RESUMEN
Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.
Asunto(s)
Citoplasma/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Difusión , Células HEK293 , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Nanopartículas/química , Nanopartículas/metabolismo , Tamaño de la Partícula , Plásmidos/genética , Plásmidos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Reología , Ribosomas/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteína 1 del Complejo de la Esclerosis Tuberosa/antagonistas & inhibidores , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/metabolismoRESUMEN
BACKGROUND: U.S. construction workers experience high rates of injury that can lead to chronic pain. This pilot study examined nonpharmacological (without medication prescribed by healthcare provider) and pharmacological (e.g., prescription opioids) pain management approaches used by construction workers. METHODS: A convenience sample of U.S. construction workers was surveyed, in partnership with the U.S. National Institute for Occupational Safety and Health (NIOSH) Construction Sector Program. Differences in familiarity and use of nonpharmacological and pharmacological pain management approaches, by demographics, were assessed using logistic regression models. A boosted regression tree model examined the most influential factors related to pharmacological pain management use, and potential reductions in use were counterfactually modeled. RESULTS: Of 166 (85%) of 195 participants reporting pain/discomfort in the last year, 72% reported using pharmacological pain management approaches, including 19% using opioids. There were significant differences in familiarity with nonpharmacological approaches by gender, education, work experience, and job title. Among 37 factors that predicted using pharmacological and non-pharmacological pain management approaches, training on the risks of opioids, job benefits for unpaid leave and paid disability, and familiarity with music therapy, meditation or mindful breathing, and body scans were among the most important predictors of potentially reducing use of pharmacological approaches. Providing these nonpharmacological approaches to workers could result in an estimated 23% (95% CI: 16%-30%) reduction in pharmacological pain management approaches. CONCLUSION: This pilot study suggests specific factors related to training, job benefits, and worker familiarity with nonpharmacological pain management approaches influence use of these approaches.
RESUMEN
Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.
Asunto(s)
Neoplasias de la Mama , Cateterismo Venoso Central , Catéteres Venosos Centrales , Trombosis , Humanos , Femenino , Rivaroxabán/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/etiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Estudios Prospectivos , Calidad de Vida , Trombosis/etiología , Trombosis/prevención & control , Trombosis/tratamiento farmacológico , Anticoagulantes/uso terapéuticoRESUMEN
Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade â ¢-â £ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade â ¢-â £ fatigue [5.2% (4/77)], Grade â ¢-â £ peripheral nerve abnormality [2.6% (2/77)] and Grade â ¢-â £ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama/patología , Femenino , Furanos/efectos adversos , Humanos , Cetonas/efectos adversos , Paclitaxel/efectos adversos , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Objective: To observe the efficacy and safety of albumin-bound paclitaxel in the treatment of metastatic breast cancer. Methods: Multi-center data of patients who accepted single-drug albumin-bound paclitaxel or combination regimens from 2013 to 2019 were collected and the efficacy and safety were evaluated. Kaplan-Meier method was used for survival analysis, while Log-rank test was used to compare the survival rates. Results: A total of 203 advanced breast cancer cases were enrolled. The median progression-free survival time (PFS) lasted for 4 months, the median overall survival(OS)was 14 months, objective response rate (ORR) was 36.0% while the disease control rate (DCR) was 81.3%. The ORRs of Luminal, human epidermal growth factor receptor 2 (HER2) overexpression and triple-negative breast cancer patients underwent albumin-bound paclitaxel treatment were 37.3%, 45.5% and 31.0%, respectively, the DCRs were 85.5%, 68.2% and 78.9%, respectively. The OS of patients with relapse or metastasis who accepted less than two and more than two chemotherapy regimens were 22 months and 11 months (P<0.000 1), the ORRs were 44.9% vs 30.4%, DCRs were 87.2% vs 77.6% (P=0.018). The ORR and DCR of patients who accepted traditional paclitaxel treatment before the albumin-bound paclitaxel treatment were 35.8% and 82.1%, respectively. The common adverse reaction of these patients was numbness of limbs, which incidence rate was 64.5% (131/203), and 61.1% (124/203) were degree 1 to 2. Other adverse reactions including decreased white blood cells, which incidence rate was 56.1% (114/203); nausea and vomit, which incidence rate was 36.9% (75/203); anemia, which incidence rate was 21.2% (43/203); decreased platelet, which incidence rate was 18.7% (38/203); hepatic dysfunction, which incidence rate was 18.2% (37/203). Conclusions: Albumin-bound paclitaxel single or combination regimen is still significant efficient for various molecular subtypes of breast cancer patients or patients with traditional paclitaxel resistance or multi-line chemotherapy failure. Early usage has better prognosis, controllable adverse reaction and prominent clinical application value.
