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1.
Biomed Phys Eng Express ; 10(5)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38906125

ABSTRACT

Purpose/Objective. Small-field measurement poses challenges. Although many high-resolution detectors are commercially available, the EPID for small-field dosimetry remains underexplored. This study aimed to evaluate the performance of EPID for small-field measurements and to derive tailored correction factors for precise small-field dosimetry verification.Material/Methods. Six high-resolution radiation detectors, including W2 and W1 plastic scintillators, Edge-detector, microSilicon, microDiamond and EPID were utilized. The output factors, depth doses and profiles, were measured for various beam energies (6 MV-FF, 6 MV-FFF, 10 MV-FF, and 10 MV-FFF) and field sizes (10 × 10 cm2, 5 × 5 cm2, 4 × 4 cm2, 3 × 3 cm2, 2 × 2 cm2, 1 × 1 cm2, 0.5 × 0.5 cm2) using a Varian Truebeam linear accelerator. During measurements, acrylic plates of appropriate depth were placed on the EPID, while a 3D water tank was used with five-point detectors. EPID measured data were compared with W2 plastic scintillator and measurements from other high-resolution detectors. The analysis included percentage deviations in output factors, differences in percentage for PDD and for the profiles, FWHM, maximum difference in the flat region, penumbra, and 1D gamma were analyzed. The output factor and depth dose ratios were fitted using exponential functions and fractional polynomial fitting in STATA 16.2, with W2 scintillator as reference, and corresponding formulae were obtained. The established correction factors were validated using two Truebeam machines.Results. When comparing EPID and W2-PSD across all field-sizes and energies, the deviation for output factors ranged from 1% to 15%. Depth doses, the percentage difference beyond dmax ranged from 1% to 19%. For profiles, maximum of 4% was observed in the 100%-80% region. The correction factor formulae were validated with two independent EPIDs and closely matched within 3%.Conclusion. EPID can effectively serve as small-field dosimetry verification tool with appropriate correction factors.


Subject(s)
Particle Accelerators , Radiometry , Radiometry/instrumentation , Radiometry/methods , Particle Accelerators/instrumentation , Equipment Design , Phantoms, Imaging , Calibration , Humans , Scintillation Counting/instrumentation , Scintillation Counting/methods , Reproducibility of Results
2.
Front Immunol ; 15: 1352330, 2024.
Article in English | MEDLINE | ID: mdl-38694513

ABSTRACT

Introduction: COVID-19 patients can develop autoantibodies against a variety of secreted and membrane proteins, including some expressed on lymphocytes. However, it is unclear what proportion of patients might develop anti-lymphocyte antibodies (ALAb) and what functional relevance they might have. Methods: We evaluated the presence and lytic function of ALAb in the sera of a cohort of 85 COVID-19 patients (68 unvaccinated and 17 vaccinated) assigned to mild (N=63), or moderate/severe disease (N=22) groups. Thirty-seven patients were followed-up after recovery. We also analyzed in vivo complement deposition on COVID-19 patients' lymphocytes and examined its correlation with lymphocyte numbers during acute disease. Results: Compared with healthy donors (HD), patients had an increased prevalence of IgM ALAb, which was significantly higher in moderate/severe disease patients and persisted after recovery. Sera from IgM ALAb+ patients exhibited complement-dependent cytotoxicity (CDC) against HD lymphocytes. Complement protein C3b deposition on patients' CD4 T cells was inversely correlated with CD4 T cell numbers. This correlation was stronger in moderate/severe disease patients. Discussion: IgM ALAb and complement activation against lymphocytes may contribute to the acute lymphopenia observed in COVID-19 patients.


