• Lateral gene transfer between prokaryotes and eukaryotes

      Sieber, K.B.; Bromley, R.E.; Hotopp, Julie C.D. (Elsevier Inc., 2017)
      Lateral gene transfer (LGT) is an all-encompassing term for the movement of DNA between diverse organisms. LGT is synonymous with horizontal gene transfer, and the terms are used interchangeably throughout the scientific literature. While LGT has been recognized within the bacteria domain of life for decades, inter-domain LGTs are being increasingly described. LGTs between bacteria and complex multicellular organisms are of interest because they challenge the long-held dogma that such transfers could only occur in closely-related, single-celled organisms. Scientists will continue to challenge our understanding of LGT as we sequence more, diverse organisms, as we sequence more endosymbiont-colonized arthropods, and as we continue to appreciate LGT events, both young and old. Copyright 2017 The Authors
    • Effect of a small molecule lipid II binder on bacterial cell wall stress

      Malin, J.; Shetty, A.C.; Daugherty, S.C. (Dove Medical Press Ltd., 2017)
      We have recently identified small molecule compounds that act as binders of Lipid II, an essential precursor of bacterial cell wall biosynthesis. Lipid II comprised a hydrophilic head group that includes a peptidoglycan subunit composed of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) coupled to a short pentapeptide moiety. This headgroup is coupled to a long bactoprenol chain via a pyrophosphate group. Here, we report on the cell wall activity relationship of dimethyl-3-methyl(phenyl)amino-ethenylcyclohexylidene-propenyl-3-ethyl-1,3-benzothiazolium iodide (compound 5107930) obtained by functional and genetic analyses. Our results indicate that compounds bind to Lipid II and cause specific upregulation of the vancomycin-resistance associated gene vraX. vraX is implicated in the cell wall stress stimulon that confers glycopeptide resistance. Our small molecule Lipid II inhibitor retained activity against strains of Staphylococcus aureus mutated in genes encoding the cell wall stress stimulon. This suggests the feasibility of developing this new scaffold as a therapeutic agent in view of increasing glycopeptide resistance. Copyright 2017 Malin et al.
    • The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections

      Sartelli, M.; Chichom-Mefire, A.; Labricciosa, F.M. (BioMed Central Ltd., 2017)
      Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections. Copyright 2017 The Author(s).
    • Transforming concepts into clinical trials and creating a multisite network: The Leadership and Operations Center of the Antibacterial Resistance Leadership Group

      Cross, H.R.; Harris, A.; Arias, R.M. (Oxford University Press, 2017)
      The Leadership and Operations Center (LOC) is responsible for facilitating, coordinating, and implementing the Antibacterial Resistance Leadership Group (ARLG) scientific agenda by engaging thought leaders; soliciting research proposals; and developing the processes, tools, and infrastructure required to operationalize studies and create and sustain the ARLG network. These efforts are ongoing as new projects are developed and the network expands and grows to address the ever-changing priorities in antibacterial resistance. This article describes the innovations, accomplishments, and opportunities of the LOC since the inception of the ARLG in 2013. Copyright The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
    • Effects of long-term water-aging on novel anti-biofilm and protein-repellent dental composite

