CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis.

Due to the limited effectiveness of current treatments, the survival rate of patients with metastatic castration-resistant prostate cancer (mCRPC) is significantly reduced. Consequently, it is imperative to identify novel therapeutic targets for managing these patients. Since the invasive ability of cells is crucial for establishing and maintaining metastasis, the aim of this study was to identify the essential regulators of invasive abilities of mCRPC cells by conducting two independent high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using siRNA technology, with protein arginine methyltransferase 7 (PRMT7) emerging as the most promising candidate. We demonstrated that its inhibition or depletion via genetic or pharmacological approaches significantly reduces invasive, migratory and proliferative abilities of mCRPC cells in vitro. Moreover, we confirmed that PRMT7 ablation reduces cell dissemination in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules by methylating various transcription factors, such as FoxK1, resulting in the loss of adhesion from the primary tumor and increased motility of mCRPC cells. Furthermore, PRMT7 higher expression correlates with tumor aggressivity and poor overall survival in prostate cancer patients. Thus, this study demonstrates that PRMT7 is a potential therapeutic target and potential biomarker for mPCa.

Public policy interventions to mitigate household food insecurity in Canada: a systematic review.

OBJECTIVE: The objective of this systematic review is to synthesise the evidence on public policy interventions and their ability to reduce household food insecurity (HFI) in Canada. DESIGN: Four databases were searched up to October 2023. Only studies that reported on public policy interventions that might reduce HFI were included, regardless of whether that was the primary purpose of the study. Title and abstract screening, full-text screening, data extraction, risk of bias and certainty of the evidence assessments were conducted by two reviewers. RESULTS: Seventeen relevant studies covering three intervention categories were included: income supplementation, housing assistance programmes and food retailer subsidies. Income supplementation had a positive effect on reducing HFI with a moderate to high level of certainty. Housing assistance programmes and food retailer studies may have little to no effect on HFI; however, there is low certainty in the evidence that could change as evidence emerges. CONCLUSION: The evidence suggests that income supplementation likely reduces HFI for low-income Canadians. Many questions remain in terms of how to optimise this intervention and additional high-quality studies are still needed.

Referral to and engagement in substance use disorder treatment within opioid intervention courts in New York: a qualitative study of implementation barriers and facilitators.

BACKGROUND: People with opioid use disorder (OUD) are frequently in contact with the court system and have markedly higher rates of fatal opioid overdose. Opioid intervention courts (OIC) were developed to address increasing rates of opioid overdose among court defendants by engaging court staff in identification of treatment need and referral for opioid-related services and building collaborations between the court and OUD treatment systems. The study goal was to understand implementation barriers and facilitators in referring and engaging OIC clients in OUD treatment. METHODS: Semi-structured interviews were conducted with OIC stakeholders (n = 46) in 10 New York counties in the United States, including court coordinators, court case managers, and substance use disorder treatment clinic counselors, administrators, and peers. Interviews were recorded and transcribed and thematic analysis was conducted, guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, employing both inductive and deductive coding. RESULTS: Results were conceptualized using EPIS inner (i.e., courts) and outer (i.e., OUD treatment providers) implementation contexts and bridging factors that impacted referral and engagement to OUD treatment from the OIC. Inner factors that facilitated OIC implementation included OIC philosophy (e.g., non-punitive, access-oriented), court organizational structure (e.g., strong court staff connectedness), and OIC court staff and client characteristics (e.g., positive medications for OUD [MOUD] attitudes). The latter two also served as barriers (e.g., lack of formalized procedures; stigma toward MOUD). Two outer context entities impacted OIC implementation as both barriers and facilitators: substance use disorder treatment programs (e.g., attitudes toward the OIC and MOUD; operational characteristics) and community environments (e.g., attitudes toward the opioid epidemic). The COVID-19 pandemic and bail reform were macro-outer context factors that negatively impacted OIC implementation. Facilitating bridging factors included staffing practices that bridged court and treatment systems (e.g., peers); barriers included communication and cultural differences between systems (e.g., differing expectations about OIC client success). CONCLUSIONS: This study identified key barriers and facilitators that OICs may consider as this model expands in the United States. Referral to and engagement in OUD treatment within the OIC context requires ongoing efforts to bridge the treatment and court systems, and reduce stigma around MOUD.

