Transcriptomics of Besnoitia besnoiti-Infected Fibroblasts Reveals Hallmarks of Early Fibrosis and Cancer Progression.

Endothelial injury, inflammatory infiltrate and fibrosis are the predominant lesions in the testis of bulls with besnoitiosis that may result in sterility. Moreover, fibroblasts, which are key players in fibrosis, are parasite target cells in a Besnoitia besnoiti chronic infection. This study aimed to decipher the molecular basis that underlies a drift toward fibrosis during the disease progression. Transcriptomic analysis was developed at two times post-infection (p.i.), representative of invasion (12 h p.i.) and intracellular proliferation (32 h p.i.), in primary bovine aorta fibroblasts infected with B. besnoiti tachyzoites. Once the enriched host pathways were identified, we studied the expression of selected differentially expressed genes (DEGs) in the scrotal skin of sterile infected bulls. Functional enrichment analyses of DEGs revealed shared hallmarks of cancer and early fibrosis. Biomarkers of inflammation, angiogenesis, cancer, and MAPK signaling stood out at 12 h p.i. At 32 h p.i., again MAPK and cancer pathways were enriched together with the PI3K-AKT pathway related to cell proliferation. Some DEGs were also regulated in the skin samples of naturally infected bulls (PLAUR, TGFß1, FOSB). We have identified potential biomarkers and host pathways regulated during fibrosis that may hold prognostic significance and could emerge as potential therapeutic targets.

Inhibition of murine colorectal cancer metastasis by targeting M2-TAM through STAT3/NF-kB/AKT signaling using macrophage 1-derived extracellular vesicles loaded with oxaliplatin, retinoic acid, and Libidibia ferrea.

Colorectal cancer is still unmanageable despite advances in target therapy. However, extracellular vesicles (EVs) have shown potential in nanomedicine as drug delivery systems, especially for modulating the immune cells in the tumor microenvironment (TME). In this study, M1 Macrophage EVs (M1EVs) were used as nanocarriers of oxaliplatin (M1EV1) associated with retinoic acid (M1EV2) and Libidibia ferrea (M1EV3), alone or in combination (M1EV4) to evaluate their antiproliferative and immunomodulatory potential on CT-26 and MC-38 colorectal cancer cell lines and prevent metastasis in mice of allograft and peritoneal colorectal cancer models. Tumors were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and epithelial-mesenchymal transition process (EMT) were analyzed in vitro in colorectal cancer cell lines. Polarization of murine macrophages (RAW264.7 cells) was also carried out. M1EV2 and M1EV3 used alone or particularly M1EV4 downregulated the tumor progression by TME immunomodulation, leading to a decrease in primary tumor size and metastasis in the peritoneum, liver, and lungs. STAT3, NF-kB, and AKT were the major genes downregulated by of M1EV systems. Tumor-associated macrophages (TAMs) shifted from an M2 phenotype (CD163) to an M1 phenotype (CD68) reducing levels of IL-10, TGF-ß and CCL22. Furthermore, malignant cells showed overexpression of FADD, APAF-1, caspase-3, and E-cadherin, and decreased expression of MDR1, survivin, vimentin, and PD-L1 after treatment with systems of M1EVs. The study shows that EVs from M1 antitumor macrophages can transport drugs and enhance their immunomodulatory and antitumor activity by modulating pathways associated with cell proliferation, migration, survival, and drug resistance.

Paraneoplastic or treatment-associated dermatomyositis: a diagnostic challenge.

Dermatomyositis (DM) is a systemic autoimmune disorder characterized by proximal myopathy and dermatological findings. Approximately 15-30% of DM cases emerge as a paraneoplastic syndrome caused by a concomitant malignancy. Although more rare, in cancer patients DM has also been reported as a possible result of toxicity of some antineoplastic agents, such as taxanes and monoclonal antibodies. Herein, we report a 35-year-old woman with metastatic breast cancer who presented with skin lesions after initiation of paclitaxel and anti-HER2 agents. Clinical, laboratory, and histological findings were consistent with the diagnosis of DM.

