The clinical pharmacology of intranasal l-methamphetamine.

BackgroundWe studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant.Methods12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 microg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured.ResultsPlasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 +/- 56.1, 124.7 +/- 106.6, and 268.1 +/- 220.5 microg for ascending exposures (mean 4.2 +/- 3.3 microg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen.ConclusionInhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant

Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans

The mechanisms of drug-induced visions are poorly understood. Very few serotonergic hallucinogens have been studied in humans in decades, despite widespread use of these drugs and potential relevance of their mechanisms to hallucinations occurring in psychiatric and neurological disorders.We investigated the mechanisms of hallucinogen-induced visions by measuring the visual and perceptual effects of the hallucinogenic serotonin 5-HT2AR receptor agonist and monoamine releaser, 3,4-methylenedioxyamphetamine (MDA), in a double-blind placebo-controlled study. We found that MDA increased self-report measures of mystical-type experience and other hallucinogen-like effects, including reported visual alterations. MDA produced a significant increase in closed-eye visions (CEVs), with considerable individual variation. Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition.Drug-induced visions may have greater intensity in people with poor sensory or perceptual processing, suggesting common mechanisms with other hallucinatory syndromes. MDA is a potential tool to investigate mystical experiences and visual perception

The Ursinus Weekly, October 23, 1961

Lettinger to lead freshmen; Kelly elected vice-president • Sororities accept sixty new sisters • Two rediscovered works highlight woodwind five\u27s Bomberger performance • Minnich, Weiss win state Young Republican offices • Lawrence calls collegians for press conference: Weekly editor represents Ursinus at Capitol confab • Ursinus to hear Maine\u27s Senator Smith; Receives honorary degree on Founders Day • Efficiency, devotion to duty mark Margaret Chase Smith • Pradervand, Zabarah come to Ursinus from Switzerland, Yemen for studies • President lauds Parents Day; Excellent preparations cited • Editorial: Credit where credit is due • Ursinus in the past • Education by travel • Letters to the editor • 30 yard run breaks Bears backs following 12-6 victory over Wilkes • Hockey lassies remain unbeaten; Defeat Swarthmore, tie Temple girls • Bakermen boot first foes; Lose third tilt to Hens, 2-0 • Hakanson\u27s heft plugs defensive hole; Massachusetts man UC\u27s middle guard • Dean Kellow talks on medical school • Dr. Armstrong organizing second European Tour • German Club members get first-hand Berlin accounthttps://digitalcommons.ursinus.edu/weekly/1301/thumbnail.jp

The Lantern Vol. 28, No. 2, Spring 1961

• A New Bedlam • A Priori • Germ Warfare • Verse for a Sympathy Card • On Lamartine\u27s Crucifix • On Art • Hope • Hymn to the Morning • An Educator Speaks • Come Out • Insemination • A Day\u27s Hope • Laura • Walking Together • 20 September 1960 • 15 October 1960 • The Governor\u27s Dog • One of the Gang • Poem • Knowledge is Freedom • To Conservative Child • Seventeen American Skating Careers at the Zenithhttps://digitalcommons.ursinus.edu/lantern/1080/thumbnail.jp

Modeling the innate inflammatory cGAS/STING pathway: sexually dimorphic effects on microglia and cognition in obesity and prediabetes

IntroductionThe prevalence of obesity, prediabetes, and diabetes continues to grow worldwide. These metabolic dysfunctions predispose individuals to neurodegenerative diseases and cognitive impairment, including dementias such as Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD). The innate inflammatory cGAS/STING pathway plays a pivotal role in metabolic dysfunction and is an emerging target of interest in multiple neurodegenerative diseases, including AD/ADRD. Therefore, our goal was to establish a murine model to specifically target the cGAS/STING pathway to study obesity- and prediabetes-induced cognitive impairment.MethodsWe performed two pilot studies in cGAS knockout (cGAS-/-) male and female mice designed to characterize basic metabolic and inflammatory phenotypes and examine the impact of high-fat diet (HFD) on metabolic, inflammatory, and cognitive parameters.ResultscGAS-/- mice displayed normal metabolic profiles and retained the ability to respond to inflammatory stimuli, as indicated by an increase in plasma inflammatory cytokine production in response to lipopolysaccharide injection. HFD feeding caused expected increases in body weight and decreases in glucose tolerance, although onset was accelerated in females versus males. While HFD did not increase plasma or hippocampal inflammatory cytokine production, it did alter microglial morphology to a state indicative of activation, particularly in female cGAS-/- mice. However, HFD negatively impacted cognitive outcomes in male, but not female animals.DiscussionCollectively, these results suggest that cGAS-/- mice display sexually dimorphic responses to HFD, possibly based on differences in microglial morphology and cognition

