Bromocriptine: Its place in type 2 diabetes Tx

For obese patients with type 2 diabetes (T2D) who do not tolerate other diabetes medications or for patients who need only a minimal reduction in glycosylated hemoglobin (A1c) to reach goal, bromocriptine may be a therapeutic agent to consider

À la Carte Cable: A Regulatory Solution to the Misinformation Subsidy

Although “fake news” is as old as mass media itself, concerns over disinformation have reached a fever pitch in our current media environment. Online media outlets’ heavy reliance on user-generated content has altered the traditional gatekeeping functions and professional standards associated with traditional news organizations. The idea of objectivity-focused informational content has primarily been substituted for a realist acceptance of the power and popularity of opinion-driven “news.” This shift is starkly visible now: mainstream news media outlets knowingly spread hoaxes, conspiracy theories, and the like. This current state of affairs is not some freak accident. The Supreme Court’s First Amendment jurisprudence has led us here. For example, the Court’s decision in Reno v. ACLU subjects government regulation of online speech to strict scrutiny review, hamstringing nearly any attempt at regulation (much less censorship) of online speech by the government. Similarly, content regulation of televised media is covered by the First Amendment’s capacious protections. And while broadcast media was once heavily regulated for content, the FCC’s adoption of deregulation resulted in the eventual repeal of a range of content limitations and requirements for licensees. Designing a content-neutral scheme to regulate media content directly is not only a complex legal problem, but it is also likely a non-starter. State actors are (rightly) unable to censor or remove content based on the ideological leanings of the content, and media disinformation directly implicates political speech about controversial topics. In an era where cross-platform news media is ubiquitous, the legal status quo has effectively ensured media platforms have near-total discretion to control—or more accurately, not control—the truthfulness of disseminated content. However, a market-based, bottom-up approach to content regulation could end-run the problems that plague government regulation of cable media. Industry research has suggested that cable “news” outlets generate more revenue from per-subscriber fees applied by cable companies than from advertising carried by those channels. In terms of cable news, per-channel costs are the highest costs in a monthly cable bill. This means that more than eighty million cable subscribers subsidize content that attracts fewer than two million viewers daily, including misinformation. This paper posits “à la carte” cable packaging as a solution to the subsidy of disinformation. Currently, cable subscribers are forced to buy programming channels even when they would rather not. This is particularly troubling in the case of news information because subscribers who wish to receive some programming are forced to subsidize other news content that may be objectionable. The resulting system of reverse compelled speech means that news organizations keep their subsidy while advocating against the interests of those footing the bill. Eliminating this involuntary subsidy flips the status quo on its head by making trustworthiness part of the bottom line, incentivizing prudent news self-regulation in an entirely content-neutral manner

Estradiol-treated mesenchymal stem cells improve myocardial recovery after ischemia

BACKGROUND: Stem cell therapy is a promising treatment modality for injured cardiac tissue. A novel mechanism for this cardioprotection may include paracrine actions. Our lab has recently shown that gender differences exist in mesenchymal stem cell (MSC) paracrine function. Estrogen is implicated in the cardioprotection found in females. It remains unknown whether 17beta-estradiol (E2) affects MSC paracrine function and whether E2-treated MSCs may better protect injured cardiac tissue. We hypothesize that E2-exposed MSCs infused into hearts prior to ischemia may demonstrate increased vascular endothelial growth factor (VEGF) production and greater protection of myocardial function compared to untreated MSCs. MATERIALS AND METHODS: Untreated and E2-treated MSCs were isolated, cultured, and plated and supernatants were harvested for VEGF assay (enzyme-linked immunosorbent assay). Adult male Sprague-Dawley rat hearts (n = 13) were isolated and perfused via Langendorff model and subjected to 15 min equilibration, 25 min warm global ischemia, and 40 min reperfusion. Hearts were randomly assigned to perfusate vehicle, untreated male MSC, or E2-treated male MSC. Transcoronary delivery of 1 million MSCs was performed immediately prior to ischemia in experimental hearts. RESULTS: E2-treated MSCs provoked significantly more VEGF production than untreated MSCs (933.2 +/- 64.9 versus 595.8 +/- 10.7 pg/mL). Postischemic recovery of left ventricular developed pressure was significantly greater in hearts infused with E2-treated MSCs (66.9 +/- 3.3%) than untreated MSCs (48.7 +/- 3.7%) and vehicle (28.9 +/- 4.6%) at end reperfusion. There was also greater recovery of the end diastolic pressure with E2-treated MSCs than untreated MSCs and vehicle. CONCLUSIONS: Preischemic infusion of MSCs protects myocardial function and viability. E2-treated MSCs may enhance this paracrine protection, which suggests that ex vivo modification of MSCs may improve therapeutic outcome

