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1.
PNAS Nexus ; 2(6): pgad138, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37325026

ABSTRACT

Examination of avian eggshell at the Old Town archaeological site in Southwestern New Mexico, United States of America, indicates that scarlet macaw (Ara macao) breeding occurred during the Classic Mimbres period (early AD 1100s). Current archaeological and archaeogenomic evidence from throughout the American Southwest/Mexican Northwest (SW/NW) suggests that Indigenous people bred scarlet macaws at an unknown location(s) between AD 900 and 1200 and likely again at the northwestern Mexico site of Paquimé post-AD 1275. However, there is a lack of direct evidence for breeding, or the location(s) of scarlet macaw breeding itself, within this area. This research, for the first time, provides evidence of scarlet macaw breeding using scanning electron microscopy of eggshells from Old Town.

2.
ACS Chem Biol ; 15(7): 1892-1900, 2020 07 17.
Article in English | MEDLINE | ID: mdl-32396332

ABSTRACT

Lipid oxidation and biosynthesis are crucial for cell survival, especially for rapidly proliferating cancer cells in a heterogeneous metabolic environment. The storage of high-energy lipid reservoirs competitively advantages the cancer cell over non-neoplastic tissue. Disrupting lipid biosynthetic processes, through modulation of fatty acid (FA) esterification or de novo lipogenesis (DNL), is of interest in drug discovery. Mimicking the in vivo environment in vitro is also vital for testing the efficacy of potential drug compounds. We present here a stable isotope tracer-based approach for examining the impact of exogenous FA and oxygen tension on the pathways that affect lipid biosynthesis, including the rates of metabolic flux. By applying tandem mass spectrometry (MS/MS) analyses to studies using parallel tracers, we characterized the impact of FA bioavailability on the positional enrichment within specific lipids. Our observations suggest that adding bioavailable FA as a carbon source preferentially biases the cellular metabolism away from DNL and toward esterification of free fatty acid pools. Additionally, we have found that this FA addition, under hypoxic conditions, led to a biased increase in the total triglyceride pool (nearly 5-fold, as compared to phospholipids), regardless of the isotope tracer utilized. We discuss the implications of this metabolic flexibility on studies that aim to characterize apparent drug efficacy.


Subject(s)
Fatty Acids/pharmacology , Lipogenesis/drug effects , Oxygen/metabolism , Phospholipids/metabolism , Triglycerides/metabolism , Carbon Isotopes/chemistry , Cell Line, Tumor , Esterification/drug effects , Fatty Acids/chemistry , Fatty Acids/metabolism , Humans , Tandem Mass Spectrometry
3.
Pediatrics ; 138(1)2016 07.
Article in English | MEDLINE | ID: mdl-27343233

ABSTRACT

CONTEXT: A high relapse rate after discontinuation of desmopressin treatment of pediatric enuresis is consistently reported. Structured withdrawal strategies have been used to prevent relapse. OBJECTIVE: To assess the efficacy of a structured withdrawal strategy of desmopressin on the relapse-free rate for desmopressin responder pediatric enuresis. DATA SOURCES: Systematic literature search up to November 2015 on Medline, Embase, Ovid, Science Direct, Google Scholar, Wiley Online Library databases, and related references without language restriction. STUDY SELECTION: Related clinical trials were summarized for systematic review. Randomized controlled trials on the efficacy of structured versus abrupt withdrawal of desmopressin in sustaining relapse-free status in pediatric enuresis were included for meta-analysis. DATA EXTRACTION: Eligible studies were evaluated according to Cochrane Collaboration recommendations. Relapse-free rate was extracted for relative risk (RR) and 95% confidence interval (CI). Effect estimates were pooled via the Mantel-Haenszel method with random effect model. RESULTS: Six hundred one abstracts were reviewed. Four randomized controlled trials (total 500 subjects) of adequate methodological quality were included for meta-analysis. Pooled effect estimates compared with the abrupt withdrawal, structured withdrawal results to a significantly better relapse-free rate (pooled RR: 1.38; 95% CI, 1.17-1.63; P = .0001). Subgroup analysis for a dose-dependent structured withdrawal regimen showed a significantly better relapse-free rate (pooled RR: 1.48; 95% CI, 1.21-1.80; P = .0001). LIMITATIONS: The small number of studies included in meta-analysis represents a major limitation. CONCLUSIONS: Structured withdrawal of desmopressin results in better relapse-free rates. Specifically, the dose-dependent structured withdrawal regimen showed significantly better outcomes.


