• Erratum: Correction to: A Systematic Review of Community Health Workers' Role in Occupational Safety and Health Research (Journal of immigrant and minority health (2018) 20 6 (1516-1531))

      Swanberg, J.E.; Nichols, H.M.; Clouser, J.M. (Springer, 2018)
      The original version of this article unfortunately contained a mistake in the affiliation of co-author Ashley M. Bush.
    • Online advertising and marketing claims by providers of proton beam therapy: Are they guideline-based?

      Corkum, M.T.; Liu, W.; Palma, D.A. (BioMed Central Ltd., 2018)
      Background: Cancer patients frequently search the Internet for treatment options, and hospital websites are seen as reliable sources of knowledge. Guidelines support the use of proton radiotherapy in specific disease sites or on clinical trials. This study aims to evaluate direct-to-consumer advertising content and claims made by proton therapy centre (PTC) websites worldwide. Methods: Operational PTC websites in English were identified through the Particle Therapy Co-Operative Group website. Data abstraction of website content was performed independently by two investigators. Eight international guidelines were consulted to determine guideline-based indications for proton radiotherapy. Univariate and multivariate logistic regression models were used to determine the characteristics of PTC websites that indicated proton radiotherapy offered greater disease control or cure rates. Results: Forty-eight PTCs with 46 English websites were identified. 60·9% of PTC websites claimed proton therapy provided improved disease control or cure. U.S. websites listed more indications than international websites (15·5 ± 5·4 vs. 10·4 ± 5·8, p = 0·004). The most common disease sites advertised were prostate (87·0%), head and neck (87·0%) and pediatrics (82·6%), all of which were indicated in least one international guideline. Several disease sites advertised were not present in any consensus guidelines, including pancreatobiliary (52·2%), breast (50·0%), and esophageal (43·5%) cancers. Multivariate analysis found increasing number of disease sites and claiming their centre was a local or regional leader in proton radiotherapy was associated with indicating proton radiotherapy offers greater disease control or cure. Conclusions: Information from PTC websites often differs from recommendations found in international consensus guidelines. As online marketing information may have significant influence on patient decision-making, alignment of such information with accepted guidelines and consensus opinion should be adopted by PTC providers. Copyright 2018 The Author(s).
    • Standard Lexicons, Coding Systems and Ontologies for Interoperability and Semantic Computation in Imaging

      Wang, K.C. (Springer New York LLC, 2018)
      Standard clinical terms, codes, and ontologies promote clarity and interoperability. Within radiology, there is a variety of relevant content resources, tools and technologies. These provide the basis for fundamental imaging workflows such as reporting and billing, and also facilitate a range of applications in quality improvement and research. This article reviews the key characteristics of lexicons, coding systems, and ontologies. A number of standards are described, including International Classification of Diseases-10-Clinical Modification (ICD-10-CM), Current Procedural Terminology (CPT), Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT), Logical Observation Identifiers Names and Codes (LOINC), and RadLex. Tools for accessing this material are reviewed, such as the National Center for Biomedical Ontology BioPortal system. Web services are discussed as a mechanism for semantic application development. Several example systems, workflows, and research applications using semantic technology are also surveyed. Copyright 2018, The Author(s).
    • A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer

      Lin, Y.; Leng, Q.; Zhan, M. (Neoplasia Press, Inc., 2018)
      The early detection of lung cancer is a major clinical challenge. Long noncoding RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly released from primary tumors or the circulating cancer cells might provide cell-free cancer biomarkers. The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer-associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls. In the development cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and RMRP) displayed a considerably high plasma level in lung cancer patients vs. cancer-free controls (all P < .001). Combined use of the plasma lncRNAs as a biomarker signature produced 84.13% sensitivity and 87.88% specificity for diagnosis of lung cancer, independent of stage and histological type of lung tumor, and patients' age and sex (all P > .05). The diagnostic value of the plasma lncRNA signature for lung cancer early detection was confirmed in the validation cohort. The plasma lncRNA signature may provide a potential blood-based assay for diagnosing lung cancer at the early stage. Nevertheless, a prospective study is warranted to validate its clinical value. Copyright 2018 The Authors
    • Golgin-97 targets ectopically expressed inward rectifying potassium channel, Kir2.1, to the trans-Golgi Network in COS-7 cells

