el bajo peso al nacer

Introducción: La arteria umbilical única tiene una incidencia del 1 % en los recién nacidos. Se le asocia frecuentemente con gemelaridad, malformaciones y crecimiento intrauterino retardado, y constituye un factor de riesgo de prematuridad, muerte fetal y neonatal. Objetivos: Determinar la prevalencia de la arteria umbilical única en gestantes, y la asociación de esta entidad con otras malformaciones y el bajo peso al nacer. Materiales y métodos: Estudio descriptivo retrospectivo, con datos obtenidos de las historias clínicas y del modelo de seguimiento lineal existente en las consultas de genética comunitaria del municipio Matanzas, de enero de 2015 a diciembre de 2019. Resultados: La prevalencia de la arteria umbilical única fue del 0,3 %. Las malformaciones más frecuentes fueron las renales; el 27,7 % de los nacimientos fueron pretérmino y el 33,3 % de los nacidos fue con un peso inferior a 2500 g. Conclusiones: La arteria umbilical única constituye un marcador para otras malformaciones. Cuando coexisten ambas existe riesgo de prematuridad y bajo peso al nacer. Se recomienda realizar examen clínico posnatal a todo recién nacido con arteria umbilical única, pesquisando defectos renales y cardíacos.

Introduction: The single umbilical artery has an incidence of 1% in newborns. It is frequently associated with twinning, malformations and delayed intrauterine growth, and is a risk factor of prematurity, fetal and neonatal death. Objective: To determine the prevalence of single umbilical artery in pregnant women and the association of this entity with other malformations and low birth weight. Materials and methods: Retrospective descriptive study, with data obtained from medical records and the linear follow-up model existing in the community genetic clinics of the municipality of Matanzas, from January 2015 to December 2019. Results: The prevalence of the single umbilical artery was 0.3%. The most frequent malformations were renal ones; 27.7% of births were pre-term and 33.3% of those born weighed less than 2500g. Conclusions: The single umbilical artery is a marker for other malformations. When both coexist there is a risk of prematurity and low birth weight. Postnatal clinical examination is recommended for all newborns with single umbilical artery, checking for renal and heart defects.

The relationship between positive and negative stress and posttraumatic growth in university students: the mediating role of resilience.

BACKGROUND: Information on understanding the mediating role of resilience in the relationship between posttraumatic growth (PTG) and positive and negative stress among students is limited. The objective of this research was to evaluate the mediating role of resilience in the relationship between positive and negative stress and PTG in university students. METHODS: The research was carried out using an associative strategy with an empirical approach and explanatory design, with a sample of 507 participants whose average age was 22.38 years ([Formula: see text]= 3.758), the sample was mostly composed of women (70.4%). RESULTS: The results allow us to describe that resilience plays a complete mediating role in the relationship between negative stress and PTG. On the other hand, mediation was partial when resilience mediated the relationship between positive stress and PTG. In addition, multigroup invariance analyses according to gender and geographic context show that there is no difference in males, females, and the region where they reside. CONCLUSION: In conclusion, the hypothesis that resilience fulfills the mediating function is ratified.

Keratocyte-Derived Myofibroblasts: Functional Differences With Their Fibroblast Precursors.

Purpose: In this study, we aim to elucidate functional differences between fibroblasts and myofibroblasts derived from a keratocyte lineage to better understand corneal scarring. Methods: Corneal fibroblasts, derived from a novel triple transgenic conditional KeraRT/tetO-Cre/mTmG mouse strain that allows isolation and tracking of keratocyte lineage, were expanded, and transformed by exposure to transforming growth factor (TGF)-ß1 to myofibroblasts. The composition and organization of a fibroblast-built matrix, deposited by fibroblasts in vitro, was analyzed and compared to the composition of an in vitro matrix built by myofibroblasts. Second harmonic generation microscopy (SHG) was used to study collagen organization in deposited matrix. Different extracellular matrix proteins, expressed by fibroblasts or myofibroblasts, were analyzed and quantified. Functional assays compared latent (TGF-ß) activation, in vitro wound healing, chemotaxis, and proliferation between fibroblasts and myofibroblasts. Results: We found significant differences in cell morphology between fibroblasts and myofibroblasts. Fibroblasts expressed and deposited significantly higher quantities of fibril forming corneal collagens I and V. In contrast, myofibroblasts expressed and deposited higher quantities of fibronectin and other non-collagenous matrix components. A significant difference in the activation of latent TGF-ß activation exists between fibroblasts and myofibroblasts when measured with a functional luciferase assay. Fibroblasts and myofibroblasts differ in their morphology, extracellular matrix synthesis, and deposition, activation of latent TGF-ß, and chemotaxis. Conclusions: The differences in the expression and deposition of extracellular matrix components by fibroblasts and myofibroblasts are likely related to critical roles they play during different stages of corneal wound healing.

