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1.
Hosp Pediatr ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716570

RESUMEN

BACKGROUND AND OBJECTIVES: Intravenous infusions have the potential to cause significant harm in patients and are associated with a high rate of adverse drug events and medication errors. Infusion pumps with dose error reduction software (DERS) can be used to reduce errors by establishing safe infusion parameters. In 2019, a quality improvement project was initiated with the aim to increase DERS compliance from 46% to 75% at our specialty institution by October 1, 2022. METHODS: An interdisciplinary group was tasked with improving compliance with DERS by identifying key drivers, including informed staff, engaged staff, and an accurate smart pump library. We used the Model for Improvement framework to guide this improvement project, and Plan-Do-Study-Act (PDSA) cycles were used to plan for interventions. PDSA cycles included drug library updates, education, and unit-level compliance reporting. Weekly average DERS compliance was monitored as the outcome measure, and weekly pump alerts per 100 infusions were monitored as a balancing measure; statistical process control charts were used to monitor measures from 2018 to 2022. RESULTS: Over the course of 25 months, 8 PDSA cycles resulted in 5 centerline improvements from a baseline mean of 46% to a final mean of 78%. Pump alerts per 100 infusions decreased from 15.9 to 6.4 with the first PDSA cycle and then continued to decrease to 3.9 with subsequent interventions. CONCLUSIONS: Although features like DERS can help ensure safe medication administration, continuous improvement efforts to increase DERS compliance without increasing alert burden are needed to ensure that benefits of this technology are optimized.

2.
Chem Sci ; 15(15): 5516-5524, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38638241

RESUMEN

This work sheds new light on the stereoselective synthesis of chiral macrocycles containing twisted aromatic units, valuable π-conjugated materials for recognition, sensing, and optoelectronics. For the first time, we use the Curtin-Hammett principle to investigate a chiral macrocyclisation reaction, revealing the potential for supramolecular π-π interactions to direct the outcome of a dynamic kinetic resolution, favouring the opposite macrocyclic product to that expected under reversible, thermodynamically controlled conditions. Specifically, a dynamic, racemic perylene diimide dye (1 : 1 P : M) is strapped with an enantiopure (S)-1,1'-bi-2-naphthol group (P-BINOL) to form two diastereomeric macrocyclic products, the homochiral macrocycle (PP) and the heterochiral species (PM). We find there is notable selectivity for the PM macrocycle (dr = 4 : 1), which is rationalised by kinetic templation from intramolecular aromatic non-covalent interactions between the P-BINOL π-donor and the M-PDI π-acceptor during the macrocyclisation reaction.

4.
Nat Commun ; 13(1): 7126, 2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36414645

RESUMEN

Surface faulting earthquakes are known to cluster in time from historical and palaeoseismic studies, but the mechanism(s) responsible for clustering, such as fault interaction, strain-storage, and evolving dynamic topography, are poorly quantified, and hence not well understood. We present a quantified replication of observed earthquake clustering in central Italy. Six active normal faults are studied using 36Cl cosmogenic dating, revealing out-of-phase periods of high or low surface slip-rate on neighboring structures that we interpret as earthquake clusters and anticlusters. Our calculations link stress transfer caused by slip averaged over clusters and anti-clusters on coupled fault/shear-zone structures to viscous flow laws. We show that (1) differential stress fluctuates during fault/shear-zone interactions, and (2) these fluctuations are of sufficient magnitude to produce changes in strain-rate on viscous shear zones that explain slip-rate changes on their overlying brittle faults. These results suggest that fault/shear-zone interactions are a plausible explanation for clustering, opening the path towards process-led seismic hazard assessments.

5.
Technol Cult ; 63(2): 450-457, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35531806

RESUMEN

The cover image of this issue of Technology and Culture is a collage crafted from two figures in this essay. On the right side of the image is a detail of a black and white photograph from around 1900 of female silk mill workers () juxtaposed on the left with detail of a color woodblock print from 1877 depicting a mock-up of the Tomioka silk mill featured in an industrial exposition staged that year in Tokyo (). The collage was composed by reversing the two figures to create a dynamic "V" designed to draw the viewer's eye from left to right and, by implication, from the glamorized rendition of silk mill work in the woodblock print to a more real-world photograph documenting actual working conditions in a silk mill. This essay provides a socio-historical matrix for, and critical analysis of, representative visual images of sericulture and silk mills.

