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1.
J Virol ; : e0077524, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007616

RESUMO

T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM-1 has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles. We found that TIM-1 on the surface of host cells significantly reduced CHIKV release efficiency in comparison to other entry factors. Removal of cell surface TIM-1 through direct cellular knock-out or altering the cellular lipid distribution enhanced CHIKV release. Over the course of infection, CHIKV was able to counteract the tethering effect by gradually decreasing the surface levels of TIM-1 in a process mediated by the nonstructural protein 2. This study highlights the importance of phosphatidylserine receptors in mediating not only the entry of CHIKV but also its release and could aid in developing cell lines capable of enhanced vaccine production. IMPORTANCE: Chikungunya virus (CHIKV) is an enveloped alphavirus transmitted by the bites of infectious mosquitoes. Infection with CHIKV results in the development of fever, joint pain, and arthralgia that can become chronic and last for months after infection. Prevention of this disease is still highly focused on vector control strategies. In December 2023, a new live attenuated vaccine against CHIKV was approved by the FDA. We aimed to study the cellular factors involved in CHIKV release, to better understand CHIKV's ability to efficiently infect and spread among a wide variety of cell lines. We found that TIM-1 receptors can significantly abrogate CHIKV's ability to efficiently exit infected cells. This information can be beneficial for maximizing viral particle production in laboratory settings and during vaccine manufacturing.

2.
Mar Pollut Bull ; 204: 116490, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38843703

RESUMO

The range of impacts of chemical dispersants on indigenous marine microbial communities and their activity remains poorly constrained. We tested the response of nearshore surface waters chronically exposed to oil leakage from a downed platform and supplied with nutrients by the Mississippi River to Corexit dispersant and nutrient additions. As assessed using 14C-labeled tracers, hexadecane mineralization potential was orders of magnitude higher in all unamended samples than in previously assessed bathypelagic communities. Nutrient additions stimulated microbial mortality but did not affect community composition and had no generalizable effect on hydrocarbon mineralization potential. By contrast, Corexit amendments caused a rapid shift in community composition and a drawdown of inorganic nitrogen and orthophosphate though no generalizable effect on hydrocarbon mineralization potential. The hydrocarbonoclastic community's response to dispersants is largely driven by the relative availability of organic substrates and nutrients, underscoring the role of environmental conditions and multiple interacting stressors on hydrocarbon degradation potential.


Assuntos
Hidrocarbonetos , Água do Mar , Poluentes Químicos da Água , Água do Mar/química , Poluentes Químicos da Água/análise , Hidrocarbonetos/análise , Nutrientes/análise , Tensoativos , Nitrogênio/análise , Alcanos/análise , Monitoramento Ambiental , Lipídeos
3.
bioRxiv ; 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38328121

RESUMO

T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of Chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce Chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles. We found that TIM-1 on the surface of host cells significantly reduced CHIKV release efficiency in comparison to other entry factors. Removal of cell surface TIM-1 through direct cellular knock-out or altering the cellular lipid distribution enhanced CHIKV release. Over the course of infection, CHIKV was able to counteract the tethering effect by gradually decreasing the surface levels of TIM-1 in a process that appears to be mediated by the nonstructural protein 2. This study highlights the importance of phosphatidylserine receptors in mediating not only the entry of CHIKV but also its release and could aid in developing cell lines capable of enhanced vaccine production.