      Zhang, N.; Zhang, K.; Melo, M.A.S. (MDPI AG, 2017)
      The aims of this study were to: (1) synthesize an anti-biofilm and protein-repellet dental composite by combining 2-methacryloyloxyethyl phosphorylcholine (MPC) with quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM); and (2) evaluate the effects of water-aging for 180 days on protein resistance, bacteria-killing ability, and mechanical properties of MPC-DMAHDM composite. MPC and DMAHDM were added into a resin composite. Specimens were stored in distilled water at 37 °C for 1, 30, 90, and 180 days. Mechanical properties were measured in three-point flexure. Protein attachment onto the composite was evaluated by a micro bicinchoninic acid approach. An oral plaque microcosm biofilm model was employed to evaluate oral biofilm viability vs. water-aging time. Mechanical properties of the MPC-DMAHDM composite after 180-day immersion matched those of the commercial control composite. The composite with 3% MPC + 1.5% DMAHDM had much stronger resistance to protein adhesion than control (p < 0.05). MPC + DMAHDM achieved much stronger biofilm-eradicating effects than MPC or DMAHDM alone (p < 0.05). Biofilm colony-forming units on the 3% MPC + 1.5% DMAHDM composite were three orders of magnitude lower than commercial control. The protein-repellent and antibacterial effects were durable and showed no loss in water-aging from 1 to 180 days. The novel MPC-DMAHDM composite possessed strong and durable resistance to protein adhesion and potent bacteria-eradicating function, while matching the load-bearing ability of a commercial dental composite. The novel MPC-DMAHDM composite represents a promising means of suppressing oral plaque growth, acid production, and secondary caries. Copyright 2017 by the authors; licensee MDPI, Basel, Switzerland.
    • The effect of antibiotic exposure and specimen volume on the detection of bacterial pathogens in children with pneumonia

      Driscoll, A.J.; Knoll, M.D.; Hammitt, L.L. (Oxford University Press, 2017)
      Background: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. Methods: PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1–59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. Results: Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%–7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%–0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. Conclusions: Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management. Copyright The Author 2017.
    • Antigliadin antibodies (AGA IgG) are related to neurochemistry in schizophrenia

      Rowland, L.M.; Demyanovich, H.K.; Wijtenburg, S.A. (Frontiers Media S.A., 2017)
      Inflammation may play a role in schizophrenia; however, subgroups with immune regulation dysfunction may serve as distinct illness phenotypes with potential different treatment and prevention strategies. Emerging data show that about 30% of people with schizophrenia have elevated antigliadin antibodies of the IgG type, representing a possible subgroup of schizophrenia patients with immune involvement. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood-brain barrier with resulting neuroinflammation. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows the quantification of certain neurochemicals in vivo thmay proxy inflammation in the brain such as myoinositol and choline-containing compounds (glycerophosphorylcholine and phosphorylcholine). The objective of this exploratory study was to examine the relationship between serum AGA IgG levels and MRS neurochemical levels. We hypothesized that higher AGA IgG levels would be associated with higher levels of myoinositol and choline-containing compounds (glycerophosphorylcholine plus phosphorylcholine GPC + PC) in the anterior cingulate cortex. Thirty-three participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder had blood drawn and underwent neuroimaging using MRS within 9 months. We found that 10/33 (30%) had positive AGA IgG (?20 U) similar to previous findings. While there were no significant differences in myoinositol and GPC + PC levels between patients with and without AGA IgG positivity, there were significant relationships between both myoinositol (r = 0.475, p = 0.007) and GPC + PC (r = 0.36, p = 0.045) with AGA IgG levels. This study shows a possible connection of AGA IgG antibodies to putative brain inflammation as measured by MRS in schizophrenia. Copyright 2017 Rowland, Demyanovich, Wijtenburg, Eaton, Rodriguez, Gaston, Cihakova, Talor, Liu, McMahon, Hong and Kelly.
    • Heat-polymerized resin containing dimethylaminododecyl methacrylate inhibits Candida albicans biofilm

      Chen, H.; Han, Q.; Zhou, X. (MDPI AG, 2017)
      The prevalence of stomatitis, especially caused by Candida albicans, has highlighted the need of new antifungal denture materials. This study aimed to develop an antifungal heat-curing resin containing quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM), and evaluate its physical performance and antifungal properties. The discs were prepared by incorporating DMADDM into the polymer liquid of a methyl methacrylate-based, heat-polymerizing resin at 0% (control), 5%, 10%, and 20% (w/w). Flexure strength, bond quality, surface charge density, and surface roughness were measured to evaluate the physical properties of resin. The specimens were incubated with C. albicans solution in medium to form biofilms. Then Colony-Forming Units, XTT assay, and scanning electron microscope were used to evaluate antifungal effect of DMADDM-modified resin. DMADDM modified acrylic resin had no effect on the flexural strength, bond quality, and surface roughness, but it increased the surface charge density significantly. Meanwhile, this new resin inhibited the C. albicans biofilm significantly according to the XTT assay and CFU counting. The hyphae in C. albicans biofilm also reduced in DMADDM-containing groups observed by SEM. DMADDM modified acrylic resin was effective in the inhibition of C. albicans biofilm with good physical properties. Copyright 2017 by the authors.
    • Predicting factors of depression, antidepressant use and positive response to antidepressants in perinatal and postpartum women

