Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate the antitumor immune response, including chimeric antigen ...receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene-modified T cells, and therapy with tumor-infiltrating lymphocytes (TILs). The outstanding results of CAR-T cells in some hematologic malignancies have launched the investigation of ACT in patients with refractory solid malignancies. However, certain characteristics of solid tumors, such as their antigenic heterogeneity and immunosuppressive microenvironment, hamper the efficacy of antigen-targeted treatments. Other ACT modalities, such as TIL therapy, have emerged as promising new strategies. TIL therapy has shown safety and promising activity in certain immunogenic cancers, mainly advanced melanoma, with an exciting rationale for its combination with immune checkpoint inhibitors. However, the implementation of TIL therapy in clinical practice is hindered by several biological, logistic, and economic challenges. In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell therapy in patients with solid tumors.
This paper presents the new L- LC induction heating generator and probes that, in resonance, are equivalent to a series resonant inverter. This equivalence is then used to compare both topologies, ...extracting the advantages and disadvantages of the L-LC usage. In addition, based on this equivalence, a design procedure is proposed that covers all possible L-LC configurations. Finally, some experimental results are presented, showing waveforms during normal and short-circuit operation.
Introducción: el Régimen Subsidiado (RS) del sistema de salud colombiano tiene problemáticas estructurales que no han sido solucionadas y son pocos los estudios que profundizan en la explicación de ...estas. Objetivo: explorar la experiencia en la dirección estratégica y gestión operativa y financiera de este régimen, sus aspectos operativos y de gestión del riesgo en esta población, así como las diferencias percibidas frente al Régimen Contributivo. Metodología: estudio cualitativo. Se utilizó el análisis del discurso desde la perspectiva sociohermenéutica como técnica analítica. Se entrevistaron diez participantes, entre directivos de aseguradoras del RS y gestores del sistema de salud. Las entrevistas fueron grabadas y anonimizadas, previo consentimiento informado. Resultados: emergen tres patrones discursivos que explican la gestión del riesgo en el RS y su diferenciación con el contributivo. Estos patrones se conectan por medio del rol de los determinantes sociales de la salud como ordenador principal de los procesos de salud-enfermedad y de atención en este régimen. A su vez, estas condiciones de vida son las que determinan de manera importante el perfil epidemiológico, acceso, costo de la atención y en general la forma cómo se consumen los servicios de salud por la población afiliada. Discusión: la literatura del aseguramiento en salud reporta que la gestión del riesgo es una función central y supone un ejercicio estratégico para el adecuado manejo de la siniestralidad para optimizar el uso de la Unidad de Pago por Capitación (UPC) asignada. Los hallazgos muestran que los determinantes sociales de la salud no están siendo tenidos en cuenta como ordenador para la atención, por lo tanto, la gestión del riesgo se centra en la atención de patologías en estados avanzados. Conclusiones: los actores perciben que en general, la situación de salud de los afiliados en este régimen es más grave, más complicada y con mayor carga, lo cual genera una tensión en materia de suficiencia de la unidad per cápita. Existe una ausencia discursiva sobre el rol del modelo de atención y su correlación con las necesidades de esta población.
Background
Patients' lack of knowledge about their own disease may function as a barrier to shared decision‐making and well‐being. This study aimed to evaluate the impact of written educational ...materials on breast cancer patients.
Methods
This multicenter, parallel, unblinded, randomized trial included Latin American women aged ≥18 years with a recent breast cancer diagnosis yet to start systemic therapy. Participants underwent randomization in a 1:1 ratio to receive a customizable or standard educational brochure. The primary objective was accurate identification of molecular subtype. Secondary objectives included identification of clinical stage, treatment options, participation in decision‐making, perceived quality of information received, and illness uncertainty. Follow‐up occurred at 7–21 and 30–51 days post‐randomization. ClinicalTrials.gov identifier: NCT05798312.
Results
One hundred sixty‐five breast cancer patients with a median age of 53 years and 61 days from diagnosis were included (customizable: 82; standard: 83). At first available assessment, 52%, 48%, and 30% identified their molecular subtype, disease stage, and guideline‐endorsed systemic treatment strategy, respectively. Accurate molecular subtype and stage identification were similar between groups. Per multivariate analysis, customizable brochure recipients were more likely to identify their guideline‐recommended treatment modalities (OR: 4.20,p = 0.001). There were no differences between groups in the perceived quality of information received or illness uncertainty. Customizable brochure recipients reported increased participation in decision‐making (p = 0.042).
Conclusions
Over one third of recently diagnosed breast cancer patients are incognizant of their disease characteristics and treatment options. This study demonstrates a need to improve patient education and shows that customizable educational materials increase patients' understanding of recommended systemic therapies according to individual breast cancer characteristics.
