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1.
Am J Prev Med ; 59(6): 873-879, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33220757

RESUMO

INTRODUCTION: Cannabis is frequently used and increasingly legalized in the U.S., and 27.7 million Americans aged ≥12 years are currently using cannabis. However, the public health effects of cannabis use in the general population remain unclear. This study examines the associations of cannabis use with all-cause and cause-specific mortality in U.S. adults. METHODS: The study included 14,818 adults (aged 20-59 years) who participated in the National Health and Nutrition Examination Survey from 2005 to 2014 and were free of cardiovascular disease or cancer at baseline. Survey participants were linked to mortality records through December 31, 2015. The outcomes included all-cause mortality, cardiovascular disease mortality, and cancer mortality. All statistical analyses were conducted in 2019. RESULTS: During 86,453 person-years of observation, 304 deaths occurred, including 39 deaths from cardiovascular disease and 79 deaths from cancer. After adjustment for a variety of potential confounders, the hazard ratios for all-cause mortality, cardiovascular disease mortality, and cancer mortality among cannabis ever users, compared with the ratios among nonusers, were 1.14 (95% CI=0.81, 1.59), 2.29 (95% CI=1.10, 4.78), and 0.67 (95% CI=0.40, 1.14), respectively. The hazard ratios for cardiovascular disease mortality among cannabis users, compared with those among nonusers, were 1.65 (95% CI=0.57, 4.89) if the use was first initiated at age ≥18 years and 3.00 (95% CI=1.41, 6.38) if the use was first initiated before age 18 years. CONCLUSIONS: Cannabis use was significantly associated with an increased risk of cardiovascular disease mortality among U.S. adults, especially among those who started using cannabis before age 18 years. The reasons and mechanisms underlying this association will require future research.

2.
Ann Surg ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33156064

RESUMO

OBJECTIVE: To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history. SUMMARY OF BACKGROUND DATA: Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women. METHODS: This was a post-hoc analysis of Women's Health Initiative participants who were beneficiaries of Medicare Parts A&B fee-for-service. AAA cases and interventions were identified from claims data. Follow-up period included Medicare coverage until death, end of follow-up or end of coverage inclusive of 2017. RESULTS: Of 101,119 participants included in the analysis, the mean age was 63 years and median follow-up was 11.3 years. Just under 10,000 (9.4%) women experienced premature menopause and 22,240 (22%) experienced early menarche. Women with premature menopause were more likely to be overweight, Black, have ≥20 pack years of smoking, history of cardiovascular disease, hypertension, and early menarche. During 1,091,840 person-years of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent surgical intervention and 45 (48%) required intervention for ruptured AAA. Premature menopause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the association was no longer significant after multivariable adjustment for demographics and cardiovascular disease risk factors. Amongst women with ≥20 pack year smoking history (n = 19,286), 2148 (11.1%) had premature menopause, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)]. Early menarche was not associated with increased risk of AAA. CONCLUSIONS: This study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. There was no significant association between premature menopause and risk of AAA amongst women who have never smoked. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the comprehensive vascular care of women.

3.
Am J Epidemiol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025002

RESUMO

The health benefits and risks of menopausal hormone therapy among women aged 50-59 years are examined in the Women's Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy post-menopausal women aged 50-79 at 40 U.S. clinical centers during 1993-1998, including 10,739 post-hysterectomy participants in a trial of conjugated equine estrogens, and 16,608 participants with uterus in the trial of these estrogens plus medroxyprogesterone acetate. Over an 18-year (median) follow-up period (1993-2016) risk for a global index, defined as the earliest of coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and all-cause mortality, is reduced with conjugated equine estrogens with hazard ratio (95% confidence interval) of 0.82 (0.71, 0.95), and with nominally significant reductions for coronary heart disease, breast cancer, hip fracture and all-cause mortality. Corresponding global index hazard ratio estimates of 1.06 (0.95, 1.19) were non-significant for combined estrogens plus progestin, but increased breast cancer risk and reduced endometrial cancer risk were observed. These results, among women 50-59, substantially agree with the worldwide observational literature, with the exception of breast cancer for estrogens alone.

