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1.
BMC Public Health ; 19(1): 186, 2019 Feb 13.
Article in English | MEDLINE | ID: mdl-30760246

ABSTRACT

BACKGROUND: Physical inactivity and unhealthy diet are modifiable behaviors that lead to several cancers. Biologically, these behaviors are linked to cancer through obesity-related insulin resistance, inflammation, and oxidative stress. Individual strategies to change physical activity and diet are often short lived with limited effects. Interventions are expected to be more successful when guided by multi-level frameworks that include environmental components for supporting lifestyle changes. Understanding the role of environment in the pathways between behavior and cancer can help identify what environmental conditions are needed for individual behavioral change approaches to be successful, and better recognize how environments may be fueling underlying racial and ethnic cancer disparities. METHODS: This cross-sectional study was designed to select participants (n = 602 adults, 40% Hispanic, in San Diego County) from a range of neighborhoods ensuring environmental variability in walkability and food access. Biomarkers measuring cancer risk were measured with fasting blood draw including insulin resistance (fasting plasma insulin and glucose levels), systemic inflammation (levels of CRP), and oxidative stress measured from urine samples. Objective physical activity, sedentary behavior, and sleep were measured by participants wearing a GT3X+ ActiGraph on the hip and wrist. Objective measures of locations were obtained through participants wearing a Qstarz Global Positioning System (GPS) device on the waist. Dietary measures were based on a 24-h food recall collected on two days (weekday and weekend). Environmental exposure will be calculated using static measures around the home and work, and dynamic measures of mobility derived from GPS traces. Associations of environment with physical activity, obesity, diet, and biomarkers will be measured using generalized estimating equation models. DISCUSSION: Our study is the largest study of objectively measured physical activity, dietary behaviors, environmental context/exposure, and cancer-related biomarkers in a Hispanic population. It is the first to perform high quality measures of physical activity, sedentary behavior, sleep, diet and locations in which these behaviors occur in relation to cancer-associated biomarkers including insulin resistance, inflammation, impaired lipid metabolism, and oxidative stress. Results will add to the evidence-base of how behaviors and the built environment interact to influence biomarkers that increase cancer risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT02094170 , 03/21/2014.


Subject(s)
Built Environment , Environmental Exposure/adverse effects , Life Style/ethnology , Neoplasms/etiology , Obesity/ethnology , Sedentary Behavior/ethnology , Adult , California , Exercise , Health Risk Behaviors , Humans , Male , Middle Aged , Neoplasms/prevention & control , Obesity/complications
2.
J Sports Sci ; 37(20): 2309-2317, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31195893

ABSTRACT

This study compared five different methods for analyzing accelerometer-measured physical activity (PA) in older adults and assessed the relationship between changes in PA and changes in physical function and depressive symptoms for each method. Older adult females (N = 144, Mage = 83.3 ± 6.4yrs) wore hip accelerometers for six days and completed measures of physical function and depressive symptoms at baseline and six months. Accelerometry data were processed by five methods to estimate PA: 1041 vertical axis cut-point, 15-second vector magnitude (VM) cut-point, 1-second VM algorithm (Activity Index (AI)), machine learned walking algorithm, and individualized cut-point derived from a 400-meter walk. Generalized estimating equations compared PA minutes across methods and showed significant differences between some methods but not others; methods estimated 6-month changes in PA ranging from 4 minutes to over 20 minutes. Linear mixed models for each method tested associations between changes in PA and health. All methods, except the individualized cut-point, had a significant relationship between change in PA and improved physical function and depressive symptoms. This study is among the first to compare accelerometry processing methods and their relationship to health. It is important to recognize the differences in PA estimates and relationship to health outcomes based on data processing method. Abbreviation: Machine Learning (ML); Short Physical Performance Battery (SPPB); Center of Epidemiologic Studies Depression Scale (CES-D); Physical Activity (PA); Activity Index (AI); Activities of Daily Living (ADL).