Functional analysis of the AUG initiator codon context reveals novel conserved sequences that disfavor mRNA translation in eukaryotes.

mRNA translation is a fundamental process for life. Selection of the translation initiation site (TIS) is crucial, as it establishes the correct open reading frame for mRNA decoding. Studies in vertebrate mRNAs discovered that a purine at -3 and a G at +4 (where A of the AUG initiator codon is numbered + 1), promote TIS recognition. However, the TIS context in other eukaryotes has been poorly experimentally analyzed. We analyzed in vitro the influence of the -3, -2, -1 and + 4 positions of the TIS context in rabbit, Drosophila, wheat, and yeast. We observed that -3A conferred the best translational efficiency across these species. However, we found variability at the + 4 position for optimal translation. In addition, the Kozak motif that was defined from mammalian cells was only weakly predictive for wheat and essentially non-predictive for yeast. We discovered eight conserved sequences that significantly disfavored translation. Due to the big differences in translational efficiency observed among weak TIS context sequences, we define a novel category that we termed 'barren AUG context sequences (BACS)', which represent sequences disfavoring translation. Analysis of mRNA-ribosomal complexes structures provided insights into the function of BACS. The gene ontology of the BACS-containing mRNAs is presented.

One-Pot, Optimized Microwave-Assisted Synthesis of Difunctionalized and B-N Co-Doped Carbon Dots: Structural Characterization.

In this work, we employed a novel microwave-assisted synthesis method to produce nitrogen and boron co-doped carbon dots (B-N co-doped CDs). To achieve optimal synthesis, we conducted a comprehensive parameter modulation approach, combining various synthesis temperatures, times, and precursor concentrations, while keeping the power constant at 150 W and pH 5. Using maximum fluorescence emission as our response variable, the best conditions were identified as 120 °C, 3 min, and a precursor concentration of 1 mg/mL. Characterization using field emission scanning electron microscopy revealed these CDs to have a spherical morphology with an average size of 10.9 ± 3.38 nm. Further high-resolution transmission electron microscopy showed an interplanar distance of 0.23 nm, which is in line with prior findings of CDs that present a 0.21 nm distance corresponding to the (100) plane of graphite. Optical properties were ascertained through UV-vis absorption, identifying distinct π-π* and n-π* transitions. Fluorescence spectroscopy highlighted an emission peak at 375 nm when excited at 295 nm, achieving a quantum yield of 56.7%. Fourier-transform infrared spectroscopy and Raman spectroscopy analyses confirmed the boronic acid and amine groups' presence, underscoring the graphitic nature of the core and the co-doping of boron and nitrogen. These empirical observations were compared with theoretical investigations through simulated Raman spectra, proposing a potential structure for the CDs. X-ray photoelectron spectroscopy further endorsed the co-doping of nitrogen and boron, along with the detection of the specified functional groups. All these characteristics could lend this nanomaterial to different types of applications such as fluorescent probes for a broad range of analytes and for fluorescent cell imaging.

Side effects screening and early intervention to impact in quality of life of patients with gynecological cancers (HALIS study).

BACKGROUND: Advances in the treatment of gynecological cancers have led to increased survival in patients with gynecological cancers. Nevertheless, patients may still experience prevalent long term consequences, including lower limb lymphedema, depression, anxiety, sexual dysfunction, malnutrition, and sarcopenia, that negatively impact their quality of life. PRIMARY OBJECTIVE: To assess the impact on self-perceived quality of life of systematic screening and early treatment of lower limb lymphedema, anxiety and depression, sexual dysfunction, and sarcopenia and malnutrition compared with standard practice. STUDY HYPOTHESIS: Systematic screening with validated questionnaires leading to early diagnosis and treatment of side effects will have a positive impact on quality of life. TRIAL DESIGN: This prospective clinical trial will randomize candidates for surgery to either standard of care or systematic screening every 2 months for 2 years. Quality of life data will be collected every 4 months. After randomization, patients in the control group will follow standard usual care. Their screening scales will not be considered. In the experimental group, positive screenings will generate an alert to the physician, and patients will be referred to the corresponding specific area (rehabilitation unit, psycho-oncology unit, sexual health unit, or nutrition unit). MAJOR INCLUSION AND XCLUSION CRITERIA: Patients aged ≥18 years with ovarian, cervical, or endometrial cancer who are candidates for surgery will be included. PRIMARY ENDPOINT: Self-reported quality of life questionnaire score. SAMPLE SIZE: 168 patients will be randomized to detect a difference of 6 points in the questionnaires. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Study completion is estimated for January 2026 and the results will be presented in May 2026. TRIAL REGISTRATION NUMBER: NCT05918770.

