Osteonecrosis of the Jaw Associated with Bisphosphonates Infusion for Treatment of Plasma Cell Myeloma-A Retrospective Observational Study of Northern Portuguese Population.

Objectives: To verify medication-related osteonecrosis of the jaw (MRONJ) frequency among patients with plasma cell myeloma (PCM) that had been treated with bisphosphonates, to identify predisposing factors that could influence the development of osteonecrosis. Methods: This observational retrospective study was performed at the Department of Hematology of Hospital Center of Porto (CHUP), Portugal. Results: The study population (n = 112) had a 15.2% (n = 17) prevalence of osteonecrosis. Clinically, bone exposure was the most frequently observed sign, present in 100% (n = 17) of the patients, followed by inflammation in 82.4% (n = 14), orofacial pain in 70.6% (n = 12), suppuration in 47.1% (n = 8), and intra or extra-oral fistula in 17.6% (n = 3) of the cases. The most frequent triggering local factor was dental extraction (82.4%). There was a dependence between the presence of extractions and the development of MRONJ (p < 0.001) but not with the time elapsed from the initiation of infusions with BPs and dental extractions (p = 0.499). In the sample of patients with multiple myeloma (MM), 13.8% were found to be more likely to develop MRONJ after an extraction. Conclusions: The most common local predisposing factor was dental extraction. No dependence was observed between the development of osteonecrosis and the time elapsed from the beginning of treatment with bisphosphonates infusions to surgical procedures.

Linear Regression of Sampling Distributions of the Mean.

We show that the simple and multiple linear regression coefficients and the coefficient of determination R2 computed from sampling distributions of the mean (with or without replacement) are equal to the regression coefficients and coefficient of determination computed with individual data. Moreover, the standard error of estimate is reduced by the square root of the group size for sampling distributions of the mean. The result has applications when formulating a distance measure between two genes in a hierarchical clustering algorithm. We show that the Pearson R coefficient can measure how differential expression in one gene correlates with differential expression in a second gene.

Osseodensification vs. Conventional Osteotomy: A Case Series with Cone Beam Computed Tomography.

Introduction: Osseodensification is a non-extraction technique using specially designed drills to increase bone density while extending an osteotomy, allowing bone to be preserved and condensed by compacting autograft during osteotomy preparation, increasing bone density around implants, and improving mechanical stability. Aim: The objective of this study is to compare conventional osteotomy and osseodensification protocols in implant placement and analyze whether there are differences in bone density. Materials and Methods: Study variables were defined, namely, osseodensification technique, conventional osteotomy technique, bone density, sex, area of location, implant dimensions, implant dimensions, and implant stability. Eligibility and exclusion criteria were defined. A step-by-step surgical protocol was developed. The surgeon and radiologist underwent intra-examiner calibration. A total of 15 patients were selected according to the eligibility criteria, and a total of 41 implants were inserted, 20 implants by conventional osteotomy and 21 by osseodensification. A cone beam computed tomography was performed one year after prosthetic rehabilitation to estimate bone density. Data were collected and recorded, and in the analysis of the association of variables, non-parametric tests were applied. Results: Significant statistical results were found in bone density values, with higher values being obtained with the osseodensification technique, that is, median density values of 1020, and median density values of 732 for the bone drilling technique. The results of the correlation between bone density in both techniques and sex, primary implant stability, implant dimensions and location area were statistically non-significant. Conclusions: Within the limitations of this study, there are differences in bone density between conventional osteotomy and osseodensification protocols. Bone density is increased with osseodensification over a study period of one year.

Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial.