Subject(s)
Accelerometry/methods , Aged/physiology , Exercise/physiology , Health Status , Activities of Daily Living , Aged/psychology , Aged, 80 and over , Algorithms , Depression/prevention & control , Exercise/psychology , Exercise Test , Female , Fitness Trackers , Gait/physiology , Humans , Machine Learning , Muscle Strength/physiology , Postural Balance/physiology , Walking/physiology
3.
BMC Public Health ; 18(1): 29, 2017 07 18.
Article in English | MEDLINE | ID: mdl-28720079

ABSTRACT

BACKGROUND: As the US population ages, there is an increasing need for evidence based, peer-led physical activity programs, particularly in ethnically diverse, low income senior centers where access is limited. METHODS/DESIGN: The Peer Empowerment Program 4 Physical Activity' (PEP4PA) is a hybrid Type II implementation-effectiveness trial that is a peer-led physical activity (PA) intervention based on the ecological model of behavior change. The initial phase is a cluster randomized control trial randomized to either a peer-led PA intervention or usual center programming. After 18 months, the intervention sites are further randomized to continued support or no support for another 6 months. This study will be conducted at twelve senior centers in San Diego County in low income, diverse communities. In the intervention sites, 24 peer health coaches and 408 adults, aged 50 years and older, are invited to participate. Peer health coaches receive training and support and utilize a tablet computer for delivery and tracking. There are several levels of intervention. Individual components include pedometers, step goals, counseling, and feedback charts. Interpersonal components include group walks, group sharing and health tips, and monthly celebrations. Community components include review of PA resources, walkability audit, sustainability plan, and streetscape improvements. The primary outcome of interest is intensity and location of PA minutes per day, measured every 6 months by wrist and hip accelerometers and GPS devices. Secondary outcomes include blood pressure, physical, cognitive, and emotional functioning. Implementation measures include appropriateness & acceptability (perceived and actual fit), adoption & penetration (reach), fidelity (quantity & quality of intervention delivered), acceptability (satisfaction), costs, and sustainability. DISCUSSION: Using a peer led implementation strategy to deliver a multi-level community based PA program can enhance program adoption, implementation, and sustainment. TRIAL REGISTRATION: ClinicalTrials.gov, USA ( NCT02405325 ). Date of registration, March 20, 2015. This website also contains all items from the World Health Organization Trial Registration Data Set.


Subject(s)
Ethnicity , Exercise , Health Promotion/methods , Peer Group , Poverty , Senior Centers , Aged , Counseling , Female , Humans , Male , Mental Health , Middle Aged , Residence Characteristics , Social Environment , Treatment Outcome , Walking
4.
J Med Entomol ; 52(2): 269-73, 2015 Mar.
Article in English | MEDLINE | ID: mdl-26336311

ABSTRACT

Geographic distribution records for the lone star tick [Amblyomma americanum (L.)] in the peer-reviewed literature are incomplete for Oklahoma, preventing accurate disease risk assessments. To address this issue and document the presence of A. americanum in available habitats throughout the state, county-scale tick records published in U.S. Department of Agriculture-Cooperative Economic Insect Reports and specimens maintained at the K.C. Emerson Entomology Museum, Oklahoma State University, were reviewed. In addition, dry ice traps and tick drags were used to collect adult and nymphal A. americanum from throughout the state. Review of published USDA reports and the local museum collection documented A. americanum in 49 total counties (35 and 35, respectively). Active surveillance efforts confirmed the presence of this tick in 50 counties from which this species had not been previously reported to be established, documenting A. americanum is established in 68 of the 77 (88.3%) counties in Oklahoma. Taken together, these data verify that A. americanum ticks are much more widespread in Oklahoma than reflected in the literature, a phenomenon likely repeated throughout the geographic range of this tick in the eastern half of North America.


Subject(s)
Ixodidae , Animals , Demography , Oklahoma
5.
Eur Urol Focus ; 10(1): 13-15, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37872079

ABSTRACT

Training of the pelvic floor muscles (PFMs) as part of a multimodal prehabilitation program that includes cardiovascular and hip strengthening and patient education can yield patient benefits after urologic surgery. A personalized, multifaceted, holistic care plan that includes PFM training should be developed by an interdisciplinary team. Further research is needed to identify the impact of PFM prehabilitation on various urologic and surgical outcomes.