Aplicación del Modelo de Adaptación de Roy en el contexto comunitario / Applying Roy's adaptation model to a community context

Introducción. Este artículo proporciona un aporte importante desde la aplicación del Modelo de Adaptación de Callista Roy a grupos. Objetivo. Promover comportamientos adaptativos a través de estrategias de atención primaria en salud dirigidas a un grupo de adultos mayores con enfermedad crónica que habitan en un municipio del departamento de Cundinamarca Colombia; Materiales y Métodos. Abordaje cualitativo tipo investigación-acción participativa. La enfermera utilizó la observación participante, y caracterizó la comunidad; además, con preguntas exploratorias les permitió reconocer sus problemas y proponer estrategias de mejora, incluso para su propia salud; posteriormente se aplicó el proceso de atención de enfermería. Resultados. Se logró valorar el comportamiento del grupo a través de los modos físico, auto-concepto o identidad grupal, la función del rol o unidad de funcionamiento de la sociedad e integridad social y la interdependencia o contexto social en el que funciona el grupo. Discusión. Aplicar el Modelo en la práctica permite reconocer situaciones negativas en los grupos para favorecer procesos de afrontamiento innovadores y controlar los estímulos ambientales en el contexto comunitario. Las habilidades en la valoración deben ser agudas ya que son la clave para la aplicación del modelo de Roy en la práctica comunitaria. Conclusiones. Se identificaron los estímulos que desencadenan los principales problemas de adaptación y se implementó un plan de cuidado con el desarrollo de estrategias para la adaptación, tales como la visita domiciliaria, encuentros intergeneracionales, participación comunitaria con grupos de apoyo creados por la municipalidad y la educación en salud con el fin de promover la adaptación del grupo.

Introduction: This article is an important contribution to the application of Callista Roy's Adaptation Model to groups. Objective: To promote adaptive behaviors through primary health care strategies for a group of chronically ill older adults living in a municipality in the department of Cundinamarca, Colombia. Materials and methods: A qualitative participatory action research approach was used. A nurse used participant observation and characterized the community; besides, with exploratory questions, the nurse enabled them to identify their problems and suggest strategies for improvement, including for their own health. Subsequently, the nursing care process was applied. Results: Group behavior was assessed through the following modes of adaptation: physiologic adaptation, self-concept or group identity, role-function adaptation or unit of social functioning and social integrity, and interdependence adaptation or social context in which the group functions. Discussion: Applying Roy's model in practice makes it possible to identify negative situations in groups, promote innovative coping processes, and control environmental stimuli in a community. Assessment skills must be sharp, as they are key to applying Roy's model to community practice. Conclusions: The stimuli that trigger the main adaptation problems were identified, and a nursing care plan was implemented developing adaptation strategies, such as home visits, intergenerational meetings, community participation with support groups created by the municipality, and health education, to promote group adaptation.

Introdução. Este artigo oferece uma contribuição importante da aplicação do Modelo de Adaptação de Callista Roy a grupos. Objetivo. Promover comportamentos adaptativos por meio de estratégias de atenção primária à saúde voltadas para um grupo de idosos com doenças crônicas que vivem em um município do departamento de Cundinamarca, Colômbia; Materiais e métodos. Abordagem de pesquisa de ação participativa qualitativa. A enfermeira utilizou a observação participante e caracterizou a comunidade; além disso, perguntas exploratórias permitiram que eles reconhecessem seus problemas e propusessem estratégias de melhoria, inclusive para sua própria saúde; posteriormente, foi aplicado o processo de assistência de enfermagem. Resultados. Foi possível avaliar o comportamento do grupo por meio de modos físicos, autoconceito ou identidade do grupo, função do papel ou unidade de funcionamento da sociedade e integridade social e interdependência ou contexto social no qual o grupo funciona. Discussão. A aplicação do Modelo na prática permite o reconhecimento de situações negativas em grupos para favorecer processos inovadores de enfrentamento e controlar os estímulos ambientais no contexto da comunidade. As habilidades de avaliação devem estar afiadas, pois são a chave para a aplicação do Modelo de Roy na prática comunitária. Conclusões. Os estímulos que desencadeiam os principais problemas de enfrentamento foram identificados e um plano de cuidados foi implementado com o desenvolvimento de estratégias de enfrentamento, como visitas domiciliares, encontros intergeracionais, participação comunitária com grupos de apoio criados pelo município e educação em saúde para promover o enfrentamento em grupo.