      Taneja, T.K.; Ma, D.; Kim, B.Y. (Frontiers Media S.A., 2018)
      The inward rectifying potassium channel, Kir2.1, is selected as cargo at the trans-Golgi network (TGN) for export to the cell surface through a unique signal-dependent interaction with the AP1 clathrin-adaptor, but it is unknown how the channel is targeted at earlier stages in the secretory pathway for traffic to the TGN. Here we explore a mechanism. A systematic screen of Golgi tethers identified Golgin-97 as a Kir2.1 binding partner. In vitro protein-interaction studies revealed the interaction is direct, occurring between the GRIP domain of Golgin-97 and the cytoplasmic domain of Kir2.1. Imaging and interaction studies in COS-7 cells suggest that Golgi-97 binds to the channel en route through the Golgi. RNA interference-mediated knockdown of Golgin-97 prevented exit of Kir2.1 from the Golgi. These observations identify Golgin-97 as a Kir2.1 binding partner that is required for targeting the channel to the TGN. Based on our studies in COS-7 cells, we propose Golgi-97 facilitates formation of AP1-dependent export carriers for Kir2.1 by coupling anterograde delivery of Kir2.1 with retrograde recycling of AP-1 containing endosomes to the TGN. Copyright 2018 Taneja, Ma, Kim and Welling.
    • Trauma Transitional Care Coordination: Protecting the most vulnerable trauma patients from hospital readmission

      Hall, E.C.; Tyrrell, R.; Scalea, T.M. (BMJ Publishing Group, 2018)
      background Unplanned hospital readmissions increase healthcare costs and patient morbidity. We hypothesized that a program designed to reduce trauma readmissions would be effective. Methods A Trauma Transitional Care Coordination (TTCC) program was created to support patients at high risk for readmission. TTCC interventions included call to patient (or caregiver) within 72 hours of discharge to identify barriers to care, complete medication reconciliation, coordination of appointments, and individualized problem solving. Information on all 30-day readmissions was collected. 30-day readmission rates were compared with center-specific readmission rates and population-based, risk-adjusted rates of readmission using published benchmarks. results 260 patients were enrolled in the TTCC program from January 2014 to September 2015. 30.8% (n=80) of enrollees were uninsured, 41.9% (n=109) reported current substance abuse, and 26.9% (n=70) had a current psychiatric diagnosis. 74.2% (n=193) attended outpatient trauma appointments within 14 days of discharge. 96.3% were successfully followed. Only 6.6% (n=16) of patients were readmitted in the first 30 days after discharge. This was significantly lower than both center-specific readmission rates before start of the program (6.6% vs. 11.3%, P=0.02) and recently published population-based trauma readmission rates (6.6% vs. 27%, P<0.001). Discussion A nursing-led TTCC program successfully followed patients and was associated with a significant decrease in 30-day readmission rates for patients with high-risk trauma. Targeted outpatient support for these most vulnerable patients can lead to better utilization of outpatient resources, increased patient satisfaction, and more consistent attainment of preinjury level of functioning or better. Level of evidence Level IV. Copyright Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved.
    • Safety and immunogenicity of an oral tablet norovirus vaccine, a phase I randomized, placebo-controlled trial

