Enhancing water quality prediction for fluctuating missing data scenarios: A dynamic Bayesian network-based processing system to monitor cyanobacteria proliferation.

Tackling the impact of missing data in water management is crucial to ensure the reliability of scientific research that informs decision-making processes in public health. The goal of this study is to ascertain the root causes associated with cyanobacteria proliferation under major missing data scenarios. For this purpose, a dynamic missing data management methodology is proposed using Bayesian Machine Learning for accurate surface water quality prediction of a river from Limia basin (Spain). The methodology used entails a sequence of analytical steps, starting with data pre-processing, followed by the selection of a reliable dynamic Bayesian missing value prediction system, leading finally to a supervised analysis of the behavioral patterns exhibited by cyanobacteria. For that, a total of 2,118,844 data points were used, with 205,316 (9.69 %) missing values identified. The machine learning testing showed the iterative structural expectation maximization (SEM) as the best performing algorithm, above the dynamic imputation (DI) and entropy-based dynamic imputation methods (EBDI), enhancing in some cases the accuracy of imputations by approximately 50 % in R2, RMSE, NRMSE, and logarithmic loss values. These findings can impact how data on water quality is being processed and studied, thus, opening the door for more reliable water management strategies that better inform public health decisions.

Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [68Ga]Ga-DOTA-TOC and [18 F]FDG PET/CT.

OBJECTIVE: The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18 F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS: We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18 F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18 F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18 F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS: The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18 F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18 F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18 F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18 F]FDG. CONCLUSIONS: The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).

Chapter 6: The Breadth and Limits of Life on Earth.

Scientific ideas about the potential existence of life elsewhere in the universe are predominantly informed by knowledge about life on Earth. Over the past ∼4 billion years, life on Earth has evolved into millions of unique species. Life now inhabits nearly every environmental niche on Earth that has been explored. Despite the wide variety of species and diverse biochemistry of modern life, many features, such as energy production mechanisms and nutrient requirements, are conserved across the Tree of Life. Such conserved features help define the operational parameters required by life and therefore help direct the exploration and evaluation of habitability in extraterrestrial environments. As new diversity in the Tree of Life continues to expand, so do the known limits of life on Earth and the range of environments considered habitable elsewhere. The metabolic processes used by organisms living on the edge of habitability provide insights into the types of environments that would be most suitable to hosting extraterrestrial life, crucial for planning and developing future astrobiology missions. This chapter will introduce readers to the breadth and limits of life on Earth and show how the study of life at the extremes can inform the broader field of astrobiology.

Chapter 1: The Astrobiology Primer 3.0.

The Astrobiology Primer 3.0 (ABP3.0) is a concise introduction to the field of astrobiology for students and others who are new to the field of astrobiology. It provides an entry into the broader materials in this supplementary issue of Astrobiology and an overview of the investigations and driving hypotheses that make up this interdisciplinary field. The content of this chapter was adapted from the other 10 articles in this supplementary issue and thus represents the contribution of all the authors who worked on these introductory articles. The content of this chapter is not exhaustive and represents the topics that the authors found to be the most important and compelling in a dynamic and changing field.

Utility of the modified 5-item frail index to predict complications and reoperations after hallux valgus percutaneous surgery. / [Artículo traducido] Utilidad del índice de fragilidad modificado de 5 items para predecir complicaciones y reoperaciones después de la cirugía percutánea de hallux valgus.

