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Background: A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification. Results: In total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy. Conclusion: ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.
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BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC). METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes. RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively). CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.
Subject(s)
Circulating Tumor DNA , Neoadjuvant Therapy , Neoplastic Cells, Circulating , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/blood , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Female , Neoadjuvant Therapy/methods , Middle Aged , Adult , Neoplastic Cells, Circulating/pathology , Neoplastic Cells, Circulating/metabolism , Biomarkers, Tumor/blood , Aged , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment OutcomeABSTRACT
CONTEXT: The growing number of females entering the armed forces has led to an increase in the number of female Veterans with spinal cord injury and diseases (SCI/D) requiring mobility devices. Limited research exists that explores whether mobility devices meet their needs in terms of comfort, fit and design. OBJECTIVE: To characterize respondents with SCI/D who use mobility devices and determine if these devices are meeting their daily needs. DESIGN: Online survey. SETTINGS: Veterans Health Administration. PARTICIPANTS: Female Veterans with SCI/D who received mobility devices in the past five years.Interventions: Participants completed an online survey regarding their challenges in obtaining and using mobility devices for their daily needs. RESULTS: 101 women with SCI/D participated in a nation-wide online survey. Respondents were mainly in their 50s and 59% were not currently employed due to their disability. Most used manual (35%) or power wheelchairs (34%). Many female Veterans felt their devices were not made with female users in mind and some felt they did not meet their needs. Opportunities to improve the assessment, follow-up, maintenance and repair processes were identified. CONCLUSIONS: Given that some female Veterans with SCI/D felt their devices did not meet all their needs, it is important for researchers to engage women in user-centered design of mobility devices and for providers to be mindful of Veterans' daily needs within all steps of the provision process in order for mobility devices to support overall function and usability.
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PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.
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OBJECTIVE: To determine whether implementation of an education-based intervention can sustainably improve upstream and downstream outcomes in intubated patients in a pediatric intensive care unit (PICU) in a low-resource country. DESIGN: Quality improvement study comparing airway-related morbidity in two previously studied patient cohorts pre-intervention (Epoch 1) and immediately post-intervention (Epoch 2) with a third cohort thirty-six months post-intervention (Epoch 3). SETTING: PICU of the largest public children's hospital in El Salvador. PATIENTS: 147 patients under 18 years requiring intubation and mechanical ventilation (MV) met inclusion criteria in the long-term follow-up period and were consecutively sampled without exclusion (Epoch 3) (compared to 98 previously studied patients in the short-term follow-up period (Epoch 2)). INTERVENTION: A low-cost, education-based intervention to close knowledge gaps, improve communication among PICU doctors, nurses, and respiratory therapists, and optimize patient outcomes. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was change in unplanned extubation (UE) between Epochs 2 and 3. Other outcomes included use of cuffed endotracheal tubes (ETT), rate of elective ETT change and days of MV. The 17 % decrease in UE previously reported for Epoch 2 was sustained in Epoch 3. There was a statistically significant increase in use of cuffed ETT from 35.7 % in Epoch 2-55.1 % in Epoch 3 (p = 0.003, z-score -2.99). There was also a statistically significant mean difference in rate of elective ETT change per 100 MV days from Epoch 2 to Epoch 3 of 1.7 (p = 0.007; 95 % CI 0.15-0.84). There was no change in MV days from Epoch 2 to Epoch 3 (p-value 0.764; 95 % CI -1.48-2.02). Beyond these quantifiable results, many unanticipated practice changes were observed three years after the initial intervention. CONCLUSIONS: Sustained improvement in upstream and downstream outcomes (UE, cuffed ETT use, elective ETT change) for intubated patients in a low-resource PICU were observed three years after a low-cost, low-touch, education-based intervention.
Subject(s)
Intensive Care Units, Pediatric , Intubation, Intratracheal , Quality Improvement , Respiration, Artificial , Humans , Male , Female , Child, Preschool , Child , Infant , Airway Extubation , Adolescent , Follow-Up StudiesABSTRACT
Plastic consumption has increased globally, and environmental issues associated with it have only gotten more severe; as a result, the search for environmentally friendly alternatives has intensified. Polyhydroxyalkanoates (PHA), as biopolymers produced by microalgae, might be an excellent option; however, large-scale production is a relevant barrier that hinders their application. Recently, innovative materials such as carbon dots (CDs) have been explored to enhance PHA production sustainably. This study added green synthesized multi-doped CDs to Scenedesmus sp. microalgae cultures to improve PHA production. Prickly pear was selected as the carbon precursor for the hydrothermally synthesized CDs doped with nitrogen, phosphorous, and nitrogen-phosphorous elements. CDs were characterized by different techniques, such as FTIR, SEM, ζ potential, UV-Vis, and XRD. They exhibited a semi-crystalline structure with high concentrations of carboxylic groups on their surface and other elements, such as copper and phosphorus. A medium without nitrogen and phosphorous was used as a control to compare CDs-enriched mediums. Cultures regarding biomass growth, carbohydrates, lipids, proteins, and PHA content were analyzed. The obtained results demonstrated that CDs-enriched cultures produced higher content of biomass and PHA; CDs-enriched cultures presented an increase of 26.9% in PHA concentration and an increase of 32% in terms of cell growth compared to the standard cultures.