4.
Physiol Rep ; 8(20): e14612, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33080110

RESUMO

Studies suggest that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has vasoprotective potential, as low levels of TRAIL cause accelerated vascular calcification, whereas exogenous TRAIL administration exhibits anti-atherosclerotic activity. The mechanism of TRAIL-mediated vasoprotection remains unclear. We studied the effects of TRAIL (100 ng/ml) on human aortic endothelial cells (HAECs) exposed to pro-atherogenic conditions; (a) oscillatory shear stress (±10 dynes/cm2 ) using the ibidi µ-slide fluidic system; (b) pro-inflammatory injury, that is, tumor necrosis factor alpha (TNF-α, 100 ng/ml) and hyperglycemia (30 mM d-glucose). End-points examined included inflammatory gene expression and reactive oxygen species (ROS) formation. TRAIL shifted the net gene expression toward an antioxidant phenotype in HAECs exposed to oscillatory shear stress. TRAIL significantly reduced ROS formation in HAECs exposed to both TNF-α and hyperglycemia. Therefore, TRAIL appears to confer atheroprotective effects on the endothelium, at least in part, by reducing oxidative stress.

5.
J Orthop Trauma ; 34(11): e401-e406, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33065664

RESUMO

OBJECTIVES: To compare the biomechanical failure properties of the fibular intramedullary nail with locking plate and lag screw fixation in the management of unstable elderly distal fibular fractures. METHODS: Twelve fresh-frozen cadaveric lower limbs (6 matched-pairs) were studied. A simulated OTA/AO 44-B fracture was created, then randomly allocated within each pair to intramedullary nail or locking plate fixation supplemented with an interfragmentary lag screw. The limbs were secured with the foot rigidly held in 20 degrees of supination, loaded to 700N and subjected to progressive external rotation until failure. RESULTS: The mean specimen age was 86.5 years (61-97). Mean torque to failure was greater in the intramedullary nail group, but did not reach statistical significance (23.5 N·m vs. 21.6 N·m; P = 0.463). The nail failed at a significantly greater angle of rotation compared with plate fixation (66.5 degrees vs. 53.3 degrees; P = 0.046). There was no significant difference between the groups with respect to construct stiffness (P = 0.673) or energy absorbed (P = 0.075). The locking plate specimens failed through plate and screw construct pull off at the implant-bone interface. In contrast, the intramedullary nail specimens failed at the lateral ligament complex, whereas the fracture-implant construct remained intact. CONCLUSION: Intramedullary nailing and locking plate fixation have similar biomechanical characteristics when tested to failure. The benefits of the minimally invasive surgery offered by the intramedullary nail make it an attractive implant in the management of these patients.

6.
J Am Geriatr Soc ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037632

RESUMO

BACKGROUND/OBJECTIVES: In the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability. DESIGN: Pragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries. SETTING: A total of 86 primary care practices within 10 U.S. healthcare systems. PARTICIPANTS: A random subsample of 743 persons aged 75 and older. MEASUREMENTS: The well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument. RESULTS: Participants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference. CONCLUSIONS: STRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being.