Oral transmission of Chagas disease from a One Health approach: A systematic review.

OBJECTIVE: To analyse acute Chagas disease (CD) outbreaks through a qualitative systematic review and discuss the determinants for its prevention and control. METHODS: Review of studies in which clinical cases of oral transmission were confirmed by parasitological and/or serological tests that included an epidemiological investigation of sources of infection, vectors and reservoirs. RESULTS: Thirty-two outbreaks (1965-2022) were analysed. The main foods involved in oral transmission outbreaks are homemade fruit juices. Different species of vectors were identified. Reservoirs were mainly dogs, rodents and large American opossums (didelphids). CONCLUSION: Under a One Health approach, environmental changes are one of the factors responsible of the rise of oral transmission of CD. Entomological surveillance of vectors and control of the changes in wild and domestic reservoirs and reinforcement of hygiene measures around food in domestic and commercial sites are needed.

Detection of Acetaminophen in Groundwater by Laccase-Based Amperometric Biosensors Using MoS2 Modified Carbon Paper Electrodes.

The use of enzyme-based biosensors for the detection and quantification of analytes of interest such as contaminants of emerging concern, including over-the-counter medication, provides an attractive alternative compared to more established techniques. However, their direct application to real environmental matrices is still under investigation due to the various drawbacks in their implementation. Here, we report the development of bioelectrodes using laccase enzymes immobilized onto carbon paper electrodes modified with nanostructured molybdenum disulfide (MoS2). The laccase enzymes were two isoforms (LacI and LacII) produced and purified from the fungus Pycnoporus sanguineus CS43 that is native to Mexico. A commercial purified enzyme from the fungus Trametes versicolor (TvL) was also evaluated to compare their performance. The developed bioelectrodes were used in the biosensing of acetaminophen, a drug widely used to relieve fever and pain, and of which there is recent concern about its effect on the environment after its final disposal. The use of MoS2 as a transducer modifier was evaluated, and it was found that the best detection was achieved using a concentration of 1 mg/mL. Moreover, it was found that the laccase with the best biosensing efficiency was LacII, which achieved an LOD of 0.2 µM and a sensitivity of 0.108 µA/µM cm2 in the buffer matrix. Moreover, the performance of the bioelectrodes in a composite groundwater sample from Northeast Mexico was analyzed, achieving an LOD of 0.5 µM and a sensitivity of 0.015 µA/µM cm2. The LOD values found are among the lowest reported for biosensors based on the use of oxidoreductase enzymes, while the sensitivity is the highest currently reported.

Effect of paediatric early warning systems (PEWS) implementation on clinical deterioration event mortality among children with cancer in resource-limited hospitals in Latin America: a prospective, multicentre cohort study.

BACKGROUND: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America. METHODS: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics. FINDINGS: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29). INTERPRETATION: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer. FUNDING: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Impact of ileostomy in the adjuvant treatment and outcome of colon cancer.

BACKGROUND: After tumor resection, a preventive diverting loop ileostomy creation is a routine surgical procedure to prevent anastomotic leakage and infections and to preclude secondary surgeries. Despite its benefits, several studies have proposed potential complications that extend the disease course by impairing the feasibility of adjuvant chemotherapy and adherence. PURPOSE: The aim of this study was to evaluate the impact of ileostomy complications on the adherence to adjuvant treatment and overall survival (OS) of colon cancer (CC) patients. METHODS: Retrospective, observational study. Patients diagnosed with colon adenocarcinoma were treated between January 2010 and December 2020 at the National Cancer Institute in Mexico. STATISTICAL ANALYSIS: χ2 and t-test, Kaplan-Meier, log-rank, and Cox regression. Statistical significance differences were assessed when p was bilaterally < 0.05. RESULTS: The most frequent complications of loop-derived ileostomy were hydro-electrolytic dehydration (50%), acute kidney injury (AKI) (26%), grade 1-2 diarrhea (28%), and grade 3-4 diarrhea (21%) (p = 0.001). Patients with complete chemotherapy did not reach the median OS. In contrast, the median OS for patients with non-complete chemotherapy was 56 months (p = 0.023). Additionally, 5-year OS reached to 100% in the early restitution group, 85% in the late restitution group, and 60% in the non-restitution group (p = 0.016). Finally, AKI (p = 0.029; 95% confidence interval (CI) 3.348 [1.133-9.895]), complete chemotherapy (p = 0.028; 95% CI 0.376 [0.105-0.940]), and reversed ileostomy (p = 0.001; 95% CI 0.125 [0.038-0.407]) remained as predictors of overall survival for patients with CC treated with a loop ileostomy. CONCLUSIONS: Our results emphasize the early stoma reversal restitution as a safe and feasible alternative to prevent severe complications related to ileostomies which improve chemotherapy adherence and overall survival of colon cancer patients. This is one of the pioneer studies analyzing the impact of ileostomy on treatment adherence and outcome of Latin American patients with colon cancer. TRIAL REGISTRATION: Retrospective study No. 2021/045, in April 2021.

