Preceding hyperinsulinemia prevents demonstration of insulin effect on fat-induced gastric inhibitory polypeptide (GIP).
The effect of insulin on fat-induced gastric inhibitory polypeptide (GIP) release has been studied in seven healthy volunteers during euglycemic blood glucose clamping. In the first protocol, insulin (0.1 U/kg/h) was infused 2 h before ingestion of 100 g fat and continued for 2 h thereafter. In protocol II, saline was infused 2 h before the fat load and the insulin infusion started at the time of fat ingestion. During both insulin infusion studies, glucose levels were clamped at the fasting level by means of the Biostator and plasma levels of insulin, C-peptide, and GIP were estimated by radioimmunoassay. The response of GIP to oral fat was inhibited by 63% if insulin infusion was started at the time of fat ingestion, whereas no inhibition was seen if a 2-h hyperinsulinemic period preceded the fat load. The plasma insulin levels were comparable at the end of each experiment, ranging from 110 to 130 microU/ml. Plasma C-peptide levels decreased during the insulin infusion and increased after fat ingestion. These findings were not the result of inhibition of gastric emptying by insulin because they could be confirmed in four volunteers with intraduodenal infusion of fat. The present data show that insulin does inhibit fat-induced GIP secretion in normal man, but preceding hyperinsulinemic glucose clamping masks this insulin effect, probably by decreasing the sensitivity of the GIP cells to insulin.


Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.
Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.


Collision cross sections of proteins and their complexes: a calibration framework and database for gas-phase structural biology.
Collision cross sections in both helium and nitrogen gases were measured directly using a drift cell with RF ion confinement inserted within a quadrupole/ion mobility/time-of-flight hybrid mass spectrometer (Waters Synapt HDMS, Manchester, U.K.). Collision cross sections for a large set of denatured peptide, denatured protein, native-like protein, and native-like protein complex ions are reported here, forming a database of collision cross sections that spans over 2 orders of magnitude. The average effective density of the native-like ions is 0.6 g cm(-3), which is significantly lower than that for the solvent-excluded regions of proteins and suggests that these ions can retain significant memory of their solution-phase structures rather than collapse to globular structures. Because the measurements are acquired using an instrument that mimics the geometry of the commercial Synapt HDMS instrument, this database enables the determination of highly accurate collision cross sections from traveling-wave ion mobility data through the use of calibration standards with similar masses and mobilities. Errors in traveling-wave collision cross sections determined for native-like protein complexes calibrated using other native-like protein complexes are significantly less than those calibrated using denatured proteins. This database indicates that collision cross sections in both helium and nitrogen gases can be well-correlated for larger biomolecular ions, but non-correlated differences for smaller ions can be more significant. These results enable the generation of more accurate three-dimensional models of protein and other biomolecular complexes using gas-phase structural biology techniques.


Shift towards larger diatoms in a natural phytoplankton assemblage under combined high-CO2 and warming conditions.
An indoor mesocosm experiment was carried out to investigate the combined effects of ocean acidification and warming on the species composition and biogeochemical element cycling during a winter/spring bloom with a natural phytoplankton assemblage from the Kiel fjord, Germany. The experimental setup consisted of a "Control" (ambient temperature of ~4.8 °C and ~535 ± 25 μatm pCO2), a "High-CO2" treatment (ambient temperature and initially 1020 ± 45 μatm pCO2) and a "Greenhouse" treatment (~8.5 °C and initially 990 ± 60 μatm pCO2). Nutrient replete conditions prevailed at the beginning of the experiment and light was provided at in situ levels upon reaching pCO2 target levels. A diatom-dominated bloom developed in all treatments with Skeletonema costatum as the dominant species but with an increased abundance and biomass contribution of larger diatom species in the Greenhouse treatment. Conditions in the Greenhouse treatment accelerated bloom development with faster utilization of inorganic nutrients and an earlier peak in phytoplankton biomass compared to the Control and High CO2 but no difference in maximum concentration of particulate organic matter (POM) between treatments. Loss of POM in the Greenhouse treatment, however, was twice as high as in the Control and High CO2 treatment at the end of the experiment, most likely due to an increased proportion of larger diatom species in that treatment. We hypothesize that the combination of warming and acidification can induce shifts in diatom species composition with potential feedbacks on biogeochemical element cycling.