      Kim, L.; Liebowitz, D.; Lin, K. (American Society for Clinical Investigation, 2018)
      BACKGROUND: Noroviruses are the leading cause of epidemic acute gastroenteritis and foodborne diarrheal disease in humans. However, there are no approved vaccines for noroviruses. Potential correlates of protection identified through human challenge studies include mucosal IgA, memory B cells, and serum-blocking antibody titers (BT50). METHODS: We conducted a single-site, randomized, double-blind, placebo-controlled clinical trial of an oral norovirus vaccine to determine safety and immunogenicity. This tablet vaccine is comprised of a nonreplicating adenovirus-based vector expressing the VP1 gene from the GI.1 norovirus strain and a double-stranded RNA adjuvant. Sixty-six adult subjects meeting inclusion/exclusion criteria were randomized 2:1 to receive a single vaccine dose or placebo, respectively. Immunogenicity was primarily assessed by serum BT50. Additional outcomes included serum ELISA titers, fecal and saliva antibody titers, memory and antibody-secreting cell (ASC) frequency, and B cell phenotyping. RESULTS: The vaccine was well-tolerated, with no dose-limiting toxicities. Adverse events were mild or moderate. The primary immunological endpoint (increase in BT50 titers) was met in the high-dose group (P = 0.0003), with 78% showing a ≥2-fold rise in titers after a single immunization. Vaccine recipients also developed mucosally primed VP1-specific circulating ASCs, IgA+ memory B cells expressing gut-homing receptor (α4β7), and fecal IgA, indicating substantial and local responses potentially relevant to prevent norovirus infection. CONCLUSION: This oral norovirus vaccine was well-tolerated and generated substantial immune responses, including systemic and mucosal antibodies as well as memory IgA/IgG. These results are a major step forward for the development of a safe and immunogenic oral norovirus vaccine.
    • Comparative genomics of the Erwinia and Enterobacter olive fly endosymbionts

      Estes, A.M.; Hearn, D.J.; Agrawal, S. (Nature Publishing Group, 2018)
      The pestivorous tephritid olive fly has long been known as a frequent host of the obligately host-associated bacterial endosymbiont, Erwinia dacicola, as well as other facultative endosymbionts. The genomes of Erwinia dacicola and Enterobacter sp. OLF, isolated from a California olive fly, encode the ability to supplement amino acids and vitamins missing from the olive fruit on which the larvae feed. The Enterobacter sp. OLF genome encodes both uricase and ureases, and the Er. dacicola genome encodes an allantoate transport pathway, suggesting that bird feces or recycling the fly’s waste products may be important sources of nitrogen. No homologs to known nitrogenases were identified in either bacterial genome, despite suggestions of their presence from experiments with antibiotic-treated flies. Comparisons between the olive fly endosymbionts and their free-living relatives revealed similar GC composition and genome size. The Er. dacicola genome has fewer genes for amino acid metabolism, cell motility, and carbohydrate transport and metabolism than free-living Erwinia spp. while having more genes for cell division, nucleotide metabolism and replication as well as mobile elements. A 6,696 bp potential lateral gene transfer composed primarily of amino acid synthesis and transport genes was identified that is also observed in Pseudomonas savastanoii pv savastanoii, the causative agent of olive knot disease. Copyright 2018, The Author(s).
    • Tetrabutylammonium Bromide-Promoted Metal-Free, Efficient, Rapid, and Scalable Synthesis of N-Aryl Amines

      Johnson, C.R.; Ansari, M.I.; Coop, A. (American Chemical Society, 2018)
      A rapid, transition metal-free, high-yielding, tetrabutylammonium bromide-promoted method of N-arylation is reported within. The optimized conditions tolerated a wide range of secondary amines and was equally effective with bromo- and chlorobenzene-including substituted aryl halides. The developed method is found to be effective for N-arylation when compared to earlier methods which involve harsh conditions, transition metals, lack of scalability, and long reaction times. Our method utilizes conventional heating only; it is readily scalable; and the products are facile to purify. Copyright 2018 American Chemical Society.
    • Variation in research designs used to test the effectiveness of dissemination and implementation strategies: A review

