bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized, Single‐Center, Double‐Blind, Placebo‐Controlled Multiple‐Dose Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Imarikiren in Healthy Adult Nonelderly and Elderly Male Subjects
Authors: Matsuno Kumi , Tanaka Shingo , Hashimoto Takamasa , Nakamichi Hiroyuki , Kagawa Tomoya , Koumura Emiko 
Published: May 2018

AbstractImarikiren hydrochloride (TAK‐272/ SCO‐272) is a novel direct renin inhibitor. This randomized, double‐blind, phase I study evaluated the safety and pharmacokinetics/pharmacodynamics of multiple oral administrations of imarikiren in healthy nonelderly (aged 20‐45 years) and elderly (aged 65‐85 years) Japanese male subjects. Subjects were randomized within 1 of 3 cohorts to receive imarikiren or placebo: Cohort 1 (imarikiren 80 mg; nonelderly), Cohort 2 (imarikiren 160 mg; nonelderly), or Cohort 3 (imarikiren 80 mg; elderly). Imarikiren or placebo was administered orally, once daily, for 7 days. Accumulation of imarikiren did not occur during the 7‐day treatment period. Area under the plasma‐concentration time curve and maximum plasma concentration of imarikiren were higher in elderly than in nonelderly subjects (52% and 39% higher, respectively). Inhibition of plasma renin activity was observed for 7 days and was maintained for at least 71 hours after the last imarikiren administration at the 80‐mg (nonelderly and elderly) and 160‐mg (nonelderly) doses. Plasma active renin concentration increased in nonelderly and elderly subjects; peak concentrations were higher on day 7 than on day 1. Increase from baseline in plasma active renin concentration was smaller in elderly than in nonelderly subjects during the 7‐day treatment period and until 71 hours after last imarikiren administration. Treatment‐emergent adverse events were reported in 33.3% (elderly) and 22.2% (nonelderly) of imarikiren subjects. Multiple oral administrations of imarikiren for 7 days were safe and well tolerated with no drug accumulation and strong and sustained suppression of plasma renin activity.
Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting
Authors: Aung Ar Kar , Tang Mei Jie , Adler Nikki Rae , de Menezes Sara Lee , Goh Michelle Sue Yen , Tee Hui Wen , Trubiano Jason Anthony , Puy Robert , Zubrinich Celia Mary , Graudins Linda Velta 
Published: May 2018

AbstractWe describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2‐year period (2015–2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1–10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4–5.5, and P = .04, OR 4.2, 95%CI 1.2–18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9–7.9, and P < .0001, OR 11.4, 95%CI 4.6–27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety.
Expanding the repertoire of aromatic chemicals by microbial production
Authors: Wu Fengli , Cao Peng , Song Guotian , Chen Wujiu , Wang Qinhong 
Published: May 2018

AbstractMicrobial production of aromatic chemicals would greatly contribute to solving the problems with fossil resource supply and environmentally sustainable development. Engineering and extending the shikimate/aromatic amino acid biosynthetic pathways are important routes for microbial production of various aromatic chemicals. With advances in metabolic engineering and synthetic biology, we can broaden the product spectrum and obtain several valuable and novel aromatic chemicals from renewable feedstocks. Here, in this review, the latest research progress on microbial production of various aromatic chemicals, and recent metabolic engineering and synthetic biology strategies targeting the central carbon metabolism, the shikimate and aromatic amino acid biosynthetic pathways are summarized and discussed. This work aims to provide some valuable tips for the construction of cost‐effective engineered strains for producing various aromatic chemicals. © 2018 Society of Chemical Industry
Differential conduction and CGRP release in visceral versus cutaneous peripheral nerves in the mouse
Authors: De Col Roberto , Messlinger Karl , Hoffmann Tali 
Published: May 2018