BACKGROUND: DESTINY-Lung01 is a multicentre, open-label, phase 2 study evaluating the antitumour activity and safety of trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpressing or HER2 (ERBB2)-mutant unresectable or metastatic non-small-cell lung cancer (NSCLC). The results of the HER2-mutant cohort (cohort 2) have been reported elsewhere. Herein, we report the primary analysis of cohorts 1 and 1A, which aimed to evaluate the activity and safety of trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg in patients with HER2-overexpressing NSCLC. METHODS: Patients aged 18 years or older with unresectable or metastatic (or both unresectable and metastatic) non-squamous NSCLC who had relapsed following or were refractory to standard treatment or for whom no standard treatment was available, with an HER2 immunohistochemistry score of 3+ or 2+ (without known HER2 mutations) and an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled at 20 specialist hospitals in France, Japan, the Netherlands, Spain, and the USA. Patients were assigned to cohorts sequentially, first to cohort 1, to receive trastuzumab deruxtecan 6·4 mg/kg (cohort 1), then to cohort 1A, to receive trastuzumab deruxtecan 5·4 mg/kg, both administered intravenously once every 3 weeks. The primary endpoint was confirmed objective response rate by independent central review and was assessed in the full analysis set, which included all patients who signed an informed consent form and were enrolled in the study. Safety was assessed in all enrolled patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT03505710, and is ongoing (closed to recruitment). FINDINGS: Between Aug 27, 2018, and Jan 28, 2020, 49 patients were enrolled in cohort 1 (median age 63·0 years [IQR 58·0-68·0], 30 [61%] male, 19 [39%] female, and 31 [63%] White), and from June 16 to Dec 9, 2020, 41 patients were enrolled in cohort 1A (median age 62·0 years [IQR 56·0-66·0], 22 [54%] male, 19 [46%] female, and 31 [76%] White). As of data cutoff (Dec 3, 2021), the median treatment duration was 4·1 months (IQR 1·4-7·1) in cohort 1 and 5·5 months (1·4-8·7) in cohort 1A, and median follow-up was 12·0 months (5·4-22·4) in cohort 1 and 10·6 months (4·5-13·5) in cohort 1A. Confirmed objective response rate by independent central review was 26·5% (95% CI 15·0-41·1; 13 of 49, all partial responses) in cohort 1 and 34·1% (20·1-50·6; 14 of 41; two complete responses and 12 partial responses) in cohort 1A. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (12 [24%] of 49 in cohort 1, none in cohort 1A), pneumonia (six [12%] and two [5%], respectively), fatigue (six [12%] and three [7%], respectively), and disease progression (six [12%] and four [10%], respectively). Drug-related treatment-emergent adverse events of grade 3 or worse occurred in 26 (53%) of 41 patients in cohort 1 and nine (22%) of 49 patients in cohort 1A. Drug-related serious adverse events were reported in ten (20%) patients and three (7%) patients, respectively. Deaths due to treatment-emergent adverse events occurred in ten (20%) patients in cohort 1 (disease progression in six (12%) patients and bronchospasm, hydrocephalus, respiratory failure, and pneumonitis in one [2%] patient each), and in seven (17%) patients in cohort 1A (due to disease progression in four (10%) patients and dyspnoea, malignant neoplasm, and sepsis in one (2%) patient each). One death due to a treatment-emergent adverse event was determined to be due to study treatment by the investigator, which was in cohort 1 (pneumonitis). Independent adjudication of interstitial lung disease or pneumonitis found that drug-related interstitial lung disease or pneumonitis occurred in ten (20%) patients in cohort 1 (two [4%] grade 1, five [10%] grade 2, and three [6%] grade 5) and two (5%) patients in cohort 1A (one [2%] grade 2 and one [2%] grade 5). An additional patient in cohort 1A had grade 4 pneumonitis after the data cutoff, which was subsequently adjudicated as drug-related grade 5 interstitial lung disease or pneumonitis. INTERPRETATION: Given the low antitumour activity of existing treatment options in this patient population, trastuzumab deruxtecan might have the potential to fill a large unmet need in HER2-overexpressing NSCLC. Our findings support further investigation of trastuzumab deruxtecan in patients with HER2-overexpressing NSCLC. FUNDING: Daiichi Sankyo and AstraZeneca.

Assessment of Oral Health Status in a Prison Population in Northern Portugal.