      Mazzucca, S.; Tabak, R.G.; Pilar, M. (Frontiers Media S. A, 2018)
      Background: The need for optimal study designs in dissemination and implementation (D & I) research is increasingly recognized. Despite the wide range of study designs available for D & I research, we lack understanding of the types of designs and methodologies that are routinely used in the field. This review assesses the designs and methodologies in recently proposed D & I studies and provides resources to guide design decisions. Methods: We reviewed 404 study protocols published in the journal Implementation Science from 2/2006 to 9/2017. Eligible studies tested the efficacy or effectiveness of D & I strategies (i.e., not effectiveness of the underlying clinical or public health intervention); had a comparison by group and/or time; and used ?1 quantitative measure. Several design elements were extracted: design category (e.g., randomized); design type [e.g., cluster randomized controlled trial (RCT)]; data type (e.g., quantitative); D & I theoretical framework; levels of treatment assignment, intervention, and measurement; and country in which the research was conducted. Each protocol was double-coded, and discrepancies were resolved through discussion. Results: Of the 404 protocols reviewed, 212 (52%) studies tested one or more implementation strategy across 208 manuscripts, therefore meeting inclusion criteria. Of the included studies, 77% utilized randomized designs, primarily cluster RCTs. The use of alternative designs (e.g., stepped wedge) increased over time. Fewer studies were quasi-experimental (17%) or observational (6%). Many study design categories (e.g., controlled pre-post, matched pair cluster design) were represented by only one or two studies. Most articles proposed quantitative and qualitative methods (61%), with the remaining 39% proposing only quantitative. Half of protocols (52%) reported using a theoretical framework to guide the study. The four most frequently reported frameworks were Consolidated Framework for Implementing Research and RE-AIM (n = 16 each), followed by Promoting Action on Research Implementation in Health Services and Theoretical Domains Framework (n = 12 each). Conclusion: While several novel designs for D & I research have been proposed (e.g., stepped wedge, adaptive designs), the majority of the studies in our sample employed RCT designs. Alternative study designs are increasing in use but may be underutilized for a variety of reasons, including preference of funders or lack of awareness of these designs. Promisingly, the prevalent use of quantitative and qualitative methods together reflects methodological innovation in newer D & I research. Copyright 2018 Mazzucca, Tabak, Pilar, Ramsey, Baumann, Kryzer, Lewis, Padek, Powell and Brownson.
    • Data of unhealthy food availability in hospitals

      Champ, C.E.; Iarrobino, N.A.; Haskins, C.P. (Elsevier Inc., 2018)
      In our manuscript, we present the food choices available at vending machines in government-run Veterans Affairs Hospitals. The data in this article includes both a quantification of the beverages and packages foods available, along with a comparison of recommendations and sugar content to the government-issued USDA Dietary Guidelines 2015-2020. For further discussion on the results of this study, refer to the full manuscript "Lead by Poor Example: An Assessment of Snacks, Soda, and Junk Food Availability in Veterans Affairs Hospitals" (Champ et al., 2018) [1]. © 2018 The Authors
    • A comparison of QM/MM simulations with and without the Drude oscillator model based on hydration free energies of simple solutes

      K�nig, G.; Pickard, F.C.; IV (MDPI AG, 2018)
      Maintaining a proper balance between specific intermolecular interactions and non-specific solvent interactions is of critical importance in molecular simulations, especially when predicting binding affinities or reaction rates in the condensed phase. The most rigorous metric for characterizing solvent affinity are solvation free energies, which correspond to a transfer from the gas phase into solution. Due to the drastic change of the electrostatic environment during this process, it is also a stringent test of polarization response in the model. Here, we employ both the CHARMM fixed charge and polarizable force fields to predict hydration free energies of twelve simple solutes. The resulting classical ensembles are then reweighted to obtain QM/MM hydration free energies using a variety of QM methods, including MP2, Hartree-Fock, density functional methods (BLYP, B3LYP, M06-2X) and semi-empirical methods (OM2 and AM1). Our simulations test the compatibility of quantum-mechanical methods with molecular-mechanical water models and solute Lennard-Jones parameters. In all cases, the resulting QM/MM hydration free energies were inferior to purely classical results, with the QM/MM Drude force field predictions being only marginally better than the QM/MM fixed charge results. In addition, the QM/MM results for different quantum methods are highly divergent, with almost inverted trends for polarizable and fixed charge water models. While this does not necessarily imply deficiencies in the QM models themselves, it underscores the need to develop consistent and balanced QM/MM interactions. Both the QM and the MM component of a QM/MM simulation have to match, in order to avoid artifacts due to biased solute-solvent interactions. Finally, we discuss strategies to improve the convergence and efficiency of multi-scale free energy simulations by automatically adapting the molecular-mechanics force field to the target quantum method. Copyright 2018 by the authors.
    • A RhoA–YAP–c-Myc signaling axis promotes the development of polycystic kidney disease