AbstractCutaneous afferent nerves convey sensory information from the external, visceral nerves from the internal environment. The saphenous nerve arising from lumbar dorsal root ganglia and the vagus nerve originating in the nodosum ganglia are prototypic examples of such cutaneous and visceral nerves. Despite a common sensory role, these two nerves have distinct embryonic origin and vary in neuropeptide expression. Because of their distinct physiological roles, it is plausible that they differ also in conductive properties. We have tested calcitonin gene‐related peptide (CGRP) release in these nerves in response to electrical and chemical stimulation. Electrical stimulation at 3, 6, and 9 Hz increased the release in saphenous but not vagus nerves, with 6 Hz being the most potent stimulus. Similarly, both capsaicin and a depolarizing solution of 60 mM KCl evoked CGRP release in saphenous but not vagus nerves. Simultaneous recording of the superimposed (compound) action potentials of these nerves revealed that only saphenous nerves exhibit a progressive and marked activity‐dependent slowing of conduction velocity in response to electrical stimulation at 3, 6, and 9 Hz (30%, 44%, and 50%, respectively). Capsaicin caused an unexpected decrease in conduction latency (i.e., speeding) in contrast to the slowing seen in other nerves. Exposure of axons to 1 µM TTX rapidly blocked conduction in all nerves. Together our results demonstrate that vagus and saphenous primary afferents reveal different activation and conductive properties, presumably correlating their particular physiological roles in transmitting sensory signals. © 2018 Wiley Periodicals, Inc.
The competitive vs. complementary bacteria‐fungi interactions promote microbial release of Fe(III)‐fixed phosphorus: the roles of exogenous C application
Authors: Zhang Shirong , Ding Xiaodong 
Published: May 2018

AbstractThe phosphorus deficiency is very common in Fe(III)‐rich soil, and one of the key point is to clarify the condition in release or desorption of phosphorus from the Fe(III)‐rich minerals. The present study was to explore the effect of labile carbon on microbial reduction of Fe(III) and release of phosphorus in root‐free sub‐tropical soil. A two‐compartment microcosm was collected, in which the roots of Medicago sativa L. cultivar ‘Aohan' were confined within one compartment by a barrier of 30‐μm nylon mesh, while mycorrhizal hyphae could penetrate to the second compartment. Arbuscular mycorrhizal fungi (Funelliformis mosseae) were added to the root compartment and iron‐reducing bacteria (Klebsiella pneumoniae) were added to the hyphal compartment. Hyphal compartments were provided with two levels of additional carbon (0 and 23 mg C kg−1 soil as sodium acetate) and eight levels of inorganic phosphorus (0 to 35 mg P kg−1 soil as KH2PO4). At low phosphorus levels (< 5 mg P kg−1 soil), shoot biomass, and total biomass phosphorus were substantially less with added carbon in the presence of iron‐reducing bacteria. Carbon had little effect without iron‐reducing bacteria. At higher phosphorus levels (> 15 mg P kg−1 soil), the effect of added carbon was reversed; that is shoot biomass and total biomass phosphorus were greater with added carbon. Available soil phosphorus showed a similar response to added carbon—less at low levels of phosphorus and greater at higher levels of phosphorus. Microbial phosphorus in the presence of iron‐reducing bacteria was always higher with added carbon at all corresponding levels of soil phosphorus. Taken together, these results show that some phosphorus mobilized by iron‐reducing bacteria was converted into microbiological phosphorus, but there was an obligatory requirement for labile carbon for this to happen—reducing the amount of phosphorus that was absorbed by the mycorrhizal hyphae. Iron‐reducing bacteria and mycorrhizae showed a competitive interaction at lower levels of available soil phosphorus, and a complementary, or possibly a carbon‐dependent synergistic function at higher levels of available phosphorus. These results demonstrate that phosphorus released from ferralsols by iron‐reducing bacteria is positively mediated by both phosphorus and labile carbon and, hence, that phosphorus release and mobilization by iron‐reducing bacteria is likely to be enhanced by additions of exogenous carbon.
Longitudinal Ultrasound Curriculum Incorporation at West Virginia University School of Medicine: A Description and Graduating Students' Perceptions
Authors: Minardi Joseph , Ressetar Holly , Foreman Theresa , Craig Kristen , Sharon Melinda , Bassler John , Davis Stephen , Machi Anthony , Cottrell Scott , Denne Nicolas , Ferrari Norman , Landreth Kenneth , Palmer Bruce , Schaefer Gregory , Tallaksen Robert , Wilks David , Williams Dorian 
Published: May 2018

