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PloS One 2022Though clinically similar, Ebola virus disease and Marburg virus disease are caused by different viruses. Of the 30 documented outbreaks of these diseases in sub-Saharan... (Randomized Controlled Trial)
Randomized Controlled Trial
First-in-human study to evaluate safety, tolerability, and immunogenicity of heterologous regimens using the multivalent filovirus vaccines Ad26.Filo and MVA-BN-Filo administered in different sequences and schedules: A randomized, controlled study.
BACKGROUND
Though clinically similar, Ebola virus disease and Marburg virus disease are caused by different viruses. Of the 30 documented outbreaks of these diseases in sub-Saharan Africa, eight were major outbreaks (≥200 cases; five caused by Zaire ebolavirus [EBOV], two by Sudan ebolavirus [SUDV], and one by Marburg virus [MARV]). Our purpose is to develop a multivalent vaccine regimen protecting against each of these filoviruses. This first-in-human study assessed the safety and immunogenicity of several multivalent two-dose vaccine regimens that contain Ad26.Filo and MVA-BN-Filo.
METHODS
Ad26.Filo combines three vaccines encoding the glycoprotein (GP) of EBOV, SUDV, and MARV. MVA-BN-Filo is a multivalent vector encoding EBOV, SUDV, and MARV GPs, and Taï Forest nucleoprotein. This Phase 1, randomized, double-blind, placebo-controlled study enrolled healthy adults (18-50 years) into four groups, randomized 5:1 (active:placebo), to assess different Ad26.Filo and MVA-BN-Filo vaccine directionality and administration intervals. The primary endpoint was safety; immune responses against EBOV, SUDV, and MARV GPs were also assessed.
RESULTS
Seventy-two participants were randomized, and 60 (83.3%) completed the study. All regimens were well tolerated with no deaths or vaccine-related serious adverse events (AEs). The most frequently reported solicited local AE was injection site pain/tenderness. Solicited systemic AEs most frequently reported were headache, fatigue, chills, and myalgia; most solicited AEs were Grade 1-2. Solicited/unsolicited AE profiles were similar between regimens. Twenty-one days post-dose 2, 100% of participants on active regimen responded to vaccination and exhibited binding antibodies against EBOV, SUDV, and MARV GPs; neutralizing antibody responses were robust against EBOV (85.7-100%), but lower against SUDV (35.7-100%) and MARV (0-57.1%) GPs. An Ad26.Filo booster induced a rapid further increase in humoral responses.
CONCLUSION
This study demonstrates that heterologous two-dose vaccine regimens with Ad26.Filo and MVA-BN-Filo are well tolerated and immunogenic in healthy adults.
CLINICALTRIALS.GOV
NCT02860650.
Topics: Adolescent; Adult; Animals; Antibodies, Neutralizing; Antibodies, Viral; Ebola Vaccines; Ebolavirus; Glycoproteins; Hemorrhagic Fever, Ebola; Humans; Marburgvirus; Middle Aged; Nucleoproteins; Vaccines, Combined; Vaccinia virus; Young Adult
PubMed: 36197845
DOI: 10.1371/journal.pone.0274906 -
Sensors (Basel, Switzerland) Apr 2022Industrial workplaces expose workers to a high risk of injuries such as Work-related Musculoskeletal Disorders (WMSDs). Exoskeletons are wearable robotic technologies... (Review)
Review
Industrial workplaces expose workers to a high risk of injuries such as Work-related Musculoskeletal Disorders (WMSDs). Exoskeletons are wearable robotic technologies that can be used to reduce the loads exerted on the body's joints and reduce the occurrence of WMSDs. However, current studies show that the deployment of industrial exoskeletons is still limited, and widespread adoption depends on different factors, including efficacy evaluation metrics, target tasks, and supported body postures. Given that exoskeletons are not yet adopted to their full potential, we propose a review based on these three evaluation dimensions that guides researchers and practitioners in properly evaluating and selecting exoskeletons and using them effectively in workplaces. Specifically, evaluating an exoskeleton needs to incorporate: (1) efficacy evaluation metrics based on both subjective (e.g., user perception) and objective (e.g., physiological measurements from sensors) measures, (2) target tasks (e.g., manual material handling and the use of tools), and (3) the body postures adopted (e.g., squatting and stooping). This framework is meant to guide the implementation and assessment of exoskeletons and provide recommendations addressing potential challenges in the adoption of industrial exoskeletons. The ultimate goal is to use the framework to enhance the acceptance and adoption of exoskeletons and to minimize future WMSDs in industrial workplaces.
