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1.
Burns ; 50(4): 841-849, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472006

RESUMO

BACKGROUND: Frailty and comorbidities are important outcome determinants in older patients (age ≥65) with burns. A Geriatric Burn Bundle (Geri-B) was implemented in 2019 at a regional burn center to standardize care for older adults. Components included frailty screening and protocolized geriatric co-management, malnutrition screening with nutritional support, and geriatric-centered pain regimens. METHODS: This study aimed to qualitatively evaluate the implementation of Geri-B using the Proctor Framework. From June-August 2022, older burn-injured patients, burn nurses, and medical staff providers (attending physicians and advanced practice providers) were surveyed and interviewed. Transcribed interviews were coded and thematically analyzed. From May 2022 to August 2023, the number of inpatient visits aged 65 + with a documented frailty screening was monitored. RESULTS: The study included 23 participants (10 providers, 13 patients). Participants highly rated Geri-B in all implementation domains. Most providers rated geriatric care effectiveness as 'good' or 'excellent' after Geri-B implementation. Providers viewed it as a reminder to tailor geriatric care and a safeguard against substandard geriatric care. Staffing shortages, insufficient protocol training, and learning resources were reported as implementation barriers. Many providers advocated for better bundle integration into the hospital electronic health record (EHR) (e.g., frailty screening tool, automatic admission order sets). Most patients felt comfortable being asked about their functional status with strong patient support for therapy services. The average frailty screening completion rate from May 2022 to August 2023 was 86%. CONCLUSIONS: Geri-B was perceived as valuable for the care of older burn patients and may serve as a framework for other burn centers.


Assuntos
Queimaduras , Fragilidade , Avaliação Geriátrica , Pacotes de Assistência ao Paciente , Humanos , Queimaduras/terapia , Idoso , Masculino , Feminino , Avaliação Geriátrica/métodos , Pacotes de Assistência ao Paciente/métodos , Idoso de 80 Anos ou mais , Unidades de Queimados/organização & administração , Manejo da Dor/métodos , Desnutrição/terapia , Idoso Fragilizado , Apoio Nutricional/métodos
2.
Nat Commun ; 15(1): 1442, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365882

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and multiple types of B cell malignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributes to viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorly understood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the de novo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cell proliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediated pyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion or pharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primary effusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanism underpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and other diseases.


Assuntos
Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/metabolismo , Glicólise , Carcinogênese , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Nucleotídeos/metabolismo
3.
Biol Invasions ; : 1-17, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37362907

RESUMO

The goal of most invasive species suppression programs is to achieve long-term sustained reductions in population abundance, yet removal programs can be stymied by density-dependent population responses. We tested a harvest removal strategy for invasive Rusty Crayfish (Faxonius rusticus) at two nearshore native fish spawning habitats in northern Lake Michigan. Changes in average Rusty Crayfish densities were evaluated with a before-after reference-impact study design. We removed 3182 Rusty Crayfish, primarily adults (> 20 mm carapace length), at two sites over two harvest seasons, expending 17,825 trap days in effort. Generalized linear modeling results suggested a statistically significant reduction in Rusty Crayfish densities was achieved at one reef, Little Traverse Bay (LTB Crib). Reduced densities were sustained over the egg maturation period for native fish and into the following year after removal ceased. By late summer/early fall, between consecutive suppression efforts in 2018 and 2019, we observed a threefold increase in pre-removal densities. Size-frequency histograms from diver quadrat surveys showed higher abundances of juvenile (< 20 mm carapace length) size classes the following spring and summer at LTB Crib compared to its paired reference site. Stock-recruit curves fit to count data, pooled across all sites, provided further evidence of density-dependence. With a proviso that we only conducted two seasons of consecutive suppression, this study highlights an important aspect of invasive species management and raises questions about the efficacy of adult-only crayfish removal strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-023-03076-6.

