Translation initiation factor eIF1A rescues hygromycin B sensitivity caused by deleting the carboxy-terminal tail in the GPN-loop GTPase Npa3.

The essential yeast protein GPN-loop GTPase 1 (Npa3) plays a critical role in RNA polymerase II (RNAPII) assembly and subsequent nuclear import. We previously identified a synthetic lethal interaction between a mutant lacking the carboxy-terminal 106-amino acid tail of Npa3 (npa3ΔC) and a bud27Δ mutant. As the prefoldin-like Bud27 protein participates in ribosome biogenesis and translation, we hypothesized that Npa3 may also regulate these biological processes. We investigated this proposal by using Saccharomyces cerevisiae strains episomally expressing either wild-type Npa3 or hypomorphic mutants (Npa3ΔC, Npa3K16R, and Npa3G70A). The Npa3ΔC mutant fully supports RNAPII nuclear localization and activity. However, the Npa3K16R and Npa3G70A mutants only partially mediate RNAPII nuclear targeting and exhibit a higher reduction in Npa3 function. Cell proliferation in these strains displayed an increased sensitivity to protein synthesis inhibitors hygromycin B and geneticin/G418 (npa3G70A > npa3K16R > npa3ΔC > NPA3 cells) but not to transcriptional elongation inhibitors 6-azauracil, mycophenolic acid or 1,10-phenanthroline. In all three mutant strains, the increase in sensitivity to both aminoglycoside antibiotics was totally rescued by expressing NPA3. Protein synthesis, visualized by quantifying puromycin incorporation into nascent-polypeptide chains, was markedly more sensitive to hygromycin B inhibition in npa3ΔC, npa3K16R, and npa3G70A than NPA3 cells. Notably, high-copy expression of the TIF11 gene, that encodes the eukaryotic translation initiation factor 1A (eIF1A) protein, completely suppressed both phenotypes (of reduced basal cell growth and increased sensitivity to hygromycin B) in npa3ΔC cells but not npa3K16R or npa3G70A cells. We conclude that Npa3 plays a critical RNAPII-independent and previously unrecognized role in translation initiation.

Nucleocytoplasmic shuttling of the GPN-loop GTPase Gpn3 is regulated by serum and cell density in MCF-12A mammary cells.

The best-known function of the essential GPN-loop GTPase Gpn3 is to contribute to RNA polymerase II assembly, a prerequisite for its nuclear targeting. Although this process occurs in the cytoplasm, we have previously shown that Gpn3 enters the cell nucleus before being polyubiquitinated. Here, we show that inhibiting Crm1-mediated nuclear export with leptomycin B, or the proteasome with MG132, caused the nuclear accumulation of recombinant and endogenous Gpn3 in MCF-12A cells. When added simultaneously, leptomycin B and MG132 had an additive effect. Analysis of Gpn3 primary sequence revealed the presence of at least five nuclear export sequence (NES) motifs, with some having a higher exposure to the solvent in the GTP-bound than GDP-bound state in a Gpn3 structural model. Inactivation of any of these NESes led to some degree of Gpn3 nuclear accumulation, although mutating NES1 or NES3 had the more robust effect. MCF-12A cells expressing exclusively a NES-deficient version of Gpn3R-Flag proliferated slower than cells expressing Gpn3R-Flag wt, indicating that nuclear export is important for Gpn3 function. Next, we searched for physiological conditions regulating Gpn3 nucleocytoplasmic shuttling. Interestingly, whereas Gpn3R-Flag was both nuclear and cytoplasmic in low-density growing MCF-12A cells, it was exclusively cytoplasmic in high-density areas. Furthermore, Gpn3R-Flag was cytoplasmic, mostly perinuclear, in sparse but starved MCF-12A cells, and serum-stimulation caused a rapid, although transient, Gpn3R-Flag nuclear accumulation. We conclude that Gpn3 nucleocytoplasmic shuttling is regulated by cell density and growth factors, and propose that Gpn3 has an unknown nuclear function positively linked to cell growth and/or proliferation.

Child and family characteristics in multisystemic therapy for child abuse and neglect (MST-CAN): Are there associations with treatment outcome?

Evidence-based indication for targeted interventions is a central approach in the field of child welfare and psychotherapy. This study explored the characteristics of children and families referred to Multisystemic Therapy for Child Abuse and Neglect (MST-CAN) in Switzerland and their associations with treatment outcomes. We sought to identify subgroups of children and families referred to MST-CAN and understand their specific needs and alignment with the program. We identified five distinct subgroups of children: (a) those characterized by clinically significant "social withdrawal" and "anxiety/depression," (b) with multiple clinically significant emotional and behavioral problems, (c) with predominantly externalizing problems, (d) with no pathological findings at all, with parents who were less stressed and had fewer mental health problems, and (e) with mainly internalizing problems and parents whose mental health problems deteriorated during treatment. Investigating the fit of children and families referred to treatment programs can enhance the understanding of their healthcare needs and enable more individualized interventions.