7.
JAMA Netw Open ; 3(9): e2016747, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926116

RESUMO

Importance: Understanding changes in frailty in relation to cancer diagnosis can inform optimal selection of cancer treatments and survivorship care. Objective: To investigate associations of prediagnostic frailty and change in frailty status with mortality after a cancer diagnosis. Design, Setting, and Participants: This multicenter, prospective cohort study included 7257 community-dwelling, postmenopausal women in the United States who had frailty assessed at the Women's Health Initiative (WHI) enrollment (1993-1998) and the 3-year visit who were subsequently diagnosed as having invasive cancer. The data were analyzed from January 7, 2019, to June, 8, 2020. Exposure: Frailty scores were defined from validated questionnaire items conceptually aligned with the Fried frailty phenotype, including at least 3 of the following characteristics: self-reported unintentional weight loss, exhaustion, low physical activity, and muscle weakness or impaired walking. Physical function components of the frailty score were updated a median of 10 (range, 1-18) times. Main Outcomes and Measures: Using multivariable-adjusted Cox proportional hazards models, this study examined associations of prediagnostic frailty (at the 3-year visit, before cancer diagnosis) and prediagnostic changes in frailty (from enrollment to the 3-year visit) with mortality. Women were followed up beginning from cancer diagnosis for mortality outcomes through March 2018. In linear mixed-effects models with frailty scores as a function of time since cancer diagnosis, this study evaluated whether the time slope, ie, the rate of change in frailty score, increased after cancer diagnosis. Results: This study included 7257 women in the WHI cohort who completed frailty assessments at enrollment and the 3-year WHI visit before cancer diagnosis and subsequently developed cancer. Cancer cases included 2644 breast cancers (36%), 822 lung cancers (11%), 691 colorectal cancers (10%), 445 endometrial cancers (6%), and 286 ovarian cancers (4%). At the 3-year visit, prior to cancer diagnosis, the mean (SD) age was 63 (7) years, and 1161 of 7257 (16%) of participating women met criteria for frailty; 2129 of 7257 (29%) were prefrail, and 3967 of 7257 (55%) were nonfrail. Over a median follow-up of 5.8 years after cancer diagnosis (range, 1 day to 19.9 years), 3056 women died. After multivariable adjustment, women who were frail (vs nonfrail) before cancer diagnosis had an increased risk of mortality after cancer diagnosis (hazard ratio [HR], 1.40; 95% CI, 1.26-1.55; P for trend <.001). Sustained frailty (21% [1537 of 7257] of women) or worsening frailty (22% [1578 of 7257]) vs being consistently nonfrail (45% [3266 of 7257]) before cancer diagnosis increased the risk of mortality after cancer diagnosis (HR, 1.25; 95% CI, 1.14-1.38 and 1.22; 95% CI, 1.11-1.34, respectively; P for trend <.001). In linear mixed-effects models, the rate of increase in physical frailty over time was statistically significantly higher after cancer diagnosis. Conclusions and Relevance: Sustained and worsening frailty before cancer diagnosis was associated with an increased risk of mortality after cancer diagnosis in postmenopausal women. Furthermore, the rate of decline in physical function accelerated after cancer diagnosis. Frailty assessment could provide valuable information and perhaps prompt interventions to reduce and preempt worsening of physical frailty after cancer diagnosis.

8.
J Am Heart Assoc ; 9(19): e014629, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32975173

RESUMO

Background Food insecurity is a global leading public health challenge that affects not only developing countries but also developed countries, including the United States. About 50 million Americans are food insecure. In this study we examined the associations of the adult food insecurity with all-cause and cardiovascular disease mortality in a nationally representative sample of US adults. Methods and Results We included 27 188 US adults (age ≥40 years of age) who participated in the US National Health and Nutrition Examination Survey from 1999 to 2014. Food insecurity status was assessed using the Food Security Survey Module developed by the US Department of Agriculture. Mortality from all causes and cardovascular disease was ascertained through data linkage to the National Death Index through December 31, 2015. We used multivariable Cox proportional hazards regression with sampling weights to estimate hazard ratios (HRs) and 95% CIs of all-cause and cardiovascular disease mortality, according to food security status. During 205 389 person-years of the period, 5039 deaths occurred, including 1084 cardiovascular disease deaths. After adjustment for age, sex, race/ethnicity, education, income, and dietary and lifestyle factors, participants with very low food security had higher risk of all-cause and cardiovascular disease mortality, with multivariable-adjusted HRs of 1.32 (95% CI, 1.07-1.62), and 1.53 (95% CI, 1.04-2.26), respectively, compared with those with high food security. Conclusions Food insecurity is significantly associated with increased risk of excess death from cardiovascular disease and all causes in US adults.

9.
Medicina (Kaunas) ; 56(9)2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32932766

RESUMO

The role of the microbiome in health and disease helps to provide a scientific understanding of key concepts in Ayurveda. We now recognize that virtually every aspect of our physiology and health is influenced by the collection of microorganisms that live in various parts of our body, especially the gut microbiome. There are many external factors which influence the composition of the gut microbiome but one of the most important is diet and digestion. Ayurveda and other systems of traditional health have for thousands of years focused on diet and digestion. Recent research has helped us understand the connection between the microbiome and the many different prevention and therapeutic treatment approaches of Ayurveda.