Impact of atrial fibrillation in onco-hematological patients in Europe: a targeted literature review.

INTRODUCTION: Atrial fibrillation (AF) is a common complication in cancer patients, and the increased risk associated with certain therapies poses a major challenge. The objective was to determine the clinical and economic burden of AF in onco-hematological patients in Europe. AREAS COVERED: A targeted literature review was completed for observational, retrospective and case studies, and reviews on AF in onco-hematology published between January 2010 and 2022 in PubMed, Science Direct, Medes and IBECS. The search was based on epidemiology, cost, health-related quality of life (HRQoL), disease burden and management, and patient journey. Thirty-one studies fulfilled eligibility criteria. Annual incidence of AF during treatment varies up to 25%, and increased with first-generation Bruton tyrosine kinase inhibitors (BTKi). Risk factors include age ≥65, prior AF or hypertension, hyperlipidemia and ibrutinib use. Complications are managed with anticoagulants and/or antiarrhythmics, and regular monitoring. When AF is no longer controllable, dose reduction or discontinuation is recommended. No data on costs, HRQoL and patient journey were identified. EXPERT OPINION: There is scarce and heterogeneous information on AF in onco-hematology in Europe. Available evidence reports a higher risk of AF associated with first-generation BTKi. Further studies are needed to understand the burden of AF in these patients.

Unprecedented recent regional increase in organic carbon and lithogenic fluxes in high altitude Pyrenean lakes.

We have conducted a monitoring survey and paleolimnological study of a W-E transect of six high altitude lakes (1870-2630 m asl) in the western and central Pyrenees (Spain) to evaluate the regional response to current global change in high altitude Mediterranean mountains. The reconstructed Total Organic Carbon (TOCflux) and lithogenic (Lflux) fluxes during the last 1200 years show the expected variability as lakes differ in altitude, geological and climate settings, limnological properties and human impact history. However, all show unique patterns after 1850 CE, particularly during the Great Acceleration (after 1950 CE). Recent Lflux increase could be related to higher erodibility by rainfall and run-off during the longer snow-free season in the Pyrenees. In all sites, higher TOCflux and geochemical (lower δ13COM, lower C/N) and biological (diatom assemblages) signatures since 1950 CE suggest an increase in algal productivity, likely favored by warmer temperatures and higher nutrient deposition. These recent, unprecedented Lflux and TOCflux increases, in spite of their diverse history and limnological properties of the lakes, demonstrate the regional impact of the Great Acceleration not only in the ecological dynamics of alpine lakes but also in the hydrological cycle in high altitude mountain watersheds.

Kras oncogene ablation prevents resistance in advanced lung adenocarcinomas.

KRASG12C inhibitors have revolutionized the clinical management of patients with KRASG12C-mutant lung adenocarcinoma. However, patient exposure to these inhibitors leads to the rapid onset of resistance. In this study, we have used genetically engineered mice to compare the therapeutic efficacy and the emergence of tumor resistance between genetic ablation of mutant Kras expression and pharmacological inhibition of oncogenic KRAS activity. Whereas Kras ablation induces massive tumor regression and prevents the appearance of resistant cells in vivo, treatment of KrasG12C/Trp53-driven lung adenocarcinomas with sotorasib, a selective KRASG12C inhibitor, caused a limited antitumor response similar to that observed in the clinic, including the rapid onset of resistance. Unlike in human tumors, we did not observe mutations in components of the RAS-signaling pathways. Instead, sotorasib-resistant tumors displayed amplification of the mutant Kras allele and activation of xenobiotic metabolism pathways, suggesting that reduction of the on-target activity of KRASG12C inhibitors is the main mechanism responsible for the onset of resistance. In sum, our results suggest that resistance to KRAS inhibitors could be prevented by achieving a more robust inhibition of KRAS signaling mimicking the results obtained upon Kras ablation.