Topics: Benchmarking; Exoskeleton Device; Humans; Industry; Musculoskeletal Diseases; Posture
PubMed: 35408328
DOI: 10.3390/s22072714 -
World Journal of Clinical Cases Apr 2022() is a clinically rare and aggressive fungus mainly found in contaminated water, wetlands, decaying plants, stagnant water, and potted plants in hospitals. The lung,...
BACKGROUND
() is a clinically rare and aggressive fungus mainly found in contaminated water, wetlands, decaying plants, stagnant water, and potted plants in hospitals. The lung, bone, joint, eye, brain, skin, and other sites are easily infected, and there is a marked risk of misdiagnosis. There have been few case reports of infection by of the lumbar vertebrae; most reports have focused on infection of the lung.
CASE SUMMARY
An otherwise healthy 60-year-old man presented with a 4-mo history of lumbosacral pain, stooping, and limited walking. The symptoms were significantly aggravated 10 d prior to hospitalization, and radiating pain in the back of his left lower leg developed, which was so severe that he could not walk. Movement of the lumbar spine was significantly limited, anterior flexion was about 30°; backward extension, right and left lateral curvature, and rotational mobility were about 10°; tenderness of the spinous processes of the lumbar 3-5 vertebrae was evident, and the muscle strength of both lower limbs was grade IV. Imaging suggested bony destruction of the lumbar 3, 4, and 5 vertebrae and sacral 1 vertebra; in addition, the corresponding intervertebral spaces were narrowed and the lumbar 5 vertebra was posteriorly displaced and unstable. Lumbar vertebral infection was also noted, and the possibility of lumbar tuberculosis was considered. We first performed surgical intervention on the lesioned lumbar vertebrae, cleared the infected lesion, and performed stable fixation of the lesioned vertebral body using a lumbar internal fixation device, which restored the stability of the lumbar vertebrae. Cytological and pathological examination of the lesioned tissue removed during surgery confirmed infection of the lumbar vertebrae; on this basis, the patient was administered voriconazole. At the 6-mo follow-up, efficacy was significant, no drug-related side effects were observed, and imaging examination showed no evidence of recurrence.
CONCLUSION
infection can occur in immunocompetent individuals with no history of near drowning. Voriconazole is effective for the treatment of infection of the lumbar vertebrae for which it is suitable as the first-line therapy.
PubMed: 35647125
DOI: 10.12998/wjcc.v10.i10.3251 -
Frontiers in Aging Neuroscience 2019The etiology of neurodegenerative disorders such as dementia is complex and incompletely understood. Interest in a developmental perspective to these pathologies is... (Review)
Review
The etiology of neurodegenerative disorders such as dementia is complex and incompletely understood. Interest in a developmental perspective to these pathologies is gaining momentum. An early supportive social environment seems to have important implications for social, affective and cognitive abilities across the lifespan. Attachment theory may help to explain the link between these early experiences and later outcomes. This theory considers early interactions between an infant and its caregiver to be crucial to shaping social behavior and emotion regulation strategies throughout adult life. Furthermore, research has demonstrated that such early attachment experiences can, potentially through epigenetic mechanisms, have profound neurobiological and cognitive consequences. Here we discuss how early attachment might influence the development of affective, cognitive, and neurobiological resources that could protect against cognitive decline and dementia. We argue that social relations, both early and late in life, are vital to ensuring cognitive and neurobiological health. The concepts of brain and cognitive reserve are crucial to understanding how environmental factors may impact cognitive decline. We examine the role that attachment might play in fostering brain and cognitive reserve in old age. Finally, we put forward the concept of affective reserve, to more directly frame the socio-affective consequences of early attachment as protectors against cognitive decline. We thereby aim to highlight that, in the study of aging, cognitive decline and dementia, it is crucial to consider the role of affective and social factors such as attachment.
PubMed: 31333443
DOI: 10.3389/fnagi.2019.00161 -
Environmental Research Jun 2024Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in...
BACKGROUND
Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in muscle physiology and reduced contractile strength associated with glyphosate exposure, while epidemiological studies have shown associations between glyphosate exposure and adverse health outcomes in critical biological systems affecting muscle function.
METHODS
This study used data from a nationally representative survey of the non-institutionalized U.S. general population (NHANES, n = 2132). Urine glyphosate concentrations were determined by ion chromatography with tandem mass spectrometry. Hand grip strength (HGS) was measured using a Takei Dynamometer, and relative strength estimated as the ratio between HGS in the dominant hand and the appendicular lean mass (ALM) to body mass index (ALMBMI) ratio. Low HGS and low relative HGS were defined as 1 sex-, age- and race-specific SD below the mean. Physical function limitations were identified as significant difficulty or incapacity in various activities.
