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1.
Curr Pharm Teach Learn ; 16(10): 102138, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38955061

RESUMEN

BACKGROUND: Pharmacy students completing Internal Medicine rotations may be exposed to different stylistic approaches from providers on routine activities like patient rounds. This may be beneficial as students can learn in different ways. Conversely, extensive exposure to approaches that do not suit them may hinder student learning or lead students to feel they don't belong in a clinical setting. EDUCATIONAL ACTIVITY: This study sought to assess how students of different personality types perceived benefits to their learning based on the rounding styles of two providers. One provider (Dr. Bedside) used a team-based, bedside rounding method with direct patient interaction, while the other (Dr. Table) used a tableside team-based discussion for each patient. In the final week of a 5-week Internal Medicine APPE rotation, a cohort of ten students completed a 12-item survey that collected details on two personality assessments and assessed perspectives of the two rounding styles. EVALUATION FINDINGS: Ten students completed the personality assessments and survey. Students represented a diverse set of StrengthsFinder strengths and DOPE personality types, with the highest concentration (60%) of students receiving the Executing strength. All students agreed or strongly agreed that the exposure to two different rounding styles was valuable to their learning, with 80% of students preferring Dr. Bedside's approach. ANALYSIS OF EDUCATIONAL ACTIVITY: Overall, no trends were identified between preference of rounding style and results from personality assessments, which indicates the current approach of exposing students to two rounding styles does not negatively impact certain learners based on DOPE and StrengthsFinders personality types.

2.
Malar J ; 23(1): 169, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811947

RESUMEN

BACKGROUND: The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055). METHODS: This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony. RESULTS: A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field. CONCLUSION: While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.


Asunto(s)
Anopheles , Control de Mosquitos , Mosquitos Vectores , Zambia , Animales , Control de Mosquitos/métodos , Anopheles/efectos de los fármacos , Anopheles/fisiología , Mosquitos Vectores/efectos de los fármacos , Mosquitos Vectores/fisiología , Femenino , Masculino , Estudios Transversales , Malaria/prevención & control , Malaria/transmisión , Estaciones del Año , Insecticidas/farmacología , Azúcares , Humanos , Conducta Alimentaria
3.
Front Oncol ; 13: 1272740, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38130988

RESUMEN

Introduction: Pancreatic squamous cell carcinoma is a rare type of pancreatic cancer of ductal origin, composing an estimated 0.5 - 5% of pancreatic ductal malignancies. As a result, epidemiology, treatment options, and associated outcomes are poorly understood and understudied. Our aim was two-fold: to evaluate demographic trends and analyze overall survival (OS) associated with different treatment modalities for this rare malignancy. Methods: Patients with pancreatic squamous cell carcinoma diagnosed between 1992 and 2019 were eligible and reviewed utilizing the Surveillance, Epidemiology, and End Results Registry (SEER) database. Data was analyzed using SPSS and python packages lifelines and pandas. Variables of interest included stage at diagnosis as well as the receipt of surgery, radiotherapy, and/or chemotherapy. Five-year OS curves were analyzed using Kaplan-Meier probability stratified by treatment modality. Results: Of 342 cases of pancreatic squamous cell carcinoma, 170 (49.7%) were females and 172 (50.3%) were males. 72 (21.1%) of patients received radiotherapy, 123 (35.9%) patients received chemotherapy, and 47 (13.7%) received surgery. Patients who were diagnosed under the age of 50 had prolonged survival time compared to those diagnosed over the age of 50 (12 vs 8 months, respectively, p < 0.001). This trend was evident despite the lack of a significant association between age at diagnosis and presence of metastases (p = 0.524). The median OS was 3 months for the entire cohort and there was a significant difference in median survival time noted across treatment modalities: OS was prolonged in those receiving surgery compared to those receiving chemotherapy or radiotherapy alone (30 vs 2 months, respectively, (p<0.001)). Receipt of radiotherapy was not associated with a significant difference in OS compared to those who did not receive radiotherapy. Conclusion: Pancreatic squamous cell carcinoma is a rare subtype of pancreatic cancer and typically portends a poor prognosis. As demonstrated by our study, surgery offers prolonged overall survival compared to other treatment modalities. Age at diagnosis and presence of metastatic disease are also important prognostic factors likely related to patients' ability to tolerate surgery or physician willingness to offer surgery. Given the importance of surgery on outcomes, it may be reasonable to offer it in the oligometastatic setting in patients who are otherwise a good candidate. Future research on larger cohorts is warranted to investigate the role that modality selection plays in overall survival rates in this understudied malignancy.

4.
Prog Transplant ; 32(3): 203-211, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35686356

RESUMEN

Introduction: Early change of insurance coverage after kidney transplantation may be associated with worse graft outcomes. We examine how return to employment moderates the hazard of graft failure associated with exit from Medicare within 36 months after transplantation. Design: Patients undergoing kidney transplantation covered by Medicare between January 2005 and December 2016 were identified in the United Network for Organ Sharing (UNOS) database. A composite outcome of graft failure or death was analyzed across four groups: (1) no change in coverage within the first 3 years post-transplant, and no return to work (2) no change in coverage, return to work (3) change in coverage, no return to work (4) change in coverage, return to work. Results: The sample included 46 120 patients; 28% changed insurance coverage from Medicare posttransplant. Among patients who returned to work (36%), change in coverage from Medicare to other insurance was associated with lower hazard of death or graft failure (hazard ratio: 0.93; 95% confidence interval: 0.87, 0.99; P = 0.030). Conclusions: Exit from Medicare was associated with patient and graft survival greater than 3 years after transplant, depending on return to work. Among patients returning to work, changes in insurance from Medicare to private coverage were associated with favorable outcomes.