Subject(s)
Autoantibodies , COVID-19 , Complement Activation , Immunoglobulin M , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/blood , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Female , Middle Aged , Autoantibodies/blood , Autoantibodies/immunology , Complement Activation/immunology , SARS-CoV-2/immunology , Aged , Adult , Lymphocytes/immunology , Prevalence , CD4-Positive T-Lymphocytes/immunology , Lymphopenia/immunology , Lymphopenia/blood , Complement C3b/immunology
3.
Mol Psychiatry ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454079

ABSTRACT

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

6.
Int J Mol Sci ; 24(21)2023 Oct 29.
Article in English | MEDLINE | ID: mdl-37958703

ABSTRACT

The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of outbreaks. It remains uncertain as to when the next lethal coronavirus will emerge, though its eventual emergence appears to be inevitable. New mutations in evolving SARS-CoV-2 variants have provided resistance to current antiviral drugs, monoclonal antibodies, and vaccines, reducing their therapeutic efficacy. This underscores the urgent need to investigate alternative therapeutic approaches. Sigma receptors have been unexpectedly linked to the SARS-CoV-2 life cycle due to the direct antiviral effect of their ligands. Coronavirus-induced cell stress facilitates the formation of an ER-derived complex conducive to its replication. Sigma receptor ligands are believed to prevent the formation of this complex. Repurposing FDA-approved drugs for COVID-19 offers a timely and cost-efficient strategy to find treatments with established safety profiles. Notably, diphenhydramine, a sigma receptor ligand, is thought to counteract the virus by inhibiting the creation of ER-derived replication vesicles. Furthermore, lactoferrin, a well-characterized immunomodulatory protein, has shown antiviral efficacy against SARS-CoV-2 both in laboratory settings and in living organisms. In the present study, we aimed to explore the impact of sigma receptor ligands on SARS-CoV-2-induced mortality in ACE2-transgenic mice. We assessed the effects of an investigational antiviral drug combination comprising a sigma receptor ligand and an immunomodulatory protein. Mice treated with sigma-2 receptor ligands or diphenhydramine and lactoferrin exhibited improved survival rates and rapid rebound in mass following the SARS-CoV-2 challenge compared to mock-treated animals. Clinical translation of these findings may support the discovery of new treatment and research strategies for SARS-CoV-2.


Subject(s)
COVID-19 , Receptors, sigma , Animals , Mice , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Lactoferrin , Ligands , Diphenhydramine
7.
Mil Med ; 188(Suppl 6): 41-44, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37948219

ABSTRACT

INTRODUCTION: Knowing when suicidal ideation (SI) or suicide attempt (SA) is most likely to occur in a deployed environment would aid in focusing prevention efforts. This study aims to determine when evacuation for SA and SI is most likely to occur based on the absolute and relative number of months in a deployed setting. MATERIALS AND METHODS: This is a case-control study of active-duty military personnel evacuated from the U.S. Central Command area of responsibility for SI or an SA between April 1, 2020, and March 30, 2021. The arrival month and expected departure month were identified for all the included evacuees. The month of evacuation and proportion of completed deployment were compared. Secondary outcomes of mental health diagnosis or need for a waiver was also examined. RESULTS: A total of 138 personnel evacuated for SI or attempted suicide during the 12-month study period were included in the analysis. Evacuations occurring during month 3 of deployment were significantly higher (P < .0001) than those during other months. The 30% and 50% completion point of deployment had statistically higher frequencies of evacuations for SI/SA (<.0001). A secondary analysis revealed that 25.4% of the individuals had a documented preexisting behavioral health condition before deployment (P < .0001). CONCLUSION: Specific points along a deployment timeline were significant predictors for being evacuated for SI and SA.


Subject(s)
Military Personnel , Suicide, Attempted , Humans , Suicide, Attempted/psychology , Suicidal Ideation , Case-Control Studies , Incidence , Military Personnel/psychology , Risk Factors
8.
J Child Adolesc Trauma ; 16(3): 597-605, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37593055

ABSTRACT

Child mental health researchers often focus on interventions that improve externalizing problems (i.e., disruptive, aggressive, and impulsive behaviors), due to the relationship between children's externalizing behaviors and social, emotional, and academic disparities. School-based mental health counselors work to reduce externalizing problems due to the relationship between these behaviors and school-based problems, such as bullying victimization, school adjustment difficulties, and suspension. Children with complex trauma histories often exhibit externalizing problems. Unfortunately, limited research examines school trauma screening and guidelines for schools to effectively distinguish behavioral and trauma-related symptoms. As a result, we examined whether children's trauma symptoms predicted their externalizing problems that prompted referrals for school-based mental health counseling interventions at three Title-I elementary schools.