6.
Adv Emerg Nurs J ; 44(1): 63-73, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35089284

RESUMEN

The objectives of this study were to measure perceived stress, burnout, and utilization and perceived benefit of wellness practices among emergency medicine (EM) nurse practitioners (NPs) and physician assistants (PAs). An additional aim was to evaluate attributions of stress to racism and the COVID-19 pandemic. A 28-item electronic survey of ED NPs/PAs at 3 hospitals was used to measure respondents' perceived stress (Perceived Stress Scale), stress attributed to COVID-19 and systemic racism, burnout (2-item measure), and utilization and helpfulness of wellness practices. The sample consisted of 53 ED NPs/PAs respondents (response rate 42.4%). More than one half (58.5%) reported burnout from their job, and a majority (58.5%) reported moderate to high stress. Burnout was reported by 70% of female respondents compared with 30.8% of male respondent (p = 0.002). A large majority (70%) of Black respondents reported concerns about experiencing racism at work, and 58.8% reported higher levels of stress attributed to racism. Respondents reported meals during shifts, community donated personal protective equipment, flexible work hours, and societal offerings of financial support (e.g., Internal Revenue Service stimulus check) as helpful. The COVID-19 pandemic and the impact of systemic racism are significant contributors to the stress and burnout of NPs/PAs. Female ED NPs/PAs disproportionally share the burden of burnout. Strategies to reduce burnout should be prioritized by institutional leadership. In addition, a majority of Black ED NPs/PAs are concerned about experiencing racism at work and report moderate to high stress associated with racism in general. There is an urgent need to address racism in the workplace with training on implicit bias, systemic racism, and allyship behavior.


Asunto(s)
Agotamiento Profesional , COVID-19 , Medicina de Emergencia , Enfermeras Practicantes , Asistentes Médicos , Sesgo Implícito , Agotamiento Profesional/epidemiología , Femenino , Hospitales , Humanos , Masculino , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios , Racismo Sistemático
7.
Dev Med Child Neurol ; 64(4): 481-487, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34553369

RESUMEN

AIM: To compare listening and spoken language outcomes after cochlear implantation for children born preterm and at term, and to examine patterns associated with additional disabilities or gestational age. METHOD: Children were included if they underwent cochlear implantation in 2013 or 2014 and had complete 5-year follow-up data available. An analysis of assessment data recorded annually was conducted, including outcomes as measured by the Category of Auditory Performance (CAP), the Speech Intelligibility Rating, Second Edition (SIR 2) scale, and the British Picture Vocabulary Scales, Third Edition (BPVS-3). Analyses were conducted to measure the impact of preterm birth and of additional causes of disability on these outcomes. RESULTS: Eighty-two children (39 males, 43 females; median corrected age at first cochlear implantation 28.5mo [interquartile range 16.3-48.5]) were included in the study. Children who underwent cochlear implantation experienced significant improvements as measured by the CAP, SIR 2, and BPVS-3. Comparable improvements were seen in the groups born at term and preterm. Children with additional disabilities experienced significant improvement in all measures but performed less well than children without additional disabilities. INTERPRETATION: Infants born preterm benefit from cochlear implantation to a degree comparable to their peers born at term. Additional disabilities may limit improvements in speech intelligibility, listening performance, and receptive vocabulary. Children with additional disabilities, nonetheless, derived significant benefit from cochlear implantation; additional benefits of cochlear implantation for this subgroup may go unmeasured by the outcome tools used in this study.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Nacimiento Prematuro , Percepción del Habla , Niño , Sordera/cirugía , Femenino , Humanos , Lactante , Recién Nacido , Lenguaje , Desarrollo del Lenguaje , Masculino , Embarazo , Inteligibilidad del Habla , Resultado del Tratamiento
8.
Acad Emerg Med ; 28(9): 974-981, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34358387

RESUMEN

INTRODUCTION: Discrimination based on race is a known source of stress in individuals and is a contributor to poor health outcomes in patients. However, less is known about how the experiences of racism impact the stress levels of emergency health care workers (EHCWs). OBJECTIVES: The goal of this study was to assess the impact that racism has on the stress of EHCWs. METHODS: An anonymous electronic cross-sectional survey of EHCWs including attending physicians, resident physicians, advanced practice providers, nurses, and staff at three large metropolitan hospitals was administered in the summer of 2020. The survey evaluated the stress related to systemic racism and the COVID-19 pandemic in addition to the wellness measures utilized to cope with these stressors. The focus of this article is the impact of systemic racism on EHCWs. RESULTS: Of the 576 eligible participants, the total number of respondents utilized for analysis was 260. Overall, 64% of participants were very concerned about the state of racism in the United States, and 30% reported moderate-high or high stress resulting from racism. When stratified by race, 46% of Black participants reported moderate-high or high stress resulting from racism, compared to 31% of other participants of color and 23% of White participants (p = 0.002). CONCLUSION: Systemic racism is a significant concern and source of stress for EHCWs. Additional research about systemic racism, its impact on medical providers, and more importantly, active strategies to reduce and ultimately eliminate it in health care is needed.