Subject(s)
Antidiuretic Agents/therapeutic use , Deamino Arginine Vasopressin/therapeutic use , Enuresis/drug therapy , Child , Humans , Recurrence , Withholding Treatment
4.
Rehabil Psychol ; 60(1): 51-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25621920

ABSTRACT

OBJECTIVE: This study examined the relationship between hearing impairment and mental distress. We hypothesized that fear of negative evaluation by others and avoidant communication strategies are associated with increased symptoms of depression. METHOD: Hearing-impaired adults (N = 105) who signed up for a stress management course completed the Hospital Anxiety and Depression Scale (HAD; Zigmond & Snaith, 1983), the Fear of Negative Evaluation Scale (FNE; Watson & Friend, 1969), and the Conversation Tactics Checklist (CONV; Hallam et al., 2007). The participants' ratings of subjective hearing disability were assessed on a 5-point Likert scale and pure-tone audiometry obtained. Hierarchical multiple regression analysis was used to assess associations between fear of negative evaluation, avoidance, and symptoms of depression. RESULTS: OBJECTIVE hearing impairment was moderate or less for 81% (n = 87) of participants, and the correlation between subjective hearing disability and objective hearing impairment was not significant. Multiple regression analysis showed that fear of negative evaluation and avoidant communication strategies contributed significantly to the variance in depression symptoms, and the total explained variance was 41.7%, F(5, 93) = 13.32, p = .000. Subjective and objective hearing disability did not make significant contributions. CONCLUSION: Symptoms of depression appear to be closely related to fear of negative evaluation by others and use of avoidant communication strategies. Future clinical studies should address whether targeting these problems in rehabilitation interventions decreases depressive symptoms among hearing-impaired individuals.


Subject(s)
Communication , Employee Performance Appraisal , Fear/psychology , Hearing Loss/psychology , Stress, Psychological/psychology , Adult , Aged , Female , Hearing Loss/complications , Humans , Interpersonal Relations , Male , Middle Aged , Norway , Stress, Psychological/complications , Young Adult
5.
Int J Audiol ; 54(4): 227-33, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25328031

ABSTRACT

OBJECTIVE: To develop a cognitive therapy program to reduce mental distress among hearing-impaired employees. DESIGN: In a pilot study we measured the development of mental distress and avoidant coping among hearing-impaired employees. Levels of mental distress were assessed using the hospital anxiety and depression scale (HAD), and the extent of avoidance with conversation tactics checklist CONV(AVOID). The findings were compared with the development in a treatment as usual (TAU) sample. STUDY SAMPLE: Fifteen participants with an equal distribution of male and female participants (M = 49.2 years) took part. The majority had mild to moderate hearing impairment. RESULTS: The program appeared to be feasible and the adherence was good. The mean depression score was identical at pre- and post-intervention in the intervention group, and increased from 2.9 (SD 2.1) to 3.1 (SD 2.0) in the TAU group. Symptoms of anxiety (p < 0.01, 95 % CI (.82, 3.98)) and avoidant communication (p < 0.05, 95% CI (.5, 4.61)) decreased significantly in the intervention group, while an opposite pattern was observed during the TAU program. CONCLUSIONS: The program showed promising results. However, the preliminary results should be further investigated in a randomized controlled trial using a larger sample.