Mid-term symptomatic relief after platelet-rich plasma infiltration in vulvar lichen sclerosus.

PURPOSE: Vulvar lichen sclerosus (LS) is a chronic, progressive, autoimmune dermatologic condition that causes cutaneous changes accompanied by pruritus and pain. There remains a small population with vulvar LS refractory to topical corticosteroids. Injection of platelet-rich plasma (PRP) has been reported to have positive effects on tissue repair. The aim of this pilot study was to evaluate changes in symptom scores during and after PRP vulvar infiltration. METHODS: Three PRP infiltrations were administered to 28 female postmenopausal patients with biopsy-proved LS with unsatisfactory response to steroid therapy. Change in score according to the Clinical Scoring System for Vulvar Lichen Sclerosus (CSS) was measured on six occasions over the course of a year. We used growth curve modeling to measure change over the period of the study. RESULTS: Women in our study experienced a statistically significant improvement in auto-assessed symptoms of vulvar lichen sclerosus, and this improvement appears to be maintained throughout the monitoring year. CONCLUSION: Platelet-rich plasma may have a role in symptom relief in certain cases of patients with LS that do not respond to first-line therapy.

Comparison of virtual reality and physical simulation training in first-year radiography students in South America.

INTRODUCTION: The aim of this study was to comparatively evaluate the learning outcomes achieved by first-year radiography students educated with either virtual reality (VR) simulation training or physical simulation training. The implementation of VR has been proposed to enhance learning in radiography students and provide a more effective and efficient approach to simulation. However, the learning outcomes achieved with this approach have not been widely investigated. METHODS: Through stratified randomisation, 188 radiography students were allocated to one of two matched groups: a VR group (using Virtual Medical Coaching's Radiography simulation) and a physical simulation group (using Philips' X-ray equipment). Both groups were taught 31 radiography views over one 25-week semester. Both groups were assessed in an Objective Structured Clinical Examination (OSCE), using actors as patients in a physical X-ray environment. Assessment was conducted by assigning objective count scores for five assessment criteria. RESULTS: The VR group achieved shorter OSCE duration and fewer errors in moving equipment and patient positioning: these results were statistically significant (P < 0.00). There was no significant difference in the frequency of errors in radiographic exposure setting between the VR and the physical simulation group. The current findings concur with the limited number of published studies concerning VR simulation in radiography. CONCLUSIONS: The results of this study demonstrated superior effectiveness and efficiency in the VR group. This provides preliminary evidence to introduce VR simulation in the host institution and provide evidence that it may be possible to replace the use of physical simulation across other years of the degree. Further research investigating these possibilities is warranted.

Adrenal Grafts in the Central Nervous System: Chromaffin and Chromaffin Progenitor Cell Transplantation.

Chromaffin cells are neuroendocrine cells that synthesize and release catecholamines and neuroactive molecules. They have been used experimentally in animal models and preclinical studies as a source for cell replacement therapy in Parkinson's disease. The long-term cell survival of these cells in the nervous system is limited, and the observed motor improvements are highly variable. An alternative source for transplantation is chromaffin progenitor cells. These cells have the capacity of self-renewal and to form spheres under low attachment conditions. They release higher quantities of dopamine than chromaffin cells and can differentiate into dopaminergic-like neurons in vitro. The transplantation of these cells into Parkinson's disease animal models has shown to induce stronger motor improvements and better survival rates than chromaffin cells. However, several aspects of chromaffin progenitor cell transplantation remain to be elucidated. Here, we describe methods to isolate and culture chromaffin and chromaffin progenitor cells from the adult cattle adrenal glands. We also describe the procedure for their transplantation into the nervous system and give recommendations for their histological analysis.