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Background: This work describes a sustainable and replicable initiative to optimize multi-disciplinary care and uptake of clinical best practices for patients in a pediatric intensive care unit in Low/Middle Income Countries and to understand the various factors that may play a role in the reduction in child mortality seen after implementation of the Quality Improvement Initiative. Methods: This was a longitudinal assessment of a quality improvement program with the primary outcome of intubated pediatric patient mortality. The program was assessed 36 months following implementation of the quality improvement intervention using a t-test with linear regression to control for co-variates. An Impact Pathway model was developed to describe potential pathways for improvement, and context was added with an exploratory analysis of adoption of the intervention and locally initiated interventions. Results: 147 patients were included in the sustainability cohort. Comparing the initial post-implementation cohort to the sustainability cohort, the overall PICU unexpected extubations per 100 days mechanical ventilation decreased significantly from baseline (6.98) to the first year post intervention (3.52; p < 0.008) but plateaued without further significant decrease in the final cohort (3.0; p = 0.73), whereas the mortality decreased from 22.4 (std 0.42) to 9.5% (std 0.29): p value: 0.002 (confidence intervals: 0.05;0.21). The regression model that examined age, sex, diagnosis and severity of illness (via aggregate Pediatric Risk of Mortality (PRISM) scores between epochs) yielded an adjusted R-squared (adjusting for the number of predictors) value of 0.046, indicating that approximately 4.6% of the variance in mortality was explained by the predictors included in the model. The overall significance of the regression model was supported by an F-statistic of 3.198 (p = 0.00828). age, weight, diagnosis, and severity of illness. 15 new and locally driven quality practices were observed in the PICU compared to the initial post-implementation time period. The Impact Pathway model suggested multiple unique potential pathways connecting the improved patient outcomes with the intervention components. Conclusion: Sustained improvements were seen in the care of intubated pediatric patients. While some of this improvement may be attributable to the intervention, it appears likely that the change is multifactorial, as evidenced by a significant number of new quality improvement projects initiated by the local clinical team. Although currently limited by available data, the use of Driver Diagram and Impact Pathway models demonstrates several proposed causal pathways and holds potential for further elucidating the complex dynamics underlying such improvements.
Subject(s)
Intensive Care Units, Pediatric , Quality Improvement , Humans , Male , Female , Child, Preschool , Infant , Child , Longitudinal Studies , Developing Countries , Child Mortality , Respiration, Artificial/statistics & numerical dataABSTRACT
BACKGROUND: The increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain. METHODS: A sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals' health status. The significant level for the bivariate analysis was established at 0.05. RESULTS: Perceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 [2,32-27.41]) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 [1.40-4.29]). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence. CONCLUSION: The long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.
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PURPOSE: Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer. METHODS: A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data. RESULTS: Personalized Signatera assays detected ctDNA ahead of clinical or radiologic relapse in 30 of the 34 patients who relapsed (patient-level sensitivity of 88.2%). Relapse was predicted with a lead interval of up to 38 months (median, 10.5 months; range, 0-38 months), and ctDNA positivity was associated with shorter relapse-free survival (P < .0001) and overall survival (P < .0001). All relapsing triple-negative patients (n = 7/23) had a ctDNA-positive test within a median of 8 months (range, 0-19 months), while the 16 nonrelapsed patients with triple-negative breast cancer remained ctDNA-negative during a median follow-up of 58 months (range, 8-99 months). The four patients who had negative tests before relapse all had hormone receptor-positive (HR+) disease and conversely, five of the 122 nonrelapsed patients (all HR+) had an occasional positive test. CONCLUSION: Serial postoperative ctDNA assessment has strong prognostic value, provides a potential window for earlier therapeutic intervention, and may enable more effective monitoring than current clinical tests such as cancer antigen 15-3. Our study provides evidence that those with serially negative ctDNA tests have superior clinical outcomes, providing reassurance to patients with breast cancer. For select cases with HR+ disease, decisions about treatment management might require serial monitoring despite the ctDNA-positive result.