Asunto(s)
Paclitaxel Unido a Albúmina , Neoplasias de la Mama Triple Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Recurrencia Local de Neoplasia , Paclitaxel , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
The environment has been continuously exposed to heavy metals by various routes, from both natural and artificial sources. In particular, heavy metals in water can affect aquatic organisms adversely, even at very low concentrations, and can lead to the disturbance of the ecosystem balance and biodiversity. Ecological risk assessments are conducted to protect the environment from such situations, primarily by deriving the predicted no-effect concentration (PNEC) from the species sensitivity distribution (SSD). This study developed the SSDs based on the species living in Korean freshwater for four heavy metals including cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn). The species compositions of the SSDs were examined, and three types of PNECs were derived by applying different assessment factors (AF). In addition, the occurrence and concentrations of heavy metals in Korean rivers were investigated, and the ecological risk assessment was carried out to compare the SSDs with the environmental concentrations. The SSDs were developed using a sufficient number of species, but the missing data of plants and insects provided an incomplete species composition. The results show that Cd and Pb in the environmental concentrations of rivers would not cause any risk to aquatic organisms from the derived PNEC. However, some organisms might be adversely affected by the concentrations of Zn, and a small amount of risk was expected under the conservative PNEC. The distribution of Cu in the rivers was not considered to be safe for aquatic organisms because the average environmental concentrations potentially affected the proportion of the SSD, and the environmental concentrations exceeded the PNECs. The concentrations of Cu and Zn in industrial waters indicated a considerable risk to aquatic organisms, and the probability of exceeding the PNECs appeared to be quite high. Therefore, this study indicates that additional actions and parallel field studies are required based on the risk posed to aquatic organisms by Cu and Zn in four Korean rivers.
Asunto(s)
Metales Pesados/toxicidad , Ríos , Contaminantes Químicos del Agua/toxicidad , Organismos Acuáticos/efectos de los fármacos , Cobre/análisis , Cobre/toxicidad , Ecosistema , Agua Dulce , Metales Pesados/análisis , Probabilidad , República de Corea , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Zinc/análisis , Zinc/toxicidadRESUMEN
Many studies have demonstrated that heavy metals existing as a mixture in the atmospheric environment cause adverse effects on human health and are important key factors of cytotoxicity; however, little investigation has been conducted on a toxicological study of a metal mixture from atmospheric fine particulate matter. The objective of this study was to predict the combined effects of heavy metals in aerosol by using in vitro human cells and obtain a suitable mixture toxicity model. Arsenic, nickel, and lead were selected for mixtures exposed to A549 human lung cancer cells. Cell proliferation (WST-1), glutathione (GSH), and interleukin (IL)-8 inhibition were observed and applied to the prediction models of mixture toxicity, concentration addition (CA) and independent action (IA). The total mixture concentrations were set by an IC10-fixed ratio of individual toxicity to be more realistic for mortality and enzyme inhibition tests. The results showed that the IA model was statistically closer to the observed results than the CA model in mortality, indicating dissimilar modes of action. For the GSH inhibition, the results predicted by the IA and CA models were highly overestimated relative to mortality. Meanwhile, the IL-8 results were stable with no significant change in immune reaction related to inflammation. In conclusion, the IA model is a rapid prediction model in heavy metals mixtures; mortality, as a total outcome of cell response, is a good tool for demonstrating the combined toxicity rather than other biochemical responses.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Arsénico/toxicidad , Neoplasias Pulmonares/patología , Metales Pesados/toxicidad , Células A549 , Aerosoles , Proliferación Celular/efectos de los fármacos , Glutatión/metabolismo , Humanos , Concentración 50 Inhibidora , Interleucina-8/metabolismo , Modelos BiológicosRESUMEN
OBJECTIVES: Examine trends and patterns of work-related musculoskeletal disorders (WMSDs) among construction workers in the USA, with an emphasis on older workers. METHODS: WMSDs were identified from the 1992-2014 Survey of Occupational Injuries and Illnesses (SOII), and employment was estimated from the Current Population Survey (CPS). Risk of WMSDs was measured by number of WMSDs per 10â 000 full-time equivalent workers and stratified by major demographic and employment subgroups. Time series analysis was performed to examine the trend of WMSDs in construction. RESULTS: The number of WMSDs significantly dropped in the US construction industry, following the overall injury trends. However, the rate of WMSDs in construction remained higher than in all industries combined; the median days away from work increased from 8â days in 1992 to 13â days in 2014, and the proportion of WMSDs for construction workers aged 55 to 64â years almost doubled. By occupation, construction labourers had the largest number of WMSD cases, while helpers, heating and air-conditioning mechanics, cement masons and sheet metal workers had the highest rates of WMSDs. The major cause of WMSDs in construction was overexertion, and back injuries accounted for more than 40% of WMSDs among construction workers. The estimated wage loss for private wage-and-salary construction workers was $46 million in 2014. CONCLUSIONS: Construction workers continue to face a higher risk of WMSDs. Ergonomic solutions that reduce overexertion-the primary exposure for WMSDs-should be adopted extensively at construction sites, particularly for workers with a higher risk of WMSDs.