4.
J Environ Manage ; 351: 119664, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042073

RESUMO

Recent trends in wildfire area burned have been characterized by large patches with high densities of standing dead trees, well outside of historical range of variability in many areas and presenting forest managers with difficult decisions regarding post-fire management. Post-fire tree harvesting, commonly called salvage logging, is a controversial management tactic that is often undertaken to recoup economic loss and, more recently, also to reduce future fuel hazard, especially when coupled with surface fuel reduction. It is unclear, however, whether the reductions in future fuels translate to meaningful changes to reburn fire behavior, particularly in the context of potentially detrimental effects of harvest on other ecosystem services. We used observed post-fire snag structure in four high severity burn scars located in the Western United States that had variable post-fire snag basal area (13.3-63.9 mg ha-2) to initialize a simulation study of future coarse and fine woody fuel hazard and associated reburn fire behavior and effects. We compared untreated controls to intensive and intermediate intensity harvest treatments, both simulated and actual. All treatments showed some number of years of extreme fire behavior during which flame lengths exceeded thresholds associated with wildfire resistance to control, implying that future fuel reductions achieved by the treatments did not translate to conditions conducive for effective reburn fire management. Harvested stands had less severe soil fire effects (soil heating and smoldering duration) than untreated controls, explained by lower predicted peak coarse woody fuels (CWD) in the harvested stands. At higher pre-treatment snag basal area, harvested stands better maintained CWD within the range desired to maintain ecosystem functions such as nutrient cycling and wildlife habitat. These simulation results indicate that, even with reduced fuel hazard, salvage treatments may still be associated with severe fire behavior for some time after wildfire, but achieved reductions in coarse woody fuels may also reduce some soil fire effects. Tradeoffs in the effects of post-fire harvest must be considered carefully in the context of forest regeneration, local conditions that govern salvage methods, snag fall and decomposition, and associated potential reburn fire effects.


Assuntos
Ecossistema , Incêndios , Florestas , Árvores , Solo
5.
Front Microbiol ; 14: 1278791, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029077

RESUMO

Bacteriophages such as γ and AP50c have been shown to infect strains of Bacillus anthracis with high specificity, and this feature has been exploited in the development of bacterial detection assays. To better understand the emergence of phage resistance, and thus the potential failure of such assays, it is important to identify the host and phage receptors necessary for attachment and entry. Using genetic approaches, the bacterial receptors of AP50c and γ have been identified as sap and GamR, respectively. A second AP50c-like phage, Wip1, also appears to use sap as a receptor. In parallel with this work, the cognate phage-encoded receptor binding proteins (RBPs) have also been identified (Gp14 for γ, P28 for AP50c, and P23 for Wip1); however, the strength of evidence supporting these protein-protein interactions varies, necessitating additional investigation. Here, we present genetic evidence further supporting the interaction between sap and the RBPs of AP50c and Wip1 using fluorescently tagged proteins and a panel of B. anthracis mutants. These results showed that the deletion of the sap gene, as well as the deletion of csaB, whose encoded protein anchors sap to the bacterial S-layer, resulted in the loss of RBP binding. Binding could then be rescued by expressing these genes in trans. We also found that the RBP of the γ-like prophage λBa03 relied on csaB activity for binding, possibly by a different mechanism. RBPλBa03 binding to B. anthracis cells was also unique in that it was not ablated by heat inactivation of vegetative cells, suggesting that its receptor is still functional following incubation at 98°C. These results extend our understanding of the diverse attachment and entry strategies used by B. anthracis phages, enabling future assay development.

6.
Lancet Glob Health ; 11(6): e969-e975, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37116530

RESUMO

We describe an effort to develop a consensus-based research agenda for mental health and psychosocial support (MHPSS) interventions in humanitarian settings for 2021-30. By engaging a broad group of stakeholders, we generated research questions through a qualitative study (in Indonesia, Lebanon, and Uganda; n=101), consultations led by humanitarian agencies (n=259), and an expert panel (n=227; 51% female participants and 49% male participants; 84% of participants based in low-income and middle-income countries). The expert panel selected and rated a final list of 20 research questions. After rating, the MHPSS research agenda favoured applied research questions (eg, regarding workforce strengthening and monitoring and evaluation practices). Compared with research priorities for the previous decade, there is a shift towards systems-oriented implementation research (eg, multisectoral integration and ensuring sustainability) rather than efficacy research. Answering these research questions selected and rated by the expert panel will require improved partnerships between researchers, practitioners, policy makers, and communities affected by humanitarian crises, and improved equity in funding for MHPSS research in low-income and middle-income countries.


Assuntos
Saúde Mental , Sistemas de Apoio Psicossocial , Humanos , Masculino , Feminino , Pesquisa Qualitativa , Pobreza , Países em Desenvolvimento
7.
Microbiol Resour Announc ; 12(2): e0131322, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36719207

RESUMO

Mutants of the attenuated Bacillus anthracis (Sterne) strain 7702 that are resistant to phage AP50c have been previously described. Here, we report the draft genome assemblies of the parent strain, several phage-resistant derivatives, and mutants of genes in the pathways for synthesis and assembly of the S-layer.