Caracterización de los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de Camagüey

Introducción: El cáncer bucal continúa siendo una de las neoplasias malignas en ascenso, de acuerdo con su incidencia y el importante número de muertes cada año. En este sentido, se han desarrollado programas de salud para la población que garantizan la pesquisa, la prevención y la atención de las enfermedades. Objetivo: Caracterizar a los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey durante el período 2018-2022. Métodos: Se realizó un estudio descriptivo transversal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey en un universo de 218 pacientes, que acudieron al Servicio de Cirugía de Cabeza y Cuello del año 2018 al 2022 y tuvieron como diagnóstico cáncer bucal. La muestra se delimitó a 113 pacientes que cumplieron con los criterios de inclusión y exclusión. Resultados: El cáncer bucal predominó en el sexo masculino con 89 (78,76 %) en los años 2019 y 2021. Hubo mayor frecuencia en pacientes de piel blanca con 97 (85,84 %) y el año 2021 mostró mayor número de estos enfermos. La lengua fue la más afectada con 43 (30,05 %) pacientes, seguida por el suelo de boca en 18 (15,92 %) y las encías en 17 (15,04 %) pacientes. Según el estadio existió un predominio del IV en 61 (53,98 %) enfermos, seguido por el III con un 18,58 % de pacientes diagnosticados. Conclusiones: Prevaleció del sexo masculino en el grupo de 60 a 79 años y los pacientes de piel blanca fueron los más afectados. La localización de las lesiones se manifestó con mayor incidencia en la lengua y los estadios IV y III de la enfermedad son los más representativos en el momento del diagnóstico.

Introduction: Oral cancer continues to be one of the malignant neoplasms on the rise, according to its incidence and the significant number of deaths each year. In this sense, health programs have been developed for the population that guarantee screening, prevention and care of the diseases. Objective: To characterize patients with oral cancer at the María Curie Oncological Teaching Provincial Hospital in Camagüey province during the period 2018-2022. Methods: A cross-sectional descriptive study was carried out in the María Curie Oncological Teaching Provincial Hospital of Camagüey province in a universe of 218 patients, who attended the Head and Neck Surgery Service from 2018 to 2022 and had oral cancer as diagnosis. The sample was limited to 113 patients who met the inclusion and exclusion criteria. Results: Oral cancer predominated in the male sex with 89 (78.76%) in the years 2019 and 2021. There was a higher incidence in patients with white skin with 97 (85.84%) and the year 2021 showed a higher number of these patients. The tongue was the most affected with 43 (30.05%) patients, followed by the floor of the mouth in 18 (15.92%) and the gums in 17 (15.04%) patients. According to stage there was a predominance of stage IV in 61 (53.98%) patients, followed by stage III with 18.58% of patients diagnosed. Conclusions: Male sex prevailed in the 60 to 79 years age group and white skin patients were the most affected. The location of the lesions manifested with greater incidence on the tongue and stages IV and III of the disease are the most representative at the time of diagnosis.

Can scuba diving transform the lives of people with physical impairments? A mixed methods study.

PURPOSE: This study aimed to: (1) test and explain the type of experience scuba diving is among people with physical impairments based on the experience-type framework; (2) assess and describe their personality based on the Big Five domains; and (3) identify if personality, years diving, and diving level predict experience-type. METHODS: An explanatory sequential mixed methods design was employed. The quantitative phase used a cross-sectional survey (n = 103). The qualitative phase used follow-up interviews with 15 participants divided into 3 case study groups. Joint displays with meta-inferences integrated the data. RESULTS: Quantitative and qualitative findings concurred on scuba being a transformative experience. 82.52% of survey participants reported scuba as a transformative experience, with no significant differences on experience impact based on impairment category (p = 0.56), impairment onset (p = 0.66), gender (p = 0.08), race/ethnicity (p = 0.51), or age (p = 0.07). Big Five personality domains, years diving, or diving level did not predict experience impact (R2 = 0.14, F(12,90) = 1.304, p = 0.2305). Data strand results differed on salient personality domains. Seven qualitative themes emerged, five on experience-type and two on personality. CONCLUSIONS: We recommend the exploration of scuba diving as a prospective rehabilitation intervention.

Innovative rehabilitation interventions that provide positive experiences and long-term health benefits to people with physical impairments are needed.Participants reported that scuba diving had a positive transformative impact in their lives through positive emotions, peace/relaxation, personal growth, development of skills, social connections, physical and mental healing, and lasting behavioral changes.Reporting scuba diving as a transformative experience was not influenced by the scuba divers' personality domains, diving level, demographic characteristics, or the number of years they had been diving.Authors recommend the consideration and further exploration of scuba diving as a prospective physical and psychosocial rehabilitation intervention.