10.
J Vasc Surg ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32882349

RESUMO

OBJECTIVE: Few studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative. METHODS: Women's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a). RESULTS: The mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations. CONCLUSIONS: We found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences.

11.
J Am Heart Assoc ; 9(14): e016845, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32662311

RESUMO

Background The Short Physical Performance Battery (SPPB) is an inexpensive, reliable, and easy-to-implement measure of lower-extremity physical function. Strong evidence links SPPB scores with all-cause mortality, but little is known about its relationship with incident cardiovascular disease (CVD). Methods and Results Women (n=5043, mean age=79±7) with no history of myocardial infarction or stroke completed 3 timed assessments-standing balance, strength (5 chair stands), and usual gait speed (4 m walk)-yielding an SPPB score from 0 (worst) to 12 (best). Women were followed for CVD events (myocardial infarction, stroke, or CVD death) up to 6 years. Hazard ratios were estimated for women with Very Low (0-3), Low (4-6), Moderate (7-9), and High (10-12) SPPB scores using Cox proportional hazard models adjusted for demographic, behavioral, and health-related variables including objective measurements of physical activity, blood pressure, lipids, and glucose levels. Restricted cubic splines tested linearity of associations. With 361 CVD cases, crude incidence rates/1000 person-years were 41.0, 24.3, 16.1, and 8.6 for Very Low, Low, Moderate, and High SPPB categories, respectively. Corresponding fully adjusted hazard ratios (95% CIs) were 2.28 (1.50-3.48), 1.70 (1.23-2.36) 1.49 (1.12-1.98), and 1.00 (referent); P-trend <0.001. The dose-response relationship was linear (linear P<0.001; nonlinear P>0.38). Conclusions Results suggest SPPB may provide a measure of cardiovascular health in older adults beyond that captured by traditional risk factors. Because of its high test-retest reliability and low administrative burden, the SPPB should be a routine part of office-based CVD risk assessment.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32667778

RESUMO

Hexagonal boron nitride (h-BN) has been considered a promising dielectric for two-dimensional (2D) material-based electronics due to its atomically smooth and charge-free interface with an in-plane lattice constant similar to that of graphene. Here, we report atomic layer deposition of boron nitride (ALD-BN) using BCl3 and NH3 precursors directly on thermal SiO2 substrates at a relatively low temperature of 600 °C. The films were characterized by x-ray photoelectron spectroscopy, atomic force microscopy, and transmission electron microscopy wherein the uniform, atomically smooth, and nanocrystalline layered-BN thin film growth is observed. The growth rate is ~0.042 nm/cycle at 600 °C, a temperature significantly lower than that of h-BN grown by chemical vapor deposition (CVD). The dielectric properties of the ALD-BN measured from Metal Oxide Semiconductor Capacitors (MOSCAPs) are comparable with that of SiO2. Moreover, the ALD-BN exhibits a two-fold increase in carrier mobility of graphene field effect transistors (G-FETs/ALD-BN/SiO2) due to the less surface charge density and inert surface of ALD-BN in comparison to that of G-FETs fabricated on bare SiO2. Therefore, this work suggests that the transfer-free deposition of ALD-BN on SiO2 may be a promising candidate as a substrate for high performance graphene devices.

13.
N Engl J Med ; 383(2): 129-140, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640131

RESUMO

BACKGROUND: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).


Assuntos
Acidentes por Quedas/prevenção & controle , Lesões Acidentais/prevenção & controle , Administração dos Cuidados ao Paciente/métodos , Acidentes por Quedas/mortalidade , Acidentes por Quedas/estatística & dados numéricos , Lesões Acidentais/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Vida Independente , Masculino , Medicina de Precisão , Medição de Risco , Fatores de Risco
14.
Nat Commun ; 11(1): 3097, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32555194

RESUMO

Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose. This revealed that BMAT resists insulin- and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Medula Óssea/metabolismo , Glucose/metabolismo , Animais , Western Blotting , Feminino , Homeostase/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tomografia por Emissão de Pósitrons , Ratos , Esqueleto/metabolismo
15.
Burns ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32475797