Subject(s)
Breast Neoplasms , Circulating Tumor DNA , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/blood , Breast Neoplasms/surgery , Circulating Tumor DNA/blood , Middle Aged , Prognosis , Follow-Up Studies , Aged , Adult , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/genetics , Retrospective Studies , Aged, 80 and overABSTRACT
PURPOSE: Biomechanical superiority of intramedullary nails over extramedullary implants has been proved for subtrochanteric fractures. Nevertheless, postoperative management of these patients has not changed, with high rates of protected weight-bearing after intramedullary nailing. The purpose of this study is to determine the mechanical complications of immediate postoperative full weigh-bearing for subtrochanteric femur fractures in elderly patients treated with a cephalomedullary nail. METHODS: We performed a retrospective case series study from patients treated with a cephalomedullary nail for subtrochanteric fractures (AO/OTA 31A.3 and 32A-32C) over a nine-year period. Patients in the immediate full weight-bearing (IFWB) group received orders for immediate full weight bear as tolerated on postoperative 48 h. Patients in the non- or limited- weight-bearing (NLWB) group received orders not to full weight bear in the immediate postoperative. RESULTS: There were five (2.7%) cases of implant failure including four cutouts and one nail breakage that needed a reoperation. Of them, one (2.2%) followed the NLWB protocol and four (2.9%) followed the IFWB protocol. Mean length of stay was 7.9 days (median 8, range 3-21) in the NLWB group and 10.7 days (median 8, range 2-60) in the IWBAT group. The NLWB group observed a 2.8-day shorter postoperative length of stay when compared to the IFWB, but the median remained equal. CONCLUSION: This study suggests that geriatric patients with subtrochanteric fractures treated by intramedullary nailing and in which a good fracture reduction was achieved, may be able to tolerate immediate postoperative full weight-bearing, not increasing reoperation rates due to implant failure.
Subject(s)
Bone Nails , Fracture Fixation, Intramedullary , Hip Fractures , Weight-Bearing , Humans , Fracture Fixation, Intramedullary/methods , Fracture Fixation, Intramedullary/instrumentation , Fracture Fixation, Intramedullary/adverse effects , Female , Male , Retrospective Studies , Hip Fractures/surgery , Aged , Aged, 80 and over , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Reoperation/statistics & numerical data , Prosthesis FailureABSTRACT
Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE) y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo o en el posparto y manteniéndolas a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)
This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs),such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational ageand/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developingvascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheralvascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOswhen assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact,adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the otherhand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOscould strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients.Various healthcare system options exist to improve the transition of care for women with APOs between differenthealthcare professionals and implement long-term VR reduction strategies. One potential process could involveincorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)
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Humans , Female , Pregnancy , Consensus , Obstetrics , Gynecology , Postpartum PeriodABSTRACT
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most common form of chronic liver disease. It exists as either simple steatosis or its more progressive form, metabolic dysfunction-associated steatohepatitis (MASH), formerly, non-alcoholic steatohepatitis (NASH). The global prevalence of MASLD is estimated to be 32% among adults and is projected to continue to rise with increasing rates of obesity, type 2 diabetes, and metabolic syndrome. While simple steatosis is often considered benign and reversible, MASH is progressive, potentially leading to the development of cirrhosis, liver failure, and hepatocellular carcinoma. Treatment of MASH is therefore directed at slowing, stopping, or reversing the progression of disease. Evidence points to improved liver histology with therapies that result in sustained body weight reduction. Incretin-based molecules, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs), alone or in combination with glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon receptor agonists, have shown benefit here, and several are under investigation for MASLD/MASH treatment. In this review, we discuss current published data on GLP-1, GIP/GLP-1, GLP-1/glucagon, and GLP-1/GIP/glucagon RAs in MASLD/MASH, focusing on their efficacy on liver histology, liver fat, and MASH biomarkers.