Estimación de factores de riesgo del retardo en la cicatrización en pacientes quemados / Estimation of Risk Factors for Delayed Healing in Burn Patients

Introducción: La atención al paciente con retardo en la cicatrización parte de la optimización en sus cuidados. La reversión del cuadro requiere del conocimiento de los factores de riesgo. La literatura nacional e internacional describen factores locales o relacionados con la herida y generales o relacionados al estado general del paciente. Objetivo: Estimar los factores de riesgo del retardo en la cicatrización en pacientes quemados. Métodos: Estudio analítico de casos y control en pacientes quemados ingresados en el Servicio de Caumatología del Hospital Universitario Manuel Ascunce Domenech en el período 2017 a 2021. La población objeto de estudio comprendió a 267 pacientes. Se calculó el odds ratio y el intervalo de confianza. Resultados: El desarrollo de retardo en la cicatrización resultó tres veces y media más probable en pacientes quemados con 45 años y más, odds ratio 3,591. Además, fue nueve veces más probable en enfermedades crónicas asociadas, hasta seis veces en quemaduras no accidentales, 163 veces en la complicación local y 89 veces en la complicación sistémica. Conclusiones: Los factores de riesgo del retardo en la cicatrización en pacientes quemados identificados fueron los siguientes: edad de 45 años y más, presencia de comorbilidad, el fuego directo como agente causal, el modo de producción no accidental, la presencia de más de seis zonas anatómicas afectadas, la quemadura hipodérmica, la quemadura de 20 porciento de superficie corporal quemada y más de extensión, el apoyo de la lesión, el índice cubano de pronóstico con riesgo vital, la complicación local y la complicación sistémica(AU)

Introduction: The care for the patient with delayed healing starts from the optimization of their care. Reversing such condition requires knowledge of the risk factors. The national and international literature describes local factors related to the injury and general factors related to the patient's general condition. Objective: To estimate the risk factors for delayed healing in burn patients. Methods: An analytical case-control study was carried out with burn patients admitted to the caumatology service at Hospital Universitario Manuel Ascunce Domenech in the period from 2017 to 2021. The study population consisted of 267 patients. Odds ratio and confidence interval were calculated. Results: The development of delayed healing was three and a half times more likely in burn patients aged 45 years or over (odds ratio: 3.591). In addition, it was nine times more likely for associated chronic diseases, up to six times in nonaccidental burns, 163 times in local complications, and 89 times in systemic complications. Conclusions: The identified risk factors for delayed healing in burn patients were the following: age 45 years or over, presence of comorbidity, direct fire as causative agent, nonaccidental way of production, presence of more than six affected anatomical areas, hypodermic burn, burn extension of 20 percent or over on the burned body surface, injury contact pressure, the Cuban index of prognostic vital risk, as well as the local or the systemic complications(AU)

Interaction between the mitochondrial adaptor MIRO and the motor adaptor TRAK.

MIRO (mitochondrial Rho GTPase) consists of two GTPase domains flanking two Ca2+-binding EF-hand domains. A C-terminal transmembrane helix anchors MIRO to the outer mitochondrial membrane, where it functions as a general adaptor for the recruitment of cytoskeletal proteins that control mitochondrial dynamics. One protein recruited by MIRO is TRAK (trafficking kinesin-binding protein), which in turn recruits the microtubule-based motors kinesin-1 and dynein-dynactin. The mechanism by which MIRO interacts with TRAK is not well understood. Here, we map and quantitatively characterize the interaction of human MIRO1 and TRAK1 and test its potential regulation by Ca2+ and/or GTP binding. TRAK1 binds MIRO1 with low micromolar affinity. The interaction was mapped to a fragment comprising MIRO1's EF-hands and C-terminal GTPase domain and to a conserved sequence motif within TRAK1 residues 394 to 431, immediately C-terminal to the Spindly motif. This sequence is sufficient for MIRO1 binding in vitro and is necessary for MIRO1-dependent localization of TRAK1 to mitochondria in cells. MIRO1's EF-hands bind Ca2+ with dissociation constants (KD) of 3.9 µM and 300 nM. This suggests that under cellular conditions one EF-hand may be constitutively bound to Ca2+ whereas the other EF-hand binds Ca2+ in a regulated manner, depending on its local concentration. Yet, the MIRO1-TRAK1 interaction is independent of Ca2+ binding to the EF-hands and of the nucleotide state (GDP or GTP) of the C-terminal GTPase. The interaction is also independent of TRAK1 dimerization, such that a TRAK1 dimer can be expected to bind two MIRO1 molecules on the mitochondrial surface.

Evaluation and validation of reference genes for RT-qPCR gene expression in Naegleria gruberi.