Asunto(s)
Trasplante de Riñón , Anciano , Empleo , Supervivencia de Injerto , Humanos , Cobertura del Seguro , Medicare , Estados Unidos
5.
Microbiol Spectr ; 10(3): e0234621, 2022 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-35579457

RESUMEN

Novel bacterial isolates with the capabilities of lignin depolymerization, catabolism, or both, could be pertinent to lignocellulosic biofuel applications. In this study, we aimed to identify anaerobic bacteria that could address the economic challenges faced with microbial-mediated biotechnologies, such as the need for aeration and mixing. Using a consortium seeded from temperate forest soil and enriched under anoxic conditions with organosolv lignin as the sole carbon source, we successfully isolated a novel bacterium, designated 159R. Based on the 16S rRNA gene, the isolate belongs to the genus Sodalis in the family Bruguierivoracaceae. Whole-genome sequencing revealed a genome size of 6.38 Mbp and a GC content of 55 mol%. To resolve the phylogenetic position of 159R, its phylogeny was reconstructed using (i) 16S rRNA genes of its closest relatives, (ii) multilocus sequence analysis (MLSA) of 100 genes, (iii) 49 clusters of orthologous groups (COG) domains, and (iv) 400 conserved proteins. Isolate 159R was closely related to the deadwood associated Sodalis guild rather than the tsetse fly and other insect endosymbiont guilds. Estimated genome-sequence-based digital DNA-DNA hybridization (dDDH), genome percentage of conserved proteins (POCP), and an alignment analysis between 159R and the Sodalis clade species further supported that isolate 159R was part of the Sodalis genus and a strain of Sodalis ligni. We proposed the name Sodalis ligni str. 159R (=DSM 110549 = ATCC TSD-177). IMPORTANCE Currently, in the paper industry, paper mill pulping relies on unsustainable and costly processes to remove lignin from lignocellulosic material. A greener approach is biopulping, which uses microbes and their enzymes to break down lignin. However, there are limitations to biopulping that prevent it from outcompeting other pulping processes, such as requiring constant aeration and mixing. Anaerobic bacteria are a promising alternative source for consolidated depolymerization of lignin and its conversion to valuable by-products. We presented Sodalis ligni str. 159R and its characteristics as another example of potential mechanisms that can be developed for lignocellulosic applications.


Asunto(s)
Enterobacteriaceae , Lignina , Anaerobiosis , Animales , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Enterobacteriaceae/genética , Lignina/metabolismo , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Simbiosis
6.
Medchemcomm ; 10(8): 1445-1456, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31534659

RESUMEN

Numerous members of the combretastatin and chalcone families of natural products function as inhibitors of tubulin polymerization through a binding interaction at the colchicine site on ß-tubulin. These molecular scaffolds inspired the development of many structurally modified derivatives and analogues as promising anticancer agents. A productive design blueprint that involved molecular hybridization of the pharmacophore moieties of combretastatin A-4 (CA4) and the chalcones led to the discovery of two promising lead molecules referred to as KGP413 and SD400. The corresponding water-soluble phosphate prodrug salts of KGP413 and SD400 selectively damaged tumor-associated vasculature, thus highlighting the potential development of these molecules as vascular disrupting agents (VDAs). These previous studies prompted our current investigation of conformationally restricted chalcones. Herein, we report the synthesis of cyclic chalcones and related analogues that incorporate structural motifs of CA4, and evaluation of their cytotoxicity against human cancer cell lines [NCI-H460 (lung), DU-145 (prostate), and SK-OV-3 (ovarian)]. While these molecules proved inactive as inhibitors of tubulin polymerization (IC50 > 20 µM), eight molecules demonstrated good antiproliferative activity (GI50 < 20 µM) against all three cancer cell lines, and compounds 2j and 2l demonstrated sub-micromolar cytotoxicity. To the best of our knowledge these molecules represent the most potent (based on GI50) cyclic chalcones known to date, and are promising lead molecules for continued investigation.

7.
Microbiol Resour Announc ; 8(18)2019 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-31048387

RESUMEN

The complete genome sequence of the gammaproteobacterial isolate Serratia quinivorans 124R consists of 5 Mb over 2 scaffolds and a G+C content of 52.85%. Genes relating to aromatic metabolism reflect its isolation on organosolv lignin as a sole carbon source under anoxic conditions as well as the potential for lignin biorefinery applications.

8.
Tetrahedron Lett ; 59(40): 3594-3599, 2018 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-31156276

RESUMEN

Antibody-drug conjugates (ADCs) represent an emerging class of biopharmaceutical agents that deliver highly potent anticancer agents (payloads) selectively to tumors or components associated with the tumor microenvironment. The linker, responsible for the connection between the antibody and payload, is a crucial component of ADCs. In certain examples the linker is composed of a cleavable short peptide which imparts an additional aspect of selectivity. Especially prevalent is the cathepsin B cleavable Mc-Val-Cit-PABOH linker utilized in many pre-clinical ADC candidates, as well as the FDA approved ADC ADCETRIS® (brentuximab vedotin). An alternative route for the synthesis of the cathepsin B cleavable Mc-Val-Cit-PABOH linker is reported herein that involved six steps from l-Citrulline and proceeded with a 50% overall yield. In this modified route, the spacer (a para-aminobenzyl alcohol moiety) was incorporated via HATU coupling followed by dipeptide formation. Importantly, this route avoided undesirable epimerization and proceeded with improved overall yield. Utilizing this methodology, a drug-linker construct incorporating a potent small-molecule inhibitor of tubulin polymerization (referred to as KGP05), was synthesized as a representative example.

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