RESUMO

BACKGROUND: Burn injuries are a major cause of morbidity and mortality worldwide. Despite advances in therapeutic strategies for the management of patients with severe burns, the sequelae are pathophysiologically profound, up to the systemic and metabolic levels. Management of patients with a severe burn injury is a long-term, complex process, with treatment dependent on the degree and location of the burn and total body surface area (TBSA) affected. In adverse conditions with limited resources, efficient triage, stabilisation, and rapid transfer to a specialised intensive care burn centre is necessary to provide optimal outcomes. This initial lag time and the form of primary treatment initiated, from injury to specialist care, is crucial for the burn patient. This study aims to investigate the efficacy of a novel visco-elastic burn dressing with a proprietary bio-stimulatory marine mineral complex (MXC) as a primary care treatment to initiate a healthy healing process prior to specialist care. METHODS: A new versatile emergency burn dressing saturated in a >90% translucent water-based, sterile, oil-free gel and carrying a unique bio-stimulatory marine mineral complex (MXC) was developed. This dressing was tested using LabSkin as a burn model platform. LabSkin a novel cellular 3D-dermal organotypic full thickness human skin equivalent, incorporating fully-differentiated dermal and epidermal components that functionally models skin. Cell and molecular analysis was carried out by in vitro Real-Time Cellular Analysis (RTCA), thermal analysis, and focused transcriptomic array profiling for quantitative gene expression analysis, interrogating both wound healing and fibrosis/scarring molecular pathways. In vivo analysis was also performed to assess the bio-mechanical and physiological effects of this novel dressing on human skin. RESULTS: This hybrid emergency burn dressing (EBD) with MXC was hypoallergenic, and improved the barrier function of skin resulting in increased hydration up to 24 h. It was demonstrated to effectively initiate cooling upon application, limiting the continuous burn effect and preventing local tissue from damage and necrosis. xCELLigence RTCA® on primary human dermal cells (keratinocyte, fibroblast and micro-vascular endothelial) demonstrated improved cellular function with respect to tensegrity, migration, proliferation and cell-cell contact (barrier formation) [1]. Quantitative gene profiling supported the physiological and cellular function finding. A beneficial quid pro quo regulation of genes involved in wound healing and fibrosis formation was observed at 24 and 48 h time points. CONCLUSION: Utilisation of this EBD + MXC as a primary treatment is an effective and easily applicable treatment in cases of burn injury, proving both a cooling and hydrating environment for the wound. It regulates inflammation and promotes healing in preparation for specialised secondary burn wound management. Moreover, it promotes a healthy remodelling phenotype that may potentially mitigate scarring. Based on our findings, this EBD + MXC is ideal for use in all pre-hospital, pre-surgical and resource limited settings.

16.
Sci Total Environ ; 737: 139702, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32531510

RESUMO

Observed multiple adverse effects of livestock production have led to increasing calls for more sustainable livestock production. Quantitative analysis of adverse effects, which can guide public debate and policy development in this area, is limited and generally scattered across environmental, human health, and other science domains. The aim of this study was to bring together and, where possible, quantify and aggregate the effects of national-scale livestock production on 17 impact categories, ranging from impacts of particulate matter, emerging infectious diseases and odor annoyance to airborne nitrogen deposition on terrestrial nature areas and greenhouse gas emissions. Effects were estimated and scaled to total Dutch livestock production, with system boundaries including feed production, manure management and transport, but excluding slaughtering, retail and consumption. Effects were expressed using eight indicators that directly express Impact in the sense of the Drivers-Pressures-State-Impact-Response framework, while the remaining 14 express Pressures or States. Results show that livestock production may contribute both positively and negatively to human health with a human disease burden (expressed in disability-adjusted life years) of up to 4% for three different health effects: those related to particulate matter, zoonoses, and occupational accidents. The contribution to environmental impact ranges from 2% for consumptive water use in the Netherlands to 95% for phosphorus transfer to soils, and extends beyond Dutch borders. While some aggregation across impact categories was possible, notably for burden of disease estimates, further aggregation of disparate indicators would require normative value judgement. Despite difficulty of aggregation, the assessment shows that impacts receive a different contribution of different animal sectors. While some of our results are country-specific, the overall approach is generic and can be adapted and tuned according to specific contexts and information needs in other regions, to allow informed decision making across a broad range of impact categories.