Chorea.
Two weeks after starting the oral contraceptive pill, a 16-year-old girl developed increasingly violent chorea and an evolving psychosis with prominent hallucinations, ideas of reference, and paranoia. An erythematous skin rash subsequently developed and Sydenham's chorea (SC) was diagnosed. Following neuroleptic medication and steroids, her chorea and psychosis subsided. This case illustrates that severe psychotic features can occur in SC. It is recommended that antistreptolysin O titres and antibasal ganglia antibodies are checked early in patients with evolving movement disorders and prominent neuropsychiatric features, as the window for modifying the course of this immune-mediated disorder may be narrow.


2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide Radical (PTIO•) Trapping Activity and Mechanisms of 16 Phenolic Xanthones.
This study used the 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) trapping model to study the antioxidant activities of 16 natural xanthones in aqueous solution, including garcinone C, γ-mangostin, subelliptenone G, mangiferin, 1,6,7-trihydroxy-xanthone, 1,2,5-trihydroxyxanthone, 1,5,6-trihydroxyxanthone, norathyriol, 1,3,5,6-tetrahydroxy-xanthone, isojacareubin, 1,3,5,8-tetrahydroxyxanthone, isomangiferin, 2-hydroxyxanthone, 7-O-methylmangiferin, neomangiferin, and lancerin. It was observed that most of the 16 xanthones could scavenge the PTIO• radical in a dose-dependent manner at pH 4.5 and 7.4. Among them, 12 xanthones of the para-di-OHs (or ortho-di-OHs) type always exhibited lower half maximal inhibitory concentration (IC50) values than those not of the para-di-OHs (or ortho-di-OHs) type. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis revealed that most of these xanthones gave xanthone-xanthone dimers after incubation with PTIO•, except for neomangiferin. Based on these data, we concluded that the antioxidant activity of phenolic xanthone may be mediated by electron-transfer (ET) plus H⁺-transfer mechanisms. Through these mechanisms, some xanthones can further dimerize unless they bear huge substituents with steric hindrance. Four substituent types (i.e., para-di-OHs, 5,6-di-OHs, 6,7-di-OHs, and 7,8-di-OHs) dominate the antioxidant activity of phenolic xanthones, while other substituents (including isoprenyl and 3-hydroxy-3-methylbutyl substituents) play a minor role as long as they do not break the above four types.


Scatter of orthopaedic research: can orthopods stay up-to-date with research?
The volume of orthopaedic literature is increasing exponentially, becoming more widely scattered among journals. The rate of increase in orthopaedics is greater than other specialties. We aimed to identify the number of different journals an orthopaedic surgeon would need to read to stay up-to-date with current evidence. We searched PubMed for all orthopaedic-related systematic reviews (SR) and randomized controlled trials (RCT) published in 2011 using MESH (Medical Subject Headings) terms. The search was based on the Australian Orthopaedic Association syllabus of March 2011. The results of the search were exported to EndNote, then Microsoft Excel. We then calculated the least number of journals needed to read 25%, 50% and 100% of the articles. This was done separately for SRs and RCTs. We found 1400 orthopaedic RCTs spread over 392 journals. Ten journals contained 25% of the articles, 36 journals contained 50% and 114 journals contained 75%. Three hundred journals contained three or fewer RCTs. We found 354 orthopaedic-relevant SRs spread over 152 journals. Six journals contained 25% of the articles, 23 journals contained 50% and 63 journals contained 75%. Ninety-three journals contained only one SR. Our results demonstrate the vast scatter of orthopaedic research. Four orthopaedic RCTs are published every day. To read even 25% of the new RCTs and SRs published in orthopaedics, a surgeon would require a subscription to 13 different journals monthly, a costly and time-consuming endeavour.