ObjectivesSonography is a clinical tool being incorporated in multiple medical specialties with evidence of improved patient care and cost. Some schools have begun implementing ultrasound curricula. We hope to build upon that foundation and provide another potential framework of incorporation. There are several barriers, including curricular space, equipment and physical space, adequate faculty, and performing assessment.MethodsAt West Virginia University, we began a longitudinal ultrasound curriculum in 2012 with incorporation of didactic and practical sessions into gross anatomy, our systems‐based second‐year curriculum, physical diagnosis course, and clinical rotations. We included both written and practical assessment from the onset. After the initial 4 years, the first graduates were surveyed on their perceptions of the curriculum. Responses were correlated with specialty choice and clinical campus site.ResultsBased on our survey (90% response rate), students felt sonography was useful for anatomical understanding and patient care. Overall, 93% of our respondents reviewed the curriculum favorably. Qualitative feedback was very positive, with students desiring more ultrasound education and more required components, specifically in clinical rotations.ConclusionsBased on these results, some changes have already been implemented, including decreased student‐to‐instructor ratios, more open scan time, and more required components. The breadth of formal assessment has increased. Multiple pilot programs for clinical rotations are being developed. There is an ongoing need for faculty development and continued assessment of ultrasound competency.
Placental Location and the Development of Hypertensive Disorders of Pregnancy
Authors: Salama‐Bello Rosana , Duncan Jose R. , Howard Samantha L. , Song Jun , Schenone Mauro H. 
Published: May 2018

ObjectivesAbnormal placentation is an important factor in the pathogenesis of preeclampsia. As a result of diminished blood flow, the incidence of preeclampsia might be higher in patients with laterally located placentas compared to patients with centrally located placentas. The objective of this study was to evaluate the relationship between placental location and the development of hypertensive disorders of pregnancy.MethodsPatients with singleton pregnancies who were seen in our ultrasound unit and delivered at our institution from October 2014 to April 2015 were included. The incidence of hypertensive disorders was compared in those with a lateral placental location and those with centrally located placentas (placental locations other than lateral). Baseline characteristics and pregnancy outcomes were compared between groups. The χ2 test, Fisher exact test, Mann‐Whitney U test, and t test were used when appropriate. P < .05 was considered significant.ResultsWe included 464 patients; 411 (88.57%) had centrally located placentas, and 53 (11.42%) had laterally located placentas. The incidence of hypertensive disorders of pregnancy was similar between groups (21% versus 19%; P = .71). Gestational age at delivery (P = .73), and small for gestational age (P = .96) were also similar between our study groups.ConclusionsIn our study, there was no difference in the rate of hypertensive disorders of pregnancy between patients with central and laterally located placentas.
Previous Gestational Diabetes Increases Atherogenic Dyslipidemia in Subsequent Pregnancy and Postpartum
Authors: Prados Montserrat , Flores‐Le Roux Juana A. , Benaiges David , Llauradó Gemma , Chillarón Juan J. , Paya Antoni , Pedro‐Botet Juan 
Published: May 2018

AbstractIn a cohort of women with previous gestational diabetes mellitus (GDM), we aimed to ascertain whether women with abnormal glucose tolerance 1‐year postdelivery had a more atherogenic lipid profile during and after pregnancy than those with normal glucose tolerance. A prospective cohort study with longitudinal design between January 2004 and March 2016 was conducted. Three hundred and six (56.8%) of 537 women diagnosed with GDM during the studied period attended a control visit during the first year after delivery. Of these, 112 (36.6%) had prediabetes and 16 (5.2%) had type 2 diabetes mellitus. No significant differences during pregnancy were found in total, low‐density lipoprotein, high‐density lipoprotein (HDL) cholesterol, and triacylglycerol (TAG) concentrations among the three groups. Only HDL cholesterol and TAG levels differed significantly among groups at 2 and 12 months after delivery. Logistic regression analysis revealed pregnancy HDL and glucose metabolism status to be associated with the HDL cholesterol concentration 1‐year postdelivery. Furthermore, the only independent factor associated with TAG levels 1 year after delivery was the gestational TAG concentration. In summary, an overweight multiethnic group of women with prior GDM presented a high incidence of postpartum dysglycemia (41.8%). HDL‐cholesterol and TAG levels, both components of the metabolic syndrome, differed significantly among the three study groups in the glucose‐metabolism status at 2 and 12 months after delivery. Women with previous GDM must be followed up in the postpartum period for early detection and management of lipid and glucose disorders.
Parameters in fractional laser assisted delivery of topical anesthetics: Role of laser type and laser settings
Authors: Meesters Arne A. , Nieboer Marilin J. , Kezic Sanja , de Rie Menno A. , Wolkerstorfer Albert 
Published: May 2018