Mujeres transgénero viviendo con síntomas asociados al tratamiento antirretroviral: estudio fenomenológico

Objetivo: Comprender las experiencias de mujeres transgénero con VIH que viven con síntomas asociados al tratamiento antirretroviral en Bucaramanga. Material y Método: se realizó un estudio fenomenológico basado en el método de Colaizzi durante los meses de febrero a marzo de 2022; los participantes fueron invitados a contribuir en el estudio por intermedio de una madre transgénero, contactada a través de una red comunitaria; se utilizó un muestreo de "bola de nieve"; el primer contacto se realizó de manera telefónica con cada una de las posibles participantes, verificando los criterios de inclusión; se realizaron entrevistas a profundidad y la saturación teórica se dio al realizar la séptima entrevista, pero se decidió completar 10 entrevistas para ampliar el análisis. Resultados: Se identificaron 5 unidades temáticas: cerrando los ojos a la verdad, experimentado expresiones negativas, entre el ir y venir de los síntomas, generando estrategias para el control de síntomas y renaciendo a una nueva vida. Conclusiones: En las mujeres transgénero, la experiencia de síntomas asociados al tratamiento antirretroviral, es un proceso difícil, pero se posibilita por el apoyo en el control de síntomas y el apoyo familiar y social.

Objective: To understand the experiences of HIV-positive transgender women living with antiretroviral treatment-related symptoms in Bucaramanga, Colombia. Material and Method: A phenomenological study was conducted based on Colaizzi's, between February and March 2022; participants were invited to contribute to the study through a Transgender mother, contacted through a community network; a snowball sampling method was used, the initial contact was made via telephone with each potential participant, verifying inclusion criteria; in-depth interviews were conducted and theoretical saturation was achieved after the seventh interview, but it was decided to complete 10 interviews to further expand the analysis. Results: Five thematic units were identified: closing eyes to the truth, experiencing negative expressions, the coming and going of symptoms, generating strategies for symptom control, and rebirth to a new life. Conclusion: Among transgender women, the experience of symptoms associated with antiretroviral treatment is a difficult process, but is made possible by symptom management support, as well as family and social support.

Objetivo: Compreender as vivências de mulheres transgênero com HIV que convivem com sintomas associados ao tratamento antirretroviral em Bucaramanga, Colômbia. Material e Método: Foi realizado um estudo fenomenológico baseado no método de Colaizzi durante os meses de fevereiro a março de 2022; os participantes foram convidados a contribuir para o estudo através de uma mãe transgênero, contactada através de uma rede comunitária; foi utilizada amostragem "bola de neve"; o primeiro contato foi feito por telefone com cada um dos possíveis participantes, verificando os critérios de inclusão; foram realizadas entrevistas em profundidade e a saturação teórica ocorreu quando foi realizada a sétima entrevista, mas optou-se por realizar 10 entrevistas para ampliar a análise. Resultados: Foram identificadas cinco unidades temáticas: fechar os olhos para a verdade, vivenciar expressões negativas, o ir e vir dos sintomas, gerar estratégias para o controle dos sintomas e renascer para uma nova vida. Conclusão: Entre as mulheres transgênero, a experiência dos sintomas associados ao tratamento antirretroviral é um processo difícil, mas que é possível graças ao apoio na gestão dos sintomas e ao apoio familiar e social.

Incertidumbre en cuidadores en asociación con la carga de síntomas de pacientes terminales / Uncertainty in caregivers in association with symptom burden of terminally ill patients / Incerteza nos cuidadores em associação com a carga de sintomas de pacientes terminais

Objetivo: Determinar el nivel de incertidumbre del cuidador familiar (CF) de la persona hos-pitalizada en fase terminal y su asociación con carga de síntomas y funcionalidad del paciente. Materiales y método: Estudio observacional de tipo corte transversal, donde se identificó la prevalencia de incertidumbre en el CF de pacientes hospitalizados en fase terminal usando la escala de incertidumbre. Adicionalmente, se evaluó la carga de síntomas mediante escala Edmonton del paciente terminal hospitalizado en una institución de salud de alta complejidad. Resultados: La muestra incluyó información de 69 CF y pacientes terminales hospitalizados. El 85,51% de los cuidadores tuvo un nivel de incertidumbre medio. Se observó un nivel es-tadísticamente significativo de incertidumbre menor en el CF, a mayor intensidad de dolor del paciente (p=0,04), al igual que en náuseas (p=0,0004), depresión (p=0,03) y ansiedad (p=0,025) según carga de síntomas. Discusión: La vivencia del cuidador de un paciente terminal, refle-jada en la incertidumbre frente a la enfermedad de este, se relaciona principalmente con la de-pendencia funcional del enfermo, debido probablemente al impacto que su falta de suficiencia puede generar en las rutinas diarias del cuidador familiar, lo cual, puede alterar completamente la dinámica familiar y generar sobrecarga, estrés, ansiedad y trastornos en la comunicación. Conclusión: La mayoría de CF de pacientes terminales son mujeres en edad productiva, con carga familiar, y con nivel de incertidumbre medio alto frente a la enfermedad del paciente. La incertidumbre del cuidador familiar es diferente según los síntomas que presenta el paciente.