INTRODUCTION: The modified 5-item frailty index (mFI-5) has been recently proposed as a useful tool for predicting postoperative complications in orthopedic surgery. We aimed to analyze the utility of this score in predicting complications and reoperations after hallux valgus (HV) deformity surgery. METHODS: 551 patients undergoing percutaneous HV corrective surgery were retrospectively reviewed. The mFI-5 was calculated based and patients were categorized in three groups: 1) non-frail: patients without any of the 5 comorbidities, 2) pre-frail: patients with one comorbidity and 3) frail: patients with two or more comorbidities. Complications and surgical reoperations were recorded. RESULTS: In the study period 772 percutaneous surgeries were performed to correct HV deformity, 551 patients were included with a median age of 60 (IQR 48-70). Three hundred eighty-nine patients were non-frail (70.6%), 132 were pre-frail (23.9%) and 30 were frail (5.4%). 75 patients suffered complications (13.6%). Even though the rate of complications was higher in frailty patients (23.3%) compared with pre-frail (13.6%) and non frail (12.8%), no significant differences were observed among groups. 48 patients required reoperation (8.7%) but the rate of reoperations among frailty groups was not significantly different (P=.11). Frailty patients had worse AOFAS scores at final follow up (P=.011). CONCLUSION: The mFI-5 was not useful to predict postoperative complications and reoperations after hallux valgus corrective surgery. Therefore, other factors should be considered when analyzing the risk of complications after HV corrective surgery.

Perception of learning by anatomy teachers in the COVID-19.

The discipline of anatomy is one of the pillars of training in higher education courses in health area. Since its origin, this discipline has used the traditional method as an educational strategy. Since then, the discipline has undergone changes, including other teaching methods, such as active methodologies. With the COVID-19 pandemic, declared in March 2020 and the closure of higher education institutions, the teaching of anatomy was impacted, since it was necessary to adapt the modality of face-to-face teaching to remote teaching. The present study aims to evaluate the perception of teachers regarding students' anatomy learning in relation to the types of methodologies applied in remote teaching during the pandemic. For such, a cross-sectional study was carried out, which analyzed the answers of 101 anatomy teachers. The results showed that there was no statistically significant difference regarding teachers' perception of learning in relation to the type of methodology used in remote teaching during the pandemic. There was also no difference in comparing perceptions regarding the type of methodology used before and during the pandemic. Given this, these data encourage the need for reflection in the academic community and new studies with educators and students, in order to identify factors that may improve the quality of anatomy learning.

Fungal identification in the air and water of a hemodialysis unit in Brazil.

The presence of fungi in healthcare settings, including hemodialysis units, represents a significant risk for immunocompromised patients. This study aimed to investigate the occurrence of fungi in the air and water of a hemodialysis unit located in a tertiary public hospital in Maceió, Alagoas, Brazil. Over a period of three consecutive months, monthly air samples were collected and analyzed using the spontaneous sedimentation technique on Petri dishes containing Sabouraud Dextrose Agar (SDA). Simultaneously, water samples (100 mL) were collected from four specific water distribution points and subjected plating on SDA. Fungi were phenotypically identified based on their macroscopic and microscopic characteristics. In total, 498 colony-forming units (CFUs) of fungi were isolated, with 86 CFUs originating from the air and 412 CFUs from the water. Regarding the water samples, a higher concentration of fungal CFUs was observed in the potable water from the supply network (229 CFUs). Unexpectedly, 23 CFUs were identified in the reverse osmosis samples and 11 CFUs in the storage tank, which are post-treatment points where the presence of microorganisms is not desired. The fungus Cladosporium spp. was the most prevalent in both air and water samples, followed by Penicillium spp. in the air and Rhodotorula spp. in the water. These findings underscore the need to implement effective control and monitoring measures for fungi in the hemodialysis unit to ensure patient safety.

Utility of the modified 5-item frail index to predict complications and reoperations after hallux valgus surgery.