Background and ObjectivesEfficacy of topical anesthetics can be enhanced by pretreatment of the skin with ablative fractional lasers. However, little is known about the role of parameters such as laser modality and laser density settings in this technique. Aims of this study were to compare the efficacy of pretreatment with two different ablative fractional laser modalities, a CO2 laser and an Er:YAG laser, and to assess the role of laser density in ablative fractional laser assisted topical anesthesia.Study Design/Materials and MethodsIn each of 15 healthy subjects, four 10 × 10 mm test regions on the back were randomized to pretreatment (70–75 μm ablation depth) with CO2 laser at 5% density, CO2 laser at 15% density, Er:YAG laser at 5% density or Er:YAG laser at 15% density. Articaine hydrochloride 40 mg/ml + epinephrine 10 μg/ml solution was applied under occlusion to all four test regions. After 15 minutes, a pass with the CO2 laser (1,500 μm ablation depth) was administered as pain stimulus to each test region. A reference pain stimulus was given on unanesthetized skin. The main outcome parameter, pain, was scored on a 0–10 visual analogue scale (VAS) after each pain stimulus.ResultsMedian VAS scores were 1.50 [CO2 5%], 0.50 [CO2 15%], 1.50 [Er:YAG 5%], 0.43 [Er:YAG 15%], and 4.50 [unanesthetized reference]. VAS scores for all pretreated test regions were significantly lower compared to the untreated reference region (P < 0.01). We found no significant difference in VAS scores between the CO2 and the Er:YAG laser pretreated regions. However, VAS scores were significantly lower at 15% density compared to 5% density for both for the CO2 laser (P < 0.05) and the Er:YAG laser (P < 0.01). Pretreatment with the CO2 laser was considered slightly more painful than pretreatment with Er:YAG laser by the subjects.ConclusionFractional laser assisted topical anesthesia is effective even with very low energy settings and an occlusion time of only 15 minutes. Both the CO2 laser and the Er:YAG laser can be used to assist topical anesthesia although the CO2 laser pretreatment is experienced as more painful. In our study settings, using articaine/epinephrine solution and an occlusion time of 15 minutes, a density of 15% was more effective than 5%. Lasers Surg. Med. 50:813–818, 2018. © 2018 Wiley Periodicals, Inc.
Incorporation of photobiomodulation therapy into a therapeutic exercise program for knee osteoarthritis: A placebo‐controlled, randomized, clinical trial
Authors: de Paula Gomes Cid A. F. , Leal‐Junior Ernesto C. P. , Dibai‐Filho Almir V. , de Oliveira Adriano R. , Bley André S. , Biasotto‐Gonzalez Daniela A. , de Tarso Camillo de Carvalho Paulo 
Published: May 2018

ObjectiveTo investigate the clinical effects of incorporation of phototherapy in a therapeutic exercise program for individuals with knee osteoarthritis (OA) when compared to a group that received exercise alone and to a group that received exercise + placebo phototherapy.Materials and MethodsThis is a randomized, blinded and placebo‐controlled trial. Thus, sixty male and female individuals aged 40–80 years with knee pain in the previous 6 months participated of the study, with diagnosis of unilateral knee OA based on the criteria established by the American College of Rheumatology and radiographic confirmation and Grades 2 or 3 of the Kellgren‐Lawrence Classification. The individuals were equally divided in the groups exercise alone, exercise + active phototherapy (nine‐diode cluster device: one 905 nm super‐pulsed diode laser, four 875 nm LED and four 640 nm LED; energy per quadrant: 7.85 J; total energy: 23.55 J per session), or exercise + placebo phototherapy. Treatments were performed twice a week for 5 consecutive weeks. Patients were evaluated before and after the sessions of treatment. The outcome measures were: Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Lower Extremity Functional Scale (LEFS), Numerical Rating Pain Scale (NRPS), pressure pain threshold (PPT) in two points of knee, muscle strength, and the Functional Reach Test (FRT).ResultsExercise + active phototherapy was significantly more effective than exercise alone (mean difference [MD] = 2.75, 95% confidence interval [CI] = 3.17 to 2.32) and exercise + placebo phototherapy (MD = 2.38, 95% CI = 2.79 to 1.96) only with regard to the NRPS, considering minimal clinically important difference. No clinical significant results were found for function, the pressure pain threshold, muscle strength or balance.ConclusionsThe combination of phototherapy and an exercise program is effective at reducing pain intensity among individuals with knee osteoarthritis than exercise alone or exercise + placebo phototherapy in a short‐term protocol. Lasers Surg. Med. 50:819–828, 2018. © 2018 Wiley Periodicals, Inc.
Fractional CO2 laser treatment for vaginal laxity: A preclinical study
Authors: Kwon Tae‐Rin , Kim Jong Hwan , Seok Joon , Kim Jae Min , Bak Dong‐Ho , Choi Mi‐Ji , Mun Seok Kyun , Kim Chan Woong , Ahn Seungwon , Kim Beom Joon 
Published: May 2018