Subject(s)
Incretins , Non-alcoholic Fatty Liver Disease , Humans , Incretins/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Diabetes Mellitus, Type 2/drug therapyABSTRACT
AIMS: To describe the overall fat distribution patterns independent of body mass index (BMI) in participants with type 2 diabetes (T2D) in the SURPASS-3 MRI substudy by comparison with sex- and BMI-matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52. METHODS: For each study participant at baseline and Week 52 (N = 296), a VCG of ≥150 participants with the same sex and similar BMI was identified from the UK Biobank imaging study (N = 40 172). Average visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT) and liver fat (LF) levels and the observed standard deviations (SDs; standardized normal z-scores: z-VAT, z-aSAT and z-LF) were calculated based on the matched VCGs. Differences in z-scores between baseline and Week 52 were calculated to describe potential shifts in fat distribution pattern independent of weight change. RESULTS: Baseline fat distribution patterns were similar across pooled tirzepatide (5, 10 and 15 mg) and insulin degludec (IDeg) arms. Compared with matched VCGs, SURPASS-3 participants had higher baseline VAT (mean [SD] z-VAT +0.42 [1.23]; p < 0.001) and LF (z-LF +1.24 [0.92]; p < 0.001) but similar aSAT (z-aSAT -0.13 [1.11]; p = 0.083). Tirzepatide-treated participants had significant decreases in z-VAT (-0.18 [0.58]; p < 0.001) and z-LF (-0.54 [0.84]; p < 0.001) but increased z-aSAT (+0.11 [0.50]; p = 0.012). Participants treated with IDeg had a significant change in z-LF only (-0.46 [0.90]; p = 0.001), while no significant changes were observed for z-VAT (+0.13 [0.52]; p = 0.096) and z-aSAT (+0.09 [0.61]; p = 0.303). CONCLUSION: In this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z-VAT and z-LF, while z-aSAT was increased from an initially negative value, suggesting a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.
Subject(s)
Body Fat Distribution , Diabetes Mellitus, Type 2 , Aged , Female , Humans , Male , Middle Aged , Body Mass Index , Diabetes Mellitus, Type 2/drug therapy , Gastric Inhibitory Polypeptide , Glucagon-Like Peptide-2 Receptor , Hypoglycemic Agents/therapeutic use , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/diagnostic imaging , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and postprandial glucose (PPG) values. RESEARCH DESIGN AND METHODS: Participant subgroups with low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG were defined according to the median values of these measures. RESULTS: All tirzepatide doses and basal insulins were associated with decreased HbA1c, FSG, and PPG values from baseline to week 52 in all subgroups (P < 0.05). Within each subgroup, HbA1c and PPG decreases were greater with tirzepatide than insulin (P < 0.05). FSG decreases were generally similar. There were no differential treatment effects by FSG/PPG subgroup. CONCLUSIONS: In this post hoc analysis, tirzepatide was associated with superior glycemic control compared with insulin, irrespective of baseline glycemic pattern.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Insulin Glargine , Insulin, Long-Acting , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Male , Female , Blood Glucose/drug effects , Blood Glucose/metabolism , Middle Aged , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Insulin, Long-Acting/therapeutic use , Insulin Glargine/therapeutic use , Insulin Glargine/administration & dosage , Aged , Glycated Hemoglobin/metabolism , Glucagon-Like Peptide-2 Receptor , Gastric Inhibitory PolypeptideABSTRACT
In the current research, our objective was to explore how men assess and assign blame to both a man and a woman who are victims of workplace mobbing, depending on whether they identify as feminist or egalitarian. It is well recognized that the label "feminist" carries distinct connotations when applied to individuals of different genders. However, it remains unclear whether these varied connotations are due to the label itself or its underlying meaning. Given that the feminist label has been traditionally stigmatized, we aimed to disentangle the influence of the label from its semantic content. To achieve this, we compared the evaluations and attributions of victim blame directed toward targets labeled as feminist with those labeled with a similar but more neutral term-that is, egalitarian-as well as with unlabeled targets. Considering that much of the previous research in this area has focused on samples predominantly composed of women, we aimed to investigate how men respond to these labels. Through three experiments involving male participants (N = 628), we presented fictitious scenarios depicting a man or a woman who were victims of workplace mobbing due to their identification as feminist or egalitarian. The key finding of our research is that the feminist label, rather than its semantic content, significantly influences the evaluations and assignment of blame expressed by men who strongly adhere to traditional male role norms. These findings underscore the importance of these labels (feminist and egalitarian) in social judgments, particularly when applied to victims of workplace mobbing.
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The World Health Organization's Unity Studies global initiative provides a generic preparedness and readiness framework for conducting detailed investigations and epidemiological studies critical for the early and ongoing assessment of emerging respiratory pathogens of pandemic potential. During the COVID-19 pandemic, the initiative produced standardized investigation protocols and supported Member States to generate robust and comparable data to inform public health decision making. The subsequent iteration of the initiative is being implemented to develop revised and new investigation protocols, implementation toolkits and work to build a sustainable global network of sites, enabling the global community to be better prepared for the next emerging respiratory pathogen with epidemic or pandemic potential.