8.
Addict Behav ; 136: 107483, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36084416

RESUMO

INTRODUCTION: Electronic cigarettes ("e-cigarettes") are commonly promoted as a less-harmful alternative to combustible cigarettes, yet many individuals concurrently use both products ("dual users"). Little is known about the extent to which dual users' perceptions of the addictive properties of these products differ, or to what extent there are differences in the factors that elicit craving for each product. METHODS: An online survey evaluated beliefs about the addictive properties of cigarettes vs e-cigarettes and the situational and affective precipitants of product craving, on a scale from 1 to 10, in a sample of Canadian adults that reported past-month use of combustible and e-cigarettes (N = 175; 79 female). RESULTS: Participants rated cigarettes as more addictive than e-cigarettes, and on average reported higher levels of dependence on combustible cigarettes. While the addictive properties of both combustible and e-cigarettes were largely attributed to nicotine, non-nicotine factors (e.g. flavouring, other non-nicotine ingredients) were believed to make a relatively stronger contribution to the addictive properties of e-cigarettes, particularly among women. Participants reported greater increases in craving for combustible cigarettes in response to negative affective states and situational factors, and these effects were strongest among participants that displayed greater dependence on combustible tobacco relative to e-cigarettes. CONCLUSIONS: Dual users perceived cigarettes to be more addictive than e-cigarettes and attributed the addictive properties of each product to different factors. Further, cravings for combustible cigarettes were more strongly linked to certain negative affective states and situational factors relative to e-cigarettes. Findings suggest that there may be limited substitutability between combustible and e-cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adulto , Canadá , Fissura , Feminino , Humanos , Nicotina
9.
Telemed J E Health ; 29(3): 425-431, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35867048

RESUMO

Background: This study sought to examine the complex relationship between individual and environmental characteristics, broadband access, device type (computer or smartphone), and telehealth utilization as it relates to the digital divide. Methods: We analyzed a combination of electronic health record and publicly available zip code-level data for 2,770 men seeking treatment on a large, nationally available, direct-to-consumer telehealth platform. Using logistic regression, we determined the likelihood of accessing the platform through a smartphone (vs. a computer) based on key features of the environment, including broadband access and income, and demographic characteristics, including age and race. Results: We found that living in areas with higher rates of broadband adoption significantly decreased the likelihood of accessing virtual care using a smartphone (odds ratio [OR] = 0.17, p < 0.001). Compared with the 18-29 age category, the odds of accessing virtual care using a smartphone decreased for men between the age categories of 40-59 (OR = 0.63, p < 0.01) and over 60 (OR = 0.29, p < 0.001) years. Belonging to historically marginalized communities of color (Black, Hispanic, and Native American) almost doubled the odds of using a smartphone to access the platform (OR = 1.8, p < 0.001). Broadband availability and median area income were not significantly associated with mobile use. Conclusions: Telehealth platform design and policy solutions intended to expand access to virtual care should be flexible enough to accommodate the sometimes competing needs of patients who are at the greatest risk of being left behind.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde , Telemedicina , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Smartphone , Registros Eletrônicos de Saúde , Demografia
10.
J Phys Ther Educ ; 37(2): 94-101, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38478822