Naegleria gruberi is a free-living amoeboflagellate commonly found in freshwater and in soils around the world. It is a non-pathogenic relative of Naegleria fowleri, which is the etiologic agent of Primary Amoebic Meningoencephalitis (PAM). PAM occurs world-wide and it is considered a rare disease, but its fatality rate is high (96%) mainly because of delay in initiation of treatment due to misdiagnosis and lack of a specific treatment. The analysis of gene expression by quantitative real-time PCR in N. gruberi could be a highly efficient means to understand the pathogenicity of N. fowleri and also to find drug targets. Accurate RT-qPCR analysis requires correct normalization of gene expression data using reference genes (RG), whose expression should be constant under different experimental conditions. In this study, six genes, representing the most frequently used housekeeping genes, were selected for evaluation as reference genes in N. gruberi. The expression and stability of these genes was evaluated employing four algorithms (geNorm, NormFinder, BestKeeper and RefFinder). This work shows significant variations of the stability of RGs depending on the algorithms employed and on the experimental conditions (i.e. logarithmic, stationary, heat-shock and oxidative stress). The geNorm, NormFinder and RefFinder analysis of all the experimental conditions in combination revealed that ACT and G6PD were the most stable RGs. While BestKeeper analysis showed that 18S and TBP were the most stable RGs. Moreover, normalization of HSP90 gene expression with the most stable RGs resulted in an upregulation whereas when the normalization was done with the unstable RGs, the gene expression was not reliable. Hence, the implications of this study are relevant to gene expression studies in N. gruberi.

Systematic review: fluid biomarkers and machine learning methods to improve the diagnosis from mild cognitive impairment to Alzheimer's disease.

Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years from the initial diagnosis. Diagnosis of cognitive impairment in dementia is typically based on clinical evaluation, neuropsychological assessments, cerebrospinal fluid (CSF) biomarkers, and neuroimaging. The main goal of diagnosing MCI is to determine its cause, particularly whether it is due to Alzheimer's disease (AD). However, only a limited percentage of the population has access to etiological confirmation, which has led to the emergence of peripheral fluid biomarkers as a diagnostic tool for dementias, including MCI due to AD. Recent advances in biofluid assays have enabled the use of sophisticated statistical models and multimodal machine learning (ML) algorithms for the diagnosis of MCI based on fluid biomarkers from CSF, peripheral blood, and saliva, among others. This approach has shown promise for identifying specific causes of MCI, including AD. After a PRISMA analysis, 29 articles revealed a trend towards using multimodal algorithms that incorporate additional biomarkers such as neuroimaging, neuropsychological tests, and genetic information. Particularly, neuroimaging is commonly used in conjunction with fluid biomarkers for both cross-sectional and longitudinal studies. Our systematic review suggests that cost-effective longitudinal multimodal monitoring data, representative of diverse cultural populations and utilizing white-box ML algorithms, could be a valuable contribution to the development of diagnostic models for AD due to MCI. Clinical assessment and biomarkers, together with ML techniques, could prove pivotal in improving diagnostic tools for MCI due to AD.

Predicción de toxicidad de la quimioterapia y radioterapia en el paciente oncológico quirúrgico

Fundamento la toxicidad asociada a los tratamientos de quimioterapia y radioterapia eleva la morbilidad y la mortalidad en los pacientes oncológicos. Objetivo diseñar un modelo predictivo de toxicidad de la quimioterapia y la radioterapia en el paciente oncológico quirúrgico. Métodos estudio analítico, de casos y controles, en pacientes oncológicos quirúrgicos que cumplieron los criterios de inclusión para la predicción de toxicidad preoperatoria, en el periodo enero a diciembre de 2022, en el Hospital Provincial Docente Oncológico María Curie, de Camagüey. Mediante el paquete estadístico Statistical Package for the Social Sciences, se seleccionó una muestra aleatoria de 334 pacientes, 197 sin toxicidad (grupo control) y 137 con toxicidad (grupo de estudio). Se realizó estimación de predictores de toxicidad mediante regresión logística binaria. Se seleccionó el modelo de mejor ajuste. Resultados el modelo en el paso tres predice un porcentaje global de 83,5 % con respecto a los valores observados. La sensibilidad resultó ser de 81,8; y la especificidad, 84,8. El modelo presentó buen poder discriminativo. Las variables en la ecuación fueron: hipertensión arterial, fracción de eyección del ventrículo izquierdo y anemia. La comparación de la predicción con la realidad, mediante curva Receiver Operating Characteristic determinó un área bajo la curva de 0,901. Conclusión se obtuvo una función de regresión logística que permitió la estimación de la probabilidad de toxicidad en pacientes oncológicos quirúrgicos electivos, la cual proporcionó una herramienta para su predicción desde el preoperatorio.

Foundation the toxicity associated with chemotherapy and radiotherapy treatments increases morbidity and mortality in cancer patients. Objective to design a predictive model of chemotherapy and radiotherapy toxicity in surgical cancer patients. Methods analytical, case-control study, in surgical oncology patients who met the inclusion criteria for the prediction of preoperative toxicity, from January to December 2022, at the María Curie Provincial Teaching Oncology Hospital in Camagüey. Using the Statistical Package for the Social Sciences, a random sample of 334 patients was selected, 197 without toxicity (control group) and 137 with toxicity (study group). Toxicity predictors were estimated using binary logistic regression. The model with the best fit was selected. Results the model in step three predicts an overall percentage of 83.5% with respect to the observed values. The sensitivity turned out to be 81.8; and the specificity, 84.8. The model presented good discriminative power. The variables in the equation were: arterial hypertension, left ventricular ejection fraction, and anemia. The comparison of the prediction with reality, using the Receiver Operating Characteristic curve, determined an area under the curve of 0.901. Conclusion a logistic regression function was obtained that allowed the estimation of the toxicity probability elective surgical cancer patients, which provided a tool for its prediction from the preoperative period.