Asunto(s)
Industria de la Construcción , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/etiología , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Traumatismos Ocupacionales/epidemiología , Absentismo , Adolescente , Adulto , Distribución por Edad , Anciano , Traumatismos de la Espalda , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Sistema Musculoesquelético/lesiones , Factores de Riesgo , Ausencia por Enfermedad , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment. METHOD: We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients' clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment. RESULTS: Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve. CONCLUSIONS: During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.
Asunto(s)
Antipsicóticos/farmacología , Sistema Límbico , Red Nerviosa , Corteza Prefrontal , Risperidona/farmacología , Esquizofrenia , Sustancia Blanca , Adolescente , Adulto , Antipsicóticos/administración & dosificación , Imagen de Difusión Tensora , Estudios de Seguimiento , Humanos , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/efectos de los fármacos , Sistema Límbico/patología , Sistema Límbico/fisiopatología , Estudios Longitudinales , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/efectos de los fármacos , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , Risperidona/administración & dosificación , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/patología , Sustancia Blanca/fisiopatología , Adulto JovenRESUMEN
This study confirms that botulinum neurotoxin type A (BoNT-A) decreases capsular contracture and elucidates a possible mechanism. Silicone blocks were implanted subcutaneously in 20 mice. The experimental groups received BoNT-A (1, 2·5 or 5 U) instilled into the subcutaneous pocket. After 30 days, periprosthetic capsules were harvested and evaluated. The effect of BoNT-A on the differentiation of human dermal fibroblasts to myofibroblasts in culture was examined by Western blot analysis. Changes in transforming growth factor-beta1 (TGF-ß1) expression in cultured fibroblasts were determined by enzyme-linked immunosorbent assay (ELISA). In in vivo study, the thickness of capsules (P < 0·05) and the number of alpha-smooth muscle actin (α-SMA)(+) cells in capsules (P < 0·05) were significantly decreased in the experimental groups. TGF-ß1 was significantly underexpressed in the experimental groups (P < 0·05). In in vitro study, BoNT-A did not significantly affect fibroblast viability. Western blot analysis showed that α-SMA protein levels were significantly decreased in the experimental groups (P < 0·05). Based on ELISA, the amount of TGF-ß1 was significantly decreased in the experimental groups (P < 0·05), especially cells treated with a high dose of BoNT-A (P < 0·001). This study confirms that BoNT-A prevents capsular formation around silicone implants, possibly by blocking TGF-ß1 signalling and interrupting the differentiation of fibroblasts to myofibroblasts.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Implantes de Mama , Contractura/prevención & control , Neurotoxinas/administración & dosificación , Geles de Silicona , Actinas/metabolismo , Animales , Western Blotting , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Ratones , Modelos Animales , Miofibroblastos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
A variety of anti-neuronal cell membrane antibodies such as voltage-gated potassium channel antibody, N-methyl-D-aspartate-2B-antibody, and glutamic acid decarboxylase antibody, are correlated with limbic encephalitis (LE). In this study on patients with LE, the clinical manifestations, psychology Wechsler Adult Intelligence Scale, cerebrospinal fluid, electrophysiology, magnetic resonance imaging, and anti-immune therapy were studied and immunological determination was conducted; it was found that patients of Chinese Han nationality showed 2 types of clinical manifestations: simple and complex. Lesions could also be divided into focal and scalable lesions, and the clinical manifestations and lesions scopes were associated with various antibodies and antibody types. The prognosis may improve if early diagnosis is conducted and early anti-immune therapy is implemented in LE patients.