Asunto(s)
COVID-19 , Racismo , Estudios Transversales , Personal de Salud , Humanos , Pandemias , SARS-CoV-2 , Estados Unidos
9.
Nicotine Tob Res ; 23(11): 1928-1935, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34228120

RESUMEN

INTRODUCTION: In response to high rates of youth tobacco use, many states and localities are considering regulations on flavored tobacco products. The purpose of this study was to assess whether flavored tobacco restrictions (FTRs) in Massachusetts curb youth tobacco use over time and whether a dose-response effect of length of policy implementation on tobacco-related outcomes exists. AIMS AND METHODS: Using a quasiexperimental design, two municipalities with a FTR (adopting municipalities) were matched to a comparison municipality without a FTR. Surveys were administered before (December 2015) and after (January and February 2018) policy implementation to high school students in these municipalities (more than 2000 surveys completed at both timepoints). At follow-up, adopting municipalities had a policy in place for 1 and 2 years, respectively. In 2019, focus groups were conducted with high school students in each municipality. RESULTS: Increases seen in current tobacco use from baseline to follow-up were significantly smaller in adopting municipalities compared to the comparison (-9.4% [-14.2%, -4.6%] and -6.3% [-10.8%, -1.8%], respectively). However, policy impact was greater in one adopting municipality despite shorter length of implementation. Focus groups indicated reasons for differential impact, including proximity to localities without FTRs. CONCLUSIONS: Restrictions implemented in adopting municipalities had positive impacts on youth tobacco awareness and use 1-2 years postimplementation. Policy impact varies depending on remaining points of access to flavored tobacco, as such policy effectiveness may increase as more localities restrict these products. IMPLICATIONS: In response to high rates of youth flavored tobacco use (including flavored vape products), federal, state, and localities have passed FTRs that reduce availability of flavored tobacco in youth-accessible stores. Previous research has found that FTRs may curb youth tobacco use in the short-term; however, the long-term effectiveness remains unknown.This is the first study to show FTRs can curb youth tobacco use and reduce youth awareness of tobacco prices and brands even 2 years after policy passage. Municipality-specific factors, including proximity to localities without FTRs, may attenuate policy impact, highlighting the importance of widespread policy adoption.


Asunto(s)
Nicotiana , Productos de Tabaco , Adolescente , Aromatizantes , Humanos , Massachusetts/epidemiología , Uso de Tabaco
10.
Front Immunol ; 12: 620386, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936035

RESUMEN

Cytomegalovirus (CMV) is one of the most commonly recognized opportunistic pathogens and remains the most influential known parameter in shaping an individual's immune system. As such, T cells induced by CMV infection could have a long-term impact on subsequent immune responses. Accumulating evidence indicates that memory T cells developed during past bacterial and viral infection can cross-react with unrelated pathogens, including transplant antigens, and can alter responses to de novo infections, vaccines, cancers, or rejection. Therefore, careful examination of T cell responses elicited by CMV is warranted to understand their potentially beneficial or harmful roles in future major immune events. Our detailed exploration of the distribution, phenotype, TCR repertoire and transcriptome of CD4+ T cells within CMV seropositive healthy individuals using high-dimensional flow cytometry and single cell multi-omics sequencing reveals that CMV seropositivity has highly significant age-independent effects, leading to a reduction in CD4+ naïve T cells and an expansion of CD4+ effector memory T cells and CD45RA+ effector memory T cells. These induced CD4+ effector memory T cells undergo a specific differentiation trajectory resulting in a subpopulation of CD57+CD27-CD28-CD244+ CD4+ T cells with cytotoxic function and TCR oligoclonality for optimal controlled coexistence with cytomegalovirus. Through gene set enrichment analysis, we found that this subpopulation is similar to virus-specific CD8+ T cells and T cells that mediate acute rejection in patients using tacrolimus and belatacept, a selective costimulation blocker. Together, these data suggest that memory CD4+ T cells induced by cytomegalovirus are formed via a distinct differentiation program to acquire cytotoxic function and can be potentially detrimental to transplant patients adopting costimulation blockade immunosuppressive regimen.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular/inmunología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Citomegalovirus/inmunología , Interacciones Huésped-Patógeno/inmunología , Abatacept/farmacología , Abatacept/uso terapéutico , Adulto , Antígenos CD/metabolismo , Biomarcadores , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/metabolismo , Citotoxicidad Inmunológica , Femenino , Perfilación de la Expresión Génica , Humanos , Memoria Inmunológica , Inmunofenotipificación , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
11.
Antimicrob Agents Chemother ; 65(8): e0234520, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34031048