      Vu, H.; Shaya, F.T. (Bentham Science Publishers B.V., 2017)
      In the United States, there is a disparity in knowledge of nationwide depression prevalence, the antidepressant use and the antidepressant responses during perinatal/postpartum periods. Objective: This study investigated the predicting factors of depression, antidepressant use and positive antidepressant response during the perinatal/postpartum periods. Method: The 2007-2012 National Health and Nutrition Examination Surveys (NHANES) were combined to identify adult pregnant women, those within the 18-month postpartum period (n=492) and their depression statuses via demographics, health care accessibility, antidepressant use and illicit drug use information. The characteristics of different study groups were compared (depression versus no-depression groups, antidepressant users versus non-antidepressant users, and antidepressant responders versus antidepressant nonresponders). Multivariable logistic regression analysis was used to predict factors of perinatal depression (PND)/ postpartum depression (PPD), antidepressant use and antidepressant positive response in PND/PPD. Results: PND/PPD individuals had higher rates of mental health visits. No predicting factor for developing PND/PPD was shown. Antidepressant users were significantly older with insurance and recent health checkups/ mental visits. Being below the poverty level and having some health care accessibility are predictors for being on antidepressants. Recent non-illicit drug use is a predictor for PND/PPD symptom improvement while on antidepressants. Conclusion: The group of those with social-economic disadvantages was more likely to be on antidepressants for PND/PPD. Illicit drug users were less likely to show improvement with antidepressants. The safety and efficacy of antidepressant use during this period is controversial. More studies need to focus on the barriers involving antidepressant treatments, the safety and outcomes of antidepressants for PND/PPD management. Copyright 2017 Vu and Shaya.
    • Perioperative management and monitoring of antiplatelet agents: A focused review on aspirin and P2Y12 inhibitors

      Mazzeffi, M.A.; Lee, K.; Taylor, B. (Korean Society of Anesthesiologists, 2017)
      Platelets play pivotal roles in hemostasis as well as pathological arterial thrombosis. The combination of aspirin and a P2Y12 inhibitor has become the mainstay therapy in the ageing population with cardiovascular conditions, particularly during and after percutaneous coronary intervention. A number of novel P2Y12 inhibitors has become available in the recent years, and they markedly vary in pharmacokinetic and pharmacodynamic properties. Perioperative physicians today face a challenge of preventing hemorrhage due to platelet inhibitors, while minimizing thrombotic risks. There are several point-of-care platelet function tests available in the peri-procedural assessment of residual platelet aggregation. However, these platelet function tests are not standardized in terms of sample processing, agonist type and potency as well as methods of detecting platelet activity. Understanding the differences in pharmacological properties of antiplatelet agents, principles of platelet function tests, and pertinent hemostatic strategies may be useful to anesthesiologists and intensivists who manage perioperative issues associated with antiplatelet agents. The objectives of this review are: 1) to discuss clinical data on aspirin and P2Y12 inhibitors relating to perioperative bleeding, 2) to outline different features of point-of-care platelet function tests, and 3) to discuss therapeutic options for the prevention and treatment of bleeding associated with antiplatelet agents. Copyright the Korean Society of Anesthesiologists, 2017.
    • Improving antiretroviral therapy adherence in resource-limited settings at scale: A discussion of interventions and recommendations