9.
J Addict Dis ; : 1-16, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37602811

ABSTRACT

INTRODUCTION: Person-centered care (PCC) is an ethical imperative with eight domains, but operation of some PCC domains in substance use disorder (SUD) treatment has been underexplored. OBJECTIVE: We sought to identify strategies for operationalizing eight PCC domains in SUD treatment facilities and themes across these strategies. METHODS: We recruited 36 clients and staff from a large publicly funded behavioral health system for individual, semi-structured qualitative interviews. Interviews explored preferences and care experiences for each PCC domain. We analyzed data using iterative categorization, identifying specific operationalization strategies and themes across operationalization strategies within each domain. RESULTS: PCC operationalization themes for residential SUD treatment included addressing social vulnerability of clients (e.g., through assistance with housing and navigation of criminal/legal systems), involving peer support specialists (e.g., to provide emotional support and aid transition out of care), supporting the client's family throughout treatment (e.g., providing progress updates; increasing visitation opportunities in residential treatment), and facilitating patient choice within each domain (e.g., treatment type; housing type; roommate preferences in residential treatment.). DISCUSSION & CONCLUSION: Some PCC operationalization strategies are unique to SUD treatment. Several PCC operationalization strategies applied to multiple domains, suggesting conceptual overlap between domains.

10.
Subst Abuse Treat Prev Policy ; 18(1): 45, 2023 07 17.
Article in English | MEDLINE | ID: mdl-37461114

ABSTRACT

BACKGROUND: While person-centered care (PCC) includes multiple domains, residential substance use disorder (SUD) treatment clients may value certain domains over others. We sought to identify the PCC domains most valued by former residential SUD treatment clients. We also sought to explore conceptual distinctions between potential theoretical PCC subdomains. METHODS: We distributed an online survey via social media to a national convenience sample of former residential SUD treatment clients. Respondents were presented with ten PCC domains in an online survey: (a) access to evidence-based care; (b) integration of care; (c) diversity/respect for other cultures; (d) individualization of care; (e) emotional support; (f) family involvement in treatment; (g) transitional services; (h) aftercare; (i) physical comfort; and (j) information provision. Respondents were asked to select up to two domains they deemed most important to their residential SUD treatment experience. We used descriptive statistics to identify response frequencies and logistic regression to predict relationships between selected domains and respondents' race, gender, relationship status, parenting status, and housing stability. RESULTS: Our final sample included 435 former residential SUD treatment clients. Diversity and respect for different cultures was the most frequently selected domain (29%), followed by integration of care (26%), emotional support (26%), and individualization of care (26%). Provision of information was the least frequently chosen domain (3%). Race and ethnicity were not predictive of selecting respect for diversity. Also, parental status, relationship status and gender were not predictive of selecting family integration. Employment and housing status were not predictive of selecting transitional services. CONCLUSIONS: While residential SUD treatment facilities should seek to implement PCC across all domains, our results suggest facilities should prioritize (a) operationalizing diversity, (b) integration of care, and (c) emotional support. Significant heterogeneity exists regarding PCC domains deemed most important to clients. PCC domains valued by clients cannot be easily predicted based on client demographics.