Subject(s)
Pelvic Floor , Preoperative Exercise , Humans , Pelvic Floor/surgery
6.
Article in English | MEDLINE | ID: mdl-37694554

ABSTRACT

BACKGROUND: The relationship between amino acids, B vitamins, and their metabolites with D3-creatine (D3Cr) dilution muscle mass, a more direct measure of skeletal muscle mass, has not been investigated. We aimed to assess associations of plasma metabolites with D3Cr muscle mass, as well as muscle strength and physical performance in older men from the Osteoporotic Fractures in Men cohort study. METHODS: Out of 1 425 men (84.2 ±â€…4.1 years), men with the lowest D3Cr muscle mass (n = 100), slowest walking speed (n = 100), lowest grip strength (n = 100), and a random sample (n = 200) serving as a comparison group to the low groups were included. Metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Metabolite differences between the low groups and random sample and their relationships with the muscle outcomes adjusted for confounders and multiple comparisons were assessed using t-test/Mann-Whitney-Wilcoxon and partial correlations, respectively. RESULTS: For D3Cr muscle mass, significant biomarkers (p < .001) with ≥10% fold difference and largest partial correlations were tryptophan (Trp; r = 0.31), kynurenine (Kyn)/Trp; r = -0.27), nicotinamide (Nam)/quinolinic acid (Quin; r = 0.21), and alpha-hydroxy-5-methyl-tetrahydrofolate (hm-THF; r = -0.25). For walking speed, hm-THF, Nam/Quin, and Quin had the largest significance and fold difference, whereas valine (r = 0.17), Trp (r = 0.17), HKyn/Xant (r = -0.20), neopterin (r = -0.17), 5-methyl-THF (r = -0.20), methylated folate (r = -0.21), and thiamine (r = -0.18) had the strongest correlations. Only hm-THF was correlated with grip strength (r = -0.21) and differed between the low group and the random sample. CONCLUSIONS: Future interventions focusing on how the Trp metabolic pathway or hm-THF influences D3Cr muscle mass and physical performance declines in older adults are warranted.


Subject(s)
Creatine , Muscle Strength , Male , Humans , Aged , Cohort Studies , Muscle Strength/physiology , Hand Strength/physiology , Physical Functional Performance , Muscles , Nutrients , Muscle, Skeletal
7.
Med Sci Sports Exerc ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38598351

ABSTRACT

PURPOSE: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VO 2 peak) declines with aging and correlates with mortality and morbidity. Cardiopulmonary Exercise Testing (CPET) is the criterion method to assess CRF, but its feasibility, validity and reliability in older adults is unclear. Our objective was to design and implement a dependable, safe and reliable CPET protocol in older adults. METHODS: VO 2 peak was measured by CPET, performed using treadmill exercise in 875 adults ≥70 years in the Study of Muscle, Mobility and Aging (SOMMA). The protocol included a symptom-limited peak (maximal) exercise and two submaximal walking speeds. An adjudication process was in place to review tests for validity if they met any prespecified criteria [VO 2 peak < 12.0 ml/kg/min; maximum heart rate (HR) <100 bpm; respiratory exchange ratio (RER) <1.05 and a rating of perceived exertion <15]. A subset (N = 30) performed a repeat test to assess reproducibility. RESULTS: CPET was safe and well tolerated, with 95.8% of participants able to complete the VO 2 peak phase of the protocol. Only 56 (6.4%) participants had a risk alert and only two adverse events occurred: a fall and atrial fibrillation. Mean ± SD VO 2 peak was 20.2 ± 4.8 mL/kg/min, peak HR 142 ± 18 bpm, and peak RER 1.14 ± 0.09. Adjudication was indicated in 47 tests; 20 were evaluated as valid, 27 as invalid (18 data collection errors, 9 did not reach VO 2 peak). Reproducibility of VO 2 peak was high (intraclass correlation coefficient = 0.97). CONCLUSIONS: CPET was feasible, effective and safe for older adults, including many with multimorbidity or frailty. These data support a broader implementation of CPET to provide insight into the role of CRF and its underlying determinants of aging and age-related conditions.

8.
Article in English | MEDLINE | ID: mdl-38761087

ABSTRACT

Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Proinflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. Five hundred and five men (85.0 ±â€…4.2 years) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein [CRP], alpha-1-acid glycoprotein [AGP] and a subsample [n = 305] with interleukin [IL-6, IL-1ß, IL-17A] and tumor necrosis factor-α [TNF-α]) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23%-92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p < .05). 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), TRP, xanthurenic acid (XA), KYN/TRP, 3-hydroxykynurenine (3-HK)/3-HAA, QA/3-HAA, and nicotinamide (NAM)/QA mediated the AGP relationship. 3-HAA, QA, KYN/TRP, 3-HK/XA, HKr ratio, 3-HK/3-HAA, QA/3-HAA, and NAM/QA mediated the CRP. KYN/TRP, 3-HK/XA, and NAM/QA explained the relationship for IL-6 and 3-HK/XA and QA/3-HAA for TNF-α. No mediation effect was observed for the other cytokines (indirect effect p > .05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA, and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se.