Assuntos
Gado , Esterco , Animais , Meio Ambiente , Humanos , Países Baixos , Solo
17.
J Orthop Trauma ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32427817

RESUMO

OBJECTIVES: To compare the biomechanical failure properties of the fibular intramedullary nail with locking plate and lag screw fixation in the management of unstable elderly distal fibular fractures. METHODS: Twelve fresh-frozen cadaveric lower limbs (six matched-pairs) were studied. A simulated OTA/AO 44-B fracture was created, then randomly allocated within each pair to intramedullary nail or locking plate fixation supplemented with an interfragmentary lag screw. The limbs were secured with the foot rigidly held in 20 of supination, loaded to 700N and subjected to progressive external rotation until failure. RESULTS: The mean specimen age was 86.5 years (61-97). Mean torque to failure was greater in the intramedullary nail group but did not reach statistical significance (23.5 Nm vs. 21.6 Nm; p=0.463). The nail failed at a significantly greater angle of rotation compared with plate fixation (66.5 vs. 53.3; p=0.046). There was no significant difference between the groups with respect to construct stiffness (p=0.673) or energy absorbed (p=0.075). The locking plate specimens failed through plate and screw construct pull off at the implant-bone interface. In contrast, the intramedullary nail specimens failed at the lateral ligament complex, whilst the fracture-implant construct remained intact. CONCLUSION: Intramedullary nailing and locking plate fixation have similar biomechanical characteristics when tested to failure. The benefits of the minimally invasive surgery offered by the intramedullary nail make it an attractive implant in the management of these patients. LEVEL OF EVIDENCE: V - Cadaveric study.

18.
J Mech Behav Biomed Mater ; 109: 103751, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32347212

RESUMO

Trabecular bone is a cellular composite material comprising primarily of mineral and organic phases and its mechanical response to loads is time-dependent. The contribution of the organic phase to the time-dependent behaviour of bone is not yet understood. We investigated the time-dependent response of demineralised trabecular bone through tensile multiple-load-creep-unload-recovery experiments. We found that demineralised trabecular bone's time-dependent response is nonlinearly related to the applied stress levels - it stiffens with increased stress levels. Our results also indicated that the time-dependent behaviour is associated with the original bone volume ratio (BV/TV). Irrecoverable strain exists, even at the low strain levels, but are not associated with BV/TV. Furthermore, we found that the nonlinear viscoelastic model can accurately predict the time-dependent behaviour of the trabecular bone's organic phase, which can be incorporated together with the properties of mineral to generate a composite model of bone. This study will help to provide a better understanding of this natural composite material.

19.
Am J Epidemiol ; 189(9): 972-981, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32314781

RESUMO

Dual-outcome intention-to-treat hazard rate analyses have potential to complement single-outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes to obtain further insight into influences of menopausal hormone therapy on chronic disease. As part of the Women's Health Initiative, randomized, placebo-controlled hormone therapy trials of conjugated equine estrogens (CEE) among posthysterectomy participants and of these same estrogens plus medroxyprogesterone acetate (MPA) among participants with an intact uterus were carried out at 40 US clinical centers (1993-2016). These data provide the context for analyses covering the trial intervention periods and a nearly 20-year (median) cumulative duration of follow-up. The rates of multiple outcome pairs were significantly influenced by hormone therapy, especially over cumulative follow-up, providing potential clinical and mechanistic insights. For example, among women randomized to either regimen, hazard ratios for pairs defined by fracture during intervention followed by death from any cause were reduced and hazard ratios for pairs defined by gallbladder disease followed by death were increased, though these findings may primarily reflect single-outcome associations. In comparison, hazard ratios for diabetes followed by death were reduced with CEE but not with CEE + MPA, and those for hypertension followed by death were increased with CEE + MPA but not with CEE.


Assuntos
Terapia de Reposição de Estrogênios , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Doenças Cardiovasculares/epidemiologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Fraturas Ósseas/epidemiologia , Doenças da Vesícula Biliar/epidemiologia , Humanos , Incidência , Análise de Intenção de Tratamento , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco , Estados Unidos/epidemiologia
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