Background and ObjectiveVarious studies have investigated treatment for vaginal laxity with microablative fractional carbon dioxide CO2 laser in humans; however, this treatment has not yet been studied in an animal model. Herein, we evaluate the therapeutic effects of fractional CO2 laser for tissue remodeling of vaginal mucosa using a porcine model, with the aim of improving vaginal laxity.Study Design/Materials and MethodsThe fractional CO2 laser enables minimally invasive and non‐incisional procedures. By precisely controlling the laser energy pulses, energy is sent to the vaginal canal and the introitus area to induce thermal denaturation and contraction of collagen. We examined the effects of fractional CO2 laser on a porcine model via clinical observation and ultrasound measurement. Also, thermal lesions were histologically examined via hematoxylin–eosin staining, Masson's trichrome staining, and Elastica van Gieson staining and immunohistochemistry.ResultsThe three treatment groups, which were determined according to the amount of laser‐energy applied (60, 90, and 120 mJ), showed slight thermal denaturation in the vaginal mucosa, but no abnormal reactions, such as excessive hemorrhaging, vesicles, or erythema, were observed. Histologically, we also confirmed that the denatured lamina propria induced by fractional CO2 laser was dose‐dependently increased after laser treatment. The treatment groups also showed an increase in collagen and elastic fibers due to neocollagenesis and angiogenesis, and the vaginal walls became firmer and tighter because of increased capillary and vessel formation. Also, use of the fractional CO2 laser increased HSP (heat shock protein) 70 and collagen type I synthesis.ConclusionOur results show that microablative fractional CO2 laser can produce remodeling of the vaginal connective tissue without causing damage to surrounding tissue, and the process of mucosa remodeling while under wound dressings enables collagen to increase and the vaginal wall to become thick and tightened. Lasers Surg. Med. 50:940–947, 2018. © 2018 Wiley Periodicals, Inc.
Poly(hydroxyl propyl methacrylate)‐b‐Poly(oligo ethylene glycol methacrylate) Thermoresponsive Block Copolymers by RAFT Polymerization
Authors: Karatza Anna , Pispas Stergios 
Published: May 2018

AbstractThermoresponsive amphiphilic poly(hydroxyl propyl methacrylate)‐b‐poly(oligo ethylene glycol methacrylate) block copolymers (PHPMA‐b‐POEGMA) are synthesized by RAFT polymerization, with different compositions and molecular weights. The copolymers are molecularly characterized by size‐exclusion chromophotography, and 1H NMR spectroscopy. Dynamic light scattering (DLS) and static light scattering (SLS) experiments in aqueous solutions show that the copolymers respond to temperature variations via formation of self‐organized nanoscale aggregates. Aggregate structural characteristics depend on copolymer composition, molecular weight, and ionic strength of the solution. Fluorescence spectroscopy experiments confirm the presence of less hydrophilic domains within the aggregates at higher temperatures. The thermoresponsive behavior of the PHPMA‐b‐POEGMA block copolymers is attributed to the particular solubility characteristics of the hydrophilic, water insoluble PHPMA block that are modulated by the presence of the water soluble POEGMA block.