4.
Front Mol Neurosci ; 16: 1112927, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063370

RESUMO

Introduction: Nicotine dependence is one of the main causes of preventable diseases in the United States. Nicotine-seeking and avoidance behavioral assays in larval zebrafish could be used for identifying potential new pharmacotherapeutics in an early phase of drug discovery and could facilitate the identification of genes and genomic variations associated with nicotine-seeking and avoidance behavior. Methods: A new three-choice behavioral assay has been developed for the identification of nicotine-seeking and avoiding larval zebrafish. The three choices are represented by three compartments of a gradient maze. Video-recording and subsequent quantitative analysis of the swimming track was carried out using EthovisionXT (Noldus). Results: Three behavioral phenotypes could be identified. Nicotine-seeking larval zebrafish occupied nicotine compartments for longer periods and entered the nicotine-containing compartments most frequently. Nicotine-avoiders spent most of the cumulative time in the water compartment or entered the water compartment most frequently. Non-seekers remained in the center compartment for most of the time. In the gradient maze, about 20-30% of larval zebrafish had a preference for low nicotine concentrations whereas nicotine avoidance was stronger at higher nicotine concentrations. Lower concentrations of nicotine (0.63 µM, 6.3 µM) resulted in higher percentages of nicotine seekers whereas high nicotine concentrations (63 µM, 630 µM) resulted in higher percentages of nicotine avoiders. Pre-treatment of larval zebrafish with nicotine slightly increased the percentage of nicotine avoiders at lower nicotine concentrations. Treatment with varenicline strongly increased the percentage of nicotine avoiders at lower nicotine concentrations. Conclusion: The results show that larval zebrafish have individual preferences for nicotine that could change with drug treatment. The three-choice gradient maze assay for larval zebrafish provides a new testing paradigm for studying the molecular and cellular mechanisms of nicotine action and the discovery of potential new pharmacotherapeutics for the treatment of smoking cessation.

5.
Digit Health ; 9: 20552076231165972, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37009306

RESUMO

Objective: Development of personalized sleep-wake management tools is critical to improving sleep and functional outcomes for shift workers. The objective of the current study was to test the performance, engagement and usability of a mobile app (SleepSync) for personalized sleep-wake management in shift workers that aid behavioural change and provide practical advice by providing personalized sleep scheduling recommendations and education. Methods: Shift workers (n = 27; 20 healthcare and 7 from other industries) trialled the mobile app for two weeks to determine performance, engagement and usability. Primary outcomes were self-reported total sleep time, ability to fall asleep, sleep quality and perception of overall recovery on days off. Secondary performance outcomes included sleep disturbances (insomnia and sleep hygiene symptoms, and sleep-related impairments) and mood (anxiety, stress and depression) pre- and post-app use. Satisfaction with schedule management, integration into daily routine and influence on behaviour were used to determine engagement, while the usability was assessed for functionality and ease of use of features. Results: Total sleep time (P = .04), ability to fall asleep (P < .001), quality of sleep (P = .001), insomnia (P = .02), sleep hygiene (P = .01), sleep-related impairments (P = .001), anxiety (P = .001), and stress (P = .006) were all improved, with non-significant improvements in recovery on days off (P = .19) and depression (P = .07). All measures of engagement and usability were scored positively by the majority of users. Conclusions: This pilot trial provides preliminary evidence of the positive impact of the SleepSync app in improving sleep and mood outcomes in shift workers, and warrants confirmation in a larger controlled trial.

6.
J Sleep Res ; 32(2): e13730, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36193767

RESUMO

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.


Assuntos
Sono , Tolerância ao Trabalho Programado , Humanos , Austrália , Duração do Sono , Actigrafia
7.
Manag Biol Invasion ; 13(1): 45-67, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35664708

RESUMO

At least 65 aquatic plant species have been identified as part of a surveillance list of non-native species that pose a threat to biodiversity and ecosystem services in the Laurentian Great Lakes. Early detection of these potentially invasive aquatic plants (IAP) could minimize impacts of novel incursions and facilitate successful eradication. We developed, implemented, and then adaptively refined a probabilistic boat-based sampling design that aimed to maximize the likelihood of detecting novel IAP incursions in large (400+ hectares) Great Lakes coastal areas. Surveys were conducted from 2017 to 2019 at five Great Lakes locations - St Joseph River (MI), Saginaw River (MI), Milwaukee (WI), Cleveland (OH), and the Detroit River (MI). Aquatic plant communities were characterized across the five sites, with a total of 61 aquatic plant species detected. One-fifth of the species detected in our surveys were non-native to the Great Lakes basin. Sample-based species rarefaction curves, constructed from detection data from all surveys combined at each location, show that the estimated sample effort required for high confidence (> 95%) detection of all aquatic plants at a site, including potentially invasive species, varies (< 100 sample units for Detroit River; > 300 sample units for Milwaukee, roughly equivalent to 6 to 18 days sampling effort, respectively). At least 70% of the estimated species pool was detected at each site during initial 3-day surveys. Leveraging information on detection patterns from initial surveys, including depth and species richness strata, improved survey efficiency and completeness at some sites, with detection of at least 80% of the estimated species pool during subsequent surveys. Based on a forest-based classification and regression method, a combination of just five variables explained 70% or more of the variation in observed richness at all sites (depth, fetch, percent littoral, distance to boat ramps and distance to marinas). We discuss how the model outcomes can be used to inform survey design for other Great Lakes coastal areas. The survey design we describe provides a useful template that could be adaptively improved for early detection of IAP in the Great Lakes.