      Haberer, J.E.; Sabin, L.; Amico, K.R. (Wiley Blackwell, 2017)
      Introduction: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. Methods: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-Analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low-And middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. Conclusions: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS. Copyright 2017 Haberer JE et al.
    • Novel galeterone analogs act independently of AR and AR-V7 for the activation of the unfolded protein response and induction of apoptosis in the CWR22Rv1 prostate cancer cell model

      McCarty, D.J.; Huang, W.; Kane, M.A. (Impact Journals LLC, 2017)
      The androgen receptor (AR) has long been the primary target for the treatment of prostate cancer (PC). Despite continuous efforts to block AR activity through ligand depletion, AR antagonism, AR depletion and combinations thereof, advanced PC tumors remain resilient. Herein, we evaluate two galeterone analogs, VNPT-178 and VNLG-74A, in PC cell models of diverse androgen and AR dependence attempting to delineate their mechanisms of action and potential clinical utility. Employing basic biochemical techniques, we determined that both analogs have improved antiproliferative and anti-AR activities compared to FDA-approved abiraterone and enzalutamide. However, induction of apoptosis in these models is independent of the AR and its truncated variant, AR-V7, and instead likely results from sustained endoplasmic reticulum stress and deregulated calcium homeostasis. Using in silico molecular docking, we predict VNPT-178 and VNLG-74A bind the ATPase domain of BiP/Grp78 and Hsp70-1A with greater affinity than the AR. Disruption of 70 kDa heat shock protein function may be the underlying mechanism of action for these galeterone analogs. Therefore, despite simultaneously antagonizing AR activity, AR and/or AR-V7 expression alone may inadequately predict a patient's response to treatment with VNPT-178 or VNLG-74A. Future studies evaluating the context-specific limitations of these compounds may provide clarity for their clinical application. Copyright McCarty et al.
    • Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells

      Lucendo-Villarin, B.; Filis, P.; Swortwood, M.J. (Springer Verlag, 2017)
      The liver is a dynamic organ which is both multifunctional and highly regenerative. A major role of the liver is to process both endo and xenobiotics. Cigarettes are an example of a legal and widely used drug which can cause major health problems for adults and constitute a particular risk to the foetus, if the mother smokes during pregnancy. Cigarette smoke contains a complex mixture of thousands of different xenobiotics, including nicotine and polycyclic aromatic hydrocarbons. These affect foetal development in a sex-specific manner, inducing sex-dependant molecular responses in different organs. To date, the effect of maternal smoking on the foetal liver has been studied in vitro using cell lines, primary tissue and animal models. While these models have proven to be useful, poor cell phenotype, tissue scarcity, batch-to-batch variation and species differences have led to difficulties in data extrapolation toward human development. Therefore, in this study we have employed hepatoblasts, derived from pluripotent stem cells, to model the effects of xenobiotics from cigarette smoke on human hepatocyte development. Highly pure hepatocyte populations (>90%) were produced in vitro and exposed to factors present in cigarette smoke. Analysis of ATP levels revealed that, independent of the sex, the majority of smoking derivatives tested individually did not deplete ATP levels below 50%. However, following exposure to a cocktail of smoking derivatives, ATP production fell below 50% in a sex-dependent manner. This was paralleled by a loss metabolic activity and secretory ability in both female and male hepatocytes. Interestingly, cell depletion was less pronounced in female hepatocytes, whereas caspase activation was ~twofold greater, indicating sex differences in cell death upon exposure to the smoking derivatives tested. Copyright 2017, The Author(s).
    • Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density curve to determine time of replanning