Subject(s)
Substance-Related Disorders , Humans , Substance-Related Disorders/therapy , Patient-Centered Care , Residential Treatment
11.
Med Care ; 61(Suppl 1): S12-S20, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36893414

ABSTRACT

BACKGROUND: The delivery of adult primary care (APC) shifted from predominately in-person to modes of virtual care during the COVID-19 pandemic. It is unclear how these shifts impacted the likelihood of APC use during the pandemic, or how patient characteristics may be associated with the use of virtual care. METHODS: A retrospective cohort study using person-month level datasets from 3 geographically disparate integrated health care systems was conducted for the observation period of January 1, 2020, through June 30, 2021. We estimated a 2-stage model, first adjusting for patient-level sociodemographic, clinical, and cost-sharing factors, using generalized estimating equations with a logit distribution, along with a second-stage multinomial generalized estimating equations model that included an inverse propensity score treatment weight to adjust for the likelihood of APC use. Factors associated with APC use and virtual care use were separately assessed for the 3 sites. RESULTS: Included in the first-stage models were datasets with total person-months of 7,055,549, 11,014,430, and 4,176,934, respectively. Older age, female sex, greater comorbidity, and Black race and Hispanic ethnicity were associated with higher likelihood of any APC use in any month; measures of greater patient cost-sharing were associated with a lower likelihood. Conditional on APC use, older age, and adults identifying as Black, Asian, or Hispanic were less likely to use virtual care. CONCLUSIONS: As the transition in health care continues to evolve, our findings suggest that to ensure vulnerable patient groups receive high quality health care, outreach interventions to reduce barriers to virtual care use may be warranted.


Subject(s)
COVID-19 , Delivery of Health Care , Telemedicine , Adult , Humans , COVID-19/epidemiology , Pandemics , Retrospective Studies , Delivery of Health Care/methods
12.
Regul Toxicol Pharmacol ; 137: 105293, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36414101

ABSTRACT

The assessment of human health hazards posed by chemicals traditionally relies on toxicity studies in experimental animals. However, most chemicals currently in commerce do not meet the minimum data requirements for hazard identification and dose-response analysis in human health risk assessment. Previously, we introduced a read-across framework designed to address data gaps for screening-level assessment of chemicals with insufficient in vivo toxicity information (Wang et al., 2012). It relies on inference by analogy from suitably tested source analogues to a target chemical, based on structural, toxicokinetic, and toxicodynamic similarity. This approach has been used for dose-response assessment of data-poor chemicals relevant to the U.S. EPA's Superfund program. We present herein, case studies of the application of this framework, highlighting specific examples of the use of biological similarity for chemical grouping and quantitative read-across. Based on practical knowledge and technological advances in the fields of read-across and predictive toxicology, we propose a revised framework. It includes important considerations for problem formulation, systematic review, target chemical analysis, analogue identification, analogue evaluation, and incorporation of new approach methods. This work emphasizes the integration of systematic methods and alternative toxicity testing data and tools in chemical risk assessment to inform regulatory decision-making.


Subject(s)
Risk Assessment , Animals , Humans , Risk Assessment/methods
13.
J Dent ; 125: 104243, 2022 10.
Article in English | MEDLINE | ID: mdl-35907441

ABSTRACT

OBJECTIVES: We have previously shown fluorescent cationic starch nanoparticles (FCSNs) penetrate enamel surface porosity of active carious lesions, potentially aiding their detection. Here, we evaluate the in vitro diagnostic accuracy of FCSNs in detecting occlusal caries compared to histologic reference standard. METHODS: 100 extracted human teeth were selected with sound (50), or either non-cavitated (25) or cavitated (25) lesions. A region of interest (ROI) on the occlusal surface was assessed for fluorescence by two independent examiners, after immersion in FCSN solution, water rinse, and illumination by dental curing lamp viewed through orange UV-filter glasses. ROIs were sectioned and evaluated by histology (Downer Criteria) as a gold standard for caries presence. Cohen's Kappa was determined for inter- and intra-examiner agreement, and sensitivity, specificity, and area under the curve of Receiver Operator Curves (ROCAUC) were calculated. The analysis was repeated for the subset of "early" lesions, defined as being limited to enamel. RESULTS: FCSN use resulted in substantial inter-user (k=0.74±0.07), and high intra-user agreement (k=0.80±0.06; 0.94±0.03, by examiner). Sensitivity, specificity and ROCAUC for FCSNs were 88.9%; 94.6%; 0.92±0.06 for all, and 76.9%, 94.6%, and 0.86±0.10 for early lesions. In post hoc analysis, sensitivity seemed to be greater with the FCSN than the expert visual exam, particularly for early lesions. CONCLUSIONS/CLINICAL SIGNIFICANCE: FCSNs are a reproducible and accurate novel technology for occlusal caries detection, with high sensitivity and specificity compared to histology. Future clinical validation is necessary. FCSNs can improve early caries detection and shift treatment towards non-invasive approaches, improving oral health.