8.
Genes Dis ; 9(2): 347-357, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35224151

RESUMO

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

9.
Chronobiol Int ; 39(6): 769-780, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35176952

RESUMO

This study examined the impact of first and second night shift work on sleep and performance in mining haul truck drivers. Sleep-wake patterns were monitored using wrist actigraphy. The Karolinska Sleepiness Scale (KSS), Psychomotor Vigilance Test (PVT) and a truck simulator were administered at the start and end of the first (N1) or second (N2) night shift (19:00-07:00 h). Participants were categorised into those who demonstrated a decline in performance (increase of one or more PVT lapses [reaction time >500 msec] from the start to the end of shift) or those who did not demonstrate a decline in performance (no increase in lapses) from the start to the end of shift. Total sleep time (TST) was longer in the 24 h prior to N1 (9.05 ± 1.49 h) compared to N2 (5.38 ± 1.32 h). PVT lapses and the slowest 10% of reaction times were similar at the start and end of N1, while greater impairments on these outcomes were observed at the end of N2 compared to the end of N1 (p < .05). In contrast, subjective sleepiness was equally impaired at the end of both night shifts. PVT performance (lapses and slowest 10% of reaction times) and drive violations demonstrated a similar direction of change on N1 and N2. Participants who demonstrated a decline in performance showed reduced TST in the 48 h prior to shifts compared to those who demonstrated no decline in performance across the shift. Likely due to short sleep prior, the end of N2 was associated with pronounced performance impairments on the PVT and drive violations compared to the start of the shift. The findings suggest that drive violations may be more sensitive to sleep loss compared to the other driving measures examined in this study. This study also emphasizes the need for adequate recovery sleep between night shifts.


Assuntos
Sonolência , Tolerância ao Trabalho Programado , Ritmo Circadiano , Fadiga , Humanos , Veículos Automotores , Desempenho Psicomotor , Sono , Vigília
10.
Anesth Analg ; 134(5): 1028-1034, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35020621

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality in the United States. Subcutanous unfractionated heparin (UFH) has been used for decades for VTE prophylaxis and under many obstetric quality of care initiatives, hospitalized antepartum patients now receive doses as high as 10,000 units every 12 hours. This practice increases the likelihood of UFH administration around the time that epidural labor analgesia is requested or neuraxial analgesia for cesarean delivery is needed. To clarify the effect of UFH on coagulation, we reviewed the care of hospitalized antepartum patients receiving VTE prophylaxis with UFH to determine the incidence of concurrent abnormal activated partial thromboplastin time (aPTT) values and associated risk factors. METHODS: This retrospective cohort study used data from the University of Chicago Pharmacy database to identify hospitalized antepartum patients receiving subcutaneous UFH from June 1, 2016 to July 1, 2019. Our institutional protocol states that all patients hospitalized for antepartum conditions should receive pharmacologic prophylaxis empirically unless contraindicated. For patients receiving UFH, dosing was based on gestational age: 5000 units every 12 hours for first trimester antepartum patients, 7500 units every 12 hours for second trimester patients, and 10,000 units every 12 hours for patients in the third trimester. As per protocol, aPTT values were obtained 2 hours after the third dose of heparin, and platelet counts after 4 days. Data collection included demographics, comorbidities, heparin doses, aPTT values, platelet counts, creatinine if available, and anesthetic type and complications. Logistic regression was performed to determine the association between elevated aPTT >40 seconds and study variables. RESULTS: Of the 321 antepartum patients who received subcutaneous UFH, 33 (10.3%) had an aPTT >40 seconds, 4 of those 33 patients (12.1%) received 5000 units every 12 hours, 14 (42.2%) received 7500 units every 12 hours, and 15 (45.5%) received 10,000 units every 12 hours. The likelihood of a patient having aPTT >40 seconds was 2.8% with 5000 units every 12 hours, 18.9% with 7500 units every 12 hours, and 14.6% with 10,000 units every 12 hours. CONCLUSIONS: Elevated aPTT values are likely with total daily doses of 15,000 or 20,000 units subcutaneous UFH in hospitalized antepartum patients.