Subject(s)
Biomarkers , Inflammation , Kynurenine , Muscle, Skeletal , Tryptophan , Humans , Male , Kynurenine/metabolism , Kynurenine/analogs & derivatives , Inflammation/metabolism , Aged, 80 and over , Biomarkers/metabolism , Tryptophan/metabolism , Muscle, Skeletal/metabolism , C-Reactive Protein/metabolism , Tumor Necrosis Factor-alpha/metabolism , Sarcopenia/metabolism , 3-Hydroxyanthranilic Acid/metabolism , Cytokines/metabolism , Xanthurenates/metabolism
9.
Biopolymers ; 100(4): 422-30, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23868210

ABSTRACT

Antagonism of the calcitonin gene-related peptide (CGRP) receptor may be a useful approach for migraine treatment. Selective PEGylated peptide antagonists to the CGRP receptor are described, derived from CGRP(8-37) with polymer derivatization at an engineered lysine-25 residue. Potent PEGylated peptides with improved pharmacokinetics were identified through peptide side-chain modification to mitigate metabolic liabilities. PEGylated Ac-Trp-[Cit(11,18),hArg(24),Lys(25),Asp(31),Pro(34),1-Nal(35)]CGRP(8-37)-NH2, 9, elicits a dose-dependent reduction of intradermal CGRP-induced local blood flow in rodents with an ED50 of 0.52 mg kg(-1) without any overt adverse effects.


Subject(s)
Calcitonin Gene-Related Peptide , Receptors, Calcitonin Gene-Related Peptide
10.
Biomed Eng Educ ; 3(1): 87-93, 2023.
Article in English | MEDLINE | ID: mdl-36694612

ABSTRACT

Online course delivery has increased in prevalence, particularly due to the onset in 2020 of the COVID-19 pandemic. Biomedical engineering laboratory courses pose unique challenges when transitioning to a remote or hybrid space. Here, we describe a novel approach to online lab delivery to improve student learning and engagement in a required introductory biomedical engineering laboratory class. The presented work focuses on the implementation and assessment of a novel approach to remote lab delivery named LabMate, which is a mobile, multi-view livestreaming platform that connects students to an in-person class remotely. Surveys of student and instructor participants assessed hardware quality and areas of improvement. Focus groups with students who had taken the course in an online format previously were conducted after a demonstration of the system. Survey responses were overall positive; however, some areas of improvement were identified, such as audio quality and video quality. Students and instructors appreciated the ability to deliver class synchronously online rather than perform make-up labs. Focus group participants found LabMate to be more engaging and enjoyable than prior online lab experiences. Students and instructors preferred LabMate over other online lab delivery methods. The students found the experience to be more dynamic and engaging, providing them with the opportunity to develop some of the core competencies of a biomedical engineering student.

11.
PLoS One ; 18(9): e0292079, 2023.
Article in English | MEDLINE | ID: mdl-37756354

ABSTRACT

PURPOSE: The relationship of types of visual function to different aspects of physical function, especially strength and coordination, has been understudied, but delineation of these relationships could suggest potentially modifiable targets prior to the onset of disability. METHODS: Cross-sectional analysis of visual function (self-reported eyesight and eye disease, visual acuity, contrast sensitivity) and physical function tests in 877 older adults (mean age 76.36±5.01 years, 59.2% women, and 13.3% Black race). Separate linear regression models were constructed for short physical performance battery (SPPB), expanded SPPB (eSPPB), their components (gait speed, chair stand, balance, narrow walk), stair climb, four-square step, leg extension peak power and strength, and grip strength. RESULTS: In adjusted models, worse acuity, worse contrast sensitivity, and self-reported poor vision were significantly associated with worse performance on the eSPPB and four-square step test. Worse contrast sensitivity, but not acuity, was significantly associated with shorter balance times, slower chair stand pace, longer stair climb time, and worse SPPB score. Associations of worse acuity and contrast sensitivity with weaker leg extension power, leg strength, and grip strength were attenuated by covariate adjustment. Self-reported macular degeneration, but not cataract or glaucoma, was associated with worse performance on SPPB, eSPPB, balance, stair climb, and four-square step tests in adjusted models. Worse contrast sensitivity and macular degeneration remained associated with worse SPPB and balance after controlling for visual acuity and self-reported eyesight. CONCLUSIONS: Poor contrast sensitivity was more strongly associated with worse physical performance than acuity, especially for complex tasks that dynamically challenge coordination and balance. Future studies should examine if older adults with contrast sensitivity impairment would benefit from targeted intervention to decrease their risk of disability.


