Imaging CAR-NK cells targeted to HER2 ovarian cancer with human sodium-iodide symporter-based positron emission tomography.

Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model.NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([18F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells.Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.

Etnobotánica de los barrios antiguos de Guadalajara, Jalisco, México: el uso de plantas medicinales / Ethnobotany of the old neighborhoods from Guadalajara, Jalisco, Mexico: the use of medicinal plants

Medicinal plants have been used by various cultures since pre - Hispanic times in Mexico. In this study, the use of medicinal plants in the old neighborhoods of Guadalajara, Jalisco, Mexico is described. 137 species, 130 genera and 68 families were recorded. 34% of the species belong to Asteraceae, Lamiaceae, Malvaceae and Fabaceae families. The neighborhoods of Mexicaltzingo and San Juan de Dios are the most related to the knowledge and use of medicinal plants, while El Santuario is the least similar to the rest. The diversity of uses of medicinal plants according to the Shannon index is high (between 3.0 and 4.92). The Use Value Index showed that Matricaria chamomilla L. was the species that obtained the highest valu e (0.28), followed by Gnaphalium americanum Mill. (0.23). The age group between 51 and 85 years old has greater knowledge about medicinal plants and their uses.

Las plantas medicinales han sido utilizadas por diversas culturas desde tiempos prehispánicos en México. En este estudio, se describe el uso de plantas medicinales en los barrios antiguos de Guadalajara, Jalisco, México. Se registraron 137 especies, 130 géneros y 68 familias. El 34% de las especies pertenece a las familias Asteraceae, Lamiaceae, Malvaceae y Fabaceae. Los barrios de Mexicaltzingo y San Juan de Dios son los más parecidos en cuanto al conocimiento y uso de pl antas medicinales, mientras que El Santuario es el menos afín al resto. La diversidad de usos de las plantas medicinales de acuerdo con el índice de Shannon es alta (entre 3.0 y 4.92). El Índice de Valor de Uso mostró que Matricaria chamomilla L. fue la es pecie que obtuvo el máximo valor (0.28), seguida de Gnaphalium americanum Mill. (0.23). El grupo de entre 51 - 85 de edad posee mayor conocimiento sobre las plantas medicinales y sus usos.

Cutaneous ultrasound of the nuchal-type fibroma: diagnostic clues and surgery planning.

Nuchal-type fibroma is a rare, benign tumour, arising from the connective tissue and characterized by their usual location in the posterior neck, although extra-nuchal locations may also occur. The excision of nuchal-type fibroma is curative, although it presents as a large poorly circumscribed lesion in the dermal and subcutaneous fat layer, with adipose tissue and muscle fascicles entrapment, what can lead to partial excisions and relapses. Due to its rarity, little is known about the sonographic appearances of nuchal-type fibroma. An early identification and correct extension evaluation is essential to facilitate adequate treatment. Through two clinical cases, we illustrate in this article the utility of cutaneous ultrasound in the early diagnosis of these tumours, highlighting its role in the diagnosis but also in the pre-surgical evaluation improving margins assessment and delimitation.

Time is of the Essence: Why Goals-of-Care Conversations and Prognosis Documentation Matters in Advanced Cancer Patients in an Integrated Health System.

Background: Advanced cancer patients benefit less from aggressive therapies and more from goal-directed palliative management. Early and clearly documented goals-of-care discussions, including end-of-life decision making, are essential in this patient population. Integrated healthcare systems are comprehensive care models associated with improved quality of care and lower mortality compared to other healthcare models. The role of advance care planning within our system is understudied. Methods: Patients 18 years and older with a diagnosis of advanced-stage cancer were identified over a 6-month period. Expert panel review was performed to evaluate medical appropriateness of the selected diagnostic workup and management. The role and extent of care planning was reviewed in association with the clinical context. Results: In a cohort of 82 patients, evidence-based and individualized appropriateness of medical management was found to be consistent for all patients. Eighty-two percent of patients elected for oncologic-based treatment, 5% pursued active surveillance, and 11% did not receive treatment. Seventy-three percent of patients were referred to palliative care. Fifty-six percent of patients had a full goals-of-care conversation documented; yet only 9% of goals-of-care conversations were documented by an oncologist. Prognosis was documented fully for only 22% of patients. At the end of the study period, 43 patients were deceased (52%), further indicating the critical importance of documentation. Conclusions: Within our integrated health system, we found consistent guideline- and patient-directed diagnosis and management, along with frequent integration of palliative care services. Goals-of-care conversation and prognosis documentation, especially by the oncologist, remains an area of needed improvement.