Assuntos
Transtornos da Coagulação Sanguínea , Tromboembolia Venosa , Anticoagulantes , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Estudos de Coortes , Feminino , Heparina , Humanos , Tempo de Tromboplastina Parcial , Gravidez , Estudos Retrospectivos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle
11.
J Exp Med ; 219(2)2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34958350

RESUMO

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.


Assuntos
Modelos Animais de Doenças , Suscetibilidade a Doenças , Viroses/etiologia , Viroses/transmissão , Doenças dos Animais/transmissão , Doenças dos Animais/virologia , Animais , Biomarcadores , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Camundongos , Camundongos Knockout , Interações Microbianas , Roedores , Viroses/metabolismo
12.
Ambio ; 51(3): 531-545, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34155609

RESUMO

As largely documented in the literature, the stark restrictions enforced worldwide in 2020 to curb the COVID-19 pandemic also curtailed the production of air pollutants to some extent. This study investigates the perception of the air pollution as assessed by individuals located in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the USA. The perceptions towards air quality were evaluated by employing an online survey administered in May 2020. Participants (N = 9394) in the ten countries expressed their opinions according to a Likert-scale response. A reduction in pollutant concentration was clearly perceived, albeit to a different extent, by all populations. The survey participants located in India and Italy perceived the largest drop in the air pollution concentration; conversely, the smallest variation was perceived among Chinese and Norwegian respondents. Among all the demographic indicators considered, only gender proved to be statistically significant.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Humanos , Pandemias , Material Particulado/análise , Percepção , SARS-CoV-2
13.
Biodivers Data J ; 10: e87106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36761558

RESUMO

Background: This paper presents a quantitative and detailed description of the Fossil Lithistida Collection in the Natural History Museum, London. This collection started to be built with the first fossil sponges from the Cretaceous of Wiltshire, collected by William Smith in 1816 and 1818 for the first geological map of England. The latest specimen to enter the collection was collected from the Permo-Carboniferous of Norway by Angela Milner, a researcher at the Museum, in 2000. Although they are mostly from the Cretaceous of England, lithistids are represented from the Cambrian to Cenozoic of England. This makes this collection key for studying this group. Lithistid study will help with understanding of biosilicification evolution in sponges to unlock the changing patterns in the silica cycle in the oceans through geological time. New information: A dataset with information about all the Fossil Lithistida Collection is available through the NHM Data Portal and Suppl. material 1. This dataset includes taxonomic identifications, registration numbers of the specimens, geographic and stratigraphic details, information about specimen collectors and donors, type status and publications where the specimens have been referred.

14.
Am Heart J Plus ; 17: 100153, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-38559874

RESUMO

Background: The presence of T-wave abnormalities (TWA) on an athlete's electrocardiogram (ECG) presents as a diagnostic challenge for physicians. Types of TWA patterns classified as abnormal by inexperienced readers have not been systematically analyzed. Methods: ECGs from the 2011-2015 National Football League Scouting Combine (initially interpreted by general cardiologists) were retrospectively reviewed by expert sports cardiologists with strict application of the 2017 International Criteria. Patterns of TWA that were altered from the original interpretation were analyzed. Results: The study included 1643 athletes (mean age 22 years). There was a 67 % reduction in the number of athletes with any TWA (p < 0.001) with 111 ECGs changed to normal. Inferior TWA was the most common interpreted initial ECG abnormality altered followed by anterior and lateral. Discussion: This analysis revealed an initial high rate of TWA by non-expert readers. Tailored education programs to physicians who interpret athlete ECGs should highlight these specific T-wave patterns. We see this as an opportunity to make more clinicians aware of ECG interpretation guidelines as sports trained cardiologists are mostly self-taught.