      Cai, J.; Song, X.; Wang, W. (Cold Spring Harbor Laboratory Press, 2018)
      Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in PKD1 or PKD2 and affects one in 500-1000 humans. Limited treatment is currently available for ADPKD. Here we identify the Hippo signaling effector YAP and its transcriptional target, c-Myc, as promoters of cystic kidney pathogenesis. While transgenic overexpression of YAP promotes proliferation and tubule dilation in mouse kidneys, loss of YAP/TAZ or c-Myc suppresses cystogenesis in a mouse ADPKD model resulting from Pkd1 deficiency. Through a comprehensive kinase inhibitor screen based on a novel three-dimensional (3D) culture of Pkd1 mutant mouse kidney cells, we identified a signaling pathway involving the RhoGEF (guanine nucleotide exchange factor) LARG, the small GTPase RhoA, and the RhoA effector Rho-associated kinase (ROCK) as a critical signaling module between PKD1 and YAP. Further corroborating its physiological importance, inhibition of RhoA signaling suppresses cystogenesis in 3D culture of Pkd1 mutant kidney cells as well as Pkd1 mutant mouse kidneys in vivo. Taken together, our findings implicate the RhoA-YAP-c-Myc signaling axis as a critical mediator and potential drug target in ADPKD. Copyright 2018 Cai et al.
    • Patterns of care and outcomes with the addition of chemotherapy to radiation therapy for stage I nasopharyngeal cancer

      Verma, V.; Ryckman, J.M.; Simone, C.B. (Taylor and Francis Ltd, 2018)
      Purpose: The standard of care for stage I (T1N0) nasopharyngeal cancer (NPC) is definitive radiotherapy (RT). Given the phase III evidence supporting combined chemoradiotherapy (CRT) for stage II NPC, we investigated practice patterns and outcomes associated with administration of chemotherapy to RT alone for stage I NPC. Methods: The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) receiving curative-intent RT. Patients with unknown RT/chemotherapy status were excluded, as were benign/sarcomatous histologies and receipt of pharyngectomy. Patient, tumor, and treatment parameters were extracted. Logistic regression analysis ascertained factors associated with receipt of additional chemotherapy. Kaplan-Meier analysis was used to evaluate overall survival (OS) between patients receiving RT versus CRT. Cox proportional hazards modeling determined variables associated with receipt of OS. Results: In total, 396 patients were analyzed. Chemotherapy was delivered in 147 patients (37%). On multivariate analysis, patients treated at academic/integrated centers were less likely to receive chemotherapy (p =.008); a racial predilection was noted, as non-black/non-white patients were also less likely to receive chemotherapy (p =.006). Respective 5-year OS in patients receiving RT alone versus CRT were 77% and 75% (p =.428). Receipt of chemotherapy did not independently predict for greater OS (p =.447). Conclusions: These data do not support the routine addition of chemotherapy to definitive RT for T1N0 NPC. Copyright 2017 Acta Oncologica Foundation.
    • Melatonin attenuates hLRRK2‑induced long‑term memory deficit in a Drosophila model of Parkinson's disease

      Ran, D.; Xie, B.; Gan, Z. (Spandidos Publications, 2018)
      As the most common genetic cause of Parkinson's disease (PD), the role of human leucine-rich repeat kinase 2 (hLRRK2) in the efficacy of PD treatment is a focus of study. Our previous study demonstrated that mushroom body (MB) expression of hLRRK2 in Drosophila could recapitulate the clinical feature of sleep disturbances observed in PD patients, and melatonin (MT) treatment could attenuate the hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of MT in PD patients carrying hLRRK2 mutations; however, no further study into the impacts on memory deficit was conducted. Therefore, in the current paper, the study of the effects of MT on hLRRK2 flies was continued, to determine its potential role in the improvement of memory deficit in PD. To achieve this, the Drosophila learning and memory phases, including short- and long-term memory, were recorded; furthermore, the effect of MT on calcium channel activity during neurotransmission was detected using electrophysiology patch clamp recordings. It was demonstrated that MT treatment reversed hLRRK2-induced long-term memory deficits in Drosophila; furthermore, MT reduced MB calcium channel activities. These findings suggest that MT may exerts therapeutic effects on the long-term memory of PD patients via calcium channel modulation, thus providing indication of its potential to maintain cognitive function in PD patients. Copyright 2018, Spandidos Publications. All rights reserved.
    • Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