Otitis media tuberculosa: Presentación de un caso y revisión de la literatura europea / Tuberculous otitis media: A case presentation and review of european literature

La otitis media tuberculosa (OMT) es una afectación rara en nuestro medio que supone un reto en su diagnóstico debido a los síntomas inespecíficos que suele presentar. Este trabajo presenta nuestra experiencia en el diagnóstico de un caso de OMT en una mujer de 66 años con pérdida auditiva y otorrea crónica de más de 6 meses de evolución, que no respondía a los tratamientos convencionales. Además, se realiza una re visión de los casos publicados en los últimos 20 años (2000- 2022) en países de la Unión Europea (EU). Se incluyeron un total de 25 artículos con datos sobre 43 pacientes diagnostica dos de OMT. Las edades se situaron en un rango de: 3 meses - 87 años con un mayor porcentaje de mujeres (n=30; 69,77%). El tiempo medio de diagnóstico fue de 13,6 meses (rango, 1-72 meses). Los síntomas más comunes fueron otorrea (n=43; 100%), pérdida auditiva (n=37; 86,05%), perforación timpá nica (n=19; 44,18%), parálisis facial (n=12, 27,91%) y otalgia (n=13; 30,23%). La muestra empleada en mayor porcentaje para el diagnóstico fue la biopsia obtenida por mastoidectomía (n=34; 79,06%). Todos los pacientes fueron tratados con anti tuberculosos con una media de duración de 8,11 meses (rango, 6-12 meses). La secuela más frecuente fue la pérdida auditiva (n=28; 65,12%). La OMT debe incluirse en el diagnóstico dife rencial de las otitis supurativas crónicas ya que el diagnóstico y tratamiento precoz disminuyen la probabilidad de sufrir se cuelas irreversibles (AU)

Tuberculous otitis media (TOM) is a rare affectation in our environment that represents a challenge in its diagnosis due to the non-specific symptoms that it usually presents. This paper presents our experience in the diagnosis of a case of TOM in a 66-year-old woman with hearing loss and chronic otorrhea of more than 6 months of evolution that did not respond to con ventional treatments. In addition, a review of the cases pub lished in the last 20 years (2000-2022) in countries of the Eu ropean Union (EU) is carried out. The most common symptoms were otorrhea (n=43; 100%), hearing loss (n=37; 86.05%), eardrum perforation (n=19; 44.18%), facial paralysis (n=12, 27,91%) and ear pain (n=13; 30,23%). The most used sam ple for diagnosis was the biopsy obtained by mastoidectomy (n=34; 79.06%). All patients were given antituberculous ther apy for a mean duration of 8.11 months (range, 6-12 months). The most frequent aftereffect was hearing loss (n=28; 65.12%). TOM should be included in the differential diagnosis of chronic suppurative otitis, since early diagnosis and treatment reduce the probability of suffering irreversible sequelae (AU)

Clinical outcomes of liposomal irinotecan in advanced pancreatic adenocarcinoma patients previously treated with conventional irinotecan-based chemotherapy: a real-world study.