15.
Accid Anal Prev ; 162: 106399, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34563645

RESUMO

INTRODUCTION: Recent research suggests that COVID-19 associated stay-at-home orders, or shelter-in-place orders, have impacted intra-and-interstate travel as well as motor vehicle crashes (crashes). We sought to further this research and to understand the impact of the stay-at-home order on crashes in the post order period in Connecticut. METHODS: We used a multiple-comparison group, interrupted time-series analysis design to compare crashes per 100 million vehicle miles traveled (VMT) per week in 2020 to the average of 2017-2019 from January 1-August 31. We stratified crash rate by severity and the number of vehicles involved. We modeled two interruption points reflecting the weeks Connecticut implemented (March 23rd, week 12) and rescinded (May 20th, week 20) its stay-at-home order. RESULTS: During the initial week of the stay-at-home order in Connecticut, there was an additional 28 single vehicle crashes compared to previous years (95% confidence interval (CI): [15.8, 36.8]). However, the increase at the order onset was not seen throughout the duration. Rescinding the stay-at-home order by and large did not result in an immediate increase in crash rates. Crash rates steadily returned to previous year averages during the post-stay-at-home period. Fatal crash rates were unaffected by the stay-at-home order and remained similar to previous year rates throughout the study duration. DISCUSSION: The initial onset of the stay-at-home order in Connecticut was associated with a sharp increase in the single vehicle crash rate but that increase was not sustained for the remainder of the stay-at-home order. Likely changes in driver characteristics during and after the order kept fatal crash rates similar to previous years.


Assuntos
Condução de Veículo , COVID-19 , Acidentes de Trânsito , Connecticut/epidemiologia , Humanos , Veículos Automotores , SARS-CoV-2
16.
Genes Dis ; 8(6): 918-930, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34522718

RESUMO

As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However, the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs, especially microRNAs, may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins, Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs), which are critical for small RNA biogenesis. Here, we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of Ago1, Ago2 and Ago3 in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes, we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore, we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization, and ectopic bone formation. Collectively, our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

17.
Am J Transl Res ; 13(5): 4233-4250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150011

RESUMO

Mesenchymal stem cells (MSCs) are capable of differentiating into bone, cartilage and adipose tissues. We identified BMP9 as the most potent osteoinductive BMP although detailed mechanism underlying BMP9-regulated osteogenesis of MSCs is indeterminate. Emerging evidence indicates that autophagy plays a critical role in regulating bone homeostasis. We investigated the possible role of autophagy in osteogenic differentiation induced by BMP9. We showed that BMP9 upregulated the expression of multiple autophagy-related genes in MSCs. Autophagy inhibitor chloroquine (CQ) inhibited the osteogenic activity induced by BMP9 in MSCs. While overexpression of ATG5 or ATG7 did not enhance osteogenic activity induced by BMP9, silencing Atg5 expression in MSCs effectively diminished BMP9 osteogenic signaling activity and blocked the expression of the osteogenic regulator Runx2 and the late marker osteopontin induced by BMP9. Stem cell implantation study revealed that silencing Atg5 in MSCs profoundly inhibited ectopic bone regeneration and bone matrix mineralization induced by BMP9. Collectively, our results strongly suggest a functional autophagy pathway may play an essential role in regulating osteogenic differentiation induced by BMP9 in MSCs. Thus, restoration of dysregulated autophagic activity in MSCs may be exploited to treat fracture healing, bone defects or osteoporosis.

18.
Accid Anal Prev ; 159: 106224, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34192654

RESUMO

BACKGROUND: An inadequate rest break between shifts may contribute to driver sleepiness. This study assessed whether extending the major rest break between shifts from 7-hours (Australian industry standard) to 11-hours, improved drivers' sleep, alertness and naturalistic driving performance. METHODS: 17 heavy vehicle drivers (16 male) were recruited to complete two conditions. Each condition comprised two 13-hour shifts, separated by either a 7- or 11-hour rest break. The initial 13-hour shift was the drivers' regular work. The rest break and following 13-hour shift were simulated. The simulated shift included 5-hours of naturalistic driving with measures of subjective sleepiness, physiological alertness (ocular and electroencephalogram) and performance (steering and lane departures). RESULTS: 13 drivers provided useable data. Total sleep during the rest break was greater in the 11-hour than the 7-hour condition (median hours [25th to 75th percentile] 6.59 [6.23, 7.23] vs. 5.07 [4.46, 5.38], p = 0.008). During the simulated shift subjective sleepiness was marginally better for the 11-hour condition (mean Karolinska Sleepiness Scale [95th CI] = 4.52 [3.98, 5.07] vs. 5.12 [4.56, 5.68], p = 0.009). During the drive, ocular and vehicle metrics were improved for the 11-hour condition (p<0.05). Contrary to expectations, mean lane departures p/hour were increased during the 11-hour condition (1.34 [-0.38,3.07] vs. 0.63 [-0.2,1.47], p = 0.027). CONCLUSIONS: Extending the major rest between shifts substantially increases sleep duration and has a modest positive impact on driver alertness and performance. Future work should replicate the study in a larger sample size to improve generalisability and assess the impact of consecutive 7-hour major rest breaks.