INTRODUCTION: The modified 5-item frailty index (mFI-5) has been recently proposed as a useful tool for predicting postoperative complications in orthopedic surgery. We aimed to analyze the utility of this score in predicting complications and reoperations after hallux valgus (HV) deformity surgery. METHODS: 551 patients undergoing percutaneous HV corrective surgery were retrospectively reviewed. The mFI-5 was calculated based and patients were categorized in three groups: (1) non-frail: patients without any of the 5 comorbidities, (2) pre-frail: patients with one comorbidity and (3) frail: patients with two or more comorbidities. Complications and surgical reoperations were recorded. RESULTS: In the study period 772 percutaneous surgeries were performed to correct hallux valgus deformity, 551 patients were included with a median age of 60 (IQR 48-70). 389 patients were non-frail (70.6%), 132 were pre-frail (23.9%) and 30 were frail (5.4%). 75 patients suffered complications (13.6%). Even though the rate of complications was higher in frailty patients (23.3%) compared with pre-frail (13.6%) and non frail (12.8%), no significant differences were observed among groups. 48 patients required reoperation (8.7%) but the rate of reoperations among frailty groups was not significantly different (p=0.11). Frailty patients had worse AOFAS scores at final follow up (p=0.011). CONCLUSION: The mFI-5 was not useful to predict postoperative complications and reoperations after hallux valgus corrective surgery. Therefore, other factors should be considered when analyzing the risk of complications after HV corrective surgery.

Subsistence swine farming: seroprevalence and risk factors associated with Lawsonia intracellularis infection in the state of Minas Gerais Brazil in 2016.

Although it is considered an economically relevant and prevalent disease, little information is available on the epidemiology and risk factors of porcine proliferative enteropathy (PPE) in commercial pigs, and no publication is available on subsistence pig farming. The objectives of this study were to estimate the seroprevalence of L. intracellularis and identify associated risk factors in backyard pigs in the 12 mesoregions of the state of Minas Gerais, Brazil. Blood from pigs between 2 months and 6 years of age were sampled; an epidemiological questionnaire was applied to 288 properties investigated in 2016. Serum samples were tested for the presence of anti-L. intracellularis antibodies using an immunoperoxidase monolayer assay. The seroprevalence of L. intracellularis was 97.7% (CI 95%: 96.7-98.4), and there was no statistical difference among the prevalence of the sampled mesoregions. Only 3 of the 12 risk factors were significant when samples were analyzed from strongly seropositive animals (≥ 1:120) in a Poisson multivariate regression model. There was an interaction between properties in peri-urban areas and extensive production systems. This interaction demonstrated an increase in prevalence rates by 3.7 times (95%CI: 2.4-5.8). Properties close to dumps demonstrated an increase in prevalence rates by 2.2 times (95%CI: 0.99-4.8). In conclusion, anti-L. intracellularis antibodies were widely dispersed in subsistence pig farming's in Minas Gerais, indicating a wide circulation of the agent in this type of production system. The interactions of animals raised close to peri-urban areas, extensively, and close to landfills are risk factors for spread of PPE.

Nursing interventions in palliative care in the intensive care unit: A systematic review.

CONTEXT: Patients in palliative care are found in different places where care is provided, including the intensive care environment with important role of the nursing staff. OBJECTIVE: The aim of this systematic review was to answer the following question: which nursing interventions are aimed to the palliative care patients who are in the intensive care unit (ICU). DATA SOURCES: US National Library of Medicine (PUBMED), Virtual Health Library (BVS), SciELO, The Cochrane Library (Cochrane) and Lilacs databases were used. DATA EXTRACTION: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 36 entries published between 2010 and 2020 were used. DATA ANALYSIS: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. RESULTS: The findings demonstrated that the interventions that focus on promoting the patient's autonomy and respect their needs on ICU involves effective communication, promoting shared decision with patient and family, individualize care for each patient including the family on the daily care and decisions, maintaining basic nursing care as hygiene and comfort and encouraging self-care, as well as the involvement of nursing palliative care specialists the care is important. Other interventions included promoting a continuing education program for the nursing staff and other professionals involved in caring for patients in palliative care at ICU. CONCLUSION: This review highlighted the need for specific nursing interventions aimed at palliative care patients at ICU to promote patient autonomy and the focus on patient needs, always sharing decisions with the patient and family. However, it showed that there is a need for the continuous training of the nursing staff because factors such as the nurses' lack of technical-scientific knowledge and, concomitantly, the absence of a standardized and specific intervention model linked to a bureaucratic system, make it difficult to carry out a specialized care for this type of patient.