Background: The efficacy of combination chemotherapy beyond the first-line setting remains modest in patients with advanced pancreatic adenocarcinoma (PAC). Evidence from recent clinical studies has shown that liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) resulted in survival benefits in patients with advanced pancreatic adenocarcinoma (APAC) after progression on gemcitabine-based treatment. However, the survival benefits of nal-IRI in the third and later lines, in which limited options are available, have yet to be extensively studied. Also, some studies have shown conflicting results regarding the impact of prior treatment with conventional IRI on patient outcomes following treatment with nal-IRI. Therefore, this real-world study aimed to evaluate the efficacy and safety of nal-IRI plus 5FU-LV in advanced PAC patients who progressed on conventional IRI-containing regimens. Methods: A retrospective chart review was conducted between November 2016 to December 2022 on 30 patients diagnosed with advanced PAC who completed at least one cycle of nal-IRI plus 5-FU- LV and were previously treated with conventional IRI. Data regarding survival outcomes were retrieved. Results: Thirty patients met the inclusion criteria. Overall, 76.7% of the patients received at least two lines of therapy prior to nal-IRI. The median overall duration of nal-IRI treatment was 2.0 months (IQR: 1.3 - 3.9 months). One patient (3.3%) had a partial response, and seven patients (23.3%) had stable disease as their best response. The median progression-free survival (PFS) was 1.9 months (95% CI 1.6 - 2.0) and the 6-month PFS rate was 20.0%. The median overall survival (OS) was 5.0 months (95% CI 3.4 - 7.0), and the 6-month OS rate was 36.7%. An interval between conventional IRI and nal-IRI ≥5.5 months was significantly associated with prolonged OS of 10.2 months (95% CI 3.3 - 12.1) versus 4.3 months (95% CI 2.1 - 5.9; p =0.003). Ten patients (33.3%) experienced grade 3 adverse events, most commonly nausea, fatigue, diarrhea, and non-neutropenic fever. Conclusion: Nal-IRI plus 5FU/LV had modest survival benefits and an acceptable safety profile in patients with prior conventional IRI. A longer interval between conventional IRI and nal-IRI was associated with increased survival outcomes.

Stromal matrix directs corneal fibroblasts to re-express keratocan after injury and transplantation.

Every tissue has an extracellular matrix (ECM) with certain properties unique to it - the tissue 'niche' - that are necessary for normal function. A distinct specific population of quiescent keratocan-expressing keratocytes populate the corneal stroma during homeostasis to maintain corneal function. However, during wound healing, when there is alteration of the niche conditions, keratocytes undergo apoptosis, and activated corneal fibroblasts and myofibroblasts attempt to restore tissue integrity and function. It is unknown what the fate of activated and temporary fibroblasts and myofibroblasts is after the wound healing process has resolved. In this study, we used several strategies to elucidate the cellular dynamics of corneal wound healing and the fate of corneal fibroblasts. We injured the cornea of a novel mouse model that allows cell-lineage tracing, and we transplanted a cell suspension of in vitro-expanded corneal fibroblasts that could be tracked after being relocated into normal stroma. These transplanted fibroblasts regained expression of keratocan in vivo when relocated to a normal stromal niche. These findings suggest that transformed fibroblasts maintain plasticity and can be induced to a keratocyte phenotype once relocated to an ECM with normal signaling ECM.

Energy-saving pretreatments affect pelagic Sargassum composition and DNA metabarcoding reveals the microbial community involved in methane yield.

Sargassum spp. flood the Caribbean coastline, causing damage to the local economy and environment. Anaerobic digestion (AD) has been proposed as an attractive option for turning macroalgae into valuable resources. Sargassum spp. has a complex composition that affects the microbial composition involved in AD which generates a low methane yield. This study aimed to improve the methane yield of pelagic Sargassum, using different energy-saving pretreatments and identifying the microbial community associated with methane production. We applied different energy-saving pretreatments to algal biomass and assessed the methane yield using a biomethane potential (BMP) test. The microbial communities involved in the AD of the best- and worst-performing methanogenic systems were analyzed by high-throughput sequencing. The results showed that pretreatment modified the content of inorganic compounds, fibers, and the C:N ratio, which had a strong positive correlation with BMP. The water washing pretreatment resulted in the best methane yield, with an increase of 38%. DNA metabarcoding analysis revealed that the bacterial genera Marinilabiliaceae_uncultured, DMER64, Treponema, and Hydrogenispora, as well as the archaea genera Methanosarcina, RumEn_M2, Bathyarchaeia, and Methanomassiliicocus, dominated the microbial community with a high methane yield. This study is the first to demonstrate the microbial community structure involved in the AD of Sargassum spp. The pretreatments presented in this study can help overcome the limitations associated with methane yield.

Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan as First-line Treatment for Metastatic Pancreatic Cancer.

Purpose: Treatment of advanced pancreatic cancer with a single therapeutic at a maximal dose has been largely ineffective at increasing survival. Combination therapies are commonly studied but often limited by toxicity. We previously showed that low-dose multiagent therapy with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), and cisplatin (GTX-C) was safe, well tolerated, and effective (NCT01459614). Here, we hypothesize that adding irinotecan to GTX-C may improve survival with minimal toxicity. Experimental Design: Patients with treatment-naïve metastatic pancreatic adenocarcinoma were treated with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), cisplatin, and irinotecan (GTX-CI). Treatment consisted of capecitabine 500 mg twice daily on days 1-14 and gemcitabine 300 to 500 mg/m2, docetaxel 20 mg/m2, cisplatin 15 to 20 mg/m2, and irinotecan 20 to 60 mg/m2 on days 4 and 11 of a 21-day cycle. The primary objective was 9-month overall survival (OS). Secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and OS. Results: The regimen was well tolerated. The recommended phase II dose was gemcitabine 500 mg/m2, docetaxel 20 mg/m2, capecitabine 500 mg po bid, cisplatin 20 mg/m2, and irinotecan 20 mg/m2. Median follow-up in phase II was 11.02 months (2.37-45.17). Nine-month OS rate was 57% [95% confidence interval (CI): (41-77)]. RR was 57% [95% CI: (37-75) 50% PR and 7% CR]. DCR was 87% [95% CI: (69-96)]. Median OS and PFS were 11.02 [95% CI: (8.54-21.09)] and 8.34 [95% CI: (6.34-NA)] months, respectively. Conclusions: The addition of irinotecan to GTX-C was safe and well tolerated. While the study did not meet its primary objective, the responses were clinically meaningful using a well-tolerated regimen. Significance: We aimed to optimize the previously reported efficacious regimen of low-dose multiagent therapy with GTX-C for the treatment of metastatic pancreatic ductal adenocarcinoma by adding irinotecan. The primary objective was not met, but GTX-CI was well tolerated. The RR of 57%, median PFS of 8.3 months, median OS of 11 months, and 36-month OS rate of 19% suggest clinical benefit. Further optimization of this regimen is warranted.

La superación de los profesionales de la Cultura Física, desde la extensión universitaria

El perfeccionamiento de los tres procesos sustantivos de la universidad, la docencia, la investigación y la extensión universitaria ha sido una prioridad para la educación superior cubana que ha desarrollado una serie de cambios y transformaciones en aras de garantizar una excelente formación de los profesionales que egresan de ella. En este sentido, la investigación abordó el tema de la extensión universitaria en la superación profesional y tuvo como objetivo favorecer la superación de los docentes universitarios y su vinculación con los avances científicos en un curso de posgrado para la Licenciatura en Cultura Física y Deportes, desde la extensión universitaria. El proceso investigativo se rigió por el método dialectico-materialista y se emplearon métodos del nivel teórico como el histórico-lógico y el análisis-síntesis y del nivel empírico el análisis documental, la entrevista en profundidad y la encuesta, para interpretar los resultados obtenidos en cada etapa de la investigación. Los resultados mostraron como principales debilidades el insuficiente reconocimiento de la importancia de la extensión universitaria en el contexto docente, así como la poca producción científica relacionada con la temática. Del estudio realizado se concluye que la extensión universitaria en la superación de este profesional constituye una vía expedita para un mejor conocimiento, gestión, preservación y difusión de actividades intra- y extracurriculares y en la mejora de la calidad de vida, con el fin de contribuir a formar ciudadanos capaces de ser, conocer, hacer y convivir juntos.