      Chen, S.; Le, Q.; Mutaf, Y. (John Wiley and Sons Ltd, 2017)
      Purpose: (a) To investigate the accuracy of cone‐beam computed tomography (CBCT)–derived dose distributions relative to fanbeam–based simulation CT‐derived dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the appropriateness of replanning. Methods and materials: Image data corresponding to 40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were randomly selected. Each patient had both intensity‐modulated radiation therapy and volumetric‐modulated arc therapy plans; these 80 plans were subsequently recomputed on the CBCT images using a patient‐specific stepwise curve (Hounsfield units‐to‐density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation‐CT–derived treatment plans and CBCT‐based plans. Gamma analyses were performed using criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT‐derived doses were then used to evaluate the appropriateness of replanning decisions in 12 additional HN patients whose plans were previously revised during radiation therapy because of anatomic changes; replanning in these cases was guided by the conventional observed source‐to‐skin‐distance change‐derived approach. Results: For all disease sites, the difference in PTV mean dose was 0.1% ± 1.1%, D2% was 0.7% ± 0.1%, D95% was 0.2% ± 1.1%, D98% was 0.2% ± 1.0%, and V95% was 0.3% ± 0.8%; For 3D dose comparison, 99.0% ± 1.9%, 97.6% ± 4.4%, and 95.3% ± 6.0% of points passed the 3%/3 mm criterion of gamma analysis in high‐, medium‐, and low‐dose zones, respectively. The CBCT images achieved comparable dose distributions. In the 12 previously replanned 12 HN patients, CBCT‐based dose predicted well changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the replanning criteria, 7/12 patients could avoid replanning. Conclusions: CBCT‐based dose calculations produced accuracy comparable to that of simulation CT. CBCT‐based dosimetry can guide the decision to replan during the course of treatment. Copyright 2017 American Association of Physicists in Medicine.
    • Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

      Carlier, J.; Diao, X.; Sempio, C. (Springer New York LLC, 2017)
      DB-CHMINACA (MAB-CHMINACA) is a new synthetic cannabinoid with high potency and many reported adverse events and fatalities. The drug is currently scheduled in several countries in Europe and the USA. Analytical methods need to be developed to confirm ADB-CHMINACA intake for clinical and forensic programs. For many synthetic cannabinoids, parent compound is not detectable in biological samples after intake, making the detection of metabolites the only way to prove consumption. Therefore, detection of ADB-CHMINACA metabolites in biological specimens is critical. Since there are currently no published data on ADB-CHMINACA metabolism, we aimed to identify its major metabolites. Cryopreserved human hepatocytes were incubated with 10 μmol/L ADB-CHMINACA for 3 h. Incubations were analyzed with liquid chromatography on a biphenyl column, high resolution tandem mass spectrometry (orbitrap), and metabolite identification software. A reference standard of six commercially available potential metabolites was simultaneously analyzed under the same conditions to allow correct assignment of isomers. We detected ten major metabolites. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, as also observed with structural analogs’ metabolism. Minor reactions also occurred at the tert-butyl chain. Only two analytical standards of potential metabolites matched an actual metabolite detected in hepatocyte incubations. We recommend A9 (ADB-CHMINACA hydroxycyclohexylmethyl), A4 (ADB-CHMINACA 4″-hydroxycyclohexyl), and A6 (ADB-CHMINACA hydroxycyclohexylmethyl) as metabolite targets to document ADB-CHMINACA intake in clinical and forensic cases. Additionally, these results will guide analytical standard manufacturers to better provide suitable references for further studies on ADB-CHMINACA metabolism. Copyright 2017, The Author(s).
    • Adolescent Coordinated Transition (ACT) to improve health outcomes among young people living with HIV in Nigeria: Study protocol for a randomized controlled trial