How Temporary/Permanent Employment Status and Mindfulness Redraw Employee Organizational Citizenship Responses to Person-Organization Fit / [Cómo redibujan el estatus de empleo temporal/permanente y el mindfulness las respuestas de ciudadanía organizacional de los empleados al ajuste personaorganización]

This paper analyzes the role of temporary/permanent employment in the way employees respond to person-organization fit (P-O Fit) with organizational citizenship behaviors (OCBs), and whether mindfulness redraws this relationship. Compared to permanent employees, temporary employees may have fewer future prospects in their organization, thus leading them to engage less in this type of behavior, the potential returns of which are typically unspecified in time and are likely beyond their temporary reach. However, the self-regulatory, present-moment awareness and non-judgmental acceptance functions of mindfulness could reverse this relationship. Structural equation modeling using data from 280 employees of 10 Spanish hotels revealed that temporary (permanent) employees reacted to P-O Fit with lower (higher) OCBs, unless they were mindful, in which case their OCBs increased (decreased). The findings show that employment status and mindfulness redraw the P-O Fit - OCB relationship and that mindfulness makes temporary (permanent) employees respond to P-O Fit with increased (decreased) OCBs.(AU)

Este trabajo analiza el papel del estatus laboral temporal/permanente en la forma en que los empleados responden al ajuste persona-organización con comportamientos de ciudadanía organizacional, y si el mindfulness redibuja esta relación. En comparación con los empleados fijos, los temporales pueden tener menos perspectivas de futuro en su organización, lo que les lleva a participar menos en este tipo de comportamientos, cuyos rendimientos potenciales suelen ser indeterminados en el tiempo y probablemente están fuera de su alcance temporal. Sin embargo, las funciones de autorregulación, conciencia del momento presente y aceptación sin prejuicios del mindfulness podrían invertir esta relación. La modelización de ecuaciones estructurales con datos de 280 empleados de 10 hoteles españoles reveló que los empleados temporales (fijos) reaccionaban al ajuste persona-organización con un menor (mayor) comportamiento de ciudadanía organizacional, a menos que tuvieran mindfulness, en cuyo caso su comportamiento de ciudadanía organizacional aumentaba (disminuía). Los resultados muestran que el estatus laboral y el mindfulness redibujan la relación entre ajuste persona-organización y comportamiento de ciudadanía organizacional y que el mindfulness hace que los empleados temporales (fijos) respondan a dicho ajuste con un mayor (menor) nivel de comportamiento de ciudadanía organizacional.(AU)

Lose at sunrise, but gain at sunset: Linking social cyberloafing to psychological detachment, personal life enhancement of work, and mental health.

BACKGROUND: Previous research has demonstrated that the personal use of social media, i.e., social cyberloafing, is associated with employee mental health. However, the underlying mechanism through which social cyberloafing is related to mental health has received limited attention. OBJECTIVE: Drawing on conservation of resource theory and work/nonwork enhancement literatures, we developed and tested a model that examines health effect of social cyberloafing. As such, employees' social cyberloafing is posited as positively related to psychological detachment and personal life enhancement of work, which in turn would act as mediators that explain why social cyberloafing improves mental health. METHODS: Data from 375 Chinese employees were analyzed to test research hypotheses using the structural equation modeling and bias-corrected bootstrap method with Mplus 7.4. RESULTS: The results found that social cyberloafing is positively related to psychological detachment, but not with personal life enhancement of work. Social cyberloafing was positively related to employees' mental health through both psychological detachment and through psychological detachment and personal life enhancement of work serially. CONCLUSION: Psychological detachment alone and alongside personal life enhancement of work form part of the mechanisms explaining how and why engaging in social cyberloafing is positively associated with employees' mental health. These mechanisms offer insights to organizations into how the mental health of employees can be improved in the digital workplace.