Digital Photographic Practices as Expressions of Personhood and Identity:Variations Across School Leavers and Recent Retirees

Over the last two decades, digital photography has been adopted by young and old. Many young adults easily take photos, share them across multiple social networks using smartphones, and create digital identities for themselves consciously and unconsciously. Is the same true for older adults? As part of a larger mixed-methods study of online life in the UK, we considered digital photographic practices at two life transitions: leaving secondary school and retiring from work. In this paper, we report on a complex picture of different kinds of interactions with visual media online, and variation across age groups in the construction of digital identities. In doing so, we argue for a blurring of the distinctions between Chalfen’s ‘Kodak Culture’ and Miller and Edwards’ ‘Snaprs’. The camera lens often faces inwards for young adults: tagged ‘Selfies’ and images co-constructed with social network members commonly contribute to their digital identities. In contrast, retirees turn the camera’s lens outwards towards the world, not inwards to themselves. In concluding, we pay special attention to the digital social norms of co-creation of self and balancing convenience and privacy for people of varying ages, and what our findings mean for the future of photo-sharing as a form of self-expression, as today’s young adults grow old and retire

A Morbidity Survey of South African Primary Care

Publication of this article was funded by the Stellenbosch University Open Access Fund.The original publication is available at www.plosone.org/BibliographyBackground: Recent studies have described the burden of disease in South Africa. However these studies do not tell us which of these conditions commonly present to primary care providers, how these conditions may present and how providers make sense of them in terms of their diagnoses. Clinical nurse practitioners are the main primary care providers and need to be better prepared for this role. This study aimed to determine the range and prevalence of reasons for encounter and diagnoses found among ambulatory patients attending public sector primary care facilities in South Africa. Methodology/Principal Findings: The study was a multi-centre prospective cross-sectional survey of consultations in primary care in four provinces of South Africa: Western Cape, Limpopo, Northern Cape and North West. Consultations were coded prior to analysis by using the International Classification of Primary Care-Version 2 in terms of reasons for encounter (REF) and diagnoses. Altogether 18856 consultations were included in the survey and generated 31451 reasons for encounter (RFE) and 24561 diagnoses. Women accounted for 12526 (66.6%) and men 6288 (33.4%). Nurses saw 16238 (86.1%) and doctors 2612 (13.9%) of patients. The top 80 RFE and top 25 diagnoses are reported and ongoing care for hypertension was the commonest RFE and diagnosis. The 20 commonest RFE and diagnoses by age group are also reported. Conclusions/Significance: Ambulatory primary care is dominated by non-communicable chronic diseases. HIV/AIDS and TB are common, but not to the extent predicted by the burden of disease. Pneumonia and gastroenteritis are commonly seen especially in children. Women’s health issues such as family planning and pregnancy related visits are also common. Injuries are not as common as expected from the burden of disease. Primary care providers did not recognise mental health problems. The results should guide the future training and assessment of primary care providers.Stellenbosch University Open Access FundPublishers' Versio

Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease.

Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment

The association between alcohol exposure and self-reported health status: The effect of separating former and current drinkers

Aims: To investigate the direction and degree of potential bias introduced to analyses of drinking and health status which exclude former drinkers from exposure groups. Design: Pooled analysis of 14 waves (1997–2010) of the U.S. National Health Interview Survey (NHIS). Setting: General population-based study. Participants: 404,462 participants, from 14 waves of the NHIS, who had known self-reported health status and alcohol consumption status. Measurements: Self-reported health status was used as the indicator of health. Two approaches were used to classify alcohol consumption: (i) separation of former drinkers and current drinkers, and (ii) combined former and current drinkers. The prevalence of fair/ poor health by alcohol use, gender and age with 95% confidence intervals was estimated. The difference in prevalence of fair/ poor health status for lifetime abstainers, former drinkers, current drinkers and drinkers (former drinkers and current drinkers combined) were compared using Poisson regression with robust estimations of variance. Findings: Excluding former drinkers from drinker groups exaggerates the difference in health status between abstainers and drinkers, especially for males. Conclusions: In cohort study analyses, former drinkers should be assigned to a drinking category based on their previous alcohol consumption patterns and not treated as a discrete exposure group