Quasi-molecular lines in Lyman wings of cool DA white dwarfs; Application to FUSE observations of G231-40

We present new theoretical calculations of the total line profiles of Lyman alpha and Lyman beta which include perturbations by both neutral hydrogen AND protons and all possible quasi-molecular states of H_2 and H_2^+. They are used to improve theoretical modeling of synthetic spectra for cool DA white dwarfs. We compare them with FUSE observation of G231-40. The appearance of the line wings between Lyman alpha and Lyman beta is shown to be sensitive to the relative abundance of hydrogen ions and neutral atoms, and thereby to provide a temperature diagnostic for stellar atmospheres and laboratory plasmas.Comment: 6 pages, 4 figures, accepted for publication in Astronomy and Astrophysic

Theoretical study of the absorption spectra of the sodium dimer

Absorption of radiation from the sodium dimer molecular states correlating to Na(3s)-Na(3s) is investigated theoretically. Vibrational bound and continuum transitions from the singlet X Sigma-g+ state to the first excited singlet A Sigma-u+ and singlet B Pi-u states and from the triplet a Sigma-u+ state to the first excited triplet b Sigma-g+ and triplet c Pi-g states are studied quantum-mechanically. Theoretical and experimental data are used to characterize the molecular properties taking advantage of knowledge recently obtained from ab initio calculations, spectroscopy, and ultra-cold atom collision studies. The quantum-mechanical calculations are carried out for temperatures in the range from 500 to 3000 K and are compared with previous calculations and measurements where available.Comment: 19 pages, 8 figures, revtex, eps

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania

Objective: The objective of this study was to assess the effectiveness of a routine multivitamin supplementation program for adults living with HIV in Tanzania. Design: We conducted a retrospective cohort study of 67,707 adults enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012. Methods: The Dar es Salaam HIV care and treatment program intended to provide all adult patients with multivitamin supplements (vitamins B-complex, C, and E) free of charge; however, intermittent stockouts and other implementation issues did not afford universal coverage. We use Cox proportional hazard models to assess the time-varying association of multivitamin supplementation with mortality and clinical outcomes. Results: The study cohort contributed 41,540 and 129,315 person-years of follow-up time to the ART-naïve and ART-experienced analyses, respectively. Among 48,207 ART-naïve adults, provision of multivitamins reduced the risk of mortality (adjusted hazard ratio (aHR): 0.69; 95% CI: 0.59-0.81), incident tuberculosis (TB) (aHR: 0.83; 0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83) after adjustment for time-varying confounding. Among 46,977 ART-experienced patients, multivitamins reduced mortality (HR: 0.86; 95% CI: 0.80-0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR: 0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision multivitamins appeared to be greatest during the first year of ART and declined over time (p-value \u3c0.001). Conclusion: Multivitamin supplementation appears to be a simple, effective, safe, and scalable program to improve survival, reduce incidence of TB, and improve treatment outcomes for adult HIV patients in Tanzania