Subject(s)
Capacity Building , Pandemics , Humans , Pandemics/prevention & control , World Health Organization , Operations Research , Global HealthABSTRACT
Burkholderia glumae causes bacterial leaf blight in rice, and its global spread has been exacerbated by climate change. To understand the genetic diversity and virulence of B. glumae strains isolated from rice cultivars in Perú, 47 isolates were obtained from infected rice fields, all belonging to B. glumae, and confirmed by recA and toxB sequences. The BOX-PCR typing group has 38 genomic profiles, and these turn into seven variable number tandem repeats (VNTR) haplotypes. There was no correlation between clustering and geographical origin. Nineteen strains were selected for phenotypic characterization and virulence, using both the maceration level of the onion bulb proxy and inoculation of seeds of two rice cultivars. Several strains produced pigments other than toxoflavin, which correlated with onion bulb maceration. In terms of virulence at the seed level, all strains produced inhibition at the root and coleoptile level, but the severity of symptoms varied significantly between strains, revealing significant differences in pathogenicity. There is no correlation between maceration and virulence scores, probably reflecting different virulence mechanisms depending on the host infection stage. This is the first study to evaluate the VNTR diversity and virulence of Peruvian strains of B. glumae in two commercial cultivars.
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Latin America and Caribbean (LAC) regions were an important epicenter of the COVID-19 pandemic and SARS-CoV-2 evolution. Through the COVID-19 Genomic Surveillance Regional Network (COVIGEN), LAC countries produced an important number of genomic sequencing data that made possible an enhanced SARS-CoV-2 genomic surveillance capacity in the Americas, paving the way for characterization of emerging variants and helping to guide the public health response. In this study we analyzed approximately 300,000 SARS-CoV-2 sequences generated between February 2020 and March 2022 by multiple genomic surveillance efforts in LAC and reconstructed the diffusion patterns of the main variants of concern (VOCs) and of interest (VOIs) possibly originated in the Region. Our phylogenetic analysis revealed that the spread of variants Gamma, Lambda and Mu reflects human mobility patterns due to variations of international air passenger transportation and gradual lifting of social distance measures previously implemented in countries. Our results highlight the potential of genetic data to reconstruct viral spread and unveil preferential routes of viral migrations that are shaped by human mobility patterns.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Latin America/epidemiology , Pandemics , Phylogeny , COVID-19/epidemiology , Caribbean Region/epidemiologyABSTRACT
Bioprinting has enabled the precise spatiotemporal deposition of cells and biomaterials, opening new avenues of research in tissue engineering and regenerative medicine. Although several open-source syringe extruder adaptations for bioprinters have been published and adopted by end users, only one has been specifically adapted for the Ender series, an affordable and open-source line of thermoplastic 3D printers. Here, we introduce the Enderstruder, a cost-effective extruder attachment that uses a standard 10 mL BD syringe, positions the stepper motor at the level of the gantry, enhances x-axis stability with a linear rail, and uses the originally included stepper motor, resulting in reduced cost and simplified assembly. Furthermore, we present an iterative process to fine-tune printing profiles for high-viscosity biomaterial inks. To facilitate the implementation of our work by other researchers, we provide fully editable Cura profiles for five commonly used biomaterials. Using these five materials to validate and characterize our design, we employ the Enderstruder to print established calibration patterns and complex shapes. By presenting the Enderstruder and its iterative development process, this study contributes to the growing repository of open-source bioprinting solutions, fostering greater accessibility and affordability for researchers in tissue engineering.
ABSTRACT
Attitudes towards economic inequality are crucial to uphold structural economic inequality in democratic societies. Previous research has shown that socioeconomic status, political ideology, and the objective level of economic inequality associated with individuals' attitudes towards economic inequality. However, some have suggested that people are aware of the individual and social features that are more functional according to the level of economic inequality. Therefore, individual predispositions such as cultural values could also predict these attitudes. In the current research, we expand previous results testing whether cultural variables at the individual level predict attitudes towards economic inequality. After analysing survey data including samples from 52 countries (N = 89,565), we found that self-enhancement values predict positively, and self-transcendence negatively, attitudes towards economic inequality as the ideal economic inequality measures. This result remained significant even after controlling by socioeconomic status, political ideology, and objective economic inequality. However, this effect is only true in high and middle social mobility countries, but not in countries with low social mobility. The present research highlights how cultural values and country social mobility are crucial factors to addressing attitudes towards economic inequality.