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

Concerns About Inequality in Health, Education and Income Jointly Predict Collective Actions

Introduction: Income inequality is often tolerated and justified, but when it brings about disparities in other domains of life (e.g., health or education), it may be seen with different eyes. In this research, we aimed to explore concerns regarding economic inequality in health, education, and income, and its relationship to supporting collective actions to reduce inequality. Method: We used survey data (N = 20,204, 18 countries) from the Latinobarometer 2020. We conducted descriptive analyses, latent class analyses, and analyses of multilevel linear regression to test our hypothesis. Results: We found that people were more concerned about health access and education opportunities than income inequality. We also identified two classes of people: one class concerned about education and health and the other unconcerned about inequality in any domain. In addition, results showed that all concerns and class membership predicted greater support of collective actions to reduce inequality. Conclusions: These preliminary findings suggest that concerns about education and health disparities may serve to increase awareness of overall inequality and mobilise the public.

Introducción: La desigualdad de ingresos a menudo se tolera y justifica, pero cuando esta conlleva desigualdades en otros ámbitos de la vida (e.g., salud o educación), puede que se vea con ojos diferentes. En este artículo tratamos de explorar la preocupación por la desigualdad económica en salud, educación e ingresos, así como su relación con el apoyo a acciones colectivas para reducir la desigualdad. Método: Usamos datos secundarios (N = 20 204, 18 países) del Latinobarómetro 2020. Llevamos a cabo análisis descriptivos, análisis de clases latentes y análisis de regresión multinivel. Resultados: Encontramos que la gente estaba más preocupada por el acceso a la salud y las oportunidades en educación que por la desigualdad en el ingreso. También identificamos dos perfiles de personas: unas preocupadas por la educación y la salud, y otras poco preocupadas por la desigualdad en ninguno de los ámbitos. Además, los resultados mostraron que todas las preocupaciones y los distintos perfiles predecían un mayor apoyo a las acciones colectivas para reducir la desigualdad. Conclusiones: Estos hallazgos preliminares sugieren que la preocupación por las desigualdades en salud y educación podrían servir para aumentar la conciencia sobre la desigualdad general y movilizar al público.

What Matters Most: The Documented Goals, Values and Motivators of Advanced Cancer Patients.

BACKGROUND: Goals of care conversations are essential to delivery of goal concordant care. Infrequent and inconsistent goals of care documentation potentially limit delivery of goal concordant care. METHODS: At Kaiser Permanente San Francisco Cancer Center, a standardized documentation template was designed and implemented to increase goals of care documentation by oncologists. The centralized, prompt-based template included value clarification of the goals and values of advanced cancer patients beyond treatment preferences. Documented conversations using the template during the initial pilot period were reviewed to characterization the clinical context in which conversations were recorded. Common goals and motivators were also identified. RESULTS: A total of 178 advanced cancer patients had at least 1 documented conversation by a medical oncologist using the goals of care template. Oncologists consistently documented within the template goals of therapy and motivating factors in decision making. The most frequently documented goals of care were "Avoiding Pain and Suffering," "Physical Independence," and "Living as Long as Possible." The least recorded goal was "Comfort Focused Treatment Only." CONCLUSIONS: Review of oncologist documented goals of care conversations using a prompt-based template allowed for characterization of the clinical context, therapy goals and motivators of advanced cancer patients. Communication of goals of care conversations by oncologists using a standardized prompt-based template within a centralized location has the potential to improve delivery of goal concordant care.

Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans.

