Prescription Drug Monitoring Programs: A Policy Review and Recommendations for States

OBJECTIVE: To review existing PDMP statutes, and to provide recommendations for good legislative drafting that will create effective statutory components that will enhance the function and increase the use of PDMPs. METHODS: This policy review was conducted from July 2014 to December 2014, using articles dated January 01, 2004 to July 01, 2014. All PubMed searches were artificially limited to peer reviewed articles that were available as “free full text.” To ensure a comprehensive review of the policies, statutes from all fifty states were surveyed using the legal database, Westlaw Next. The search used terms associated with PDMPs. Each statute was reviewed by title and content to determine applicability to the study. The list of statutes compiled from Westlaw Next was compared with existing publications that survey PDMP statutes. The recommendations are based on the investigator’s experience and training in law and public health in consultation with a legislative expert, and supported by peer reviewed articles and legislative drafting guides. RESULTS: There are twelve main topical components that are addressed in existing state PDMP statutes. The policy brief’s primary three recommendations are to implement an advisory committee with an outlined membership, impose a duty for the committee to routinely review database information and to report on the findings, mandate practitioners to consult the database prior to administering controlled substances, and enact a PDMP educational component for practitioners. Appendix A of this policy review (attached) provides a full list of the recommendations for effective legislation on all twelve topical components

Digital health and universal health coverage: opportunities and policy considerations for Pacific Island health authorities

The emergence of digital health tools offer opportunities to complement and support the health system in the delivery of health services, especially in resource-constrained settings. Low- and middle-income countries have implemented various digital health interventions to support a range of health functions including patient information collection, diagnostics, supply-chain management, and remote clinical monitoring. The use of digital health in Pacific Island countries and territories (PICTs) is increasing. Effective implementation is hampered by misalignment between system design and contextual realities among other factors. Health service delivery in PICTs are highly resource sensitive, digital health must add demonstrable benefit to justify the expenditure of resources that could otherwise be allocated to facilities, equipment, staff, medicines and other commodities. This policy brief aims to identify health system challenges in the region which digital health interventions may address for decision-makers. It aims to identify policy and implementation factors to increase the likelihood of sustainable and scalable adoption of DHIs, and identify health resources to best capitalize on opportunities that digital health solutions offer. Recommendations suggest the need for each country or territory in the region to assess and determine their own priorities and opportunities, and devise digital health strategies in response. Recommendations outlined in the brief suggest the need to develop national-level digital health strategies to identify timelines and priorities, support mechanisms to strengthen digital health governance, human resource and institutional capacity. The brief aims to provide recommendations to aid relevant stakeholders to strengthen and support the use of ICTs to deliver equitable and integrated person-centered health care in the region

Conductive interpenetrating networks of polypyrrole and polycaprolactone encourage electrophysiological development of cardiac cells

Conductive and electroactive polymers have the potential to enhance engineered cardiac tissue function. In this study, an interpenetrating network of the electrically-conductive polymer polypyrrole (PPy) was grown within a matrix of flexible polycaprolactone (PCL) and evaluated as a platform for directing the formation of functional cardiac cell sheets. PCL films were either treated with sodium hydroxide to render them more hydrophilic and enhance cell adhesion or rendered electroactive with PPy grown via chemical polymerization yielding PPy–PCL that had a resistivity of 1.0 ± 0.4 kΩ cm, which is similar to native cardiac tissue. Both PCL and PPy–PCL films supported cardiomyocyte attachment; increasing the duration of PCL pre-treatment with NaOH resulted in higher numbers of adherent cardiomyocytes per unit area, generating cell densities which were more similar to those on PPy–PCL films (1568 ± 126 cells mm−2, 2880 ± 439 cells mm−2, 3623 ± 456 cells mm−2 for PCL with 0, 24, 48 h of NaOH pretreatment, respectively; 2434 ± 166 cells mm−2 for PPy–PCL). When cardiomyocytes were cultured on the electrically-conductive PPy–PCL, more cells were observed to have peripheral localization of the gap junction protein connexin-43 (Cx43) as compared to cells on NaOH-treated PCL (60.3 ± 4.3% vs. 46.6 ± 5.7%). Cx43 gene expression remained unchanged between materials. Importantly, the velocity of calcium wave propagation was faster and calcium transient duration was shorter for cardiomyocyte monolayers on PPy–PCL (1612 ± 143 μm/s, 910 ± 63 ms) relative to cells on PCL (1129 ± 247 μm/s, 1130 ± 20 ms). In summary, PPy–PCL has demonstrated suitability as an electrically-conductive substrate for culture of cardiomyocytes, yielding enhanced functional properties; results encourage further development of conductive substrates for use in differentiation of stem cell-derived cardiomyocytes and cardiac tissue engineering applications. Statement of Significance Current conductive materials for use in cardiac regeneration are limited by cytotoxicity or cost in implementation. In this manuscript, we demonstrate for the first time the application of a biocompatible, conductive polypyrrole–polycaprolactone film as a platform for culturing cardiomyocytes for cardiac regeneration. This study shows that the novel conductive film is capable of enhancing cell–cell communication through the formation of connexin-43, leading to higher velocities for calcium wave propagation and reduced calcium transient durations among cultured cardiomyocyte monolayers. Furthermore, it was demonstrated that chemical modification of polycaprolactone through alkaline-mediated hydrolysis increased overall cardiomyocyte adhesion. The results of this study provide insight into how cardiomyocytes interact with conductive substrates and will inform future research efforts to enhance the functional properties of cardiomyocytes, which is critical for their use in pharmaceutical testing and cell therapy