Nursing interventions in palliative care in the intensive care unit: A systematic review / Intervenciones de enfermería en cuidados paliativos en la unidad de cuidados

Context: Patients in palliative care are found in different places where care is provided, including the intensive care environment with important role of the nursing staff. Objective: The aim of this systematic review was to answer the following question: which nursing interventions are aimed to the palliative care patients who are in the intensive care unit (ICU). Data sources: US National Library of Medicine (PUBMED), Virtual Health Library (BVS), SciELO, The Cochrane Library (Cochrane) and Lilacs databases were used. Data extraction: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 36 entries published between 2010 and 2020 were used. Data analysis: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. Results: The findings demonstrated that the interventions that focus on promoting the patient's autonomy and respect their needs on ICU involves effective communication, promoting shared decision with patient and family, individualize care for each patient including the family on the daily care and decisions, maintaining basic nursing care as hygiene and comfort and encouraging self-care, as well as the involvement of nursing palliative care specialists the care is important. Other interventions included promoting a continuing education program for the nursing staff and other professionals involved in caring for patients in palliative care at ICU...(AU)

Contexto: Los pacientes en cuidados paliativos se encuentran en varios lugares, incluso en cuidados intensivos, y las enfermeras tienen un papel importante en el cuidado de este tipo de pacientes. Objetivo: Esta revisión sistemática buscó responder a la siguiente pregunta: ¿Cuáles son las intervenciones de enfermería dirigidas a los pacientes en cuidados paliativos en la unidad de cuidados intensivos (UCI)?. Fuentes de datos: Biblioteca Nacional de Medicina de EE. UU. (PUBMED), Biblioteca Virtual de Salud (BVS), SciELO, The Cochrane Library y Lilacs. Extracción de datos: Aplicación de los criterios de inclusión y exclusión según el método PRISMA, totalizando 36 estudios publicados entre 2010 y 2020. Análisis de datos: Los datos extraídos se analizaron con un enfoque cualitativo, por lo que no se realizó ningún análisis estadístico. Resultados: Las intervenciones que promueven la autonomía del paciente y respetan sus necesidades en la UCI involucran: comunicación efectiva, decisión compartida de individualizar el cuidado e incluir a la familia en el cuidado. Se debe mantener la higiene, el confort y la promoción del autocuidado, involucrando equipos de especialistas en cuidados paliativos, impulsando programas de educación continua para enfermeras de cuidados intensivos y otros profesionales implicados. Conclusión: Son necesarias intervenciones enfermeras dirigidas a pacientes con cuidados paliativos en la UC para promover la autonomía y satisfacer las necesidades del paciente, compartiendo siempre las decisiones con el paciente y su familia, y asimismo es necesaria la formación continua de las enfermeras en factores como el desconocimiento técnico-científico de este colectivo y, concomitantemente, la ausencia de un modelo estandarizado de intervención vinculado a un sistema burocrático. Todo ello dificulta la atención especializada a este tipo de pacientes.(AU)

Effect of the racial group and body condition score at calving on production performance and metabolic profile of buffaloes during the transition period.

This study evaluated the body condition score (BCS) at calving and breed (B) effects on milk composition, yield, performance, physiological parameters, hemogram, blood metabolites, and urinary metabolites in the transition and early lactation periods of Mediterranean (MED) and Murrah (MUR) buffaloes. Twenty MED and fifteen MUR buffaloes were distributed into four experimental treatments, in a completely randomized design, considering their racial groups and BCS (LBCS = low; HBCS = high): LBCS MED (N = 9); HBCS MED (N = 11); LBCS MUR (N = 8); HBCS MUR (N = 7). Animals were monitored during the last 21 days of gestation and first 56 days postpartum and kept under the same management and feeding conditions. During data collection, milk composition, yield, performance, physiological parameters, hemogram, blood metabolites, and urinary metabolites were evaluated. Higher milk production and fat-corrected milk were observed in MED than MUR buffaloes. Breed effects were observed on body weight, rectal temperature, glucose, urea, calcium (Ca) concentrations, and BCS effects on total protein, albumin, urea, and Ca. There were BCS effects on hematocrit, neutrophils, eosinophils, and interactions between B × BCS for lymphocytes and platelets. There were breed effects on urinary concentrations of chlorine, uric acid, and interactions between weight (W) × B on chlorine and urea. The MED buffaloes can be considered the most prepared to undergo physiological changes, including the BCS value at calving, indicating higher physiological health. Besides, this study demonstrates more considerable preparation for the calving, regardless of the body condition score at calving.