Inhibition of thromboxane synthetase potentiates the antihypertensive action of an angiotensin-converting enzyme inhibitor by a prostaglandin-dependent but kinin-independent mechanism.
Mean arterial pressure (BP) was measured in conscious, spontaneously hypertensive rats (SHR). Oral administration of the angiotensin I-converting enzyme inhibitor (ACEI) CGS 16617 significantly lowered BP. In contrast, the thromboxane synthetase inhibitor (TxSI) CGS 12970 lacked an antihypertensive action in SHR. When administered concurrently, the TxSI significantly potentiated the antihypertensive actions of the ACEI. Inhibition of thromboxane synthetase did not potentiate the antihypertensive actions of metoprolol or verapamil, indicating that a specific interaction exists between a TxSI and an ACEI. The antihypertensive actions of CGS 16617 also were potentiated by the cyclooxygenase inhibitor indomethacin, a result suggesting that CGS 12970 may enhance the action of CGS 16617 by inhibiting the action of vasoconstrictor prostaglandins produced after administration of an ACEI. The potentiation of the antihypertensive actions of CGS 16617 by CGS 12970 remained unaffected by either the kallikrein inhibitor aprotinin or a bradykinin receptor antagonist. Thus, although the interaction between an ACEI and a TxSI is a prostaglandin-dependent mechanism, it is not mediated by endogenous kinins. Inhibition of thromboxane synthetase significantly stimulated renin release and significantly attenuated the pressor response to exogenously administered angiotensin II. An increase in the dependency of BP upon the renin-angiotensin system and attenuation of the vascular actions of angiotensin II may serve to explain the potentiation of the antihypertensive action of ACEI after inhibition of thromboxane synthetase. The interaction between ACEI and TxSI was not restricted to SHR, because a TxSI potentiated the actions of an ACEI in both normotensive and deoxycorticosterone acetate/Na hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Development and Validation of a Screening Tool for Surgery-Specific Neuropathic Pain: Neuropathic Pain Scale for Postsurgical Patients.
Despite the existence of several screening tools for neuropathic pain, none of these are specific to surgery. We have developed a simple questionnaire tool, the Neuropathic Pain scale for Postsurgical patients (NeuPPS), to measure neuropathic pain in postsurgical patients. The aim was to validate this tool in a breast cancer population using an item response theory model, resulting in an easy-to-use scale. Development was based on literature reviews and interviews with patients and experts and consisted of 6 items. It was tested among 2,217 long-term breast cancer survivors, and cross-validated in another data set of breast cancer survivors with 18 months follow-up. We tested the questionnaire tool among breast cancer survivors in 2 cohorts, one nationwide and one of consecutively treated patients at Rigshospitalet, Copenhagen, Denmark. Items were assessed for criterion-related construct validity using the Rasch model, and for convergent validity by comparison to another neuropathic pain screening tool, the self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale. The selected 5-item model showed good fit, unidimensionality, monotonicity, and homogeneity. This result was reproducible in the cross-validation population. In a combined dataset with data from both studies, the model displayed a slightly lower fit, suggesting that items to some degree may vary over time. The Spearman rank correlation between the NeuPPS and S-LANSS was P = 0.57. We observed differential item functioning between the primary study population and the cross-validation population, meaning that some items behave differently at different follow-up times or study populations. With the NeuPPS, we have validated a simple and easy-to-fill-out questionnaire tool for the measurement of neuropathic pain among postsurgical patients. The items are additive, giving a total score that measures neuropathic pain symptoms. Scale validation, Rasch analysis, item response model, persistent postoperative pain, intercostobrachial nerve, neuropathy, neuropathic pain, quantitative sensory testing, breast cancer.


Planar surface plasmonic waveguide devices based on symmetric corrugated thin film structures.
Recently, a conformal surface plasmon (CSP) structure has been successfully proposed, which is very promising for application of planar plasmonic devices in the frequency ranging from microwave to mid-infrared [Proc. Natl. Acad. Sci. U.S.A. 110, 40-45 (2013)]. Here we investigated the dispersions and electromagnetic (EM) field patterns of a symmetric CSP structure in which the two sides of the planar metal strip are symmetrically corrugated by groove arrays. The symmetric CSP structure can support both the symmetric mode (even mode) and the anti-symmetric mode (odd mode) of surface wave propagation. Based on the even mode, we analyzed the EM wave coupling between two adjacent symmetry CSP strips, and then designed and analyzed two planar CSP waveguide devices in the terahertz frequency: a frequency splitter and a 3 dB directional coupler. To verify the functionality and performance of these waveguide devices, we scaled down the working frequency to microwave and designed similar devices with scaled geometry. We implemented microwave experiments on the fabricated prototypes, and the tested device performances have clearly validated the functionality of our designs. The symmetric CSP structure is believed to be very applicable in future design of novel planar plasmonic device and circuitry.