Design and Validation of a Food Frequency Questionnaire to Evaluate the Consumption of Trans Fatty Acids in the Adult Population (FFQ-TFA).

Instruments for estimating the intake of food components can be useful in the prevention and/or treatment of diseases related to improper diet. There is, at present, no scientifically validated instrument for estimating consumption of trans fatty acids (TFA) in the Mexican population. The objective of this study was to design and validate such an instrument: a questionnaire that can be used to estimate consumption of TFA from food products. The questionnaire was applied to 162 students from the Autonomous University of Querétaro (UAQ). There were two phases to the study: (1) design of a food frequency questionnaire to assess consumption of trans fatty acids (FFQ-TFA) and an eating practices questionnaire (EPQ-TFA); (2) validation of the instrument. Content validity was measured by expert review and by Aiken's V method, obtaining an overall score of 0.895. As final tests for the FFQ-TFA analysis, criterion validity was measured using Spearman's correlation (r = 0.717, p < 0.01) and a linear regression (B = 0.668), considering the results of the 24-h dietary recall (24 HR); and reproducibility or temporal stability was measured using Pearson's correlation (r = 0.406, p < 0.01). Subsequently, a Pearson correlation was applied between TFA consumption estimated by the FFQ-TFA-2 and the global score from the EPQ-TFA-2 (r = 0.351, p < 0.01). A Pearson correlation was applied between the EPQ-TFA-1 and the EPQ-TFA-2 (r = 0.575, p < 0.01). TFA consumption per day was 2.49 ± 1.32 g in the participating population, which was 1.04 ± 0.51% of their total kcal consumption.

M1-derived extracellular vesicles enhance photodynamic therapy and promote immunological memory in preclinical models of colon cancer.

Extracellular vesicles (EVs) are promising drug carriers of photosensitizers for photodynamic therapy (PDT) in cancer treatment, due to their ability to circulate in blood and enter cells efficiently. The therapeutic potential of EVs has been suggested to depend on the type and physiological state of their cell of origin. However, the effects of deriving EVs from various cells in different physiological states on their antitumor capacity are rarely evaluated. In the present study, we compared the antitumor efficacy of EV-mediated PDT by incorporating the photosensitizer Zinc Phthalocyanine (ZnPc) into EVs from multiple cells sources. ZnPc was incorporated by a direct incubation strategy into EVs derived from immune cells (M1-like macrophages and M2-like macrophages), cancer cells (B16F10 melanoma cancer cells) and external sources (milk). Our data show that all EVs are suitable carriers for ZnPc and enable efficient PDT in vitro in co-culture models and in vivo. We observed that EV-mediated PDT initiates immunogenic cell death through the release and exposure of damage associated molecular patterns (DAMPs) on cancer cells, which subsequently induced dendritic cell (DC) maturation. Importantly, of all ZnPc-EVs tested, in absence of light only M1-ZnPc displayed toxicity to MC38, but not to DC, in monoculture and in co-culture, indicating specificity for cancer over immune cells. In MC38 tumor-bearing mice, only M1-ZnPc induced a tumor growth delay compared to control in absence of light. Interestingly, M1- but not M2-mediated PDT, induced complete responses against MC38 tumors in murine models (100% versus 38% of cases, respectively), with survival of all animals up to at least 60 days post inoculation. Finally, we show that all cured animals are protected from a rechallenge with MC38 cells, suggesting the induction of immunological memory after EV-mediated PDT. Together, our data show the importance of the cell type from which the EVs are obtained and highlight the impact of the immunological state of these cells on the antitumor efficacy of EV-mediated PDT.

Myopericytoma presenting as a painful dark subungual discoloration.