RESUMO

INTRODUCTION: The COVID-19 pandemic saw physical therapist (PT) education programs in 2020 add virtual options to prepare students for hands-on clinical skills. The purpose of this research was to investigate student confidence, preparation, and clinical performance based on their choice of virtual or in-person laboratory immersion. Secondary analysis compared 2020 cohort outcomes with the previous cohort in 2019 (prepandemic). REVIEW OF LITERATURE: Virtual skill acquisition has been studied with support for effectiveness in didactic and psychomotor skill acquisition. The impact on clinical education performance is unknown. SUBJECTS: Student records from an accelerated hybrid, PT education program in 2020 (n = 91) and 2019 (n = 86). METHODS: In this mixed-method observational study, researchers analyzed a Qualtrics survey and the PT Clinical Performance Instrument (CPI) to compare student outcomes. Statistical analyses included chi-square, two-way multivariate analysis of variance (MANOVA), and Mann-Whitney U test. MAXQDA software was used to code student and clinical instructor narrative responses from the CPI related to strengths and areas for further development. RESULTS: All students in 2020 attended laboratory virtually for 9 full days, and 24% of students chose virtual laboratory for the remaining 8.5 days; 97% of students reported feeling confident going into their clinical experience (66% inpatient). No statistically significant differences were found based on instructional method (virtual or in-person) or clinical practice setting (inpatient or outpatient) for confidence, preparation, or CPI performance. Themes of wanting more time to prepare and more confidence in clinical decision making emerged from the qualitative analysis. DISCUSSION AND CONCLUSION: Results indicate no statistically significant difference for virtual versus in-person laboratory and no difference compared with the 2019 cohort. Virtual instruction effectively prepared students for their clinical experiences across all settings. Although an in-person laboratory experience may be preferred, it is possible to deliver effective experiences in a virtual setting without compromising student performance. Further research is needed to confirm findings.


Assuntos
Laboratórios , Pandemias , Humanos , Estudantes , Competência Clínica , Pessoal Técnico de Saúde
11.
Perioper Med (Lond) ; 11(1): 42, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36002866

RESUMO

BACKGROUND: Frailty increases the risk of perioperative complications, length of stay, and the need for assisted-living after discharge. As the UK population ages the number of frail patients presenting for elective surgery in the UK is likely to grow. Despite the potential benefits of early diagnosis, frailty is not uniformly screened for in UK elective surgical patients and its prevalence remains unclear. The primary aim of this study was to assess the prevalence of frailty in patients aged over 65 years undergoing elective surgery. METHODS: We performed a prospective cross-sectional observational study in eight UK hospitals. Data were collected over three consecutive days with follow-up at 30 days. HRA approval was obtained (REC 20/SC/0121) and signed informed consent obtained. Participants were eligible for inclusion if they were 65 years or older and undergoing elective surgery. Pre-operative data were collected from hospital notes by anaesthetic trainees. A member of the research team blinded to the pre-operative dataset screened each participant for frailty pre-operatively using the Reported Edmonton Frail Scale (REFS). Post-operative data were collected from the notes on day of surgery and at 30 days. Participants were defined as "frail" if they scored 8 or more on the REFS. RESULTS: Two hundred twenty eight participants were recruited during the study period of whom 218 proceeded to surgery. There were 103 females and 115 males. Median age was 75 years (interquartile range 70-80). Thirty-seven participants (17.0%) were identified as frail. Frail patients were older, had a higher ASA score, were more likely to have carers and were more likely to be anaemic or present with ECG abnormalities. There were no differences in gender, BMI, place of residence or smoking status for patients identified as frail versus non-frail. There was no difference in length-of-stay between frail and non-frail patients, although those identified as frail were less likely to be discharged to their own home. CONCLUSION: We found the prevalence of frailty in a mixed population of elective surgical patients aged 65 or over to be 17.0%. Furthermore, we found the REFS to be a practical tool for pre-operative frailty screening. Frail patients presented for elective surgery with modifiable co-morbidities which could have been optimised pre-operatively. Early screening could highlight frail patients, allowing time for pre-operative planning and evidence-based optimisations of comorbidities. We therefore encourage the adoption of frailty assessment as a routine part of pre-operative assessment.