Objective: To determine the level of uncertainty of the family caregiver (FC) of the terminally hospitalised person and its association with symptom burden and patient functionality. Mate-rials and methods: Observational cross-sectional study, in which the prevalence of uncertain-ty in the FC of terminally ill hospitalised patients was identified using the uncertainty scale. In addition, the symptom burden was assessed using the Edmonton scale in terminally ill patients hospitalised in a highly complex health institution. Results: The sample included information from 69 CF and terminally ill hospitalised patients. 85.51% of caregivers had a medium level of uncertainty. A statistically significant lower level of uncertainty was observed in the CF, the greater the intensity of the patient's pain (p=0.04), as well as in nausea (p=0.0004), de-pression (p=0.03) and anxiety (p=0.025) according to symptom burden. Discussion: The ex-perience of the caregiver of a terminally ill patient, reflected in the uncertainty of the patient's illness, is mainly related to the functional dependence of the patient, probably due to the impact that their lack of sufficiency can have on the daily routines of the family caregiver, which can completely alter the family dynamics and generate overload, stress, anxiety and communica-tion disorders. Conclusion: The majority of FC of terminally ill patients are women of produc-tive age, with a family burden, and with a medium-high level of uncertainty about the patient's illness. The uncertainty of the family caregiver is different according to the patient's symptoms

Objetivo: Determinar o nível de incerteza do cuidador familiar (CF) da pessoa hospitalizada em estado terminal e sua associação com a carga de sintomas e a funcionalidade do paciente. Mate-riais e métodos: Estudo observacional de corte transversal, no qual a prevalência de incerteza no CF de pacientes terminais hospitalizados foi identificada usando a escala de incerteza. Além dis-so, a carga de sintomas de pacientes terminais hospitalizados em uma instituição de saúde de alta complexidade foi avaliada usando a escala de Edmonton. Resultados: A amostra incluiu infor-mações de 69 pacientes com FC e pacientes terminais hospitalizados. 85,51% dos cuidadores tin-ham um nível médio de incerteza. Foi observado um nível de incerteza estatisticamente significa-tivo menor na FC quanto maior a intensidade da dor do paciente (p=0,04), bem como na náusea (p=0,0004), depressão (p=0,03) e ansiedade (p=0,025) de acordo com a carga de sintomas. Dis-cussão: A experiência do cuidador de um paciente terminal, refletida na incerteza da doença do paciente, está relacionada principalmente à dependência funcional do paciente, provavelmente devido ao impacto que sua falta de suficiência pode ter nas rotinas diárias do cuidador familiar, o que pode alterar completamente a dinâmica familiar e gerar sobrecarga, estresse, ansiedade e distúrbios de comunicação. Conclusão: A maioria dos CF de pacientes terminais são mulheres em idade produtiva, com ônus familiar e com um nível médio-alto de incerteza sobre a doença do paciente. A incerteza do cuidador familiar é diferente de acordo com os sintomas do paciente.

Identification and analysis of odorant receptors expressed in the two main olfactory organs, antennae and palps, of Schistocerca americana.

Locusts depend upon their sense of smell and provide useful models for understanding olfaction. Extending this understanding requires knowledge of the molecular and structural organization of the olfactory system. Odor sensing begins with olfactory receptor neurons (ORNs), which express odorant receptors (ORs). In insects, ORNs are housed, in varying numbers, in olfactory sensilla. Because the organization of ORs within sensilla affects their function, it is essential to identify the ORs they contain. Here, using RNA sequencing, we identified 179 putative ORs in the transcriptomes of the two main olfactory organs, antenna and palp, of the locust Schistocerca americana. Quantitative expression analysis showed most putative ORs (140) are expressed in antennae while only 31 are in the palps. Further, our analysis identified one OR detected only in the palps and seven ORs that are expressed differentially by sex. An in situ analysis of OR expression suggested ORs are organized in non-random combinations within antennal sensilla. A phylogenetic comparison of OR predicted protein sequences revealed homologous relationships among two other Acrididae species. Our results provide a foundation for understanding the organization of the first stage of the olfactory system in S. americana, a well-studied model for olfactory processing.