Asunto(s)
Autoanticuerpos/inmunología , Encefalitis Límbica/inmunología , Sistema Límbico/inmunología , Neuronas/inmunología , Adulto , Pueblo Asiatico , Western Blotting , China , Ensayo de Inmunoadsorción Enzimática , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Encefalitis Límbica/etnología , Encefalitis Límbica/terapia , Sistema Límbico/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Canales de Potasio con Entrada de Voltaje/inmunología , Pronóstico , Receptores de N-Metil-D-Aspartato/inmunología , Tomografía Computarizada por Rayos X , Escalas de WechslerRESUMEN
BACKGROUND: Falls from heights remain the most common cause of workplace fatalities among residential construction workers in the United States. METHODS: This paper examines patterns and trends of fall fatalities in U.S. residential construction between 2003 and 2010 by analyzing two large national datasets. RESULTS: Almost half of the fatalities in residential construction were from falls. In the residential roofing industry, 80% of fatalities were from falls. In addition, about one-third of fatal falls in residential construction were among self-employed workers. Workers who were older than 55 years, were Hispanic foreign-born, or employed in small establishments (1-10 employees) also had higher proportions of fatal falls in residential construction compared to those in nonresidential construction. CONCLUSIONS: The findings suggest that fall safety within the residential construction industry lags behind commercial construction and industrial settings. Fall prevention in residential construction should be enhanced to better protect construction workers in this sector.
Asunto(s)
Accidentes por Caídas/mortalidad , Accidentes de Trabajo/mortalidad , Industria de la Construcción , Empleo/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Vivienda , Traumatismos Ocupacionales/mortalidad , Adolescente , Adulto , Distribución por Edad , Anciano , Bases de Datos Factuales , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pequeña Empresa/estadística & datos numéricos , Estados Unidos , Adulto JovenRESUMEN
Aquatic toxicity of titanium dioxide nanoparticles (TiO2 NPs) to Daphnia magna was characterized using a completely stirred bioassay system intended to keep particles in suspension thereby maintaining a consistent exposure. The 48-h LC50 was 4.5 mg/L TiO2 NPs, whereas LC50 values for 7 and 14-days exposures were 2.7 and 1.9 mg/L, respectively. An exposure of 1.5 mg/L over a 21-days exposure resulted in significant reductions in fecundity. While reproduction was initially reduced in the 0.5 and 1.0 mg/L exposures, it recovered and was similar to the control by 21 days. For reproduction inhibition, NOEC was 1.0 mg/L. Exposure to 2.5 mg/L TiO2 NPs resulted in 40 % of the organisms failing to become gravid; all surviving organisms exposed to 5.0 mg/L failed to become gravid. The increased sensitivity was due to the refinement in the bioassay system that kept NP in suspension resulting in consistent exposure concentrations.
Asunto(s)
Daphnia/efectos de los fármacos , Nanopartículas/toxicidad , Titanio/toxicidad , Contaminantes Químicos del Agua/toxicidad , Análisis de Varianza , Animales , Dosificación Letal Mediana , Nivel sin Efectos Adversos Observados , Reproducción/efectos de los fármacos , Factores de Tiempo , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad CrónicaRESUMEN
Bacterial persisters constitute a small fraction of cells that transiently display multidrug tolerance, allowing them to survive antibiotic treatment and to establish a new population upon recovery from the persistent state. Here, we present a protocol to quantify post-antibiotic persister recovery kinetics and physiological states at the single-cell level. We describe steps for sample preparation, technical setup, and data acquisition using spectrophotometry. Our assay allows for the elucidation of genes and mechanisms involved in persister survival. For complete details on the use and execution of this protocol, please refer to Wilmaerts et al.1.