12.
Hosp Pharm ; 57(1): 20-25, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35521003

RESUMO

Objective: Providers often admit patients with active outpatient prescriptions for levothyroxine. During an inpatient admission, providers may instruct critically ill patients to take nothing by mouth, or nil per os (NPO). Thus, they may prescribe the intravenous (IV) formulation of levothyroxine during this period. However, levothyroxine possesses a prolonged half-life of up to 7 days; therefore, immediate transition to IV levothyroxine may not be clinically necessary in the acute NPO setting. Intravenous levothyroxine is significantly more expensive than equivalent oral doses and may prove to be a financial burden for an institution. By understanding the pharmacokinetic properties of levothyroxine, we implemented a cost-saving initiative involving a 5-day therapeutic hold of IV levothyroxine. Methods: This was a retrospective evaluation in 2 intensive care units (ICU): a 20-bed surgical/trauma ICU and an 18-bed mixed medical/surgical ICU. Patient data, utilization data, and documented pharmacist interventions were collected for 6 months prior to implementation of the 5-day IV levothyroxine therapeutic hold and for 6 months post-implementation. All patients prescribed IV levothyroxine during these timeframes were included. Results: During the 6-month pre-implementation phase, 674 doses (691 vials) of IV levothyroxine for 77 unique patients were dispensed from the 2 ICUs. During the 6-month post-implementation phase, 168 doses (188 vials) of IV levothyroxine were dispensed for 44 unique patients. Of the 44 patients (48 orders) who still received IV levothyroxine, 22.9% of orders were deemed clinically necessary by the pharmacist and were not recommended to be held under the protocol, 64.6% were due to the verifying pharmacist being unaware of the protocol, 8.3% of orders were due to protocol non-compliance, and 4.2% were verified after the 5-day hold was complete as the patient remained NPO. This pharmacy-led initiative resulted in a 75% decrease in usage post-implementation and an estimated annualized savings of $80,000. Conclusion: A pharmacy-led initiative comprised of a 5-day therapeutic hold of IV levothyroxine was feasible and led to a 75% reduction in usage and cost over a 6-month period in 2 ICU's. Future steps include additional staff education for improved protocol adherence and expanding the protocol institution-wide for an even greater cost-savings potential.

13.
Ann Pharmacother ; 56(5): 541-547, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34459268

RESUMO

BACKGROUND: Dosing variation of subcutaneous unfractionated heparin (UFH) exist for venous thromboembolism prophylaxis (VTEP). OBJECTIVE: The purpose of this study was to compare the safety and effectiveness of thrice-daily (TID) versus twice-daily (BID) administration of UFH during a heparin shortage for VTEP. METHODS: A single-center retrospective analysis was conducted in patients with orders for BID subcutaneous UFH during a heparin shortage from September 1, 2019, to February 4, 2020. These patients were matched to patients with TID subcutaneous UFH orders from January 1, 2019, to May 31, 2019. The primary outcome was the incidence of deep-vein thrombosis or pulmonary embolism confirmed by imaging during hospitalization. The secondary outcome was the incidence of major or clinically relevant nonmajor bleeding events as defined by International Society on Thrombosis and Haemostasis (ISTH) definitions. RESULTS: A total of 277 patients with orders for BID UFH and meeting inclusion criteria were evaluated and matched to patients who received TID UFH. After the exclusion criteria were implemented, 510 patients remained in the TID group. The primary outcome occurred in 4% of patients in the BID group and 3% in the TID group (P = 0.645). Major bleeding or clinically relevant nonmajor bleeding events occurred in 10% of patients in the BID group and 8% in the TID group (P = 0.310). CONCLUSION AND RELEVANCE: There was no difference in effectiveness or safety of TID versus BID subcutaneous UFH for VTEP. During a heparin shortage, transitioning patients to BID UFH for VTEP to conserve supply may be considered.


Assuntos
Heparina , Tromboembolia Venosa , Centros Médicos Acadêmicos , Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
14.
Int J Equity Health ; 20(1): 98, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33838679

RESUMO

BACKGROUND: Health social enterprises are experimenting with community health worker (CHW) models that allow for various income-generating opportunities to motivate and incentivize CHWs. Although evidence shows that improving gender equality contributes to the achievement of health outcomes, gender-based constraints faced by CHWs working with social enterprises in Africa have not yet been empirically studied. This study is the first of its kind to address this important gap in knowledge. METHODS: We conducted 36 key informant interviews and 21 focus group discussions between 2016 and 2019 (for a total of 175 individuals: 106 women and 69 men) with four health social enterprises in Uganda and Kenya and other related key stakeholders and domain experts. Interview and focus group transcripts were coded according to gender-based constraints and strategies for enhanced performance as well as key sites for intervention. RESULTS: We found that CHW programs can be more gender responsive. We introduce the Gender Integration Continuum for Health Social Enterprises as a tool that can help guide gender equality efforts. Data revealed female CHWs face seven unique gender-based constraints (compared to male CHWs): 1) higher time burden and lack of economic empowerment; 2) risks to personal safety; 3) lack of career advancement and leadership opportunities; 4) lack of access to needed equipment, medicines and transport; 5) lack of access to capital; 6) lack of access to social support and networking opportunities; and 7) insufficient financial and non-financial incentives. Data also revealed four key areas of intervention: 1) the health social enterprise; 2) the CHW; 3) the CHW's partner; and 4) the CHW's patients. In each of the four areas, gender responsive strategies were identified to overcome constraints and contribute to improved gender equality and community health outcomes. CONCLUSIONS: This is the first study of its kind to identify the key gender-based constraints and gender responsive strategies for health social enterprises in Africa using CHWs. Findings can assist organizations working with CHWs in Africa (social enterprises, governments or non-governmental organizations) to develop gender responsive strategies that increase the gender and health outcomes while improving gender equality for CHWs, their families, and their communities.


