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Journal of the Experimental Analysis of... May 2022Cocaine use is an unrelenting public health concern. To inform intervention and prevention efforts, it is crucial to develop an understanding of the clinical... (Review)
Review
Cocaine use is an unrelenting public health concern. To inform intervention and prevention efforts, it is crucial to develop an understanding of the clinical neuropharmacology of the reinforcing effects of cocaine. The purpose of this review is to evaluate and synthesize human laboratory studies that assess pharmacological manipulations of cocaine self-administration. Forty-one peer-reviewed, human cocaine self-administration studies in which participants received a pretreatment drug were assessed. The pharmacological action and treatment regimen for all drugs reviewed were considered. Drugs that increase extracellular dopamine tend to have the most consistent effects on cocaine self-administration. The ability of nondopaminergic drugs to impact cocaine reinforcement might be related to their downstream effects on dopamine, though it is difficult to draw conclusions because pharmacologically selective compounds are not widely available for human testing. The ability of acute versus chronic drug treatment to differentially affect human cocaine self-administration was not determined because buprenorphine was the only pretreatment drug that was assessed under both acute and chronic dosing regimens. Future research directly comparing acute and chronic drug treatment and/or comparing drugs with different mechanisms of action, is needed to make more conclusive determinations about the clinical neuropharmacology of cocaine reinforcement.
Topics: Cocaine; Dopamine; Dose-Response Relationship, Drug; Humans; Neuropharmacology; Reinforcement, Psychology; Self Administration
PubMed: 35229294
DOI: 10.1002/jeab.744 -
Journal of Medicine and Life May 2022Parkinson's disease (PD) is a progressive neurological disease characterized by muscle stiffness, tremor, slowness of movement, and difficulties with posture and...
Parkinson's disease (PD) is a progressive neurological disease characterized by muscle stiffness, tremor, slowness of movement, and difficulties with posture and walking. Muscle and joint pain are frequent non-motor symptoms of PD. Pain associated with PD is mainly caused by a combination of truncal dystonia, stooped posture, and muscle rigidity. However, PD deformities were rarely discussed in the literature. A 68-year-old Asian female with PD treated with Levodopa for six years complained of progressive neck pain, contractures, and subluxation of both hands in the last two years. A positron emission tomography (PET) scan revealed decreased rostrocaudal gradient uptake in both posterior putamen. After 9 months of multimodal chiropractic rehabilitation, the patient had significant improvement in symptoms, including pain resolution as per the numeric rating scale and physical and mental improvement as per the PD questionnaire. Radiographic measurement showed significantly improved postural alignment and stability. Measurement of joint motion and angles showed an improvement in hand deformity. Although PD is a neurodegenerative disease that is not curable, multimodal rehabilitation may improve neurological and musculoskeletal functions by inducing proprioceptive balance, motor strength, and joint movement. The current study may illustrate multimodal rehabilitation addressing orthopedic deformity associated with symptoms in a PD patient.
Topics: Aged; Chiropractic; Female; Humans; Neurodegenerative Diseases; Pain; Parkinson Disease; Posture
PubMed: 35815091
DOI: 10.25122/jml-2021-0418 -
Science Advances May 2023Genome-wide phenotypic screens in the budding yeast , enabled by its knockout collection, have produced the largest, richest, and most systematic phenotypic description...
Genome-wide phenotypic screens in the budding yeast , enabled by its knockout collection, have produced the largest, richest, and most systematic phenotypic description of any organism. However, integrative analyses of this rich data source have been virtually impossible because of the lack of a central data repository and consistent metadata annotations. Here, we describe the aggregation, harmonization, and analysis of ~14,500 yeast knockout screens, which we call Yeast Phenome. Using this unique dataset, we characterized two unknown genes ( and ) and showed that tryptophan starvation is a by-product of many chemical treatments. Furthermore, we uncovered an exponential relationship between phenotypic similarity and intergenic distance, which suggests that gene positions in both yeast and human genomes are optimized for function.