Papel de los factores inflamatorios sistémicos en los tumores neuroendocrinos gastroenteropancreáticos (TNE-GEP) tratados con péptidos marcados con radionúclidos (PRRT): de la biología a la teragnosis / Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis

Objetivo Los índices inflamatorios sistémicos se han validado como indicadores de inflamación sistémica como marcadores predictivos de mal pronóstico para diversas enfermedades oncológicas. Sin embargo, se desconoce el impacto pronóstico de los marcadores de inflamación sistémica en pacientes con tumores neuroendocrinos gastroenteropancreáticos (TNE-GEP) tratados con péptidos marcados con radionúclidos (PRRT). Métodos Realizamos un estudio observacional, retrospectivo, multicéntrico de 40 pacientes con TNEs-GEP y TNE de origen desconocido tratados con PRRT entre el 2016 y el 2020. Los marcadores inflamatorios sistémicos se calcularon de la siguiente manera: relación neutrófilos a linfocitos (NLR)=recuento de neutrófilos/recuento de linfocitos, relación de monocitos a linfocitos (MLR)=recuento de monocitos/recuento de linfocitos, relación de plaquetas a linfocitos (PLR)=recuento de plaquetas/recuento de linfocitos, relación de albúmina a linfocitos (ALR)=niveles de albúmina/recuento de linfocitos y relación derivada de neutrófilos a linfocitos (dNLR)=recuento de neutrófilos/(recuento de leucocitos – recuento de neutrófilos). Se utilizaron datos analíticos basales pretratamiento y después de la segunda dosis para el cálculo de los distintos índices. Resultados La mediana de edad fue de 63 años (rango 41-85), el 55% eran hombres. Los valores de corte de referencia para NLR fueron 2,61, para MLR 0,31, para PLR 110,14, para ALR 2,39 y para dNLR 1,71. Los valores de corte después de la segunda dosis fueron, para NLR 2,3, para MLR 0,3, para PLR 131,61, ALR 4,16 y dNLR 1,48. La mediana de la sobrevivencia libre de progresión (SLP) fue de 21,7 meses (IC del 95%: 10,7-32,8 m) y la supervivencia global (SG) fue de 32,1 meses (IC del 95%: 19,6-44,7 m), la SLP fue más corta en pacientes con NLR elevado (p=0,001), ALR (0,03) y dNLR (p=0,001) en el análisis basal. La tasa de control de enfermedad (DCR) fue del 81% y la tasa de respuesta objetiva (ORR) del 18% (AU)

Aim Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods We conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count – neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. Results The median age was 63 years (range 41–85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7–32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6–44.7 months), PFS was shorter in patients with elevated NLR (P=0.001), ALR (0.03), and dNLR (P=0.001) in baseline analysis. DCR was 81% and ORR 18%. Conclusions In GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors (AU)

Descripción de un método de cuantificación diferente para la carga de amiloide (DPDload) y validación de SPECT/TC en amiloidosis cardíaca / Description of a different quantification method for amyloid burden (burdenDPD) and validation of SPECT/CT in cardiac amyloidosis