Subject(s)
Macular Degeneration , Muscles , Female , Humans , Aged , Aged, 80 and over , Male , Cross-Sectional Studies , Visual Acuity , Aging
12.
medRxiv ; 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37808837

ABSTRACT

BACKGROUND: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (VO2peak) declines with aging and correlates with mortality and morbidity. Cardiopulmonary Exercise Testing (CPET) has long been the criterion method to assess CRF, but its feasibility, efficacy and reliability in older adults is unclear. The large, multicenter Study of Muscle, Mobility and Aging (SOMMA) employed CPET to evaluate the mechanisms underlying declines in mobility with aging among community-dwelling older adults. Our primary objective was to design and implement a CPET protocol in older adults that was dependable, safe, scientifically valuable, and methodologically reliable. METHODS: CPET was performed using treadmill exercise in 875 adults ≥70 years. A composite protocol included a symptom-limited peak exercise phase and two submaximal phases to assess cardiopulmonary ventilatory indices during 1) participants' preferred walking speed and 2) at slow walking speed of 1.5 mph (0.67 m/s). An adjudication process was in place to review tests for validity if they met any prespecified criteria (VO2peak <12.0 ml/kg/min; maximum heart rate (HR) <100 bpm; respiratory exchange ratio (RER) <1.05 and a rating of perceived exertion <15). A repeat test was performed in a subset (N=30) to assess reproducibility. RESULTS: CPET was safe and well tolerated, with 95.8% of participants able to complete the VO2peak phase of the protocol. Only 56 (6.4%) participants had a risk alert during any phase of testing and only two adverse events occurred during the peak phase: a fall and atrial fibrillation. The average ± standard deviation for VO2peak was 20.2 ± 4.8 mL/kg/min, peak HR 142 ± 18 bpm, and peak RER 1.14 ± 0.09. VO2peak and RER were slightly higher in men than women. Adjudication was indicated in 47 participants; 20 were evaluated as valid, 27 as invalid (18 had a data collection error, 9 did not reach VO2peak). Reproducibility of VO2peak was high (intraclass correlation coefficient=0.97). CONCLUSIONS: CPET was feasible, effective and safe for community-dwelling older adults, many of whom had multimorbidity and frailty. These data support a broader implementation of CPET to provide important insight into the role of CRF and its underlying determinants in aging and age-related conditions and diseases. Clinical Perspective: What Is New?: Performing cardiopulmonary exercise testing in a community dwelling older adult with multimorbidities or frailty is feasible and exceptionally safe under highly trained exercise physiologists and physician supervision.Reproducibility of VO2peak among community-dwelling older adults with significant clinical complexity was high (intraclass correlation coefficient=0.97).The VO2peak observed was comparable to established normative data for older adults, and adds merit to the limited data collected on VO2peak norms in older adults.What Are the Clinical Implications?: Ventilatory gas collection during clinical cardiac stress testing may be valuable to plan of care in routine management of older adults due to the important role of aerobic fitness on morbidity and mortality.Cardiopulmonary exercise testing can provide insight into the role of cardiorespiratory fitness and its underlying determinants in aging and age-related conditions and diseases.