Background: Prisoners constitute one of the disadvantaged groups and it is observed that these individuals suffer from poor oral hygiene and the prevalence of oral diseases is higher compared to the general population. Material and Methods: The aim of this study is to assess the state of the oral health in a prison population in Northern Portugal. A cross-sectional observational study was conducted involving 103 male prisoners with age between 25 and 75 years old. A questionnaire was presented to all the prisoners and an intraoral clinical examination was performed in each of them. Results: The sample mean age was 41.58 ± 8.94 years. Most participants consume sugary foods, with 32% consuming then on a daily basis. It was noticed that 13.6% of the participants do not brush their teeth. Most of the prisoners smoke (78.6%) and 70 smoke more than 10 cigarettes per day. The mean DMFT was 17.17 ± 8.23 and the component with the highest weight was the number of missing teeth, with a mean value of 13.14 ± 8.32. It was observed that 7 individuals are edentulous and 64 (62.1%) have caries lesions. It has been noted that of the 64 individuals presenting caries lesions, 47 (73.4%) eat sugary foods, however this relationship is not statistically significant. It was found that the prevalence of periodontal health was 26%, gingivitis was 32.3% and periodontitis was 41.7%. Plaque Index was evaluated according to the periodontal condition, it was observed a significantly lower level of plaque index in the periodontally healthy subjects compared to the subjects with gingivitis and the subjects with periodontitis. Conclusions: The prevalence of oral diseases in this prison population is high, as is the loss of teeth. Dental caries is the most observed oral disease, and periodontitis the most common of the periodontal diseases. Key words:Prisoners, Oral health, Caries, DMFT, Periodontitis, Oral diseases.

Purinergic P2X7 receptor expression increases in leukocytes from intra-abdominal septic patients.

Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin.

Caracterización de adultos mayores con cáncer colorrectal en la comunidad

Fundamento: el cáncer colorrectal es la neoplasia más frecuente del sistema digestivo en los adultos mayores. En Cuba es un problema de salud de primer orden por su elevada incidencia y mortalidad, constituye la tercera causa de muerte en la población general. Objetivo: caracterizar a los adultos mayores con cáncer colorrectal en el Policlínico Sur Rudesindo García del Rijo de la provincia Sancti Spíritus. Métodos: se realizó una investigación de tipo descriptiva en el Policlínico Sur Rudesindo García del Rijo del municipio y provincia Sancti Spíritus, de enero a marzo del 2019. Se trabajó con una muestra intencional de 127 adultos mayores, pertenecientes a consultorios urbanos. Las variables analizadas fueron: edad, sexo, nivel de escolaridad, estadio del cáncer colorrectal al diagnóstico, estado de salud, comorbilidades, capacidad y percepción del autocuidado y supervivencia. Para el estadio al diagnóstico se utilizó la clasificación anatomoclínica, la comorbilidad, se midió mediante el índice de Charlson y el Test de Capacidad y Percepción de Autocuidado del Adulto Mayor. La información se procesó mediante el análisis porcentual. Los resultados alcanzados se interpretaron los números con sus porcientos. Resultados: en la caracterización de la muestra predominaron las féminas, el grupo de edad entre 70 y 79 años y el nivel de escolaridad de secundaria básica. El estadio II con un mal estado de salud y la inadecuada percepción de autocuidado fue mayoritario. La comorbilidad fue moderada con una supervivencia entre 40 a 60 meses. Conclusiones: predominaron las mujeres entre los 70 y los 79 años y como nivel de escolaridad, la secundaria básica; además prevaleció el estadio II y la inadecuada percepción de autocuidado.