Assuntos
Agentes Comunitários de Saúde/psicologia , Fatores Econômicos , Empoderamento , Equidade de Gênero , Agentes Comunitários de Saúde/economia , Feminino , Grupos Focais , Humanos , Intenção , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Uganda
15.
J Neurosci Res ; 99(1): 209-222, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31912571

RESUMO

Social withdrawal and agitation/aggression are common behavioral and psychological symptoms of dementia presented by Alzheimer's disease (AD) patients, with males exhibiting more aggressive behaviors than females. Some transgenic mouse models of AD also exhibit social withdrawal and aggression, but many of these models only recapitulate the early stages of the disease. By comparison, the 5xFAD mouse model of AD exhibits rapid, progressive neurodegeneration, and is suitable for modeling cognitive and behavioral deficits at early, mid-, and late-stage disease progression. Anecdotal reports suggest that transgenic 5xFAD males exhibit high levels of aggression compared to wild-type controls, but to date, indirect genetic effects in this strain have not been studied. We measured home-cage behaviors in 5xFAD males housed in three different group-housing conditions (transgenic-only, wild-type only, and mixed-genotype) and social approach behaviors when exposed to a novel free-roaming or restrained, wild-type or transgenic conspecific. Transgenic-only home cages required earlier separation due to injuries arising from aggression compared to wild-type-only or mixed-genotype cages, despite no obvious increase in the frequency of aggressive behaviors. Transgenic 5xFAD males and females also spent less time investigating free-roaming conspecifics compared to wild-type controls, but they showed normal investigation of restrained conspecifics; the genotype of the conspecific did not affect approach behavior, and there was no aggression observed in transgenic males. These findings provide evidence in an animal model that amyloid pathology ultimately leads to avoidance of novel social stimuli, and that frequent interactions between individuals exhibiting an AD phenotype further exacerbates aggressive behaviors.


Assuntos
Agressão , Doença de Alzheimer , Comportamento Animal , Modelos Animais de Doenças , Comportamento Social , Animais , Feminino , Masculino , Camundongos , Camundongos Transgênicos
16.
Clin Infect Dis ; 72(9): e326-e333, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33269789

RESUMO

BACKGROUND: Subarachnoid neurocysticercosis (SANCC) represents the most severe and difficult to treat form of neurocysticercosis. The inflammatory response contributes significantly to the morbidity and mortality of the disease. This study sought to understand the nature and evolution of the inflammation associated with SANCC, and evaluate for predictors of time to cure. METHODS: There were 16 subjects with SANCC (basilar cistern, sylvian fissure, and/or spinal involvement) during active infection who had cerebrospinal fluid (CSF) cytokine and chemokine profiling, of whom 9 had a second CSF sample at (or following) the time of cure. The relationships between clinical parameters and cytokine/chemokine results were assessed. RESULTS: Compared to pools of healthy donor CSF, those with active SANCC showed a significant (P < .05) increase in chemokines and cytokines associated with Type 1 immunity (interferon [IFN] γ, interleukin [IL] 12p70, C-X-C Motif Ligand 10 CXCL-10); Type 2 immunity (IL-10, IL-13); IFNα2; and the chemokines Macrophage inflammatory protein MIP-1α/CCL3, MIP-1ß/CCL4, and Vascular Endothelial Growth Factor VEGF that appears to be locally (central nervous system [CNS]) produced. Compared to those with active disease, those with CSF taken at the time of cure showed a significant decrease in most of these chemokines and cytokines. Despite this, CSF from cured SANCC patients had levels of IL-10 (P = .039), CXCL-10 (P = .039), and IL-12p70 (P = .044) above those seen in CSF from uninfected subjects. High ratios of IL-12p70/IL-10 early in infections were associated with a shorter time to cure (r = -0.559; P = .027), and a high Taenia solium burden (by quantitative polymerase chain reaction) was associated with longer times to cure (r = 0.84; P = .003). CONCLUSIONS: SANCC is associated with a marked, CNS-localized cytokine-/chemokine-driven inflammatory response that largely decreases with curative therapy, though some analytes persisted above the normal range. The relative balance between proinflammatory and regulatory cytokines may be an important determinant for a cure in SANCC.