Introducción Los radiotrazadores con afinidad ósea como el [99mTc]Tc-DPD han demostrado una alta sensibilidad y especificidad en el diagnóstico no invasivo de la amiloidosis cardíaca (AC) por transtirretina (ATTR-AC). Este estudio tiene como objetivo validar el uso de la SPECT/TC y evaluar la utilidad de la cuantificación de la captación (cargaDPD) en el tejido miocárdico como información potencial sobre la carga amiloide. Métodos Se trata de un análisis retrospectivo de 46 pacientes con sospecha de AC, en el que 23 casos con ATTR-AC fueron sometidos a dos métodos de cuantificación para estimar la carga amiloide (cargaDPD) a través de imágenes planares y de una SPECT/TC. Resultados La SPECT/TC aportó un valor añadido significativo en el diagnóstico del paciente con AC (p<0,05). La estimación de la carga amiloide comprobó que la pared del VI más afectada es el tabique interventricular en la mayoría de los casos, y la existencia de una relación significativa entre la captación de Perugini y la carga de DPD. Conclusiones Validamos la necesidad de la SPECT/TC como complemento de la imagen planar en el diagnóstico de la AC-TTR. Por su parte, el cálculo de la carga amiloide continúa siendo un área de investigación compleja y requiere de más estudios, con un mayor número de pacientes, que permitan validar un método estandarizado de cuantificación de la carga de amiloide, tanto para el diagnóstico como para el seguimiento del tratamiento (AU)

Background Bone tracers such as [99mTc]Tc-DPD have shown high sensitivity and specificity in the non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-AC). This study aims to validate SPECT/CT and assess the usefulness of uptake quantification (burdenDPD) in the myocardial tissue as potential information on the amyloid burden. Methods In a retrospective analysis of 46 patients with suspected CA, 23 cases with ATTR-AC had two quantification methods conducted to estimate amyloid burden (burdenDPD) through planar scintigraphic scans and a SPECT/CT. Results SPECT/CT significantly provided an added value in the patient's diagnosis with CA (P<.05). The estimation of the amyloid burden substantiated that the most affected wall of the LV is the interventricular septum in most cases and the existence of a significant relationship between the Perugini score uptake and the burdenDPD. Conclusions We validate the need for SPECT/CT to complement planar imaging in diagnosing ATTR-AC. For its part, quantifying the amyloid load continues to be a complex area of research. It requires further studies with a larger number of patients to validate a standardized method of amyloid load quantification, both for diagnosis and treatment monitoring (AU)

Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis.

AIM: Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). METHODS: We conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count - neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. RESULTS: The median age was 63 years (range 41-85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7-32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6-44.7 months), PFS was shorter in patients with elevated NLR (p=0.001), ALR (0.03), and dNLR (p=0.001) in baseline analysis. DCR was 81% and ORR 18%. CONCLUSIONS: In GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors.

Evaluation of antibacterial and antifungal activity of antimicrobial soaps.

Soaps play an important role in our hygiene and health, as they not only have a bactericidal effect but also remove dirt from the human body. To evaluate the effectiveness of soaps with antimicrobial activity from different commercial brands sold in Brazil. Tests of the antimicrobial activity of different soaps were carried out through diffusion in agar against the microorganisms Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Acinetobacter baumannii, Proteus mirabilis, and Candida albicans. All commercial soaps tested transfer antimicrobial inhibition halo formation against S. aureus and P. aeruginosa bacteria. Only two commercial soaps inhibit the species A. baumannii and C. albicans. None of the seven products studied showed inhibition of E. cloacae, P. mirabilis, and E. coli bacteria. When comparing the information contained in the packaging of the products with the results obtained during a survey, divergences were observed. The soaps that provide greater efficiency against the tested microorganisms were presented in presentations 1 and 2, which become useful against the bacteria species S. aureus, P. aeruginosa, and A. baumannii and a fungus species C. albicans. Marks 3, 4, 5, 6, and 7 parallel the same sensitivity result opposite as bacteria of the species S. aureus and P. aeruginosa, with quantitative variation only of the inhibition halo. There was a divergence between the information contained in the packaging of the seven products under study and the results of the experimental tests.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Single and combined effects of ultraviolet radiation and triclosan during the metamorphosis of Solea senegalensis.