Myopericytoma is an uncommon benign neoplasm that arises from the perivascular myoid cells. It typically presents as a painless well-circumscribed cutaneous or soft-tissue nodule, most commonly on the extremities of adults. Histologically, it is characterized by spindle-shaped myoid-appearing cells with a concentric arrangement in vessel walls, that are immunoreactive to alpha-smooth muscle actin and often for h-caldesmon, but negative for other smooth muscle markers. Herein, we present an unusual case of a painful subungual myopericytoma presenting as a dark subungual discoloration.

Toxic erythema of chemotherapy induced by liposomal doxorubicin, a clinical case.

A 76-year-old woman presented to the medical oncology outpatient clinic with painful, burning, pruritic erythematous plaques involving both palms and axillae that had suddenly appeared five days before. Examination revealed no additional relevant findings and laboratory studies did not show any alteration. The patient had been recently diagnosed with a high-grade angiosarcoma of the breast (probably radiation induced) and after frequent local recurrences, was being treated with liposomal doxorubicin (three cycles were administered, the last of which was seven days before the appearance of the mentioned lesions). Oral corticosteroids were started, treatment with liposomal doxorubicin was stopped, and cutaneous biopsies performed that revealed features compatible with toxic erythema of chemotherapy induced by liposomal doxorubicin. Complete resolution of the cutaneous lesions was verified one month after. No signs of recurrence of angiosarcoma were documented at follow-up three months later.

Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a ß-Blocker Potentiate Doxorubicin's Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer.

One of the main reasons for cancer's low clinical response to chemotherapeutics is the highly immunosuppressive tumor microenvironment (TME). Tumor-ass ociated M2 macrophages (M2-TAMs) orchestrate the immunosuppression, which favors tumor progression. Extracellular vesicles (EVs) have shown great potential for targeted therapies as, depending on their biological origin, they can present different therapeutic properties, such as enhanced accumulation in the target tissue or modulation of the immune system. In the current study, EVs were isolated from M1-macrophages (M1-EVs) pre-treated with hyaluronic acid (HA) and the ß-blocker carvedilol (CV). The resulting modulated-M1 EVs (MM1-EVs) were further loaded with doxorubicin (MM1-DOX) to assess their effect in a mouse model of metastatic tumor growth. The cell death and cell migration profile were evaluated in vitro in 4T1 cells. The polarization of the RAW 264.7 murine macrophage cell line was also analyzed to evaluate the effects on the TME. Tumors were investigated by qRT-PCR and immunohistochemistry. MM1-DOX reduced the primary tumor size and metastases. NF-κB was the major gene downregulated by MM1-DOX. Furthermore, MM1-DOX reduced the expression of M2-TAM (CD-163) in tumors, which resulted in increased apoptosis (FADD) as well as decreased expression of MMP-2 and TGF-ß. These results suggest a direct effect in tumors and an upregulation in the TME immunomodulation, which corroborate with our in vitro data that showed increased apoptosis, modulation of macrophage polarization, and reduced cell migration after treatment with M1-EVs combined with HA and CV. Our results indicate that the M1-EVs enhanced the antitumor effects of DOX, especially if combined with HA and CV in an animal model of metastatic cancer.

Zinc-Phthalocyanine-Loaded Extracellular Vesicles Increase Efficacy and Selectivity of Photodynamic Therapy in Co-Culture and Preclinical Models of Colon Cancer.

Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.

Prácticas clínicas seguras durante la pandemia por COVID-19 / Safe clinical practices during the COVID-19 pandemic

No disponible

Necrosis intestinal asociada a la nutrición enteral por yeyunostomía / Intestinal necrosis associated with enteral nutrition by jejunostomy

No disponible

Revisión de los criterios diagnósticos para el síndrome de ovario poliquístico / Review of diagnostic criteria for polycystic ovary syndrome