13.
J Gerontol A Biol Sci Med Sci ; 78(11): 2083-2093, 2023 10 28.
Article in English | MEDLINE | ID: mdl-36754371

ABSTRACT

BACKGROUND: The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images. METHODS: The multidisciplinary SOMMA team includes 2 clinical centers (University of Pittsburgh and Wake Forest University), a biorepository (Translational Research Institute at Advent Health), and the San Francisco Coordinating Center (California Pacific Medical Center Research Institute). Enrollees were age ≥70 years, able to walk ≥0.6 m/s (4 m); able to complete 400 m walk, free of life-threatening disease, and had no contraindications to magnetic resonance or tissue collection. Participants are followed with 6-month phone contacts and annual in-person exams. At baseline, SOMMA collected biospecimens (muscle and adipose tissue, blood, urine, fecal samples); a variety of questionnaires; physical and cognitive assessments; whole-body imaging (magnetic resonance and computed tomography); accelerometry; and cardiopulmonary exercise testing. Primary outcomes include change in walking speed, change in fitness, and objective mobility disability (able to walk 400 m in 15 minutes and change in 400 m speed). Incident events, including hospitalizations, cancer diagnoses, fractures, and mortality are collected and centrally adjudicated by study physicians. RESULTS: SOMMA exceeded its goals by enrolling 879 participants, despite being slowed by the COVID-19 pandemic: 59.2% women; mean age 76.3 ± 5.0 years (range 70-94); mean walking speed 1.04 ± 0.20 m/s; 15.8% identify as other than Non-Hispanic White. Over 97% had data for key measurements. CONCLUSIONS: SOMMA will provide the foundation for discoveries in the biology of human aging and mobility.


Subject(s)
Pandemics , Walking , Humans , Female , Aged , Aged, 80 and over , Male , Cohort Studies , Walking/physiology , Aging/physiology , Muscles , Mobility Limitation
14.
Bioorg Med Chem Lett ; 22(2): 1061-7, 2012 Jan 15.
Article in English | MEDLINE | ID: mdl-22197141

ABSTRACT

In a series of bradykinin B1 antagonists, we discovered that replacement of oxopiperazine acetamides with dehydro-oxopiperazine acetamides provided compounds with enhanced activity against the B1 receptor. The synthesis and SAR leading to potent analogs with reduced molecular weight will be discussed.


Subject(s)
Acetamides/pharmacology , Bradykinin B1 Receptor Antagonists , Piperazines/pharmacology , Acetamides/chemical synthesis , Acetamides/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Piperazines/chemical synthesis , Piperazines/chemistry , Stereoisomerism , Structure-Activity Relationship
15.
Proc Natl Acad Sci U S A ; 106(43): 18155-8, 2009 Oct 27.
Article in English | MEDLINE | ID: mdl-19822748

ABSTRACT

Based on elevated concentrations of a set of "impact markers" at the onset of the Younger Dryas stadial from sedimentary contexts across North America, Firestone, Kennett, West, and others have argued that 12.9 ka the Earth experienced an impact by an extraterrestrial body, an event that had devastating ecological consequences for humans, plants, and animals in the New World [Firestone RB, et al. (2007) Proc. Natl. Acad. Sci. USA 104:16016-16021]. Herein, we report the results of an independent analysis of magnetic minerals and microspherules from seven sites of similar age, including two examined by Firestone et al. We were unable to reproduce any results of the Firestone et al. study and find no support for Younger Dryas extraterrestrial impact.

16.
J Microbiol Biol Educ ; 23(1)2022 Apr.
Article in English | MEDLINE | ID: mdl-35496683

ABSTRACT

The COVID-19 pandemic imposed many new challenges on educational systems and increased the demand for novel strategies for effectively teaching laboratory skills without in-person instruction and without access to laboratory space, including critical specialized equipment. While this novel remote instruction modality is compatible with teaching the theory behind experimental techniques, the lack of lab activities that enable learning of laboratory skills severely limits the outcome of instruction. In order to overcome this problem and effectively supplement lectures with hands-on laboratory exercises, we developed an at-home enzyme kinetics lab that provides a safe alternative to traditional enzyme kinetics instructional labs typically performed in a laboratory setting. The combination of a simple design of the activity, accessibility of equipment used, and relatively low overall cost yields an effective exercise for teaching experimental design and basic laboratory skills remotely while providing a unique opportunity for students to learn about enzyme kinetics.

17.
Bioorg Med Chem Lett ; 21(11): 3384-9, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21514825

ABSTRACT

The discovery of novel and highly potent oxopiperazine based B1 receptor antagonists is described. Compared to the previously described arylsulfonylated (R)-3-amino-3-phenylpropionic acid series, the current compounds showed improved in vitro potency and metabolic stability. Compound 17, 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide, showed EC(50) of 10.3 nM in a rabbit biochemical challenge model. The practical syntheses of chiral arylsulfonylated oxopiperazine acetic acids are also described.