The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate. Here, we have evaluated the immunogenicity of recombinant PvDBPII formulated with the adjuvants Matrix-M and GLA-SE in mice. Analysis of the antibody responses revealed comparable ELISA recognition titres as well as similar recognition of native PvDBP in P. vivax schizonts by immunofluorescence assay. Moreover, antibodies elicited by the two adjuvant formulations had similar functional properties such as avidity, isotype profile and inhibition of PvDBPII-DARC binding. Furthermore, the anti-PvDBPII antibodies were able to block the interaction of DARC with the homologous PvDBPII SalI allele as well as the heterologous PvDBPII PvW1 allele from a Thai clinical isolate that is used for controlled human malaria infections (CHMI). The cross-reactivity of these antibodies with PvW1 suggest that immunization with the PvDBPII SalI strain should neutralize reticulocyte invasion by the challenge P. vivax strain PvW1.

Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection.

There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivax Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% (n = 6) compared with unvaccinated controls (n = 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivax vaccine.

Subjective well-being, happiness, and environmental health factors related to women planning a pregnancy or pregnant, using mobile health intervention.

Objectives: To compare the environmental health results in women trying to get pregnant or pregnant using a mobile health application (Green Page) through healthcare professionals or self-completed by women, and to explore the relationship between the subjective well-being of these women with their lifestyles and environmental factors. Methods: A descriptive study with mixed methods was conducted in 2018. A mobile health survey was used in two phases. Phase 1 was a cross-sectional study through professionals (n = 1100) followed by phase 2, a convenience sampling through women's self-reporting (n = 3425). A personalized report was downloadable with health recommendations for the well-being of the mother and child. Results: Of the 3205 participants (mean age = 33 years, SD = 0.2 years), 1840 were planning a pregnancy and 1365 were pregnant. One in five pregnant women had a low level of happiness. Globally, subjective well-being and happiness were found to be negatively associated with lack of contact with nature, sedentary lifestyle, excess weight, environmental exposure, and older age in pregnancy. Precisely 45%, 60%, and 14% of women were exposed to tobacco, alcohol, and illegal drugs, respectively. The women self-reported levels of risk factors higher than when the tool was used by or through professionals. Conclusions: The use of mobile health interventions focused on environmental health during planning or pregnancy periods could help improve the quality of healthcare and foster greater involvement of women in their self-care process, thus promoting empowerment, healthier environments, and lifestyles. Ensuring equity of access and data protection are global challenges to be addressed.

Integration of Square Fiducial Markers in Patient-Specific Instrumentation and Their Applicability in Knee Surgery.

Computer technologies play a crucial role in orthopaedic surgery and are essential in personalising different treatments. Recent advances allow the usage of augmented reality (AR) for many orthopaedic procedures, which include different types of knee surgery. AR assigns the interaction between virtual environments and the physical world, allowing both to intermingle (AR superimposes information on real objects in real-time) through an optical device and allows personalising different processes for each patient. This article aims to describe the integration of fiducial markers in planning knee surgeries and to perform a narrative description of the latest publications on AR applications in knee surgery. Augmented reality-assisted knee surgery is an emerging set of techniques that can increase accuracy, efficiency, and safety and decrease the radiation exposure (in some surgical procedures, such as osteotomies) of other conventional methods. Initial clinical experience with AR projection based on ArUco-type artificial marker sensors has shown promising results and received positive operator feedback. Once initial clinical safety and efficacy have been demonstrated, the continued experience should be studied to validate this technology and generate further innovation in this rapidly evolving field.

Development of a Suite of Gadolinium-Free OATP1-Targeted Paramagnetic Probes for Liver MRI.

Five amphiphilic, anionic Mn(II) complexes were synthesized as contrast agents targeted to organic anion transporting polypeptide transporters (OATP) for liver magnetic resonance imaging (MRI). The Mn(II) complexes are synthesized in three steps, each from the commercially available trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA) chelator, with T1-relaxivity of complexes ranging between 2.3 and 3.0 mM-1 s-1 in phosphate buffered saline at an applied field strength of 3.0 T. Pharmacokinetics were assessed in female BALB/c mice by acquiring T1-weighted images dynamically for 70 min after agent administration and determining contrast enhancement and washout in various organs. Uptake of Mn(II) complexes in human OATPs was investigated through in vitro assays using MDA-MB-231 cells engineered to express either OATP1B1 or OATP1B3 isoforms. Our study introduces a new class of Mn-based OATP-targeted contrast that can be broadly tuned via simple synthetic protocols.