Ferroelectric Solitons Crafted in Epitaxial Bismuth Ferrite Superlattices

In ferroelectrics, complex interactions among various degrees of freedom enable the condensation of topologically protected polarization textures. Known as ferroelectric solitons, these particle-like structures represent a new class of materials with promise for beyond CMOS technologies due to their ultrafine size and sensitivity to external stimuli. Such polarization textures have scarcely been reported in multiferroics. Here, we report a range of soliton topologies in bismuth ferrite strontium titanate superlattices. High-resolution piezoresponse force microscopy and Cs-corrected high-angle annular dark-field scanning transmission electron microscopy reveal a zoo of topologies, and polarization displacement mapping of planar specimens reveals center-convergent and divergent topological defects as small as 3 nm. Phase field simulations verify that some of these topologies can be classed as bimerons, with a topological charge of plus and minus one, and first-principles-based effective Hamiltonian computations show that the co-existence of such structures can lead to non-integer topological charges, a first observation in a BiFeO3-based system. Our results open new opportunities in multiferroic topotronics

Genetically-controlled Vesicle-Associated Membrane Protein 1 expression may contribute to Alzheimer’s pathophysiology and susceptibility

Background Alzheimer’s disease is a neurodegenerative disorder in which extracellular deposition of β-amyloid (Aβ) oligomers causes synaptic injury resulting in early memory loss, altered homeostasis, accumulation of hyperphosphorylated tau and cell death. Since proteins in the SNAP (Soluble N-ethylmaleimide-sensitive factor Attachment Protein) REceptors (SNARE) complex are essential for neuronal Aβ release at pre-synaptic terminals, we hypothesized that genetically controlled SNARE expression could alter neuronal Aß release at the synapse and hence play an early role in Alzheimer’s pathophysiology. Results Here we report 5 polymorphisms in Vesicle-Associated Membrane Protein 1 (VAMP1), a gene encoding a member of the SNARE complex, associated with bidirectionally altered cerebellar VAMP1 transcript levels (all p < 0.05). At the functional level, we demonstrated that control of VAMP1 expression by heterogeneous knockdown in mice resulted in up to 74% reduction in neuronal Aβ exocytosis (p < 0.001). We performed a case-control association study of the 5 VAMP1 expression regulating polymorphisms in 4,667 Alzheimer’s disease patients and 6,175 controls to determine their contribution to Alzheimer’s disease risk. We found that polymorphisms associated with increased brain VAMP1 transcript levels conferred higher risk for Alzheimer’s disease than those associated with lower VAMP1 transcript levels (p = 0.03). Moreover, we also report a modest protective association for a common VAMP1 polymorphism with Alzheimer’s disease risk (OR = 0.88, p = 0.03). This polymorphism was associated with decreased VAMP1 transcript levels (p = 0.02) and was functionally active in a dual luciferase reporter gene assay (p < 0.01). Conclusions Genetically regulated VAMP1 expression in the brain may modify both Alzheimer’s disease risk and may contribute to Alzheimer’s pathophysiology

Counting adolescents in: the development of an adolescent health indicator framework for population-based settings

Changing realities in low- and middle-income countries (LMICs) in terms of inequalities, urbanization, globalization, migration, and economic adversity shape adolescent development and health, as well as successful transitions between adolescence and young adulthood. It is estimated that 90% of adolescents live in LMICs in 2019, but inadequate data exist to inform evidence-based and concerted policies and programs tailored to address the distinctive developmental and health needs of adolescents. Population-based data surveillance such as Health and Demographic Surveillance Systems (HDSS) and school-based surveys provide access to a well-defined population and provide cost-effective opportunities to fill in data gaps about adolescent health and well-being by collecting population-representative longitudinal data. The Africa Research Implementation Science and Education (ARISE) Network, therefore, systematically developed adolescent health and well-being indicators and a questionnaire for measuring these indicators that can be used in population-based LMIC settings. We conducted a multistage collaborative and iterative process led by network members alongside consultation with health-domain and adolescent health experts globally. Seven key domains emerged from this process: socio-demographics, health awareness and behaviors; nutrition; mental health; sexual and reproductive health; substance use; and healthcare utilization. For each domain, we generated a clear definition; rationale for inclusion; sub-domain descriptions, and a set of questions for measurement. The ARISE Network will implement the questionnaire longitudinally (i.e., at two time-points one year apart) at ten sites in seven countries in sub-Saharan Africa and two countries in Asia. Integrating the questionnaire within established population-based data collection platforms such as HDSS and school settings can provide measured experiences of young people to inform policy and program planning and evaluation in LMICs and improve adolescent health and well-being