Assuntos
Quimiocinas , Citocinas , Neurocisticercose , Humanos , Proteínas Inflamatórias de Macrófagos , Neurocisticercose/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
17.
One Health Outlook ; 2(1): 4, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32835167

RESUMO

There is increased recognition that complex health challenges at the human-animal-environmental interface require a transdisciplinary, "whole-of-society" approach. This philosophy is particularly pertinent in Aotearoa-New Zealand because of the country's relatively isolated island ecosystem, economic reliance on agriculture and its intensification, and existing indigenous worldview that emphasises holism and interconnectivity between humans, animals and the environment. In New Zealand, the One Health Aotearoa (OHA) alliance was established in order to better connect researchers and to address a growing number of infectious diseases challenges. The emphasis of OHA is to bring together and facilitate interactions between people from diverse disciplines, link to stakeholders and communities, and engage with policy-makers, government operational agencies, and funders, thus providing a holistic and integrative systems-thinking approach to address priority questions and achieve desired outcomes in One Health. The initial focus of OHA has been on infectious diseases, but there is increasing recognition of the potential benefits of the alliance to address broader complex issues. Greater involvement and overlap of the environmental sciences, human and animal health sciences, social science, and indigenous kaupapa Maori research is particularly critical for ensuring its success within the New Zealand context. Given the economic and cultural importance of New Zealand's "clean, green" image, a One Health approach that draws strongly on the environmental sciences makes particular sense. Furthermore, as the global environment becomes increasingly stressed by anthropogenic pressures our research may hold potential solutions for similar challenges elsewhere.

18.
J Stud Alcohol Drugs ; 81(3): 320-330, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32527384

RESUMO

OBJECTIVE: The Anglo-Celtic colonists of Australia and New Zealand brought with them heavy beer-drinking customs, and each country later developed similar temperance movements and alcohol policies. Yet their beer markets differed throughout the 20th century; for example, Australian men typically drank lager with 5% alcohol-by-volume (ABV), whereas New Zealand men drank ale with 4%ABV. We investigated the public health implications of recent developments in product availability, marketing, and country-level consumption patterns. METHOD: We analyzed official data reporting beverage- and strength-specific volumes of ethanol available for sale in beer from 2000 to 2016, a period in which the countries had similar consumption trends; and did a thematic analysis of "market intelligence" reports. RESULTS: Per capita ethanol beer sales fell in both countries, accompanied by increases in market share of higher %ABV categories. Different definitions of beer strength hampered comparison between countries. In Australia, consumption of ethanol in mid-strength beer (3.01%-3.5%ABV) increased, whereas consumption of low-strength beer (<3%ABV) decreased. In New Zealand, consumption of high-strength beer (4.351%-5%ABV) increased whereas that of traditional mid-strength beer (2.501%-4.35%ABV) decreased substantially. Market reports cited consumer health concerns and demand for "craft beer" (typically high-strength) as competing influences in both markets, and reduced-alcohol beer as "the alcoholic drinks industry's-potentially lucrative-shield against accusations of irresponsibility." CONCLUSIONS: Declines in both high- and low-strength beer in Australia have potentially important implications. In New Zealand, the failure of low-strength beer to establish significant market share, along with increased consumption of high-strength beer, are noteworthy developments. Trend data on product ethanol content warrants scrutiny in public health surveillance globally, whereas research is needed on the role of ethanol content within industry strategy.