Subject(s)
Dental Caries , Nanoparticles , Dental Caries/diagnosis , Dental Caries Susceptibility , Fluorescence , Humans , Reproducibility of Results , Sensitivity and Specificity , Starch , Water
14.
Front Immunol ; 13: 815833, 2022.
Article in English | MEDLINE | ID: mdl-35250994

ABSTRACT

The coronavirus disease-2019 (COVID-19) caused by the SARS-CoV-2 virus may vary from asymptomatic to severe infection with multi-organ failure and death. Increased levels of circulating complement biomarkers have been implicated in COVID-19-related hyperinflammation and coagulopathy. We characterized systemic complement activation at a cellular level in 49-patients with COVID-19. We found increases of the classical complement sentinel C1q and the downstream C3 component on circulating blood monocytes from COVID-19 patients when compared to healthy controls (HCs). Interestingly, the cell surface-bound complement inhibitor CD55 was also upregulated in COVID-19 patient monocytes in comparison with HC cells. Monocyte membrane-bound C1q, C3 and CD55 levels were associated with plasma inflammatory markers such as CRP and serum amyloid A during acute infection. Membrane-bounds C1q and C3 remained elevated even after a short recovery period. These results highlight systemic monocyte-associated complement activation over a broad range of COVID-19 disease severities, with a compensatory upregulation of CD55. Further evaluation of complement and its interaction with myeloid cells at the membrane level could improve understanding of its role in COVID-19 pathogenesis.


Subject(s)
COVID-19/immunology , Complement Activation/immunology , Complement System Proteins/immunology , Monocytes/immunology , Adult , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Complement Inactivating Agents/immunology , Cytokines/immunology , Female , Humans , Immunologic Factors/immunology , Male , Middle Aged , Monocytes/virology , SARS-CoV-2/immunology
15.
Am J Sports Med ; 50(6): 1659-1667, 2022 05.
Article in English | MEDLINE | ID: mdl-35302902

ABSTRACT

BACKGROUND: Fractures of the proximal fifth metatarsal bone are common injuries in elite athletes and are associated with high rates of delayed union and nonunion. Structural features of the foot may increase fracture risk in some individuals, emphasizing the need for intervention strategies to prevent fracture. Although orthotic devices have shown promise in reducing fractures of the fifth metatarsal bone, the effect of orthosis on fifth metatarsal strains is not well understood. PURPOSE: To quantify the effects of different foot orthotic constructs on principal tensile strains in the proximal fifth metatarsal bone during cadaveric simulations of level walking. An additional purpose was to investigate the relationships between structural features of the foot and corresponding strains on the fifth metatarsal bone during level walking. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 10 midtibial cadaveric specimens were attached to a 6 degrees of freedom robotic gait simulator. Strain gauges were placed at the metaphyseal-diaphyseal junction (zone II) and the proximal diaphysis (zone III) during level walking simulations using 11 different foot orthotic configurations. Images of each specimen were used to measure structural features of the foot in an axially loaded position. The peak tensile strains were measured and reported relative to the sneaker-only condition for each orthotic condition and orthotic-specific association between structural features and principal strains of both zones. RESULTS: In total, 2 of the 11 orthotic conditions significantly reduced strain relative to the sneaker-only condition in zone II. Further, 6 orthotic conditions significantly reduced strain relative to the sneaker-only condition in zone III. Increased zone II principal strain incurred during level walking in the sneaker-only condition showed a significant association with increases in the Meary's angle. Changes in zone III principal strain relative to the sneaker-only condition were significantly associated with increases in the Meary's angle and fourth-fifth intermetatarsal angle. CONCLUSION: The use of orthotic devices reduced principal strain relative to the condition of a sneaker without any orthosis in zone II and zone III. The ability to reduce strain relative to the sneaker-only condition in zone III was indicated by increasing values of the Meary's angle and levels of the fourth-fifth intermetatarsal angle. CLINICAL RELEVANCE: Clinicians can use characteristics of foot structure to determine the proper foot orthosis to potentially reduce stress fracture risk in high-risk individuals.