Subject(s)
Cognitive Behavioral Therapy/methods , Employment/psychology , Occupational Diseases/therapy , Persons With Hearing Impairments/psychology , Program Development , Stress, Psychological/therapy , Adult , Anxiety/psychology , Anxiety/therapy , Avoidance Learning , Communication , Depression/psychology , Depression/therapy , Female , Humans , Male , Middle Aged , Occupational Diseases/psychology , Pilot Projects , Psychiatric Status Rating Scales , Stress, Psychological/psychology
6.
J Pediatr Urol ; 10(4): 753-7, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24477421

ABSTRACT

OBJECTIVE: Oxybutynin is the current gold standard drug for management of overactive bladder (OAB) in children, but can have significant side effects or be difficult to administer in multiple daily doses. Herein, we report our experience with transdermal oxybutynin patch (TOP) as an alternative in a selected patient population without neuropathic compromise. MATERIALS AND METHODS: Consecutive patients assessed in a pediatric urology clinic over a 1-year period, diagnosed with OAB with minimum follow-up of 3 months, were included. TOP starting dose was 3.9 mg/day based on product design (Oxytrol). Demographics and outcomes data were retrospectively collected. Symptomatic response was defined as improvement or resolution of lower urinary tract symptoms. RESULTS: 35 children met inclusion criteria (mean age 8 years, range 4-16). Overall, 97% reported good symptom response. The main side effect was skin irritation at TOP site (35%), leading to discontinuation in 20%. There were no reports of other significant side effects. Mean bladder capacity increased from 104 ml to 148 ml at follow-up. CONCLUSIONS: Our data suggest that TOP is a viable alternative for children with non-neuropathic OAB who do not tolerate other formulations of oxybutynin. These findings highlight the potential benefit of transdermal drug delivery in the pediatric setting.


Subject(s)
Mandelic Acids/administration & dosage , Muscarinic Antagonists/administration & dosage , Urinary Bladder, Overactive/drug therapy , Administration, Cutaneous , Adolescent , Child , Child, Preschool , Female , Humans , Male , Mandelic Acids/adverse effects , Muscarinic Antagonists/adverse effects , Retrospective Studies , Transdermal Patch , Treatment Outcome , Urinary Bladder, Overactive/etiology
7.
Bioorg Med Chem Lett ; 23(18): 5066-9, 2013 Sep 15.
Article in English | MEDLINE | ID: mdl-23937978

ABSTRACT

A synthetic approach to analogues of the terpenoid natural product antheminone A is described which employs (-)-quinic acid as starting material. A key conjugate addition step proved to be unpredictable regarding its stereochemical outcome however the route allowed access to two diastereoisomeric series of compounds. The results of biological assay of the toxicity of the target compounds towards non-small-cell lung cancer cell line A549 are reported.


Subject(s)
Acetone/chemical synthesis , Acetone/pharmacology , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/pharmacology , Biological Products/chemical synthesis , Biological Products/pharmacology , Cyclohexanones/pharmacology , Acetone/analogs & derivatives , Acetone/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Biological Products/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclohexanones/chemical synthesis , Cyclohexanones/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Models, Molecular , Molecular Conformation , Stereoisomerism , Structure-Activity Relationship
9.
Org Biomol Chem ; 9(2): 504-15, 2011 Jan 21.
Article in English | MEDLINE | ID: mdl-20941422

ABSTRACT

During the studies towards the development of pentafluorophenyldimethylsilanes as a novel organosilicon cross coupling reagent it was revealed that the active silanolate and the corresponding disiloxane formed rapidly under basic conditions. The discovery that disiloxanes are in equilibrium with the silanolate led to the use of disiloxanes as cross coupling partners under fluoride free conditions. Our previous report focused on the synthesis and base induced cross coupling of aryl substituted vinyldisiloxanes with aryl halides; good yields and selectivities were achieved. As a continuation of our research, studies into the factors which influence the successful outcome of the cross coupling reaction with both alkyl and aryl substituted vinyldisiloxanes were examined and a proposed mechanism discussed. Further investigation into expanding the breadth and diversity of substituted vinyldisiloxanes in cross coupling was explored and applied to the synthesis of unsymmetrical trans-stilbenes and cyclic structures containing the trans-alkene architecture.


Subject(s)
Cross-Linking Reagents/chemistry , Silanes/chemical synthesis , Vinyl Compounds/chemical synthesis , Cyclization , Fluorides/chemistry , Molecular Structure , Stereoisomerism
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