A case for the standardized letter of recommendation in otolaryngology residency selection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102208/1/lary24431.pd

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Targeted transcriptional activation of silent oct4 pluripotency gene by combining designer TALEs and inhibition of epigenetic modifiers

Specific control of gene activity is a valuable tool to study and engineer cellular functions. Recent studies uncovered the potential of transcription activator-like effector (TALE) proteins that can be tailored to activate user-defined target genes. It remains however unclear whether and how epigenetic modifications interfere with TALE-mediated transcriptional activation. We studied the activity of five designer TALEs (dTALEs) targeting the oct4 pluripotency gene. In vitro assays showed that the five dTALEs that target distinct sites in the oct4 promoter had the expected DNA specificity and comparable affinities to their corresponding DNA targets. In contrast to their similar in vitro properties, transcriptional activation of oct4 by these distinct dTALEs varied up to 25-fold. While dTALEs efficiently upregulated transcription of the active oct4 promoter in embryonic stem cells (ESCs) they failed to activate the silenced oct4 promoter in ESC-derived neural stem cells (NSCs), indicating that as for endogenous transcription factors also dTALE activity is limited by repressive epigenetic mechanisms. We therefore targeted the activity of epigenetic modulators and found that chemical inhibition of histone deacetylases by valproic acid or DNA methyltransferases by 5-aza-2′-deoxycytidine facilitated dTALE-mediated activation of the epigenetically silenced oct4 promoter in NSCs. Notably, demethylation of the oct4 promoter occurred only if chemical inhibitors and dTALEs were applied together but not upon treatment with inhibitors or dTALEs only. These results show that dTALEs in combination with chemical manipulation of epigenetic modifiers facilitate targeted transcriptional activation of epigenetically silenced target genes

Star Formation Laws and Efficiencies across 80 Nearby Galaxies

We measure empirical relationships between the local star formation rate (SFR) and properties of the star-forming molecular gas on 1.5 kpc scales across 80 nearby galaxies. These relationships, commonly referred to as "star formation laws," aim at predicting the local SFR surface density from various combinations of molecular gas surface density, galactic orbital time, molecular cloud free-fall time, and the interstellar medium dynamical equilibrium pressure. Leveraging a multiwavelength database built for the PHANGS survey, we measure these quantities consistently across all galaxies and quantify systematic uncertainties stemming from choices of SFR calibrations and the CO-to-H$_2$ conversion factors. The star formation laws we examine show 0.3-0.4 dex of intrinsic scatter, among which the molecular Kennicutt-Schmidt relation shows a $\sim$10% larger scatter than the other three. The slope of this relation ranges $\beta\approx0.9{-}1.2$, implying that the molecular gas depletion time remains roughly constant across the environments probed in our sample. The other relations have shallower slopes ($\beta\approx0.6{-}1.0$), suggesting that the star formation efficiency (SFE) per orbital time, the SFE per free-fall time, and the pressure-to-SFR surface density ratio (i.e., the feedback yield) may vary systematically with local molecular gas and SFR surface densities. Last but not least, the shapes of the star formation laws depend sensitively on methodological choices. Different choices of SFR calibrations can introduce systematic uncertainties of at least 10-15% in the star formation law slopes and 0.15-0.25 dex in their normalization, while the CO-to-H$_2$ conversion factors can additionally produce uncertainties of 20-25% for the slope and 0.10-0.20 dex for the normalization.Comment: 10 pages main text + 2 appendices. ApJL in press. Data products available at https://www.canfar.net/storage/list/phangs/RELEASES/Sun_etal_2023 . Slides summarizing key results can be found at https://www.dropbox.com/s/5gsegexeo9n0t05/Sun_et_PHANGS_2023.pptx?dl=