RESULTS
In fully-adjusted models, the Mean Differences (MD) and 95% confidence intervals [95%CI] per doubling increase in glyphosate concentrations were -0.55 [-1.09, -0.01] kg for HGS in the dominant hand, and -0.90 [-1.58. -0.21] kg for HGS/ALMBMI. The Odds Ratios (OR) [95% CI] for low HGS, low relative HGS and functional limitations by glyphosate concentrations were 1.27 [1.03, 1.57] for low HGS; 1.43 [1.05; 1.94] for low relative HGS; 1.33 [1.08, 1.63] for stooping, crouching or kneeling difficulty; 1.17 [0.91, 1.50] for lifting or carrying items weighting up to 10 pounds difficulty; 1.21 [1.01, 1.40] for standing up from armless chair difficulty; and 1.47 [1.05, 2.29] for ascending ten steps without pause difficulty.
CONCLUSIONS
Glyphosate exposure may be a risk factor for decreased grip strength and increased physical functional limitations. More studies investigating the influence of this and other environmental pollutants on functional aging are needed.
Topics: Glyphosate; Glycine; Humans; Male; Middle Aged; Female; Aged; Herbicides; Hand Strength; Environmental Exposure; Nutrition Surveys
PubMed: 38452917
DOI: 10.1016/j.envres.2024.118547 -
Advances in Skin & Wound Care Oct 2023Dermal substitutes promote dermal regeneration and improve scar quality, but knowledge gaps remain regarding their efficacy and indications for use. The authors... (Randomized Controlled Trial)
Randomized Controlled Trial
Short- and Long-term Outcomes of an Acellular Dermal Substitute versus Standard of Care in Burns and Reconstructions: A Phase I/II Intrapatient Randomized Controlled Trial.
OBJECTIVE
Dermal substitutes promote dermal regeneration and improve scar quality, but knowledge gaps remain regarding their efficacy and indications for use. The authors investigated the safety and short- and long-term efficacy of an acellular dermal substitute in patients with full-thickness wounds.
METHODS
This intrapatient randomized controlled, open-label, phase I (safety) and phase II (efficacy) study compared treatment with Novomaix (Matricel GmbH), a dermal collagen/elastin-based scaffold, with split-thickness skin graft (STSG) only. The primary safety outcome was graft take at 5 to 7 days postsurgery. Postsurgical scar quality was assessed by measuring elasticity, color, and scores on the Patient and Observer Scar Assessment Scale at 3 months, 12 months, and 6 years.
RESULTS
Twenty-five patients were included, of which 24 received treatment allocation. Graft take and wound healing were statistically significantly lower/delayed in the dermal matrix group compared with STSG alone (P < .004). Serious adverse events were delayed epithelialization in four dermal matrix and three STSG study areas. At 12 months postsurgery, skin extension (P = .034) and elasticity (P = .036) were better for the dermal matrix group compared with the group receiving STSG alone. Other scar quality parameters at 12 months and 6 years did not differ between treatment arms.
CONCLUSIONS
The dermal substitute was a safe treatment modality for full-thickness wounds. Compared with STSG alone, time to wound healing was slightly increased. Nevertheless, scar quality at 12 months seemed somewhat improved in the wounds treated with the dermal substitute, indicative of enhanced scar maturation. In the long term, final scar quality was similar for both treatment modalities.
Topics: Humans; Cicatrix; Standard of Care; Plastic Surgery Procedures; Burns; Wound Healing
PubMed: 37729164
DOI: 10.1097/ASW.0000000000000040 -
Environmental Health Insights 2019Barrier insecticide treatments have a long history in mosquito control programs but have been used more frequently in the United States in recent years for control of... (Review)
Review
BACKGROUND AND PURPOSE
Barrier insecticide treatments have a long history in mosquito control programs but have been used more frequently in the United States in recent years for control of invasive "backyard" species (eg, ) and increases in incidence of vector-borne diseases (eg, Zika).
METHODS
We reviewed the published literature for studies investigating barrier treatments for mosquito control during the last 74 years (1944-2018). We searched databases such as PubMed, Web of Science, and Google Scholar to retrieve worldwide literature on barrier treatments.
RESULTS
Forty-four studies that evaluated 20 active ingredients (AIs) and 21 formulated products against multiple mosquito species are included. Insecticides investigated for efficacy included organochlorines (dichlorodiphenyltrichloroethane [DDT], β-hexachlorocyclohexane [BHC]), organophosphates (malathion), and pyrethroids (bifenthrin, deltamethrin, permethrin, lambda-cyhalothrin) as AIs. Study design varied with multiple methods used to evaluate effectiveness of barrier treatments. Barrier treatments were effective at lowering mosquito populations although there was variation between studies and for different mosquito species. Factors other than AI, such as exposure to rainfall and application equipment used, also influenced control efficacy.