Foundation: colorectal cancer is the most common neoplasm of the digestive system in older adults. In Cuba it is a major health problem due to its high incidence and mortality; it is the third cause of death in the general population. Objective: to characterize older adults with colorectal cancer at the Rudesindo García del Rijo Sur Polyclinic in the Sancti Spíritus province. Methods a descriptive research was carried out at the Sur Rudesindo García del Rijo Polyclinic in the municipality and province of Sancti Spíritus, from January to March 2019. We worked with an intentional sample of 127 older adults, belonging to urban clinics. The variables analyzed were: age, sex, educational level, stage of colorectal cancer at diagnosis, health status, comorbidities, capacity and perception of self-care and survival. For the stage at diagnosis, the anatomoclinical classification was used, comorbidity was measured using the Charlson index and the Self-Care Capacity and Perception Test for the Elderly. The information was processed through percentage analysis. The results achieved were interpreted as numbers with their percentages. Results: in the characterization of the sample, females, the age group between 70 and 79 years and the level of lower secondary education predominated. Stage II with a poor state of health and inadequate perception of self-care was the majority. Comorbidity was moderate with survival between 40 to 60 months. Conclusions: women between 70 and 79 years of age and lower secondary education level predominated, stage II and inadequate perception of self-care also prevailed.

Successful Closure of a Persistent Enterocutaneous Fistula with a Myocutaneous Flap.

Enterocutaneous fistulas can present with significant morbidity and mortality for affected patients, as the abnormal connection can result in exorbitant loss of enteral fluids, electrolyte disturbances, and sepsis, among other complications. We present a patient with a chronic complex enterocutaneous fistula who underwent several surgeries, resulting in a considerable amount of bowel resection. Based on history and findings of high output fistula with diverting transverse colostomy, the fistula was closed with a left rectus myocutaneous pedicle flap to avoid entering the abdominal cavity and prevent the possibility of short bowel syndrome. This case contributes to the growing body of literature supporting the use of rectus myocutaneous flaps for the closure of intractable complex enterocutaneous fistulas in patients unable to undergo resection of the affected bowel.

Differential expression of PSMC4, SKP1, and HSPA8 in Parkinson's disease: insights from a Mexican mestizo population.

Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

Caracterización de los adultos mayores con cáncer colorrectal en la comunidad / Characterization of Community Older Adults with Colorectal Cancer

Introducción: El cáncer colorrectal es la neoplasia más frecuente del sistema digestivo en los adultos mayores. En Cuba es un problema de salud de primer orden por su elevada incidencia y mortalidad, que constituye la tercera causa de muerte. Objetivo: Caracterizar a los adultos mayores con cáncer colorrectal en el Policlínico Sur de Sancti Spíritus. Métodos: Investigación de tipo descriptiva en el Policlínico Sur del municipio y la provincia de Sancti Spíritus de enero a marzo del 2019. Muestra intencional de 127 adultos mayores, pertenecientes a consultorios urbanos. Las variables: edad, sexo, escolaridad, estadio del cáncer colorrectal al diagnóstico, estado de salud, comorbilidades, capacidad y percepción del autocuidado y supervivencia. Para determinar el estadio al diagnóstico se utilizó la clasificación anatomoclínica. La comorbilidad se midió mediante el índice de Chalson mientras que para medir la capacidad y percepción del autocuidado se empleó el Test de CYPAC-AM. Resultados: En la caracterización de la muestra predominaron las mujeres, el grupo de edad entre 70 y 79 años y la escolaridad de secundaria básica. El estadio II, con un mal estado de salud y la inadecuada percepción de autocuidado, fue mayoritario. La comorbilidad fue moderada con una supervivencia entre 40 a 60 meses. Conclusiones: La adecuada caracterización de los adultos mayores con cáncer colorrectal en la comunidad posibilita trazar estrategias dirigidas a la mejora del autocuidado y el estado de salud de los gerontes desde el primer nivel de atención(AU)

Introduction: Colorectal cancer is the most frequent neoplasm of the digestive system in older adults. In Cuba, it is a highly significant health problem due to its high incidence and mortality, also being the third cause of death. Objective: To characterize older adults with colorectal cancer at Policlínico Sur of Sancti Spíritus. Methods: A descriptive research was carried out in Policlínico Sur of Sancti Spíritus Municipality and Province from January to March 2019. The intentional sample was made up of 127 older adults, belonging to urban family medical offices. The variables were age, sex, school level, stage of colorectal cancer at diagnosis, health status, comorbidities, selfcare capacity and perception, and survival. The anatomoclinical classification was used to determine the stage at diagnosis. Comorbidity was measured using the Chalson index, while the CYPAC-AM (older adult selfcare capacity and perception) test was used to measure selfcare capacity and perception. Results: In the characterization of the sample, there was a predominance of women, the age group between 70 and 79 years, and the junior high school level. Stage II prevailed, together with poor health status and inadequate selfcare perception. Comorbidity was moderate, with survival between 40 to 60 months. Conclusions: The adequate characterization of older adults with colorectal cancer in the community makes it possible to outline strategies aimed at improving selfcare and their health status from the first level of care(AU)