Asunto(s)
Antibacterianos , Escherichia coli , Análisis de la Célula Individual , Espectrofotometría , Escherichia coli/fisiología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Espectrofotometría/métodos , Análisis de la Célula Individual/métodos , Cinética , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
BACKGROUND: The U.S. Food and Drug Administration has approved four distinct formulations of botulinum toxin (BoNT) serotypes A and B (BoNTA and BoNTB) for medical use. These four products are indicated for many medical applications, but the three BoNTA formulations are the most widely used worldwide and are the only products approved for aesthetic use. The latest approval of a BoNTA with no complexing proteins (incobotulinumtoxinA) necessitates a review and discussion of differences between available formulations and the effect that these differences may have on clinical practice. OBJECTIVES: To review the history, science, safety information, and current and emerging applications of BoNT in clinical and cosmetic practice and to compare commercially available BoNTA formulations. METHODS AND MATERIALS: Publications, clinical trials, and author experience were used as a basis for an up-to-date review of BoNT and its use in human medicine. The similarities and differences between formulations are presented, and diffusion, spread, equivalency ratios, stability, and storage are discussed. RESULTS: Each commercial formulation has unique characteristics that may influence its use in aesthetic medicine. Familiarity with the similarities and differences between products will aid physicians in making patient care decisions. CONCLUSION: New formulations, emerging uses, and continued research into the science and uses of BoNTA will lead to increasingly refined therapeutic approaches and applications. Continued education is important for physicians to optimize use of the agent according to the most current evidence and approaches.
Asunto(s)
Toxinas Botulínicas/uso terapéutico , Toxinas Botulínicas/administración & dosificación , Toxinas Botulínicas/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Química Farmacéutica , Técnicas Cosméticas , HumanosRESUMEN
The final destination point of nanoparticles is the environment, where they remain a long period; therefore, a deep understanding of the relationship between nanoparticles and the environmental factors is required. Japanese medaka embryos were exposed to two differently prepared AgNPs: freshly prepared AgNPs and aged AgNPs. With these two AgNP preparations, we studied the impacts of humic acid in terms of embryonic toxicity, as well as the behavior of AgNPs. Aged AgNPs exhibited a lower lethal concentration (LC50) value (1.44mg/L) compared to fresh AgNPs (3.53mg/L) through 96h acute toxicity tests, due to the release of silver ions, as confirmed by kinetic analysis. The presence of humic acids considerably reduced the toxicity of aged AgNPs due to complexation with silver ions. Agglomeration, induced by interactions with humic acid, might reduce the bioavailability of AgNPs to Japanese medaka embryos. This study demonstrates that aged AgNPs releasing more silver ions are more toxic than fresh AgNPs, and humic acids play a role in reducing the toxicity of aged AgNPs.
Asunto(s)
Nanopartículas del Metal/toxicidad , Plata/toxicidad , Animales , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/fisiología , Sustancias Húmicas , Iones/toxicidad , Cinética , Dosificación Letal Mediana , Oryzias/embriología , Oryzias/crecimiento & desarrollo , Medición de Riesgo , Pruebas de Toxicidad Aguda , Contaminantes Químicos del Agua/toxicidadRESUMEN
Industrial exoskeletons are developed to relieve workers' physical demands in the workplace and to alleviate ergonomic issues associated with work-related musculoskeletal disorders. As a safe and economical alternative to empirical/experimental methods, modelling is considered as a powerful tool for design and evaluation of industrial exoskeletons. This systematic review aims to provide a comprehensive understanding of the current literature on the design and evaluation of industrial exoskeletons through modelling. A systematic study was conducted by general keyword searches of five electronic databases over the last two decades (2003-2022). Out of the 701 records initially retrieved, 33 eligible articles were included and analyzed in the final review, presenting a variety of model inputs, model development, and model outputs used in the modelling. This systematic review study revealed that existing modelling methods can evaluate the biomechanical and physiological effects of industrial exoskeletons and provide some design parameters. However, the modelling method is currently unable to cover some of the main evaluation metrics supported by experimental assessments, such as task performance, user experience/discomfort, change in metabolic costs etc. Standard guidelines for model construction and implementation, as well as validation of human-exoskeleton interactions, remain to be established.