Frequency of Helicobacter pylori Infection in Patients Requiring GI Endoscopy in Seven Units in Three Antioquia Subregions

Aim: To determine the frequency of Helicobacter pylori and sociodemographic factors, life habits, and personal and family history of gastroduodenal diseases in patients who required and were taken to GI endoscopy (symptomatic or by screening) in seven endoscopy units in three Antioquia subregions. Materials and methods: A cross-sectional study conducted between 2016 and 2018 included 272 participants. Sociodemographic factors, life habits, and personal and family history were related to H. pylori infection. Descriptive statistics and bivariate analysis were performed to establish the association between the variables, and multivariate analysis (binomial regression) was used to adjust the prevalence ratios of the associated factors. A p-value ≤ 0.05 was considered statistically significant. Results: The frequency of H. pylori infection was 55.9%, with differences by subregion (Valle de Aburrá metropolitan area: 54.3%, Oriente: 64%, and Urabá: 79.2%). Factors associated with H. pylori infection were male sex (adjusted prevalence ratio [APR] = 1.26; 95% confidence interval [CI] = 1.04-1.52), age 18-55 years (APR = 1.62; CI 95% = 1.22-2.16), absence of drinking water (APR = 1.40; 95% CI: 1.15-1.72) and educational level below university (APR = 1.73; 95% CI% = 1.26-2.38). Conclusion: The frequency of H. pylori was higher than in other recent studies because different diagnostic tests were used for its detection, and differences were found in the frequency of infection by region, which is explained by the heterogeneity in the populations analyzed. This study suggests the need to improve the population's living conditions to reduce H. pylori and direct measures of primary prevention of the infection, especially in family groups, men, individuals between 18 and 55 years old without drinking water, and with an educational level lower than university.

Objetivo: determinar la frecuencia de Helicobacter pylori y la presencia de factores sociodemográficos, hábitos de vida y antecedentes personales y familiares de enfermedades gastroduodenales en pacientes que requirieron y fueron llevados a endoscopia digestiva (sintomáticos o por tamización) en siete unidades de endoscopia de tres subregiones de Antioquia. Materiales y métodos: estudio transversal realizado entre 2016 y 2018 que incluyó a 272 participantes. Los factores sociodemográficos, hábitos de vida, antecedentes personales y familiares se relacionaron con la infección por H. pylori. Se realizó estadística descriptiva y análisis bivariado para establecer la asociación entre las variables y el análisis multivariado (regresión binomial) para ajustar las razones de prevalencia de los factores asociados. Un valor p ≤ 0,05 se consideró estadísticamente significativo. Resultados: la frecuencia de infección por H. pylori fue de 55,9%, con diferencias por subregión (área metropolitana del Valle de Aburrá: 54,3%, oriente: 64% y Urabá: 79,2%). Los factores asociados a la infección por H. pylori fueron sexo masculino (razón de prevalencia ajustada [RPA] = 1,26; intervalo de confianza [IC] del 95% = 1,04-1,52), edad de 18-55 años (RPA = 1,62; IC 95% = 1,22-2,16), ausencia de agua potable (RPA = 1,40; IC 95%: 1,15-1,72) y nivel educativo inferior al universitario (RPA = 1,73; IC 95% = 1,26-2,38). Conclusión: la frecuencia de H. pylori fue mayor que en otros estudios recientes porque se emplearon diferentes pruebas diagnósticas para su detección y se demostraron diferencias en la frecuencia de la infección por región, lo cual se explica por la heterogeneidad en las poblaciones analizadas. Este estudio sugiere la necesidad de mejorar las condiciones de vida de la población para reducir la infección por H. pylori y dirigir medidas de prevención primaria de la infección especialmente en los grupos familiares, en hombres, individuos entre 18 y 55 años, sin agua potable y con un nivel educativo inferior al universitario.

Assessing Acanthamoeba cytotoxicity: comparison of common cell viability assays.

Background: In vitro models for studying interactions between Acanthamoeba and host cells are crucial for understanding the pathomechanism of Acanthamoeba and assessing differences between strains and cell types. The virulence of Acanthamoeba strains is usually assessed and monitored by using cell cytotoxicity assays. The aim of the present study was to evaluate and compare the most widely used cytotoxicity assays for their suitability to assess Acanthamoeba cytopathogenicity. Methods: The viability of human corneal epithelial cells (HCECs) after co-culture with Acanthamoeba was evaluated in phase contrast microscopy. Results: It was shown that Acanthamoeba is unable to considerably reduce the tetrazolium salt and the NanoLuc® Luciferase prosubstrate to formazan and the luciferase substrate, respectively. This incapacity helped to generate a cell density-dependent signal allowing to accurately quantify Acanthamoeba cytotoxicity. The lactate dehydrogenase (LDH) assay led to an underestimation of the cytotoxic effect of Acanthamoeba on HCECs since their co-incubation negatively affected the lactate dehydrogenase activity. Discussion: Our findings demonstrate that cell-based assays using the aqueous soluble tetrazolium-formazan, and the NanoLuc® Luciferase prosubstrate products, in contrast to LDH, are excellent markers to monitor the interaction of Acanthamoeba with human cell lines and to determine and quantify effectively the cytotoxic effect induced by the amoebae. Furthermore, our data indicate that protease activity may have an impact on the outcome and thus the reliability of these tests.