Structure and thermal behavior of biobased vitrimer of lactic acid and epoxidized canola oil.

Biobased vitrimers were obtained from epoxidized canola oil (ECO) and lactic acid (LA) using zinc acetate (ZnAc) and ZnAl-layered double hydroxide (ZnAl) in the proportions of 1 and 2 wt% as transesterification catalysts. Reactions containing ECO and LA showed an average enthalpy of cure of approximately 85 mJ mg-1 and materials cured in the presence of the catalysts showed lower enthalpies of cure and decrease in the material gel content. ECO-LA reaction generated materials with rubber-like properties with Tg ranging from -15 °C to -23 °C, where the material without a catalyst showed the higher Tg value. The presence of catalysts gave the material vitrimer properties, with the softening point associated with transesterification reactions and topology freezing temperature transition at temperatures (Tv) between 195-235 °C.

Fermentation Patterns, Methane Production and Microbial Population under In Vitro Conditions from Two Unconventional Feed Resources Incorporated in Ruminant Diets.

In this study, four experimental treatments were evaluated: (T1) alfalfa hay + concentrate, (50:50%, DM); (T2) alfalfa hay + Leucaena leucocephala + concentrate, (30:20:50%, DM); (T3) alfalfa hay + prickly pear + concentrate, (30:20:50%, DM); and (T4) alfalfa hay + Leucaena leucocephala + prickly pear + concentrate, (30:10:10:50%, DM). NH3-N concentrations in T2 and T4 decreased when replaced with alfalfa hay in 20 and 10%, respectively. Treatments did not affect the concentration of total volatile fatty acids (TVFA) between T3 and T4 (p > 0.05), while the concentrations among T1 and T2 were different (p < 0.05). T2 showed a reduction of 25.5% in the methane production when compared to T1 (p < 0.05). The lowest concentrations of protozoa were observed in T2 and T4, which contained Leucaena leucocephala (T2) and Leucaena leucocephala + prickly pear (T4) (p < 0.05). The highest concentration of total methanogens was recorded in T1 and was different in T2, T3, and T4 (p < 0.05). Leucaena leucocephala, at an inclusion percentage of 20%, decreased the methane when compared to T1, whereas prickly pear increased methane production in relation to T1.

Influence of Molybdenum and Organic Sources of Copper and Sulfur on the Performance, Carcass Traits, Blood Mineral Concentration, and Ceruloplasmin Activity in Lambs.