Subject(s)
Fractures, Bone , Fractures, Stress , Metatarsal Bones , Cadaver , Fractures, Bone/prevention & control , Humans , Metatarsal Bones/injuries , Orthotic Devices , Walking
16.
Exp Econ ; 25(3): 795-823, 2022.
Article in English | MEDLINE | ID: mdl-35018135

ABSTRACT

The COVID-19 pandemic presents a remarkable opportunity to put to work all of the research that has been undertaken in past decades on the elicitation and structural estimation of subjective belief distributions as well as preferences over atemporal risk, patience, and intertemporal risk. As contributors to elements of that research in laboratories and the field, we drew together those methods and applied them to an online, incentivized experiment in the United States. We have two major findings. First, the atemporal risk premium during the COVID-19 pandemic appeared to change significantly compared to before the pandemic, consistent with theoretical results of the effect of increased background risk on foreground risk attitudes. Second, subjective beliefs about the cumulative level of deaths evolved dramatically over the period between May and November 2020, a volatile one in terms of the background evolution of the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-021-09738-3.

17.
Regul Toxicol Pharmacol ; 129: 105111, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34973387

ABSTRACT

This paper provides a systematic weight-of-evidence method for read-across analyses of data-poor chemicals. The read-across technique extrapolates toxicity from analogous chemicals for which suitable test data are available to a target chemical. To determine that a candidate analogue is the 'best' and is sufficiently similar, the evidence for similarity of each candidate analogue to the target is weighed. We present a systematic weight of evidence method that provides transparency and imposes a consistent and rigorous inferential process. The method assembles relevant information concerning structure, physicochemical attributes, toxicokinetics, and toxicodynamics of the target and analogues. The information is then organized by evidence types and subtypes and weighted in terms of properties: relevance, strength, and reliability into weight levels, expressed as symbols. After evidence types are weighted, the bodies of evidence are weighted for collective properties: number, diversity, and coherence. Finally, the weights for the types and bodies of evidence are weighed for each analogue, and, if the overall weight of evidence is sufficient for one or more analogues, the analogue with the greatest weight is used to estimate the endpoint effect. We illustrate this WoE approach with a read-across analysis for screening the organochlorine contaminant, p,p'-dichlorodiphenyldichloroethane (DDD), for noncancer oral toxicity.


Subject(s)
Toxicology/methods , Reproducibility of Results , Risk Assessment , Toxicokinetics
18.
Pain ; 163(3): e476-e487, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34224496

ABSTRACT

ABSTRACT: Exercise is the most common treatment recommended by healthcare providers for the treatment of musculoskeletal pain. We examined whether voluntary running wheel exercise improves pain and bone remodeling in rats with monosodium iodoacetate-induced unilateral knee joint pain. During acquisition of wheel running before osteoarthritis (OA) treatment, rats separated into 2 groups characterized by either high or low levels of voluntary wheel running as indicated by distance and peak speed. After the induction of knee joint OA, all rats showed diminished voluntary wheel running throughout the study. Voluntary wheel running failed to alter evoked nociceptive responses evaluated as weight asymmetry or hind paw tactile thresholds at any timepoint of the study. By contrast, relief of ongoing pain was demonstrated by conditioned place preference produced by lidocaine injection into the monosodium iodoacetate-treated knee in high but not low-running rats. Both high and low voluntary runners showed diminished trabecular bone loss compared with sedentary controls. These observations indicate that both high-intensity and low-intensity exercise is beneficial in protecting against bone remodeling in advanced OA. The data suggest that similar to clinical observation, bone remodeling does not correlate with pain. In addition, these results suggest that higher intensity exercise may relieve persistent ongoing OA pain while maintaining movement-evoked nociception. The relief of ongoing pain can potentially offer significant improvement in quality of life, whereas preservation of responses to movement-evoked pain may be especially important in protecting the joint from damage because of overuse.