A melhoria dos três processos substantivos da universidade, o ensino, a pesquisa e a extensão universitária, tem sido uma prioridade para o ensino superior cubano, que tem desenvolvido uma série de mudanças e transformações a fim de garantir uma excelente formação dos profissionais que nela se graduam. Nesse sentido, a pesquisa abordou a questão da extensão universitária no desenvolvimento profissional e seu objetivo foi promover o desenvolvimento dos professores universitários e sua vinculação com os avanços científicos em um curso de pós-graduação para o Bacharelado em Cultura Física e Esportes, a partir da perspectiva da extensão universitária. O processo de pesquisa foi regido pelo método dialético-materialista, utilizando métodos teóricos como o histórico-lógico e a análise-síntese e métodos empíricos como a análise documental, a entrevista em profundidade e o survey, para interpretar os resultados obtidos em cada etapa da pesquisa. Os resultados apontaram como principais fragilidades o insuficiente reconhecimento da importância da extensão universitária no contexto do ensino, bem como a pouca produção científica relacionada ao tema. A partir do estudo realizado, conclui-se que a extensão universitária no aprimoramento desse profissional constitui um caminho expedito para um melhor conhecimento, gerenciamento, preservação e divulgação das atividades intra e extracurriculares e na melhoria da qualidade de vida, com o objetivo de contribuir para formar cidadãos capazes de ser, saber, fazer e conviver.

The improvement of the three substantive processes of the university, teaching, research and university extension has been a priority for Cuban higher education that has developed a series of changes and transformations in order to guarantee an excellent training of the professionals who graduate from it. In this sense, the research addressed the issue of university extension in professional upgrading and had the objective of promoting the improvement of university teachers and their link with scientific advances in a postgraduate course for the Degree in Physical Culture and Sports, from the university extension. The research process was governed by the dialectical-materialist method; theoretical level methods such as historical-logical and analysis-synthesis and empirical level ones as documentary analysis, in-depth interview and survey were used to interpret the results obtained in each stage of the research. The results showed as main weaknesses the insufficient recognition of the importance of university extension in the teaching context, as well as the little scientific production related to the subject. From the study carried out, it is concluded that the university extension in the improvement of this professional constitutes an expeditious way for a better knowledge, management, preservation and dissemination of intra- and extracurricular activities and in the improvement of the quality of life, in order to contribute to form citizens capable of being, knowing, doing and living together.

A Method for Quantification of Stretch Reflex Excitability During Ballistic Reaching.

Stretch reflexes are crucial for performing accurate movements and providing rapid corrections for unpredictable perturbations. Stretch reflexes are modulated by supraspinal structures via corticofugal pathways. Neural activity in these structures is difficult to observe directly, but the characterization of reflex excitability during volitional movement can be used to study how these structures modulate reflexes and how neurological injuries impact this control, such as in spasticity after stroke. We have developed a novel protocol to quantify stretch reflex excitability during ballistic reaching. This novel method was implemented using a custom haptic device (NACT-3D) capable of applying high-velocity (270 °/s) joint perturbations in the plane of the arm while participants performed 3D reaching tasks in a large workspace. We assessed the protocol on four participants with chronic hemiparetic stroke and two control participants. Participants reached ballistically from a near to a far target, with elbow extension perturbations applied in random catch trials. Perturbations were applied before movement, during the early phase of movement, or near peak movement velocity. Preliminary results show that stretch reflexes were elicited in the stroke group in the biceps muscle during reaching, as measured by electromyographic (EMG) activity both before (pre-motion phase) and during (early motion phase) movement. Reflexive EMG was also seen in the anterior deltoid and pectoralis major in the pre-motion phase. In the control group, no reflexive EMG was seen, as expected. This newly developed methodology allows the study of stretch reflex modulation in new ways by combining multijoint movements with haptic environments and high-velocity perturbations.

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma.

A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.