This study aimed to evaluate the effects of molybdenum (Mo) and organic and inorganic sources of copper (Cu) and sulfur (S) on the performance, carcass traits, and blood concentration of these minerals in lambs. Forty male non-castrated crossbred Dorper x Santa Inês lambs (20 ± 1.2 kg of body weight and 90 ± 2 d of age) were randomly allocated into one of the ten following treatments: (T0) control, basal diet; (T1) Mo; (T2) inorganic Cu and inorganic S; (T3) inorganic Cu and organic S; (T4) organic Cu and inorganic S; (T5) organic Cu and organic S; (T6) Mo plus inorganic Cu and inorganic S; (T7) Mo plus inorganic Cu and organic S; (T8) Mo plus organic Cu and inorganic S; and (T9) Mo plus organic Cu and organic S. Regardless of the source, Mo, Cu, and S were added at levels of 10 mg, 10 mg, and 2000mg/kg DM, respectively. The mineral supplements (Mo, Cu, and S) were added into the total mixed ration (TMR) by mixing them apart with the mineral and vitamin premix and then put into the TMR. The animals were kept in individual pens and received a total mixed ration for 84 days. Body weight and blood sampling was performed every 28 days. All animals were slaughtered after 84 days, and carcass traits were evaluated. Although organic sources of Cu and S added to Mo supplementation had increased the ADG throughout the study, this effect did not reflect in the heavier final BW outcomes for this treatment. In addition, no effect of these treatments was observed on the carcass traits. The serum Cu concentration was higher for the T0 group compared to the other groups; otherwise, Mo reduced the serum Cu concentration compared to the other groups. Considering the interaction among the minerals and their sources at 84 d of study, organic sources of Cu and S treatment and Mo associated with inorganic sources of Cu plus organic S treatment had an increased serum Cu concentration compared to other groups. Regardless of time, organic sources of Cu and S increased serum S concentration. At 84 days after enrollment, serum Mo concentration was lower for the control group compared to the other groups. Further, Mo supplementation increased its blood concentration compared to the control group throughout the study. The control group had the highest ceruloplasmin activity compared to the other groups; otherwise, at 84 d of the study, either Mo or inorganic S supplementation reduced ceruloplasmin activity. Serum ceruloplasmin activity was higher when Cu supplementation, regardless of source, was associated with organic S. However, at d 84 of the study, inorganic Cu associated to organic S supplements increased serum ceruloplasmin activity. In this current study, it was not possible to identify a pattern in the variables studied, however, further studies are needed to confirm that organic sources of Cu and S interacted alone without a defined pattern.

Longitudinal Impact of the COVID-19 Pandemic on Stress and Occupational Well-Being of Mental Health Professionals: An International Study.

BACKGROUND: Increased levels of occupational stress among health professionals during the COVID-19 pandemic have been documented. Few studies have examined the effects of the pandemic on mental health professionals despite the heightened demand for their services. METHOD: A multilingual, longitudinal, global survey was conducted at 3 time points during the pandemic among members of the World Health Organization's Global Clinical Practice Network. A total of 786 Global Clinical Practice Network members from 86 countries responded to surveys assessing occupational distress, well-being, and posttraumatic stress symptoms. RESULTS: On average, respondents' well-being deteriorated across time while their posttraumatic stress symptoms showed a modest improvement. Linear growth models indicated that being female, being younger, providing face-to-face health services to patients with COVID-19, having been a target of COVID-related violence, and living in a low- or middle-income country or a country with a higher COVID-19 death rate conveyed greater risk for poor well-being and higher level of stress symptoms over time. Growth mixed modeling identified trajectories of occupational well-being and stress symptoms. Most mental health professions demonstrated no impact to well-being; maintained moderate, nonclinical levels of stress symptoms; or showed improvements after an initial period of difficulty. However, some participant groups exhibited deteriorating well-being approaching the clinical threshold (25.8%) and persistently high and clinically significant levels of posttraumatic stress symptoms (19.6%) over time. CONCLUSIONS: This study indicates that although most mental health professionals exhibited stable, positive well-being and low stress symptoms during the pandemic, a substantial minority of an already burdened global mental health workforce experienced persistently poor or deteriorating psychological status over the course of the pandemic.

Chemical Recycling of PET Using Catalysts from Layered Double Hydroxides: Effect of Synthesis Method and Mg-Fe Biocompatible Metals.

The chemical recycling of poly(ethylene terephthalate) (PET) residues was performed via glycolysis with ethylene glycol (EG) over Mg-Fe and Mg-Al oxide catalysts derived from layered double hydroxides. Catalysts prepared using the high supersaturation method (h.s.c.) presented a higher surface area and larger particles, but this represented less PET conversion than those prepared by the low supersaturation method (l.s.c.). This difference was attributed to the smaller mass transfer limitations inside the (l.s.c.) catalysts. An artificial neural network model well fitted the PET conversion and bis(2-hydroxyethyl) terephthalate (BHET) yield. The influence of Fe in place of Al resulted in a higher PET conversion of the Mg-Fe-h.s.c. catalyst (~95.8%) than of Mg-Al-h.s.c. (~63%). Mg-Fe catalysts could be reused four to five times with final conversions of up to 97% with reaction conditions of EG: PET = 5:1 and catalyst: PET = 0.5%. These results confirm the Mg-Fe oxides as a biocompatible novel catalyst for the chemical recycling of PET residues to obtain non-toxic BHET for further polymerization, and use in food and beverage packaging.