      Blanchard, T.G.; Lapidus, R.; Banerjee, V. (S. Karger AG, 2018)
      Background/Aims: Silencing of tumor suppressor genes (TSGs) and promotion of angiogenesis are associated with tumor development and metastasis. However, little is known if angiogenic molecules directly control TSGs and vice versa. Methods: A regulatory link between angiogenesis and down regulation of TSGs was evaluated using an anti-cancer agent, andrographolide (AGP) in cancer cells, mouse xenograft tissues and patient derived organoids through gene/protein expression, gene silencing, and immunohistochemical analyses. Results: AGP treatment demonstrated significant expression of RASSF1A and PTEN TSGs in colon cancer and other cancer cells, mouse tissues and organoids. Depletion of RASSF1A with siRNA limited cyclin D1 and BAX expression. SiRNA depletion of PTEN, upstream regulator of RASSF1A resulted in a 50% reduction in RASSF1A expression. Histopathological analysis of the AGP treated tumor sections showed significant reduction in vessel size, microvascular density and tumor mitotic index suggesting suppression of angiogenesis. This was corroborated by protein analysis demonstrating significant reductions in angiogenesis signaling pathway molecules VEGF165, FOXM1, and pAkt, but significant elevation of the endogenous angiogenesis inhibitor Tsp-2. Treatment of cells with exogenous VEGF prevented the suppression of angiogenesis signaling by AGP, resulting in sustained expression of pAkt, an upstream down-regulator of RASSF1A. RASSF1A expression remained low in VEGF treated cells despite the addition of AGP. Conclusion: Our results demonstrate for the first time that AGP induces RASSF1A expression in colon cancer cells and is dependent on angiogenesis signaling events. Therefore, our research may facilitate novel therapeutic options for advanced colon cancer therapy. Copyright 2018 The Author(s). Published by S. Karger AG, Basel.
    • Influence of Renal Function on the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Non-Vitamin K Antagonist Oral Anticoagulants

      Weir, M.R.; Kreutz, R. (Elsevier Ltd, 2018)
      With the growing integration of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice, questions have arisen regarding their use in special populations, including groups that may have been underrepresented in clinical trials. Patients with renal impairment, particularly in the lower echelons of renal function, are one such group. In an effort to elucidate the current evidence regarding the use of NOACs in patients with renal impairment, a systematic assessment of the literature was performed. The MEDLINE database was interrogated for studies and analyses evaluating the influence of renal function on the pharmacokinetics, pharmacodynamics, efficacy, and safety of NOACs published from January 1, 2000, through August 2, 2017. The 82 relevant publications retrieved highlight the diversity in the NOAC class regarding the impact of renal function on drug clearance, drug exposures, and clinical trial outcomes. In several large clinical trials, subgroup analyses revealed no significant differences when patients were stratified by creatinine clearance as a measure of renal function. Efficacy findings, in particular, were largely aligned with the overall population in the included studies. However, relative risks of bleeding were shown to vary, sometimes driven by changes in bleeding event rates in the comparator arm (eg, warfarin, enoxaparin). With few exceptions, minimal influence of mild renal impairment was observed on the relative efficacy and safety of NOACs. Taken together, the evidence suggests that the presence of renal impairment merits careful consideration of anticoagulant choice but should not deter physicians from appropriate use of NOACs. © 2018 Mayo Foundation for Medical Education and Research
    • Long-term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin-converting enzymes/angiotensin receptor blockers: Results from AMETHYST-DN