RESUMEN

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use. Emerging and drug-resistant fungi, toxicity, and drug-drug interactions compromise their efficacy and applicability. Consequently, new and improved antifungal therapies are urgently needed. In response to that need, we have developed NP339, a 2-kDa polyarginine peptide that is active against pathogenic fungi from the genera Candida, Aspergillus, and Cryptococcus, as well as others. NP339 was designed based on endogenous cationic human defense peptides, which are constituents of the cornerstone of immune defense against pathogenic microbes. NP339 specifically targets the fungal cell membrane through a charge-charge-initiated membrane interaction and therefore possesses a differentiated safety and toxicity profile to existing antifungal classes. NP339 is rapidly fungicidal and does not elicit resistance in target fungi upon extensive passaging in vitro. Preliminary analyses in murine models indicate scope for therapeutic application of NP339 against a range of systemic and mucocutaneous fungal infections. Collectively, these data indicate that NP339 can be developed into a highly differentiated, first-in-class antifungal candidate for poorly served invasive and other serious fungal diseases.


Asunto(s)
Antifúngicos , Micosis , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Péptidos/farmacología
12.
Am J Transplant ; 21(10): 3256-3267, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33756063

RESUMEN

Belatacept confers increased patient and graft survival in renal transplant recipients relative to calcineurin inhibitors, but is associated with an increased rate of acute rejection. Recent immunophenotypic studies comparing pretransplant T cell phenotypes of patients who reject versus those who remain stable on belatacept identified three potential "risky" memory T cell subsets that potentially underlie belatacept-resistant rejection: CD4+ CD28+ TEM , CD8+ CD28null , and CD4+ CD57+ PD1- subsets. Here, we compared key phenotypic and functional aspects of these human memory T cell subsets, with the goal of identifying additional potential targets to modulate them. Results demonstrate that TIGIT, an increasingly well-appreciated immune checkpoint receptor, was expressed on all three risky memory T cell subsets in vitro and in vivo in the presence of belatacept. Coculture of human memory CD4+ and CD8+ T cells with an agonistic anti-TIGIT mAb significantly increased apoptotic cell death of all three risky memory T cell subsets. Mechanistically, TIGIT-mediated apoptosis of risky memory T cells was dependent on FOXP3+ Treg, suggesting that agonism of the TIGIT pathway increases FOXP3+ Treg suppression of human memory T cell populations. Overall, these data suggest that TIGIT agonism could represent a new therapeutic target to inhibit belatacept-resistant rejection during transplantation.


Asunto(s)
Memoria Inmunológica , Trasplante de Riñón , Abatacept/uso terapéutico , Apoptosis , Antígenos CD28 , Linfocitos T CD8-positivos , Rechazo de Injerto/etiología , Humanos , Inmunosupresores , Trasplante de Riñón/efectos adversos , Receptores Inmunológicos , Subgrupos de Linfocitos T
13.
Am J Transplant ; 21(9): 3066-3076, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33583120

RESUMEN

Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized noninferiority trial in low immunologic risk renal transplant recipients greater than 1-year posttransplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a noninferiority comparison of renal function (eGFR) at 12 months with a noninferiority margin (NIM) of 6.0 ml/min/1.73 m2 . One hundred and sixty-six participants were randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was noninferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSAs) occurred among q2m subjects; however, only one rejection and one instance of DSA were observed in subjects adherent to the study protocol. Every 2-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with long-term follow-up will further elucidate immunologic risk. (ClinicalTrials.gov NCT02560558).


Asunto(s)
Trasplante de Riñón , Abatacept/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Receptores de Trasplantes
14.
J Neurol Neurosurg Psychiatry ; 92(3): 295-302, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33184094

RESUMEN

OBJECTIVE: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS). METHODS: We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review. RESULTS: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine. CONCLUSIONS: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.