Resumen El síndrome de ovario poliquístico, es la alteración endocrina metabólica más frecuente en mujeres en edad fértil, teniendo implicaciones a nivel reproductivo, metabólico, cardiovascular y psicosocial. Actualmente, su sobrediagnóstico corresponde a una problemática común derivada de la heterogeneidad en la aplicación de los criterios actualmente avalados para su hallazgo, lo que ha contribuido en el incremento de tratamientos innecesarios, así como los efectos negativos en la calidad de vida y el bienestar de las pacientes falsamente calificadas con este trastorno. Se realizó una búsqueda en PubMed-MENDELEY y Ovid entre los meses de Febrero a Abril del 2020, obteniendo 43 artículos relacionados con el tema, publicados en los últimos 10 años. El conocimiento por parte del personal médico capacitado sobre los consensos actuales para la correcta evaluación del síndrome y el estudio individualizado de cada caso, corresponden las medidas más apropiadas para la reducción del sobrediagnóstico. MÉD.UIS.2020;33(3):21-28

Abstract Polycystic ovary syndrome is the most frequent metabolic endocrine disorder in women of childbearing age, having implications at both the reproductive, metabolic, cardiovascular and psychosocial levels. Currently, its overdiagnosis corresponds to a common problem derived from the heterogeneity in the application of the criteria currently endorsed for its discovery, which has contributed to the increase in unnecessary treatments, as well as the negative effects on the quality of life and well-being of falsely rated patients with this disorder. A search was made in PubMed-MENDELEY and Ovid between the months of February to April of 2020, obtaining 43 articles related to the topic, published in the last 10 years. The knowledge on the part of the trained medical personnel about the current consensuses for the correct evaluation of the syndrome and the individualized study of each case, correspond to the most appropriate measures for the reduction of this event. MÉD.UIS.2020;33(3):21-28

Consideraciones clínicas para fonoaudiólogos en el tratamiento de personas con COVID-19 y traqueostomía. Parte I: Deglución / Clinical considerations for speech-language pathologists in the treatment of people with COVID-19 and tracheostomy. Part I: Swallowing

A la fecha de redacción de este artículo, más de 500 mil personas han sido afectadas por el virus SARS-CoV-2 en Chile, manifestando diferentes grados de la enfermedad COVID-19. Aquellas que sobrellevan condiciones más severas generan una condición que requiere soporte ventilatorio invasivo y tratamiento en unidades de cuidados intensivos, que de prolongarse en el tiempo deriva en la necesidad de una traqueostomía. A pesar de los beneficios que posee esta en la recuperación de personas con dificultades respiratorias, su implementación se asocia a alteraciones deglutorias que se suman a las generadas por COVID-19. Condición que supone un desafío para los/as fonoaudiólogos/as, quienes están expuestos/as al virus debido a su proceder en estructuras del tracto aerodigestivo y la realización de procedimientos potencialmente generadores de aerosol. El objetivo de este artículo es entregar orientaciones y herramientas clínicas para la intervención en la deglución de personas con traqueostomía y COVID-19. Estas emanan de un análisis pragmático de la evidencia disponible a la fecha, interpretadas bajo nuestra experiencia de atender a más de 561 personas con dicha condición. Se espera contribuir a la rehabilitación de la deglución en personas con COVID-19 y traqueostomía. Para ello se expone sobre las características de la deglución en esta población, su tratamiento, consideraciones para el uso de técnicas específicas, y orientaciones para la mejora de la calidad de vida mediante la mantención y/o recuperación de la funcionalidad deglutoria. Siempre bajo un esquema centrado en el cuidado y protección de las personas hospitalizadas y el equipo de salud.

At the time of writing this article, more than a million people have been affected by the SARS-CoV-2 virus in Chile, displaying different degrees of COVID-19 disease. Severe infections generate a condition that requires invasive ventilatory support and treatment in intensive care units, which, when extended in time, makes necessary conducting a tracheostomy. Despite its benefits for the recovery of patients with respiratory difficulties, it is linked to swallowing disorders that add to the problems generated by COVID-19. This represents a challenge for speech pathologists, who are potentially exposed to the virus because they work on structures of the aerodigestive tract and becuase they conduct procedures that may be aerosol-generating. The aim of this article is to provide guidance and clinical tools for swallowing-intervention in people with tracheostomies and COVID-19. Thees tools spring from a pragmatic analysis of the currently available evidence , interpreted based on our experience of caring more than561 infected patients. We hope to contribute to the rehabilitation of swallowing of patients with COVID-19 and a tracheostomy. The characteristics of swallowing in this population, its treatment, considerations for the use of specific techniques, and guidelines for improving the quality of life through the maintenance and/or recovery of swallowing functionality are discussed, focused caring and protecting hospitalized patients and the health team.