CONCLUSIONS
Many of the basic questions on the effectiveness of barrier insecticide applications have been answered, but several important details still must be investigated to improve precision and impact on vector-borne pathogen transmission. Recommendations are made to assist future evaluations of barrier treatments for mosquito control and to limit the potential development of insecticide resistance.
PubMed: 31263373
DOI: 10.1177/1178630219859004 -
Applied Drug Research, Clinical Trials... 2022A major goal of the Clinical and Translational Science Award programs is to build and grow clinical and translational research, including the need to ensure that study...
BACKGROUND
A major goal of the Clinical and Translational Science Award programs is to build and grow clinical and translational research, including the need to ensure that study teams are educated and adhere to best clinical research practices.
OBJECTIVE
One of the primary objectives of the Center for Clinical and Translational Science at the University of Kentucky is to help investigators implement standard operating procedures and provide resources to conduct clinical research that is rigorous, ethical and safe.
METHODS
The University of Kentucky Center for Clinical and Translational Science sought to establish a Quality Assurance/Quality Improvement program for Principal Investigator (PI) initiated clinical research studies using Center for Clinical and Translational Science services. Initiated in 2011, this program's goal was to improve research design quality and from the start of the project, "find it, fix it", leading to improved PI education, without being viewed as punitive.
RESULTS
Since the initiation of our Quality Assurance/Quality Improvement program, PI acceptance has been good and we have expanded its footprint and adjusted our review style to better match the needs of our PIs. This article discusses our experiences with Quality Assurance/Quality Improvement program development and growth.
CONCLUSION
A Quality Assurance/Quality Improvement program can be developed that is efficient, effective, educational and well accepted by all clinical research stakeholders.
PubMed: 36619690
DOI: 10.2174/2667337109666220615125134 -
International Journal of Environmental... Jan 2023A new ergonomic-risk-assessment tool was developed that combines musculoskeletal-model-based loading estimates with insights from fatigue failure theory to evaluate...
A new ergonomic-risk-assessment tool was developed that combines musculoskeletal-model-based loading estimates with insights from fatigue failure theory to evaluate full-body musculoskeletal loading during dynamic tasks. Musculoskeletal-modeling output parameters, i.e., joint contact forces and muscle forces, were combined with tissue-specific injury thresholds that account for loading frequency to determine the injury risk for muscles, lower back, and hip cartilage. The potential of this new risk-assessment tool is demonstrated for defining ergonomic interventions in terms of lifting characteristics, back and shoulder exoskeleton assistance, box transferring, stoop lifting, and an overhead wiring task, respectively. The MATE identifies the risk of WMSDs in different anatomical regions during occupational tasks and allows for the evaluation of the impact of interventions that modify specific lifting characteristics, i.e., load weight versus task repetition. Furthermore, and in clear contrast to currently available ergonomic assessment scores, the effects of the exoskeleton assistance level on the risk of WMSDs of full-body musculoskeletal loading (in particular, the muscles, lower back, and hips) can be evaluated and shows small reductions in musculoskeletal loading but not in injury risk. Therefore, the MATE is a risk-assessment tool based on a full-body, musculoskeletal-modeling approach combined with insights from the fatigue failure theory that shows the proof of concept of a shoulder and back exoskeleton. Furthermore, it accounts for subject-specific characteristics (age and BMI), further enhancing individualized ergonomic-risk assessment.
Topics: Humans; Musculoskeletal Diseases; Ergonomics; Risk Assessment; Back; Shoulder; Occupational Diseases
PubMed: 36674262
DOI: 10.3390/ijerph20021507 -
Philosophical Transactions. Series A,... Jun 2017Scientific investigations in medicine and beyond increasingly require observations to be described by more features than can be simultaneously visualized. Simply...
Scientific investigations in medicine and beyond increasingly require observations to be described by more features than can be simultaneously visualized. Simply reducing the dimensionality by projections destroys essential relationships in the data. Similarly, traditional clustering algorithms introduce data bias that prevents detection of natural structures expected from generic nonlinear processes. We examine how these problems can best be addressed, where in particular we focus on two recent clustering approaches, Phenograph and Hebbian learning clustering, applied to synthetic and natural data examples. Our results reveal that already for very basic questions, minimizing clustering bias is essential, but that results can benefit further from biased post-processing.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'.
Topics: Animals; Bias; Cluster Analysis; Computer Simulation; Epidemiologic Methods; Epidemiologic Studies; Humans; Models, Biological; Models, Statistical
PubMed: 28507238
DOI: 10.1098/rsta.2016.0293