Asunto(s)
Reposicionamiento de Medicamentos , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Animales , Evaluación de Medicamentos , Humanos
15.
PLoS One ; 15(12): e0242945, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33370348

RESUMEN

BACKGROUND: Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? METHODS AND FINDINGS: Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire-Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. CONCLUSION: In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. CLINICAL TRIAL REGISTRATION: NCT03000348; www.clinicaltrials.gov.


Asunto(s)
Cisteamina/administración & dosificación , Cisteamina/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Pulmón/efectos de los fármacos , Administración Oral , Adulto , Cisteamina/efectos adversos , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Seguridad
16.
Med Mycol ; 58(8): 1064-1072, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-32232410

RESUMEN

NP213 (Novexatin®) is a novel antifungal peptide specifically designed for the topical treatment of onychomycosis. NP213 was designed using host defense peptides (HDP), essential components of the innate immune response to infection, as a template. NP213 is a water-soluble cyclic fungicidal peptide that effectively penetrates human nail. NP213 demonstrated a promising preclinical and clinical safety profile, with no evidence of systemic exposure following topical application to the skin and nails. NP213 was efficacious in two phase IIa human trials with 43.3% of patients having no fungi detectable by culture of fragments from NP213-treated nails after 180 days in the first study and likewise 56.5% of patients were culture negative for dermatophytes after 360 days in the second phase IIa study. In both trials, NP213 was applied daily for only 28 days in marked contrast to other topical onychomycosis treatments that require application for up to 52 weeks. Patient reported outcomes from the phase IIa studies were positive with participants recording an improved appearance of their nails after only 14 days of application. All fungi identified in these studies were Trichophyton spp. NP213 (Novexatin®) is a promising, highly differentiated peptide-based candidate for the topical treatment of onychomycosis, addressing the infectious cause and cosmetic issues of this very common condition.


Asunto(s)
Antifúngicos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Onicomicosis/tratamiento farmacológico , Péptidos Cíclicos/uso terapéutico , Administración Tópica , Antifúngicos/farmacocinética , Péptidos Catiónicos Antimicrobianos/farmacocinética , Ensayos Clínicos como Asunto , Humanos , Uñas/efectos de los fármacos , Uñas/microbiología , Onicomicosis/microbiología , Péptidos Cíclicos/farmacocinética , Resultado del Tratamiento
17.
Cell Rep ; 30(5): 1282-1291.e5, 2020 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-32023448

RESUMEN

The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8+ T pool is unexpectedly comprised of both CD45RBhi and CD45RBlo populations. Relative to CD45RBlo memory T cells, CD45RBhi memory T cells have lower affinity and display greater clonal diversity, as well as a persistent CD27hi phenotype. The CD45RBhi memory population displays a homeostatic survival advantage in vivo relative to CD45RBlo memory, and long-lived high-affinity cells that persisted long term convert from CD45RBlo to CD45RBhi. Human CD45RO+ memory is comprised of both CD45RBhi and CD45RBlo populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RBhi. These data demonstrate that CD45RB status is distinct from the conventional central/effector T cell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8+ T cell responses.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica , Antígenos Comunes de Leucocito/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Adulto , Animales , Afinidad de Anticuerpos/inmunología , Células Clonales , Femenino , Homeostasis , Humanos , Coriomeningitis Linfocítica/inmunología , Coriomeningitis Linfocítica/virología , Virus de la Coriomeningitis Linfocítica/fisiología , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Fenotipo , Adulto Joven
18.
Tob Control ; 29(2): 175-182, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-30777880

RESUMEN

OBJECTIVE: This study aimed to evaluate the effectiveness of flavoured tobacco product restriction policies in reducing availability of flavoured products in Massachusetts communities. METHODS: Data were obtained from surveys of tobacco retailers conducted from July 2015 to March 2017. On a community level, flavoured product availability was defined as the per cent of retailers during a given 3-month quarter that sold flavoured cigars/cigarillos, electronic cigarettes and/or e-liquids. Communities that implemented the policy during the study period were grouped into wave 1 (n=18; 1481 retail surveys) and wave 2 (n=20; 483 retail surveys) by date of policy implementation; communities without a flavoured product restriction served as the control group (n=234; 4932 retail surveys). A difference-in-difference analysis was used to compare the change in flavoured product availability in wave 1 and wave 2 communities 3 months pre-policy and post-policy implementation to the change over the same time periods in the control group. RESULTS: From pre-policy to post-policy implementation period, communities in both waves experienced significant reductions in flavoured product availability (ranging from 27.2% to 50.9%), even after adjusting for community-level characteristics. In both waves 1 and 2, reductions in flavoured product availability were significantly greater compared with comparison communities during the same time frame, adjusting for community-level characteristics. CONCLUSIONS: Compliance with flavoured product restriction policies is high among tobacco retailers throughout Massachusetts, regardless of community demographic and retail characteristics. Reduced availability of flavoured tobacco in the retail environment has the potential to reduce youth exposure, access and use of these products.