Subject(s)
Motor Activity , Osteoarthritis, Knee , Animals , Bone Remodeling , Disease Models, Animal , Motor Activity/physiology , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/therapy , Pain/drug therapy , Pain/etiology , Quality of Life , Rats , Rats, Sprague-Dawley
19.
Biochem Biophys Res Commun ; 586: 87-92, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34837837

ABSTRACT

There is an urgent need to understand the functional effects of mutations in emerging variants of SARS-CoV-2. Variants of concern (alpha, beta, gamma and delta) acquired four patterns of spike glycoprotein mutations that enhance transmissibility and immune evasion: 1) mutations in the N-terminal domain (NTD), 2) mutations in the Receptor Binding Domain (RBD), 3) mutations at interchain contacts of the spike trimer, and 4) furin cleavage site mutations. Most distinguishing mutations among variants of concern are exhibited in the NTD, localized to sites of high structural flexibility. Emerging variants of interest such as mu, lambda and C.1.2 exhibit the same patterns of mutations as variants of concern. There is a strong likelihood that SARS-CoV-2 variants will continue to emerge with mutations in these defined patterns, thus providing a basis for the development of next line antiviral drugs and vaccine candidates.


Subject(s)
COVID-19/virology , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19/immunology , COVID-19/transmission , Evolution, Molecular , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Models, Molecular , Pandemics , Protein Conformation , Protein Interaction Domains and Motifs/genetics , Protein Interaction Domains and Motifs/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
20.
Chemosphere ; 288(Pt 3): 132639, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34687677

ABSTRACT

Polychlorinated biphenyls (PCBs) can provide crucial information into the bioaccumulation and biomagnification of POPs in marine mammals. Muscle tissue samples were obtained for detailed PCB congener specific analysis of all 209 PCBs in 11 species of marine mammals stranded across the coast of the UK between 2010 and 2013. At least 145 PCB congeners were found in each individual. The highest concentrations of PCBs were recorded in a killer whale (318 mg/kg lipid) and the highest toxic equivalent in a Risso's dolphin (1687 pg/g TEQ2005 wet). Concentrations of PCBs in the majority of samples exceeded toxic thresholds (9 mg/kg lipid) for marine mammals, highlighting the health risk they face from PCB exposure. Many PCB profiles did not fit typical 'Aroclor' signatures, but instead indicated patterns of congeners that are resistant to biotransformation and elimination. However, this study identified a novel PCB signature in a sei whale that has not yet been previously observed in marine mammals. The whale had a PCB profile that included lighter and inadvertent PCB congeners such as PCB 11, suggesting that the main source of exposure was through atmospheric deposition, rather than terrestrial discharges. Seven subsamples were chosen for chiral analysis of PCB 95, 136 and 149. The enantiomer fractions (EFs) of C-PCBs 95 and 149 were non racemic suggesting there may be enantiomer selective metabolism in marine mammals. Although there has been a shift in the literature towards emerging pollutants, this study acts as a stark reminder that PCBs continue to pose a significant risk to wildlife.


Subject(s)
Caniformia , Environmental Pollutants , Polychlorinated Biphenyls , Animals , Atlantic Ocean , Biotransformation , Environmental Pollutants/analysis , Polychlorinated Biphenyls/analysis
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