      Pitt, B.; Bakris, G.L.; Weir, M.R. (Wiley-Blackwell, 2018)
      Aims: Chronic kidney disease (CKD) in heart failure (HF) increases the risk of hyperkalaemia (HK), limiting angiotensin‐converting enzyme inhibitor (ACE‐I) or angiotensin receptor blocker (ARB) use. Patiromer is a sodium‐free, non‐absorbed potassium binder approved for HK treatment. We retrospectively evaluated patiromer's long‐term safety and efficacy in HF patients from AMETHYST‐DN. Methods and results: Patients with Type 2 diabetes, CKD, and HK [baseline serum potassium >5.0–5.5 mmol/L (mild) or >5.5–<6.0 mmol/L (moderate)], with or without HF (New York Heart Association Class I and II, by investigator judgement), on ACE‐I/ARB, were randomized to patiromer 8.4–33.6 g to start, divided twice daily. Overall, 105/304 (35%) patients had HF (75%, Class II). Mean (standard deviation) ejection fraction (EF) was 44.9% (8.2) (n = 81) in patients with HF; 26 had EF ≤40%. In HF patients, mean serum potassium decreased by Day 3 through Week 52. At Week 4, estimated mean (95% confidence interval) change in serum potassium was −0.64 mmol/L (−0.72, −0.55) in mild and −0.97 mmol/L (−1.14, −0.80) in moderate HK (both P < 0.0001). Most HF patients with mild (>88%) and moderate (≥73%) HK had normokalaemia at each visit from Weeks 12 to 52. Three HF patients were withdrawn because of high (n = 1) or low (n = 2) serum potassium. The most common patiromer‐related adverse event was hypomagnesaemia (8.6%). Conclusions: In patients with a clinical diagnosis of HF, diabetes, CKD, and HK on ACE‐I/ARB, patiromer was well tolerated and effective for HK treatment over 52 weeks. Copyright 2018 The Authors.
    • Patients’ Use and Perception of Internet-Based Orthopaedic Sports Medicine Resources

      Koenig, S.; Nadarajah, V.; Smuda, M.P. (SAGE Publications Ltd, 2018)
      Background: Current research is sparse regarding how patients with orthopaedic injuries perceive and use internet-based information resources. Hypothesis: The majority of patients use the internet to research their orthopaedic condition and are receptive to guidance from their provider. Study Design: Cross-sectional study. Methods: A total of 213 patients attending a sports medicine clinic on the East Coast of the United States were asked to complete a questionnaire regarding their use of internet-based information. Data from 185 patients were available for analysis. Bivariate and multivariate statistical analyses were used to determine the significance of identified associations. Results: Overall, 54% of patients used the internet to find information about their orthopaedic condition prior to their consultation. A higher percentage of internet users were women (P =.01), were white (P =.03), and had internet access at home (P =.02). Multivariable analysis found home internet access to be the only significant independent factor predictive of patients using internet-based information sources (P <.01). The majority of patients (61%) were neutral toward orthopaedic information found online, and only 32% of patients trusted the orthopaedic information they found online. The majority of patients (83%) reported they would be receptive to providers' guidance on which internet resources to use. Conclusion: Only half of patients use the internet to research their orthopaedic condition. Most patients were either neutral toward or did not trust the internet-based information that they found and may forgo internet sources altogether. To help patients avoid misleading information, sports medicine providers should understand how patients are using the internet and guide patients in selecting high-quality, peer-reviewed sources of information. Doing so allows physicians to proactively educate their patients even after the clinic visit. Copyright The Author(s) 2018.
    • Voltage sensing mechanism in skeletal muscle excitation-contraction coupling: Coming of age or midlife crisis?

      Hern�ndez-Ochoa, E.O.; Schneider, M.F. (BioMed Central Ltd., 2018)
      The process by which muscle fiber electrical depolarization is linked to activation of muscle contraction is known as excitation-contraction coupling (ECC). Our understanding of ECC has increased enormously since the early scientific descriptions of the phenomenon of electrical activation of muscle contraction by Galvani that date back to the end of the eighteenth century. Major advances in electrical and optical measurements, including muscle fiber voltage clamp to reveal membrane electrical properties, in conjunction with the development of electron microscopy to unveil structural details provided an elegant view of ECC in skeletal muscle during the last century. This surge of knowledge on structural and biophysical aspects of the skeletal muscle was followed by breakthroughs in biochemistry and molecular biology, which allowed for the isolation, purification, and DNA sequencing of the muscle fiber membrane calcium channel/transverse tubule (TT) membrane voltage sensor (Cav1.1) for ECC and of the muscle ryanodine receptor/sarcoplasmic reticulum Ca2+ release channel (RyR1), two essential players of ECC in skeletal muscle. In regard to the process of voltage sensing for controlling calcium release, numerous studies support the concept that the TT Cav1.1 channel is the voltage sensor for ECC, as well as also being a Ca2+ channel in the TT membrane. In this review, we present early and recent findings that support and define the role of Cav1.1 as a voltage sensor for ECC. © 2018 The Author(s).