Asunto(s)
Comercio/legislación & jurisprudencia , Sistemas Electrónicos de Liberación de Nicotina , Aromatizantes , Productos de Tabaco/legislación & jurisprudencia , Humanos , Massachusetts , Política Pública , Encuestas y Cuestionarios , Productos de Tabaco/economía
19.
Tob Control ; 29(e1): e71-e77, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-31611423

RESUMEN

BACKGROUND: Flavoured tobacco products are widely available in youth-accessible retailers and are associated with increased youth initiation and use. The city of Boston, Massachusetts restricted the sale of flavoured tobacco products, including cigars, smokeless tobacco and e-cigarettes, to adult-only retailers. This paper describes the impact of the restriction on product availability, advertisement and consumer demand. METHODS: Between January and December 2016, data were collected in 488 retailers in Boston at baseline and 469 retailers at 8-month follow-up, measuring the type, brand and flavour of tobacco products being sold. Process measures detailing the educational enforcement process, and retailer experience were also captured. McNemar tests and t-tests were used to assess the impact of the restriction on product availability. RESULTS: After policy implementation, only 14.4% of youth-accessible retailers sold flavoured products compared with 100% of retailers at baseline (p<0.001). Flavoured tobacco product advertisements decreased from being present at 58.9% of retailers to 28.0% at follow-up (p<0.001). Postimplementation, retailers sold fewer total flavoured products, with remaining products often considered as concept flavours (eg, jazz, blue). At follow-up, 64.0% of retailers reported that customers only asked for flavoured products a few times a week or did not ask at all. Retailers reported that educational visits and the flavoured product guidance list aided with compliance. CONCLUSION: Tobacco retailers across Boston were largely in compliance with the regulation. Availability of flavoured tobacco products in youth-accessible retailers declined city-wide after policy implementation. Strong educational and enforcement infrastructure may greatly enhance retailer compliance.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Adolescente , Adulto , Publicidad , Boston , Comercio , Humanos , Massachusetts , Nicotiana
20.
Am J Prev Med ; 57(6): 741-748, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31668668

RESUMEN

INTRODUCTION: To counter the high prevalence of flavored tobacco use among youth, many U.S. localities have passed policies that restrict youth access to these products. This study aims to evaluate the short-term impact of a flavored tobacco restriction policy on youth access to, and use of, flavored tobacco products in a Massachusetts community. METHODS: A community with the policy (Lowell) was matched to a community without the policy (Malden) with similar demographics, retailer characteristics, and point-of-sale tobacco policies. Product inventories were assessed in tobacco retailers in the 2 communities, and surveys were administered to high school-aged youth in those communities. Inventories and surveys were conducted around the time the policy took effect in October 2016 (baseline) and approximately 6 months later (follow-up); all data were analyzed in 2017. Chi-squared tests and difference-in-difference models were used to estimate the impact of the policy on flavored tobacco availability and youth perceptions and behaviors related to flavored tobacco use. RESULTS: Flavored tobacco availability decreased significantly in Lowell from baseline to follow-up periods by 70 percentage points (p<0.001), whereas no significant changes in flavored tobacco availability were seen in Malden. In addition, current use of both flavored and non-flavored tobacco decreased in Lowell, but increased in Malden from baseline to follow-up; these changes were significantly different between communities (flavored tobacco: -5.7%, p=0.03; non-flavored tobacco: -6.2%, p=0.01). CONCLUSIONS: Policies that restrict the sale of flavored tobacco have the potential to curb youth tobacco use in as few as 6 months.


Asunto(s)
Comercio/legislación & jurisprudencia , Aromatizantes , Política Pública , Productos de Tabaco/legislación & jurisprudencia , Uso de Tabaco/prevención & control , Adolescente , Niño , Comercio/estadística & datos numéricos , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Massachusetts/epidemiología , Evaluación de Programas y Proyectos de Salud , Instituciones Académicas/estadística & datos numéricos , Estudiantes/estadística & datos numéricos , Productos de Tabaco/estadística & datos numéricos , Uso de Tabaco/epidemiología , Adulto Joven
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