Population Older than 69 Had Similar Fatality Rates Independently If They Were Admitted in Nursing Homes or Lived in the Community: A Retrospective Observational Study during COVID-19 First Wave.

The aim of this study is to assess the influence of living in nursing homes on COVID-19-related mortality, and to calculate the real specific mortality rate caused by COVID-19 among people older than 20 years of age in the Balaguer Primary Care Centre Health Area during the first wave of the pandemic. We conducted an observational study based on a database generated between March and May 2020, analysing COVID-19-related mortality as a dependent variable, and including different independent variables, such as living in a nursing home or in the community (outside nursing homes), age, sex, symptoms, pre-existing conditions, and hospital admission. To evaluate the associations between the independent variables and mortality, we calculated the absolute and relative frequencies, and performed a chi-square test. To avoid the impact of the age variable on mortality and to assess the influence of the "living in a nursing home" variable, we established comparisons between infected population groups over 69 years of age (in nursing homes and outside nursing homes). Living in a nursing home was associated with a higher incidence of COVID-19 infection, but not with higher mortality in patients over 69 years of age (p = 0.614). The real specific mortality rate caused by COVID-19 was 2.270/00. In the study of the entire sample, all the comorbidities studied were associated with higher mortality; however, the comorbidities were not associated with higher mortality in the infected nursing home patients group, nor in the infected community patients over 69 years of age group (except for neoplasm history in this last group). Finally, hospital admission was not associated with lower mortality in nursing home patients, nor in community patients over 69 years of age.

Rational Coformer Selection in the Development of 6-Propyl-2-thiouracil Pharmaceutical Cocrystals.

Pharmaceutical multicomponent solids have proved to efficiently modulate the physicochemical properties of active pharmaceutical ingredients. In this context, polyphenols are interesting coformers for designing pharmaceutical cocrystals due to their wide safety profile and interesting antioxidant properties. The novel 6-propyl-2-thiouracil multicomponent solids have been obtained by mechanochemical synthesis and fully characterized by powder and single-crystal X-ray diffraction methods. The analysis of supramolecular synthons has been further performed with computational methods, with both results revealing a robust supramolecular organization influenced by the different positions of the hydroxyl groups within the polyphenolic coformers. All novel 6-propyl-2-thiouracil cocrystals show an enhanced solubility profile, but unfortunately, their thermodynamic stability in aqueous media is limited to 24 h.

Improvement of Akanthomyces lecanii resistance to tebuconazole through UV-C radiation and selective pressure on microbial evolution and growth arenas.

Tebuconazole (TEB) is a fungicide widely used in agriculture; however, its constant application has increased the emergence of resistant plant pathogenic fungal strains and reduced the effectiveness of fungi as biological control agents; for instance, the entomopathogenic and hyperparasitic fungus Akanthomyces lecanii, suitable for simultaneous biological control of insect pest and plant pathogenic fungi, is highly sensitive to fungicides. We carried out the induction of resistance to TEB in two wild type strains of A. lecanii by UV radiation and selective pressure in increasing fungicide gradients using a modified Microbial Evolution and Growth Arena (MEGA), to produce A. lecanii strains that can be used as biological control agent in the presence of tebuconazole. Nine UV-induced and three naturally adapted A. lecanii strains were resistant to TEB at the agriculturally recommended dose, and three irradiated strains were resistant to TEB concentration ten times higher; moreover, growth, sporulation rates, production of hydrolytic enzymes, and virulence against the hemipteran Coccus viridis, a major pest of coffee crops, were not affected in the TEB-resistant strains. These A. lecanii TEB-resistant strains would have a greater opportunity to develop and to establish themselves in fields where the fungicide is present and can be used in a combined biological-chemical strategy to improve insect and plant pathogenic fungal control in agriculture. Also, the selective pressure through modified MEGA plate methodology can be used for the adaptation of entomopathogenic filamentous fungi to withstand other chemical or abiotic stresses that limits its effectiveness for pest control.