Asunto(s)
Dispositivo Exoesqueleto , Enfermedades Musculoesqueléticas , Humanos , Industrias , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/prevención & control , Lugar de Trabajo , ErgonomíaRESUMEN
STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: This study compares reoperation rates and complications following single-level ALIF/LLIF and TLIF/PLIF. SUMMARY OF BACKGROUND DATA: Anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), transforaminal lumbar interbody fusion (TLIF), and posterior lumbar interbody fusion (PLIF) are widely used for degenerative disc disease. Lumbar interbody fusions have high rates of reoperation primarily related to adjacent segment pathology and pseudarthrosis. METHODS: The PearlDiver database was queried for patients (2010-2021) who had single-level ALIF/LLIF or TLIF/PLIF with same-day, single-level posterior instrumentation. ALIF/LLIF were combined and similarly, TLIF/PLIF were combined, given how these operations are indistinguishable with Current Procedural Terminology (CPT) coding. All patients were followed for ≥2 years and excluded if they had spinal traumas, fractures, infections, or neoplasms prior to surgery. The two cohorts, ALIF/LLIF and TLIF/PLIF, were matched 1:1 based on age, sex, Elixhauser-Comorbidity Index (ECI), smoking status, and diabetes. The primary outcome was the incidence of all-cause subsequent lumbar operations. Secondary outcomes included 90-day surgical complications. RESULTS: After 1:1 matching, each cohort contained 14,070 patients. All-cause subsequent lumbar operations were nearly identical at 5-year follow-up (9.4% ALIF/LLIF vs. 9.5% TLIF/PLIF, P=0.91) (Table 2). Survival analysis using all-cause subsequent lumbar operations as the endpoint showed an equivalent 10-year survival rate of 86.0% (95%CI: 85.2-86.8) (Figure 1). Within 90 days, TLIF/PLIF had more infections (1.3% vs. 1.7%, P=0.007) and dural injuries (0.2% vs. 0.4%, P=0.001). There was no difference in wound dehiscence, hardware complications, or medical complications (Table 3). CONCLUSION: As utilized in real-world clinical practice, single-level anterolateral versus posterior approaches for interbody fusion have no effect on long term reoperation rates.
RESUMEN
Occupational traffic accidents are a leading cause of injuries or deaths among workers. Teachers in Spain are especially concerned about the problem of commuting due to their particular labor conditions. Multiple work-related factors are associated with the risk and severity of occupational traffic-related motor vehicle crashes. The objective of this research is to analyze the influence of the variables associated with the severity of occupational traffic accidents among teachers in Spain. A logistic regression model was used for the current study. The odds ratio (OR) and confidence interval (CI) were calculated for the injured worker on a sample of 20,190 occupational traffic accidents suffered by teachers. The results showed that women, Spanish nationality, younger than 55 years, and those driving a car were more likely to suffer a light crash. In contrast, men, foreign nationalities, older than 55 years, and those riding a motorbike were more likely to suffer a serious crash. Based on these findings, motor vehicle safety training could be designed and adapted to the riskiest profiles. Additionally, effective mobility plans for commuting could help reduce work-related traffic accidents.
Asunto(s)
Accidentes de Tránsito , Conducción de Automóvil , Accidentes de Trabajo , Femenino , Humanos , Masculino , Factores de Riesgo , España/epidemiología , TransportesRESUMEN
BACKGROUND AND OBJECTIVE: Although there is controversy regarding the benefit of low-dose corticosteroid therapy in patients with septic shock, the Surviving Sepsis Campaign has advocated that low-dose intravenous hydrocortisone be used to treat adult septic shock patients. This study investigated the effect of the duration of a stress dose of hydrocortisone on survival of septic shock patients with relative adrenal insufficiency. METHODS: One hundred and thirty consecutive patients who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock were included in the study. An additional inclusion criterion was vasopressor support after fluid resuscitation. The primary end-point was 28-day mortality, and the secondary end-points were shock reversal and mortality in the intensive care unit and hospital. All eligible patients were prospectively randomized to receive hydrocortisone treatment for 3 or 7days. Hydrocortisone treatment was started at a dose of 50mg every 6h. RESULTS: Baseline data at recruitment did not differ between the two groups. After 28days, mortality did not differ between the 3- and 7-day treatment groups (33.8% vs 36.9%, P=0.629). Mortality rates in the intensive care unit and hospital did not differ significantly between the two groups. The median time to withdrawal of vasopressor therapy was 5.0days in the 3-day treatment group and 6.4days in the 7-day treatment group (P=0.102). CONCLUSIONS: This pilot study showed that in patients with septic shock and relative adrenal insufficiency, 28-day mortality did not differ between those treated with low-dose hydrocortisone for 3 or 7days.