Diving into Health: A Mixed Methods Study on the Impact of Scuba Diving in People with Physical Impairments.

The impacts of scuba diving on people with physical impairments are unknown. Grounded on the social identity approach to health, the aim of this study was to test and describe the relationships between scuba diving social identity, self-efficacy, social health, psychological health, physical health, health-related quality of life (HRQOL), and disability level among recreational scuba divers with physical impairments. A mixed methods explanatory sequential design was employed. The quantitative strand used an 80-item cross-sectional survey, with the data analyzed via a path analysis. The qualitative strand used 1:1 interviews across 3 case study groups; the data were analyzed using deductive and inductive analyses. Mixing occurred via a joint display with meta-inferences. The quantitative results (n = 78) indicated that self-efficacy was a significant predictor of social health, psychological health, physical health, HRQOL, and disability level. The qualitative findings (n = 15) consisted of six themes, whereby participants described scuba as a positive social identity that provides them with meaning, purpose, and belonging. Furthermore, they described scuba diving as a positive contributor to their self-efficacy, social health, psychological health, physical health, and quality of life. During the mixing of data, the quantitative and qualitative results did not match on the influence of scuba diving social identity on self-efficacy, social health, psychological health, physical health, HRQOL, and disability level. A further analysis revealed that the range restriction impaired the conclusive quantitative evidence on the scuba diving social identity variable. The meta-inferences derived from the data integration suggest that scuba diving plays a role in the self-efficacy, health, HRQOL, and disability level among scuba divers with physical impairments. The findings point to the potential of scuba diving as a health promotion recreational activity and rehabilitation modality for people with physical impairments.

Optimal Fast Integral Decontamination of Bacillus thuringiensis Aerosols and Fast Disinfection of Contaminated Surfaces.

Aerosolized anthrax (Bacillus anthracis) spores are of extreme health concern and can remain airborne for hours and contaminate all kinds of surfaces, constituting reservoirs from which resuspension is easily produced. The assessment of decontamination techniques must therefore consider both air and surfaces. In the present study, several kinds of disinfecting fogs were experimentally tested against Bacillus thuringiensis spores, which served as a surrogate for Bacillus anthracis, both as aerosols released into the air and spread on porous and non-porous surfaces with different positions and orientations. This technology removed Bacillus thuringiensis spores from the air in 20 min with just a 1 min application of fog. The dynamics and characteristics of the fog, related to aerosol and surface interactions, proved to be critical for optimal performance and decontamination. An optimal configuration could provide effective disinfection even on indirectly reached surfaces. In all cases, 8% hydrogen peroxide (H2O2) provided a higher disinfection rate than 2% glutaraldehyde.

Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

BACKGROUND: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection. METHODS: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity. RESULTS: Twenty patients received preoperative trotabresib and underwent resection with no delays or cancelations of surgery; 16 patients received maintenance trotabresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Six-month progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30. CONCLUSIONS: Trotabresib penetrates the blood-brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concomitant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).

Experiencias de cuidado hacia la persona con VIH/SIDA durante la formación en Enfermería / Experiences of caring for the person with HIV/AIDS during nursing education / Experiências de cuidados a pessoas com VIH/SIDA durante a educação de enfermagem

Objetivo: Comprender la vivencia del cuidado brindado a la persona que vive con VIH/SIDA durante la formación de pregrado en enfermería. Materiales y método: Estudio cualitativo, fenomenológico hermenéutico, en el que participaron 10 estudiantes del Programa de En-fermería. La información fue recolectada mediante entrevista semiestructurada, y el análisis siguió los planteamientos de Van Manen. Resultados: Emergieron 35 unidades de significado organizados en los siguientes 6 temas fenomenológicos: Construcciones sociales sobre el VIH/SIDA; Conocimientos sobre el VIH/SIDA; Espacios académicos para el aprendizaje teórico del VIH/SIDA; Vivencias relacionadas con el cuidado de la persona con VIH/SIDA durante las prácticas formativas; Sentimientos y emociones relacionados con el cuidado y at-ención al paciente con VIH/SIDA y Propuestas para el fomento de la sensibilización social y académica del cuidado en VIH/SIDA. Conclusiones: La vivencia del cuidado en VIH/SIDA, significa para los estudiantes un ejercicio de confrontación individual y colectiva frente a la deslegitimación de principios y convicciones transgeneracionales de la enfermedad, esboza además la necesidad imperante de consolidar escenarios educativos teórico-prácticos intra y extracurriculares para el abordaje del VIH, que contribuyan favorablemente en el ejercicio profesional de cuidado