Subject(s)
Acetamides/therapeutic use , Bradykinin B1 Receptor Antagonists , Inflammation/drug therapy , Pain/drug therapy , Piperazines/therapeutic use , Acetamides/chemical synthesis , Acetamides/chemistry , Animals , Dogs , Inhibitory Concentration 50 , Mice , Models, Animal , Molecular Structure , Piperazines/chemical synthesis , Piperazines/chemistry , Rabbits , Rats , Receptor, Bradykinin B1/chemistry , Stereoisomerism , Structure-Activity Relationship
18.
Bioorg Med Chem Lett ; 20(15): 4593-7, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-20573508

ABSTRACT

The bradykinin B1 receptor has been shown to mediate pain response and is rapidly induced upon injury. Blocking this receptor may provide a promising treatment for inflammation and pain. We previously reported tetralin benzyl amines as potent B1 antagonists. Here we describe the synthesis and SAR of B1 receptor antagonists with homobenzylic amines. The SAR of different linkers led to the discovery of tetralin allylic amines as potent and selective B1 receptor antagonists (hB1 IC(50)=1.3 nM for compound 16). Some of these compounds showed modest oral bioavailability in rats.


Subject(s)
Benzylamines/chemistry , Bradykinin B1 Receptor Antagonists , Sulfonamides/chemistry , Tetrahydronaphthalenes/chemistry , Administration, Oral , Animals , Pain/drug therapy , Rats , Receptor, Bradykinin B1/metabolism , Structure-Activity Relationship , Sulfonamides/pharmacokinetics , Sulfonamides/therapeutic use
19.
J Am Vet Med Assoc ; 236(3): 330-4, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-20113248

ABSTRACT

OBJECTIVE: To determine effects of pituitary pars intermedia dysfunction (Cushing's disease) and age on fecal egg count and time to egg reappearance after anthelmintic treatment in horses residing in similar environments. DESIGN: Cross-sectional study. ANIMALS: 29 healthy horses (4 to 35 years old) and 13 horses with PPID (13 to 33 years old). PROCEDURES: Fecal egg counts were performed by use of a modified Wisconsin flotation method at 2-week intervals before and after ivermectin treatment. RESULTS: Horses with PPID had higher fecal egg counts before and 8, 10, and 12 weeks after ivermectin treatment, compared with counts for site-matched healthy horses. There was no difference in the period for < 90% reduction in fecal egg counts between the 2 groups. Age did not affect fecal egg counts at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: For similar environmental conditions, horses with PPID were more likely to have higher fecal egg counts than were healthy horses. Therefore, horses with PPID may need to have a more aggressive parasite prevention program than do healthy horses. Age did not affect fecal egg counts or time to egg reappearance after anthelmintic treatment, which suggested age alone does not likely require special consideration when designing a parasite control program for adult horses.


Subject(s)
Aging , Anthelmintics/therapeutic use , Helminthiasis, Animal/drug therapy , Horse Diseases/drug therapy , Pituitary Diseases/veterinary , Pituitary Gland, Intermediate , Animals , Feces/parasitology , Female , Helminthiasis, Animal/parasitology , Horse Diseases/parasitology , Horses , Male , Parasite Egg Count/veterinary , Pituitary Diseases/complications , Time Factors
20.
Vet Ther ; 11(4): E1-8, 2010.
Article in English | MEDLINE | ID: mdl-21308664

ABSTRACT

There is no labeled treatment for dogs with American canine hepatozoonosis (ACH), but the drug therapies discussed in this article, although not rapidly curative, may be successful in alleviating acute clinical signs, prolonging life, reducing the number of clinical relapses, and enhancing quality of life. This article also describes a pilot trial conducted to assess the efficacy of a novel treatment approach with ponazuril as a stand-alone parasiticide administered for 4 weeks without follow-up decoquinate treatment. Although extended ponazuril treatment in combination with NSAID administration did ameliorate acute clinical signs associated with ACH, the parasite was not completely cleared with this treatment protocol alone. Long-term decoquinate therapy remains a critical component of successful treatment of ACH.


Subject(s)
Antiprotozoal Agents/therapeutic use , Apicomplexa/isolation & purification , Dog Diseases/drug therapy , Protozoan Infections, Animal/drug therapy , Animals , Apicomplexa/drug effects , Arthropod Vectors , Dog Diseases/parasitology , Dogs , Pilot Projects , Protozoan Infections, Animal/parasitology
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