Assuntos
Consumo de Bebidas Alcoólicas/tendências , Cerveja/análise , Etanol/análise , Indústrias/tendências , Marketing/estatística & dados numéricos , Austrália , Comércio/tendências , Humanos , Nova Zelândia , Saúde Pública
19.
BMC Infect Dis ; 20(1): 359, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434480

RESUMO

BACKGROUND: Substantial numbers of patients are now receiving either immunosuppressive therapies or chemotherapy. There are significant risks in such patients of developing opportunistic infections or re-activation of latent infections, with higher associated morbidity and mortality. The aim of this quality improvement project was to determine how effective 5 different specialties were in assessing and mitigating risks of developing opportunistic infections or re-activation of latent infections in patients undergoing immunosuppressive therapies. METHODS: This was a single centre audit where records of patients attending clinics providing immunosuppressive therapies were reviewed for the following: evidence of screening for blood-borne virus [BBV] infections, varicella and measles immunity, latent/active TB or hypogammaglobulinaemia, and whether appropriate vaccines had been advised or various infection risks discussed. These assessments were audited against both national and international guidelines, or a cross-specialty consensus guideline where specific recommendations were lacking. Two sub-populations were also analysed separately: patients receiving more potent immunosuppression and black and minority ethnic [BME] patients,. RESULTS: For the 204 patients fulfilling the inclusion criteria, BBV, varicella/measles and latent TB screening was inconsistent, as was advice for vaccinations, with few areas complying with specialty or consensus guidelines. Less than 10% of patients in one specialty were tested for HIV. In BME patients screening for HIV [60%], measles [0%] and varicella [40%] immunity and latent [30%] or active [20%] TB was low. Only 38% of patients receiving potent immunosuppression received Pneumocystis prophylaxis, with 3 of 4 specialties providing less than 15% of patients in this category with prophylaxis. CONCLUSIONS: Compliance with guidelines to mitigate risks of infection from immunosuppressive therapies was either inconsistent or poor for most specialties. New approaches to highlight such risks and assist appropriate pre-immunosuppression screening are needed.


Assuntos
Doenças Transmissíveis/diagnóstico , Fidelidade a Diretrizes , Terapia de Imunossupressão/efeitos adversos , Adulto , Varicela/diagnóstico , Varicela/prevenção & controle , Controle de Doenças Transmissíveis , Doenças Transmissíveis/etiologia , Inglaterra , Feminino , Hospitais/estatística & dados numéricos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores , Masculino , Sarampo/diagnóstico , Sarampo/prevenção & controle , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico por imagem , Pneumonia por Pneumocystis/prevenção & controle , Estudos Retrospectivos , Vacinação , Viroses/diagnóstico , Viroses/prevenção & controle
20.
Health Promot Int ; 35(6): 1320-1330, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003808

RESUMO

Climate change is a major threat to public health worldwide. Conversely, well-designed action to mitigate climate change offers numerous opportunities to improve health and equity. Despite this, comprehensive climate action has not been forthcoming within New Zealand. The media plays an important role in shaping public opinion and support for policy change. Previous literature has suggested that certain types of framing may be more effective than others at encouraging support for climate action and policy. This includes positive, personally relevant framing, as well as key journalistic tools which appear counter-intuitive, such as an increase in human interest stories and 'sensationalist' framing. We undertook a qualitative thematic analysis of climate change and health media coverage in two online New Zealand news outlets to understand how the issue was framed, and how it may be framed more effectively to encourage climate action. We compared the framing used by journalists in mainstream media outlet the New Zealand Herald Online (NZHO) with that of contributors to independent news repository site Scoop. Content in both outlets emphasized the threat unchecked climate change poses to health, which overshadowed the positive health opportunities of climate action. The NZHO was more prone to negative framing, and more likely to favour stories which could be sensationalized and were international in scope. We considered the possible effectiveness of the framing we found for attracting greater media attention and encouraging support for climate action and policy.


Assuntos
Mudança Climática , Meios de Comunicação de Massa , Humanos , Nova Zelândia , Saúde Pública , Opinião Pública
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