Topics: Humans; Saccharomyces cerevisiae
PubMed: 37235661
DOI: 10.1126/sciadv.adg5702 -
Applied Ergonomics May 2022Improper manual material handling (MMH) techniques are shown to lead to low back pain, the most common work-related musculoskeletal disorder. Due to the complex nature...
Improper manual material handling (MMH) techniques are shown to lead to low back pain, the most common work-related musculoskeletal disorder. Due to the complex nature and variability of MMH and obtrusiveness and subjectiveness of existing hazard analysis methods, providing systematic, continuous, and automated risk assessment is challenging. We present a machine learning algorithm to detect and classify MMH tasks using minimally-intrusive instrumented insoles and chest-mounted accelerometers. Six participants performed standing, walking, lifting/lowering, carrying, side-to-side load transferring (i.e., 5.7 kg and 12.5 kg), and pushing/pulling. Lifting and carrying loads as well as hazardous behaviors (i.e., stooping, overextending and jerky lifting) were detected with 85.3%/81.5% average accuracies with/without chest accelerometer. The proposed system allows for continuous exposure assessment during MMH and provides objective data for use with analytical risk assessment models that can be used to increase workplace safety through exposure estimation.
Topics: Accelerometry; Humans; Lifting; Musculoskeletal Diseases; Shoes; Walking; Workplace
PubMed: 35144123
DOI: 10.1016/j.apergo.2022.103693 -
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 -
Neuron Mar 2022In this issue of Neuron, Yu et al. (2022) uncovered a sensory pathway by which social touch can activate oxytocin neurons in the hypothalamus. Their stimulation...
In this issue of Neuron, Yu et al. (2022) uncovered a sensory pathway by which social touch can activate oxytocin neurons in the hypothalamus. Their stimulation protocol could deliver pleasant sensory stimuli to juvenile mice, increasing their later-life social interactions.
Topics: Animals; Hypothalamus; Mice; Neurons; Oxytocin; Touch; Touch Perception
PubMed: 35298915
DOI: 10.1016/j.neuron.2022.02.021 -
Environmental Research Mar 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.
PubMed: 38452917
DOI: 10.1016/j.envres.2024.118547 -
Annals of Surgery Oct 2023Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis of the Role of Total Pancreatectomy as an Alternative to Pancreatoduodenectomy in Patients at High Risk for Postoperative Pancreatic Fistula: Is it a Justifiable Indication?
OBJECTIVE
Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF).
SUMMARY BACKGROUND DATA
TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking.
METHODS
Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien-Dindo grade ≥IIIa) on the short-term and quality of life.
RESULTS
After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PD did not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P =0.857).
CONCLUSIONS
This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bail-out procedure, the comparable long-term quality of life is reassuring.
Topics: Humans; Pancreatectomy; Pancreaticoduodenectomy; Pancreatic Fistula; Quality of Life; Pancreas; Postoperative Complications
PubMed: 37161977
DOI: 10.1097/SLA.0000000000005895 -
Scientific Reports Oct 2023Linguistic experience plays a clear role in accounting for variability in sentence comprehension behavior across individuals and across sentence types. We aimed to...
Linguistic experience plays a clear role in accounting for variability in sentence comprehension behavior across individuals and across sentence types. We aimed to understand how individual differences in reading experience predict reading behavior. Corpus analyses revealed the frequencies with which our experimental items appeared in written and spoken language. We hypothesized that reading experience should affect sentence comprehension most substantially for sentence types that individuals primarily encounter through written language. Readers with more text exposure were faster and more accurate readers overall, but they read sentence types biased to written language particularly faster than did readers with less text exposure. We see clear effects of text exposure on sentence comprehension in ways that allow explicit links between written and spoken corpus statistics and behavior. We discuss theoretical implications of effects of text exposure for experience-based approaches to sentence processing.
Topics: Humans; Comprehension; Individuality; Language; Linguistics; Reading
PubMed: 37798346
DOI: 10.1038/s41598-023-43801-8 -
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