Nogo-A Expression in the Brain of Mice with Cerebral Malaria

Cerebral malaria (CM) is associated with a high rate of transient or persistent neurological sequelae. Nogo-A, a protein that is highly expressed in the endoplasmic reticulum (ER) of the mammalian central nervous system (CNS), is involved in neuronal regeneration and synaptic plasticity in the injured CNS. The current study investigates the role of Nogo-A in the course of experimental CM. C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. Brain homogenates of mice with different clinical severity levels of CM, infected animals without CM and control animals were analyzed for Nogo-A up-regulation by Western blotting and immunohistochemistry. Brain regions with Nogo-A upregulation were evaluated by transmission electron microscopy. Densitometric analysis of Western blots yielded a statistically significant upregulation of Nogo-A in mice showing moderate to severe CM. The number of neurons and oligodendrocytes positive for Nogo-A did not differ significantly between the studied groups. However, mice with severe CM showed a significantly higher number of cells with intense Nogo-A staining in the brain stem. In this region ultrastructural alterations of the ER were regularly observed. Nogo-A is upregulated during the early course of experimental CM. In the brain stem of severely affected animals increased Nogo-A expression and ultrastructural changes of the ER were observed. These data indicate a role of Nogo-A in neuronal stress response during experimental CM

Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer

Neoadjuvant and adjuvant chemotherapies provide survival benefits to breast cancer patients, in particular in estrogen receptor negative (ER-) cancers, by reducing rates of recurrences. It is assumed that the benefits of (neo)adjuvant chemotherapy are due to the killing of disseminated, residual cancer cells, however, there is no formal evidence for it. Here, we provide experimental evidence that ER- breast cancer cells that survived high-dose Doxorubicin and Methotrexate based chemotherapies elicit a state of immunological dormancy. Hallmark of this dormant phenotype is the sustained activation of the IRF7/IFN-beta/IFNAR axis subsisting beyond chemotherapy treatment. Upregulation of IRF7 in treated cancer cells promoted resistance to chemotherapy, reduced cell growth and induced switching of the response from a myeloid derived suppressor cell-dominated immune response to a CD4(+)/CD8(+) T cell-dependent anti-tumor response. IRF7 silencing in tumor cells or systemic blocking of IFNAR reversed the state of dormancy, while spontaneous escape from dormancy was associated with loss of IFN-beta production. Presence of IFN-beta in the circulation of ER- breast cancer patients treated with neoadjuvant Epirubicin chemotherapy correlated with a significantly longer distant metastasis-free survival. These findings establish chemotherapy-induced immunological dormancy in ER- breast cancer as a novel concept for (neo)adjuvant chemotherapy activity, and implicate sustained activation of the IRF7/IFN-beta/IFNAR pathway in this effect. Further, IFN-beta emerges as a potential predictive biomarker and therapeutic molecule to improve outcome of ER- breast cancer patients treated with (neo)adjuvant chemotherapy.Peer reviewe

Loss of PTEN Is Not Associated with Poor Survival in Newly Diagnosed Glioblastoma Patients of the Temozolomide Era

Introduction: Pre-temozolomide studies demonstrated that loss of the tumor suppressor gene PTEN held independent prognostic significance in GBM patients. We investigated whether loss of PTEN predicted shorter survival in the temozolomide era. The role of PTEN in the PI3K/Akt pathway is also reviewed. Methods: Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2007 and 2010. Cox proportional hazards analysis was used to calculate the independent effects of PTEN expression, age