      Sam-Agudu, N.A.; Pharr, J.R.; Bruno, T. (BioMed Central Ltd., 2017)
      Background: Adolescents living with HIV (ALHIV) have worse health outcomes than other populations of people living with HIV. Contributing factors include lack of standard and comprehensive procedures for ALHIV transitioning from pediatric to adult care. This has contributed to poor retention at, and following transition, which is problematic especially in high ALHIV-burden, resource-limited settings like Nigeria. Methods: Using a two-arm cluster randomized control design, the Adolescent Coordinated Transition (ACT) trial will measure the comparative effectiveness of a graduated transition and organized support group intervention against the usual practice of abrupt transfer of Nigerian ALHIV from pediatric to adult care. This study will be conducted at 12 secondary and tertiary healthcare facilities (six intervention, six control) across all six of Nigeria's geopolitical zones. The study population is 13- to 17-year-old ALHIV (N = 216, n = 108 per study arm) on antiretroviral therapy. Study participants will be followed through a 12-month pre-transfer/transition period and for an additional 24 months post transfer/transition. The primary outcome measure is the proportion of ALHIV retained in care at 12 and 24 months post transfer. Secondary outcome measures are proportions of ALHIV achieving viral suppression and demonstrating increased psychosocial wellbeing and self-efficacy measured by psychometric tests including health locus of control, functional social support, perceived mental health, and sexual risk and behavior. Discussion: We hypothesize that the ACT intervention will significantly increase psychosocial wellbeing, retention in care and ultimately viral suppression among ALHIV. ACT's findings have the potential to facilitate the development of standard guidelines for transitioning ALHIV and improving health outcomes in this population. The engagement of a consortium of local implementing partners under the Nigeria Implementation Science Alliance allows for nationwide study implementation and expedient results dissemination to program managers and policy-makers. Ultimately, ACT may also provide evidence to inform transitioning guidelines not only for ALHIV but for adolescents living with other chronic diseases in resource-limited settings. Trial registration: ClinicalTrials.gov, ID: NCT03152006. Registered on May 12, 2017. Copyright 2017 The Author(s).
    • A Deep Proteome Analysis Identifies the Complete Secretome as the Functional Unit of Human Cardiac Progenitor Cells

      Sharma, S.; Mishra, R.; Bigham, G.E. (Lippincott Williams and Wilkins, 2017)
      Rationale: Cardiac progenitor cells are an attractive cell type for tissue regeneration, but their mechanism for myocardial remodeling is still unclear. Objective: This investigation determines how chronological age influences the phenotypic characteristics and the secretome of human cardiac progenitor cells (CPCs), and their potential to recover injured myocardium. Methods and Results: Adult (aCPCs) and neonatal (nCPCs) cells were derived from patients aged >40 years or <1 month, respectively, and their functional potential was determined in a rodent myocardial infarction model. A more robust in vitro proliferative capacity of nCPCs, compared with aCPCs, correlated with significantly greater myocardial recovery mediated by nCPCs in vivo. Strikingly, a single injection of nCPC-derived total conditioned media was significantly more effective than nCPCs, aCPC-derived TCM, or nCPC-derived exosomes in recovering cardiac function, stimulating neovascularization, and promoting myocardial remodeling. High-resolution accurate mass spectrometry with reverse phase liquid chromatography fractionation and mass spectrometry was used to identify proteins in the secretome of aCPCs and nCPCs, and the literature-based networking software identified specific pathways affected by the secretome of CPCs in the setting of myocardial infarction. Examining the TCM, we quantified changes in the expression pattern of 804 proteins in nCPC-derived TCM and 513 proteins in aCPC-derived TCM. The literature-based proteomic network analysis identified that 46 and 6 canonical signaling pathways were significantly targeted by nCPC-derived TCM and aCPC-derived TCM, respectively. One leading candidate pathway is heat-shock factor-1, potentially affecting 8 identified pathways for nCPC-derived TCM but none for aCPC-derived TCM. To validate this prediction, we demonstrated that the modulation of heat-shock factor-1 by knockdown in nCPCs or overexpression in aCPCs significantly altered the quality of their secretome. Conclusions: A deep proteomic analysis revealed both detailed and global mechanisms underlying the chronological age-based differences in the ability of CPCs to promote myocardial recovery via the components of their secretome. Copyright 2016 American Heart Association, Inc.
    • Patient preferences for venous thromboembolism prophylaxis after injury: A discrete choice experiment