Assuntos
Condução de Veículo , Tolerância ao Trabalho Programado , Acidentes de Trânsito , Austrália , Humanos , Masculino , Veículos Automotores , Sono , Vigília
19.
JAMA Cardiol ; 6(7): 745-752, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33662103

RESUMO

Importance: The major North American professional sports leagues were among the first to return to full-scale sport activity during the coronavirus disease 2019 (COVID-19) pandemic. Given the unknown incidence of adverse cardiac sequelae after COVID-19 infection in athletes, these leagues implemented a conservative return-to-play (RTP) cardiac testing program aligned with American College of Cardiology recommendations for all athletes testing positive for COVID-19. Objective: To assess the prevalence of detectable inflammatory heart disease in professional athletes with prior COVID-19 infection, using current RTP screening recommendations. Design, Setting, and Participants: This cross-sectional study reviewed RTP cardiac testing performed between May and October 2020 on professional athletes who had tested positive for COVID-19. The professional sports leagues (Major League Soccer, Major League Baseball, National Hockey League, National Football League, and the men's and women's National Basketball Association) implemented mandatory cardiac screening requirements for all players who had tested positive for COVID-19 prior to resumption of team-organized sports activities. Exposures: Troponin testing, electrocardiography (ECG), and resting echocardiography were performed after a positive COVID-19 test result. Interleague, deidentified cardiac data were pooled for collective analysis. Those with abnormal screening test results were referred for additional testing, including cardiac magnetic resonance imaging and/or stress echocardiography. Main Outcomes and Measures: The prevalence of abnormal RTP test results potentially representing COVID-19-associated cardiac injury, and results and outcomes of additional testing generated by the initial screening process. Results: The study included 789 professional athletes (mean [SD] age, 25 [3] years; 777 men [98.5%]). A total of 460 athletes (58.3%) had prior symptomatic COVID-19 illness, and 329 (41.7%) were asymptomatic or paucisymptomatic (minimally symptomatic). Testing was performed a mean (SD) of 19 (17) days (range, 3-156 days) after a positive test result. Abnormal screening results were identified in 30 athletes (3.8%; troponin, 6 athletes [0.8%]; ECG, 10 athletes [1.3%]; echocardiography, 20 athletes [2.5%]), necessitating additional testing; 5 athletes (0.6%) ultimately had cardiac magnetic resonance imaging findings suggesting inflammatory heart disease (myocarditis, 3; pericarditis, 2) that resulted in restriction from play. No adverse cardiac events occurred in athletes who underwent cardiac screening and resumed professional sport participation. Conclusions and Relevance: This study provides large-scale data assessing the prevalence of relevant COVID-19-associated cardiac pathology with implementation of current RTP screening recommendations. While long-term follow-up is ongoing, few cases of inflammatory heart disease have been detected, and a safe return to professional sports activity has thus far been achieved.


Assuntos
Atletas/estatística & dados numéricos , COVID-19/epidemiologia , Cardiopatias/epidemiologia , Programas de Rastreamento/métodos , Adulto , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Volta ao Esporte , SARS-CoV-2 , Estados Unidos/epidemiologia , Adulto Jovem
20.
PLoS One ; 16(2): e0245886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33524042

RESUMO

The restrictive measures implemented in response to the COVID-19 pandemic have triggered sudden massive changes to travel behaviors of people all around the world. This study examines the individual mobility patterns for all transport modes (walk, bicycle, motorcycle, car driven alone, car driven in company, bus, subway, tram, train, airplane) before and during the restrictions adopted in ten countries on six continents: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. This cross-country study also aims at understanding the predictors of protective behaviors related to the transport sector and COVID-19. Findings hinge upon an online survey conducted in May 2020 (N = 9,394). The empirical results quantify tremendous disruptions for both commuting and non-commuting travels, highlighting substantial reductions in the frequency of all types of trips and use of all modes. In terms of potential virus spread, airplanes and buses are perceived to be the riskiest transport modes, while avoidance of public transport is consistently found across the countries. According to the Protection Motivation Theory, the study sheds new light on the fact that two indicators, namely income inequality, expressed as Gini index, and the reported number of deaths due to COVID-19 per 100,000 inhabitants, aggravate respondents' perceptions. This research indicates that socio-economic inequality and morbidity are not only related to actual health risks, as well documented in the relevant literature, but also to the perceived risks. These findings document the global impact of the COVID-19 crisis as well as provide guidance for transportation practitioners in developing future strategies.


Assuntos
COVID-19/epidemiologia , Pandemias , Meios de Transporte , Humanos , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários , Viagem
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