Consideraciones clínicas para fonoaudiólogos en el tratamiento de personas con COVID-19 y traqueostomía. Parte II: Mejorando la fonación para facilitar la comunicación / Clinical considerations for speech-language pathologists in the treatment of people with COVID-19 and tracheostomy. Part II: Improving phonation to facilitate communicatio

La enfermedad COVID-19 fue declarada pandemia por la Organización Mundial de la Salud. Su presentación más severa genera una condición que requiere tratamiento en unidades de cuidados intensivos, condición que al prolongarse en el tiempo requiere la implementación de una traqueostomía para facilitar la entrega de soporte ventilatorio invasivo. Si bien este dispositivo posee importantes ventajas que favorecen la recuperación y rehabilitación, también es cierto que genera diversas complicaciones en la comunicación de las personas, condición que se suma a los efectos propios del COVID-19 y la frecuente historia de intubación endotraqueal previa. El objetivo de este artículo es proveer orientaciones y herramientas clínicas para el tratamiento de la fonación para la comunicación en personas con traqueostomía y COVID-19. Se considera para ello las recomendaciones de la literatura existentes a la fecha, bajo un análisis pragmático y basado en nuestra experiencia de atender a más de 561 personas con esta condición. Se exponen las características de la comunicación en esta población, su tratamiento, consideraciones para el uso de técnicas específicas y orientaciones para la mejora de la calidad de vida. Siempre con un enfoque orientado al cuidado y protección de las/os usuarias/os y el equipo de salud, en particular fonoaudiólogas y fonoaudiólogos del país.

The COVID-19 disease was declared a pandemic by the World Health Organization. When most severe, it generates a condition that requires treatment in intensive care units, which, when extended in time, requires implementing of a tracheostomy to facilitate invasive ventilatory support. Although ventilatory support has important advantages that favor recovery and rehabilitation, it generates various complications for patients' communication, a condition that adds to the effects of COVID-19 and the frequent history of previous endotracheal intubation. The aim of this article is to provide guidance and clinical tools for the treatment of phonation to facilitate communication in people with tracheostomy and COVID-19. For this, the recommendations of the existing available literature are considered, under a pragmatic analysis and based on our experience of treating more than 561 infected patients. The characteristics of communication in this population, its treatment, considerations for the use of specific techniques and guidelines to improve quality of life are exposed. Always with an approach oriented to the care and protection of users and the health team, in particular speech-language pathologists in the country.

Exploiting the Natural Properties of Extracellular Vesicles in Targeted Delivery towards Specific Cells and Tissues.

Extracellular vesicles (EVs) are important mediators of intercellular communication that participate in many physiological/pathological processes. As such, EVs have unique properties related to their origin, which can be exploited for drug delivery applications in cell regeneration, immunosuppression, inflammation, cancer treatment or cardioprotection. Moreover, their cell-like membrane organization facilitates uptake and accumulation in specific tissues and organs, which can be exploited to improve selectivity of cargo delivery. The combination of these properties with the inclusion of drugs or imaging agents can significantly improve therapeutic efficacy and selectivity, reduce the undesirable side effects of drugs or permit earlier diagnosis of diseases. In this review, we will describe the natural properties of EVs isolated from different cell sources and discuss strategies that can be applied to increase the efficacy of targeting drugs or other contents to specific locations. The potential risks associated with the use of EVs will also be addressed.