Ultraviolet radiation (UV) and triclosan (TCS) affect the early development of marine fish; however, the corresponding molecular mechanisms are still not fully understood. Therefore, this work aims to study the effects of the single and combined exposure to these stressors during the thyroid-regulated metamorphosis of the flatfish Solea senegalensis. Sub-lethal exposure (5.89 kJ m-2 UV and/or 0.546 and 1.090 mg L-1 TCS for 48 h) was performed at the beginning of metamorphosis (13 days after hatching, dah), followed by a period in clean media until complete metamorphosis (24 dah). Malformations, metamorphosis progression, length, behavior and the expression of thyroid axis-related genes were studied. TCS induced malformations, decreased swimming performance, and induced metamorphosis acceleration at 15 dah, followed by a significant metamorphosis delay. Such effects were more noticeable in the presence of UV. The down-regulation of five thyroid axis-related genes occurred after exposure to TCS (15 dah), and after 9 days in clean media two genes were still down-regulated. UV exposure increased the effect of TCS by further down-regulating gene expression immediately after the exposure. Since several effects persisted after the period in clean media, implications of these stressors (mainly TCS) on the ecological performance of the species are suggested.

Molecular docking studies and evaluation of the antiretroviral activity and cytotoxicity of the species Lafoensia pacari Saint-Hilaire.

Interest in antiviral plant species has grown exponentially and some have been reported to have anti-HIV properties. This research aims to perform the bio-guided phytochemical fractionation by antiretroviral activity of Lafoensia pacari stem barks. This in vitro experimental study involved the preparation of plant material, obtention of ethanolic extract, fractionation, purification, identification and quantification of fractions, acid-base extraction, nuclear magnetic resonance, HIV-1 RT inhibition test and molecular docking studies. From the bio-guided fractionation by the antiretroviral activity there was a higher activity in the acetanolic subfractions, highlighting the acetate subfraction - neutrals with 60.98% of RT inhibition and ellagic acid with 88.61% of RT inhibition and absence of cytotoxicity. The macrophage lineage cytotoxicity assay showed that the chloroform fraction was more toxic than the acetate fraction. The analysis of the J-resolved spectrum in the aromatic region showed a singlet at 7.48 and 6.93 ppm which was identified as ellagic acid and gallic acid, respectively. The 5TIQ enzyme obtained better affinity parameter with the ellagic acid ligand, which was confirmed by the HSQC-1H-13C spectra. Gallic acid was also favorable to form interaction with the 5TIQ enzyme, being confirmed through the HSQC-1H-13C spectrum. From the PreADMET evaluation it was found that ellagic acid is a promising molecule for its RT inhibition activity and pharmacokinetic and toxicity parameters.

Trypanosoma cruzi modulates lipid metabolism and highjacks phospholipids from the midgut of Rhodnius prolixus.

Chagas disease is potentially life-threatening and caused by the protozoan parasite Trypanosoma cruzi. The parasite cannot synthesize some lipids and depends on the uptake of these lipids from its vertebrate and invertebrate hosts. To achieve this, T. cruzi may need to modify the physiology of the insect host for its own benefit. In this study, we investigated the interaction of T. cruzi (Y strain) with its insect vector Rhodnius prolixus and how it manipulates the vector lipid metabolism. We observed a physiological change in lipid flux in of infected insects. In the fat body of infected insects, triacylglycerol levels decreased by 80.6% and lipid storage droplet-1(LSD-1) mRNA levels were lower, when compared to controls. Lipid sequestration by infected midguts led to increased levels of 5' AMP-activated protein kinase (AMPK) phosphorylation and activation in the fat body, inhibiting the synthesis of fatty acids and stimulating their oxidation. This led to reduced lipid levels in the fat body of infected insets, despite the fact that T. cruzi does not colonize this tissue. There was a 3-fold increase, in lipid uptake and synthesis in the midgut of infected insects. Finally, our results suggest that the parasite modifies the lipid flux and metabolism of its vector R. prolixus through the increase in lipid delivery from the fat body to midgut that are then scavenge by T cruzi.