Objective: To understand the experience of care provided to the person living with HIV/AIDS during undergraduate nursing education. Method: Qualitative, hermeneutic phenom-enological study, in which 10 students of the Nursing Program participated. The information was collected through semi-structured interviews, and the analysis followed Van Manen's approaches. Results: 35 units of meaning emerged, organized into the following 6 phenom-enological themes: social constructions about HIV/AIDS; Knowledge about HIV/AIDS; Ac-ademic spaces for theoretical learning about HIV/AIDS; Experiences related to the care of the person with HIV/AIDS during formative practices; Feelings and emotions related to the care and attention to the patient with HIV/AIDS and Proposals for the promotion of social and academic awareness of HIV/AIDS care. Conclusions: The experience of HIV/AIDS care, means for students an exercise of individual and collective confrontation against the del-egitimization of principles and transgenerational convictions of the disease, it also outlines the imperative need to consolidate intra and extracurricular theoretical-practical educational sce-narios for the approach to HIV, which contribute favorably in the professional exercise of care.

Objectivo: Compreender a experiência dos cuidados prestados às pessoas que vivem com VIH/SIDA durante a formação de enfermagem universitária. Materiais e métodos: Estudo qualitativo e hermenêutico fenomenológico, no qual participaram 10 estudantes do Programa de Enfermagem. A informação foi recolhida através de entrevistas semi-estruturadas, e a análise seguiu a abordagem de Van Manen. Resultados: emergiram 35 unidades de signifi-cado, organizadas nos seguintes 6 temas fenomenológicos: construções sociais sobre VIH/SIDA; Conhecimento sobre VIH/SIDA; Espaços académicos para aprendizagem teórica so-bre VIH/SIDA; Experiências relacionadas com os cuidados da pessoa com VIH/SIDA du-rante as práticas formativas; Sentimentos e emoções relacionadas com os cuidados e atenção ao doente com VIH/SIDA e Propostas para a promoção da consciência social e académica dos cuidados com VIH/SIDA. Conclusões: Para os estudantes, a experiência dos cuidados de VIH/SIDA é um exercício de confrontação individual e colectiva face à deslegitimação de princípios e convicções transgeracionais da doença. Também delineia a necessidade im-perativa de consolidar cenários teórico-práticos intra e extracurriculares para a abordagem do VIH, que contribuem favoravelmente para o exercício profissional dos cuidadoS

Factores de riesgo asociados a defectos congénitos de genitales externos y gónadas masculinas

Introducción: Los defectos congénitos del tracto urogenital se encuentran entre las anomalías más encontradas en el feto o neonato, lo que da una idea de su extraordinaria importancia clínica, unido a las escasas investigaciones en la provincia Camagüey, sobre factores de riesgo asociados a los defectos congénitos de genitales externos y gónadas masculinas. Objetivo: Determinar los factores de riesgo asociados a defectos congénitos de genitales externos y gónadas masculinas. Métodos: Se realizó un estudio correlacional del tipo retrospectivo en el Hospital Pediátrico Eduardo Agramonte Piña en el periodo de enero de 2013 a diciembre de 2020. El universo se conformó por los 96 pacientes que fueron intervenidos quirúrgicamente por presentar defectos congénitos de los genitales externos y gónadas masculinas. Para determinar la asociación de los factores de riesgo con la aparición de defectos congénitos se empleó la prueba de independencia, en caso de p<0,05 se consideró asociación significativa. Para medir la magnitud de la asociación estadística entre las variables se utilizó el coeficiente Phi, se consideró mientras más fuerte a uno fuera su valor, más correlacionadas se encontraron las variables estudiadas. Resultados: La criptorquidia fue la forma clínica con mayor número de pacientes, seguida de la hipospadias y la hidrocele. La asociación entre los padres trabajadores agrícolas y la hipospadias y la criptorquidia con padres trabajadores industriales, resultaron significativas. El hecho que la madre fuera fumadora pasiva, constituyó una variable con asociación significativa, tanto para la aparición de hipospadias como de criptorquidia. El ser fumadora pasiva fue el factor de riesgo que tuvo mayor correlación con la aparición de los defectos congénitos. Conclusiones: Existieron factores de riesgo con asociación significativa a la aparición de defectos congénitos de genitales externos y gónadas masculinas.

Introduction: Congenital defects of the urogenital tract are among the anomalies most found in the fetus or neonate, which gives an idea of ​​their extraordinary clinical importance, together with the few investigations in the Camagüey province, on risk factors associated with congenital defects of external genitalia and male gonads. Objective: To determine the risk factors associated with congenital defects of the external genitalia and male gonads. Methods: A retrospective correlational study was carried out at the Eduardo Agramonte Piña Pediatric Hospital from January 2013 to December 2020. The universe was made up of the 96 patients who underwent surgery for presenting congenital defects of the external genitalia and male gonads. To determine the association of the risk factors with the appearance of congenital defects, the independence test was used; in case of p<0.05, a significant association was considered. To measure the magnitude of the statistical association between the variables, the Phi coefficient was used, it was considered that the stronger its value was, the more correlated the studied variables were found. Results: Cryptorchidism was the clinical form with the highest number of patients, followed by hypospadias and hydrocele. The association between farm worker parents and hypospadias and cryptorchidism with industrial worker parents was significant. The fact that the mother was a passive smoker was a variable with a significant association, both for the appearance of hypospadias and cryptorchidism. Being a passive smoker was the risk factor that had the highest correlation with the appearance of birth defects. Conclusions: There were risk factors with a significant association with the appearance of congenital defects of the external genitalia and male gonads.

Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma.

Background: Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. Methods: In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. Results: The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Conclusions: Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings.

Modelo de gestión de riesgo del programa de recuperación precoz de la cirugía colorectal electiva / Risk management model of the early recovery program of the elective colorectal surgery

Introducción: La gestión de riesgo perioperatorio sustentado en los programas o protocolos de recuperación precoz o mejorada después de la cirugía valida la calidad en los cuidados perioperatorios con disminución de la incidencia de morbilidad y mortalidad basado en la evidencia de un conjunto de acciones que cubren todo el período perioperatorio. Objetivo: Validar el programa de recuperación precoz después de la cirugía colorectal en los pacientes quirúrgicos electivos en los hospitales Provincial Docente de Oncología María Curie, Universitario Manuel Ascunce Domenech de la provincia de Camagüey y General Universitario Carlos Manuel de Céspedes y del Castillo en la provincia de Granma. Métodos: La investigación se ejecutó en dos fases. En la Fase I se realizó validación externa e interna del programa de recuperación precoz de la cirugía colorectal electiva por consulta de expertos mediante escala Likert. En la Fase II se realizó un estudio piloto experimental con dos grupos de 119 pacientes cada uno. Resultados: La mayor parte de los pacientes del grupo de estudio, 97,5 por ciento tuvieron una recuperación precoz óptima basada en no dolor, no íleo paralítico, no complicaciones cardiovasculares, ni respiratorias perioperatorias. El 94,1 por ciento de grupo de estudio egresó en condición de vivo, con una estadía de cinco días en promedio, inferior a los nueve del grupo control. Conclusiones: El programa de recuperación precoz muestra disminución de la incidencia de morbilidad y mortalidad así como reducción de estadía hospitalaria. Con beneficios tanto para el paciente como para los servicios de salud(AU)

Introduction: Perioperative risk management supported by programs or protocols for early or improved recovery after surgery validates the quality of perioperative care, with a decrease in the incidence of morbidity and mortality based on the evidence of a set of actions covering the entire perioperative period. Objective: To validate the program for early recovery after colorectal surgery in elective surgical patients at María Curie Provincial Teaching Oncological Hospital and Manuel Ascunce Domenech University Hospital, both in Camagüey Province, as well as at Carlos Manuel de Céspedes General University Hospital in Granma Province. Methods: The research was carried out in two phases. In phase I, external and internal validation of the early recovery program for elective colorectal surgery was carried out by means of expert consultation using a Likert scale. In phase II, an experimental pilot study was carried out with two groups of 119 patients each. Results: Most of the patients in the study group (97.5 percent) had optimal early recovery, based on the fact that they did not present pain, paralytic ileus, either cardiovascular or respiratory complications perioperatively. 94.1 percent of the patients in the study group were discharged in the condition of living, with an average hospital stay of five days, lower than the nine days of the control group. Conclusions: The early recovery program shows a decrease in the incidence of morbidity and mortality, as well as a reduction in hospital stay, with benefits for both the patient and the health services(AU)

Synthetic negative genome screen of the GPN-loop GTPase NPA3 in Saccharomyces cerevisiae.

The GPN-loop GTPase Npa3 is encoded by an essential gene in the yeast Saccharomyces cerevisiae. Npa3 plays a critical role in the assembly and nuclear accumulation of RNA polymerase II (RNAPII), a function that may explain its essentiality. Genetic interactions describe the extent to which a mutation in a particular gene affects a specific phenotype when co-occurring with an alteration in a second gene. Discovering synthetic negative genetic interactions has long been used as a tool to delineate the functional relatedness between pairs of genes participating in common or compensatory biological pathways. Previously, our group showed that nuclear targeting and transcriptional activity of RNAPII were unaffected in cells expressing exclusively a C-terminal truncated mutant version of Npa3 (npa3∆C) lacking the last 106 residues naturally absent from the single GPN protein in Archaea, but universally conserved in all Npa3 orthologs of eukaryotes. To gain insight into novel cellular functions for Npa3, we performed here a genome-wide Synthetic Genetic Array (SGA) study coupled to bulk fluorescence monitoring to identify negative genetic interactions of NPA3 by crossing an npa3∆C strain with a 4,389 nonessential gene-deletion collection. This genetic screen revealed previously unknown synthetic negative interactions between NPA3 and 15 genes. Our results revealed that the Npa3 C-terminal tail extension regulates the participation of this essential GTPase in previously unknown biological processes related to mitochondrial homeostasis and ribosome biogenesis.