      Haac, B.E.; O'Hara, N.N.; Mullins, C.D. (BMJ Publishing Group, 2017)
      Objective Limited evidence for the optimal venous thromboembolism (VTE) prophylaxis regimen in orthopaedic trauma leads to variability in regimens. We sought to delineate patient preferences towards cost, complication profile, and administration route (oral tablet vs. subcutaneous injection). Design Discrete choice experiment (DCE). Setting Level 1 trauma center in Baltimore, USA. Participants 232 adult trauma patients (mean age 47.9 years) with pelvic or acetabular fractures or operative extremity fractures. Primary and secondary outcome measures Relative preferences and trade-off estimates for a 1% reduction in complications were estimated using multinomial logit modelling. Interaction terms were added to the model to assess heterogeneity in preferences. Results Patients preferred oral tablets over subcutaneous injections (marginal utility, 0.16; 95% CI: 0.11 - 0.21, P<0.0001). Preferences changed in favor of subcutaneous injections with an absolute risk reduction of 6.98% in bleeding, 4.53% in wound complications requiring reoperation, 1.27% in VTE, and 0.07% in death from pulmonary embolism (PE). Patient characteristics (sex, race, type of injury, time since injury) affected patient preferences (P<0.01). Conclusions Patients preferred oral prophylaxis and were most concerned about risk of death from PE. Furthermore, the findings estimated the trade-offs acceptable to patients and heterogeneity in preferences for VTE prophylaxis. Copyright Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
    • Occipital dysembryoplastic neuroepithelial tumor presenting as adult-onset temporal epilepsy

      Patira, R.; Nathan, C.; Zubkov, S. (Elsevier Inc., 2017)
      Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor which commonly presents as childhood-onset temporal lobe epilepsy (TLE). We present a case of histologically proven DNET with a clinical presentation and scalp EEG suggestive of adult-onset TLE. MRI showed an occipital lesion. PET showed abnormal metabolism of the occipital lesion and the ipsilateral temporal lobe; raising concern for an abnormal functional network reorganization. Intracranial EEG showed interictal spikes and seizures originating from the occipital lesion with no seizures emanating from the temporal lobe. Occipital DNET due to their chronic nature can reorganize the network and mimic TLE. Copyright 2017 The Authors
    • Impact of health policy changes on emergency medicine in Maryland stratified by socioeconomic status

      Pimentel, L.; Anderson, D.; Golden, B. (eScholarship, 2017)
      Introduction: On January 1, 2014, the financing and delivery of healthcare in the state of Maryland (MD) profoundly changed. The insurance provisions of the Patient Protection and Affordable Care Act (ACA) began implementation and a major revision of MD's Medicare waiver ushered in a Global Budget Revenue (GBR) structure for hospital reimbursement. Our objective was to analyze the impact of these policy changes on emergency department (ED) utilization, hospitalization practices, insurance profiles, and professional revenue. We stratified our analysis by the socioeconomic status (SES) of the ED patient population. Methods: We collected monthly mean data including patient volume, hospitalization percentages, payer mix, and professional revenue from January 2013 through December 2015 from a convenience sample of 11 EDs in Maryland. Using regression models, we compared each of the variables 18 months after the policy changes and a six-month washout period to the year prior to ACA/GBR implementation. We included the median income of each ED's patient population as an explanatory variable and stratified our results by SES. Results: Our 11 EDs saw an annualized volume of 399,310 patient visits during the study period. This ranged from a mean of 41 daily visits in the lowest volume rural ED to 171 in the highest volume suburban ED. After ACA/GBR, ED volumes were unchanged (95% confidence interval [CI] [-1.58-1.24], p=.817). Hospitalization percentages decreased significantly by 1.9% from 17.2% to 15.3% (95% CI [-2.47%-1.38%], p<.001). The percentage of uninsured patients decreased from 20.4% to 11.9%.This 8.5% change was significant (95% CI [-9.20%-7.80%], p<.001). The professional revenue per relative value unit increased significantly by 3.97 (95% CI [3.20-4.74], p<.001). When stratified by the median patient income of each ED, changes in each outcome were significantly more pronounced in EDs of lower SES. Conclusion: Health policy changes at the federal and state levels have resulted in significant changes to emergency medicine practice and finances in MD. Admission and observation percentages have been reduced, fewer patients are uninsured, and professional revenue has increased. All changes are significantly more pronounced in EDs with patients of lower SES. Copyright 2017 Pimentel et al.