Risk Factors Associated with COVID-19 Mortality in the State of Durango, Mexico.

The coronavirus disease 2019 (COVID-19) has caused over six million deaths worldwide since its emergence in Wuhan China, factors associated with COVID-19 mortality, such as comorbidities, age, and observed symptomatology still remain a major subject of study. In the present work, a total of 16,345 SARS-CoV-2 positive cases from Durango Mexico diagnosed from May 2020 to December 2021 were analyzed to establish an association of COVID-19 mortality with clinical and demographic variables in a case-control study. Selected variables include patient age, smoking status, sex, presence of comorbidities such as hypertension, diabetes and obesity, as well as patient symptomatology such as fever, dyspnea, abdominal pain and diarrhea. Results indicate that among analyzed data, the median age was 43 years; 54% were female, with a mortality rate of 5.66%. Multivariate regression analysis indicated that the comorbidities associated with the highest risk factor were advanced age (>60) with an odds ratio of 4.127 (IC 95%, 3.37-5.05), hypertension with 1.961 (IC 95%, 1.57-2.45), diabetes with 1.753 (IC 95%, 1.39-2.20) and obesity with 1.413 (IC 95%, 1.11-1.78) respectively. On the other hand, the symptom associated with the highest risk factor was dyspnea with an odds ratio of 18.369 (IC 95%, 14.42-23.39). Our data suggests an association between hypertension and old age with COVID-19 mortality. Other findings include the prevalence of dyspnea, polypnea and cyanosis as a major predictor for COVID-19 mortality, as well as lower mortality risks among health workers.

Design of a Whole-Cell Biosensor Based on Bacillus subtilis Spores and the Green Fluorescent Protein To Monitor Arsenic.

A green fluorescent protein (GFP)-based whole-cell biosensor (WCB-GFP) for monitoring arsenic (As) was developed in Bacillus subtilis. To this end, we designed a reporter gene fusion carrying the gfpmut3a gene under the control of the promoter/operator region of the arsenic operon (Pars::gfpmut3a) in the extrachromosomal plasmid pAD123. This construct was transformed into B. subtilis 168, and the resultant strain was used as a whole-cell biosensor (BsWCB-GFP) for the detection of As. The BsWCB-GFP was specifically activated by inorganic As(III) and As(V), but not by dimethylarsinic acid [DMA(V)], and exhibited high tolerance to the noxious effects of arsenic. Accordingly, after 12 h exposure, B. subtilis cells carrying the Pars::gfpmut3a fusion exhibited 50 and 90% lethal doses (LD50 and LD90) to As(III) of 0.89 mM and As 1.71 mM, respectively. Notably, dormant spores from the BsWCB-GFP were able to report the presence of As(III) in a concentration range from 0.1 to 1,000 µM 4 h after the onset of germination. In summary, the specificity and high sensitivity for As, as well as its ability to proliferate under concentrations of the metal that are considered toxic in water and soil, makes the B. subtilis biosensor developed here a potentially important tool for monitoring environmental samples contaminated with this pollutant. IMPORTANCE Arsenic (As) contamination of groundwater is associated with serious worldwide health risks. Detection of this pollutant at concentrations that are established as permissible for water consumption by WHO is a matter of significant interest. Here, we report the generation of a whole-cell biosensor for As detection in the Gram-positive spore former B. subtilis. This biosensor reports the presence of inorganic As, activating the expression of the green fluorescent protein (GFP) under the control of the promoter/operator of the ars operon. The biosensor can proliferate under concentrations of As(III) that are considered toxic in water and soil and detect this ion at concentrations as low as 0.1 µM. Of note, spores of the Pars-GFP biosensor exhibited the ability to detect As(III) following germination and outgrowth. Therefore, this novel tool has the potential to be directly applied to monitor As contamination in environmental samples.

Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRASG12C-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated non-small-cell lung cancer (NSCLC) and untreated CNS metastases have a worse prognosis than similar patients without KRAS mutations. Adagrasib has previously demonstrated CNS penetration preclinically and cerebral spinal fluid penetration clinically. We evaluated adagrasib in patients with KRASG12C-mutated NSCLC and untreated CNS metastases from the KRYSTAL-1 trial (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), in which adagrasib 600 mg was administered orally, twice daily. Study outcomes included the safety and clinical activity (intracranial [IC] and systemic) by blinded independent central review. Twenty-five patients with KRASG12C-mutated NSCLC and untreated CNS metastases were enrolled and evaluated (median follow-up, 13.7 months); 19 patients were radiographically evaluable for IC activity. Safety was consistent with previous reports of adagrasib, with grade 3 treatment-related adverse events (TRAEs) in 10 patients (40%) and one grade 4 (4%) and no grade 5 TRAEs. The most common CNS-specific TRAEs included dysgeusia (24%) and dizziness (20%). Adagrasib demonstrated an IC objective response rate of 42%, disease control rate of 90%, progression-free survival of 5.4 months, and median overall survival of 11.4 months. Adagrasib is the first KRASG12C inhibitor to prospectively demonstrate IC activity in patients with KRASG12C-mutated NSCLC and untreated CNS metastases, supporting further investigation in this population.

Brain structural and functional correlates of the heterogenous progression of mixed transcortical aphasia.

Mixed transcortical aphasia (MTCA) is characterized by non-fluent speech and comprehension deficits coexisting with preserved repetition. MTCA may evolve to less severe variants of aphasias or even to full language recovery. Mechanistically, MCTA has traditionally been attributed to a disconnection between the spared left perisylvian language network (PSLN) responsible for preserved verbal repetition, and damaged left extrasylvian networks, which are responsible for language production and comprehension impairments. However, despite significant advances in in vivo neuroimaging, the structural and functional status of the PSLN network in MTCA and its evolution has not been investigated. Thus, the aim of the present study is to examine the status of the PSLN, both in terms of its functional activity and structural integrity, in four cases who developed acute post-stroke MTCA and progressed to different types of aphasia. For it, we conducted a neuroimaging-behavioral study performed in the chronic stage of four patients. The behavioral profile of MTCA persisted in one patient, whereas the other three patients progressed to less severe types of aphasias. Neuroimaging findings suggest that preserved verbal repetition in MTCA does not always depend on the optimal status of the PSLN and its dorsal connections. Instead, the right hemisphere or the left ventral pathway may also play a role in supporting verbal repetition. The variability in the clinical evolution of MTCA may be explained by the varying degree of PSLN alteration and individual premorbid neuroanatomical language substrates. This study offers a fresh perspective of MTCA through the lens of modern neuroscience and unveils novel insights into the neural underpinnings of repetition.

Pathways to eating disorder care: A European multicenter study.

BACKGROUND: The aim of this study was to assess barriers and facilitators in the pathways toward specialist care for eating disorders (EDs). METHODS: Eleven ED services located in seven European countries recruited patients with an ED. Clinicians administered an adapted version of the World Health Organization "Encounter Form," a standardized tool to assess the pathways to care. The unadjusted overall time needed to access the ED unit was described using the Kaplan-Meier curve. RESULTS: Four-hundred-nine patients were recruited. The median time between the onset of the current ED episode and the access to a specialized ED care was 2 years. Most of the participants did not directly access the specialist ED unit: primary "points of access" to care were mental health professionals and general practitioners. The involvement of different health professionals in the pathway, seeking help for general psychiatric symptoms, and lack of support from family members were associated with delayed access to ED units. CONCLUSIONS: Educational programs aiming to promote early diagnosis and treatment for EDs should pay particular attention to general practitioners, in addition to mental health professionals, and family members to increase awareness of these illnesses and of their treatment initiation process.