The mountain chain of the Sierra Madre de Chiapas in southern Mexico is globally significant for its biodiversity and is one of the most important coffee production areas of Mexico. It provides water ...for several municipalities and its biosphere reserves are important tourist attractions. Much of the forest cover outside the core protected areas is in fact coffee grown under traditional forest shade. Unless this (agro)forest cover can be sustained, the biodiversity of the Sierra Madre and the environmental services it provides are at risk. We analyzed the threats to livelihoods and environment from climate change through crop suitability modeling based on downscaled climate scenarios for the period 2040 to 2069 (referred to as 2050s) and developed adaptation options through an expert workshop. Significant areas of forest and occasionally coffee are destroyed every year by wildfires, and this problem is bound to increase in a hotter and drier future climate. Widespread landslides and inundations, including on coffee farms, have recently been caused by hurricanes whose intensity is predicted to increase. A hotter climate with more irregular rainfall will be less favorable to the production of quality coffee and lower profitability may compel farmers to abandon shade coffee and expand other land uses of less biodiversity value, probably at the expense of forest. A comprehensive strategy to sustain the biodiversity, ecosystem services and livelihoods of the Sierra Madre in the face of climate change should include the promotion of biodiversity friendly coffee growing and processing practices including complex shade which can offer some hurricane protection and product diversification; payments for forest conservation and restoration from existing government programs complemented by private initiatives; diversification of income sources to mitigate risks associated with unstable environmental conditions and coffee markets; integrated fire management; development of markets that reward sustainable land use practices and forest conservation; crop insurance programs that are accessible to smallholders; and the strengthening of local capacity for adaptive resource management.
Bacterial pneumonia and meningitis are vaccine-preventable diseases. Sentinel surveillance provides relevant information about their behavior.
To present the data from sentinel surveillance carried ...out at the Fundación HOMI, Fundación Hospital Pediátrico La Misericordia in 2016.
We conducted a descriptive study from January 1 to December 31, 2016, on the daily surveillance of patients under 5 years of age diagnosed with pneumonia or bacterial meningitis according to PAHO's definitions. We identified the microorganisms using the automated VITEKTM 2 system. Bacterial isolates were sent to the Microbiology Group at the Colombian Instituto Nacional de Salud for confirmation, serotyping, phenotypic, and genotypic characterization. Antimicrobial susceptibility profiles were established.
From 1,343 suspected cases of bacterial pneumonia, 654 (48.7%) were probable, 84% had complete Hib vaccination schedules, and 87% had complete pneumococcal vaccination schedules for age. Blood culture was taken in 619 (94.6%) and 41 (6.6%) were positive while S. pneumoniae was isolated in 17 (41%) of them. The most frequent serotype was 19A in five cases (29.4%), and four 19A serotypes were associated with the reference isolate ST320. The incidence rate of probable bacterial pneumonia was 7.3 cases/100 hospitalized patients, and lethality was 2.1%. As for bacterial meningitis, 22 suspected cases were reported, 12 (54%) were probable, four (33%) were confirmed: two by Escherichia coli and two by group C N. meningitidis. The incidence of probable bacterial meningitis was 0.14 cases/100 hospitalized patients.
Streptococcus pneumoniae serotypes 19A and 3 were the most frequent cause of pneumonia. Spn19A is related to the multi-resistant clone ST320. Strengthening and continuing this strategy will allow understanding the impact of vaccination.
Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors ...involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.
Apoptosis and later autolysis are biological processes which take place in
during industrial fermentation processes, which involve costly and time-consuming aging periods. Therefore, the ...identification of potential cell death biomarkers can contribute to the creation of a long-term strategy in order to improve and accelerate the winemaking process. Here, we performed a proteomic analysis based on the detection of possible apoptosis and autolysis protein biomarkers in two industrial yeast strains commonly used in post-fermentative processes (sparkling wine secondary fermentation and biological aging) under typical sparkling wine elaboration conditions. Pressure had a negatively effect on viability for flor yeast, whereas the sparkling wine strain seems to be more adapted to these conditions. Flor yeast strain experienced an increase in content of apoptosis-related proteins, glucanases and vacuolar proteases at the first month of aging. Significant correlations between viability and apoptosis proteins were established in both yeast strains. Multivariate analysis based on the proteome of each process allowed to distinguish among samples and strains. The proteomic profile obtained in this study could provide useful information on the selection of wine strains and yeast behavior during sparkling wine elaboration. Additionally, the use of flor yeasts for sparkling wine improvement and elaboration is proposed.
Summary The objective of the current study was to determine the short-term effects of trigger point dry needling (TrP-DN) alone or combined with neuroscience education on pain, disability, ...kinesiophobia and widespread pressure sensitivity in patients with mechanical low back pain (LBP). Twelve patients with LBP were randomly assigned to receive either TrP-DN (TrP-DN) or TrP-DN plus neuroscience education (TrP-DN + EDU). Pain intensity (Numerical Pain Rating Scale, 0–10), disability (Roland–Morris Disability Questionnaire-RMQ-, Oswestry Low Back Pain Disability Index-ODI), kinesiophobia (Tampa Scale of Kinesiophobia-TSK), and pressure pain thresholds (PPT) over the C5–C6 zygapophyseal joint, transverse process of L3 vertebra, second metacarpal, and tibialis anterior muscle were collected at baseline and 1-week after the intervention. Patients treated with TrP-DN + EDU experienced a significantly greater reduction of kinesiophobia ( P = 0.008) and greater increases in PPT over the transverse process of L3 ( P = 0.049) than those patients treated only with TrP-DN. Both groups experienced similar decreases in pain, ODI and RMQ, and similar increases in PPT over the C5/C6 joint, second metacarpal, and tibialis anterior after the intervention (all, P > 0.05). The results suggest that TrP-DN was effective for improving pain, disability, kinesiophobia and widespread pressure sensitivity in patients with mechanical LBP at short-term. The inclusion of a neuroscience educational program resulted in a greater improvement in kinesiophobia.
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