Adolescent blood pressure in a cohort study of sickle cell disease.
Previous studies on low blood pressure in patients with homozygous sickle cell (SS) disease have sought new hypotheses on the mechanism of low blood pressure but have not analyzed the role of known determinants such as weight. Blood pressure has been measured by an automated oscillometric method in 220 patients with SS disease, 144 with sickle cell-hemoglobin C disease (both groups aged, 9.5 to 18.5 years) and 122 control subjects with a normal hemoglobin genotype (aged 16.0 to 18.5 years) participating in a cohort study from birth. Significant age-related increases in systolic and mean arterial pressure occurred in sickle cell-hemoglobin C disease but not in SS disease. Further analyses were confined to a subgroup of 51 patients with SS, 41 patients with sickle cell-hemoglobin C, and 97 subjects with normal hemoglobin, aged 16.0 to 18.5 years in whom simultaneous measurements of height, weight, arm circumference, and hematologic test results were also available. Crude analyses showed significantly lower systolic, diastolic, and mean arterial pressure in SS disease compared with control subjects with normal hemoglobin, but further analysis showed the systolic difference to be confined to males and all differences disappeared after adjustment for weight. No differences occurred in sickle cell-hemoglobin C disease. These results suggest that the lower blood pressure in SS disease is attributable to low weight and that no further mechanisms need be postulated.


Quantitative analysis of bandpass-filtered Fourier transform infrared interferograms.
The feasibility of performing quantitative analysis with short segments of bandpass-filtered Fourier transform infrared (FT-IR) interferograms is demonstrated. The protocol developed in this work addresses four limitations that hinder the use of FT-IR spectroscopy in nonlaboratory applications: (1) the need for a rugged, low-cost, and reliable spectrometer, (2) the lack of representative background spectra for use in acquiring absorbance spectra of the target analyte, (3) the presence of overlapping spectral bands that interfere with the analyte determination, and (4) the difficulty in obtaining useful information from data collected near the limit of detection. In this work, spectral information pertaining to a specific analyte band of interest is isolated directly from a short interferogram segment by the application of narrow-bandpass digital filters. When processed in this way, the filtered interferogram segments contain compound-specific information that can be utilized for quantitative analysis. Successful use of a univariate calibration procedure with filtered interferogram data of benzene and nitrobenzene of varying concentrations is demonstrated. Calibrations based on filtered interferogram segment magnitudes vs concentration yield models with values of R2 in excess of 99%. These results are obtained without the use of a separate background or reference interferogram. This interferogram-based analysis is shown to perform analogously to a conventional spectral-based analysis, with the interferogram method being more efficient in terms of data collection and computational requirements.


Filamentous Bacteriophage Promote Biofilm Assembly and Function.
Biofilms-communities of bacteria encased in a polymer-rich matrix-confer bacteria with the ability to persist in pathologic host contexts, such as the cystic fibrosis (CF) airways. How bacteria assemble polymers into biofilms is largely unknown. We find that the extracellular matrix produced by Pseudomonas aeruginosa self-assembles into a liquid crystal through entropic interactions between polymers and filamentous Pf bacteriophages, which are long, negatively charged filaments. This liquid crystalline structure enhances biofilm function by increasing adhesion and tolerance to desiccation and antibiotics. Pf bacteriophages are prevalent among P. aeruginosa clinical isolates and were detected in CF sputum. The addition of Pf bacteriophage to sputum polymers or serum was sufficient to drive their rapid assembly into viscous liquid crystals. Fd, a related bacteriophage of Escherichia coli, has similar biofilm-building capabilities. Targeting filamentous bacteriophage or the liquid crystalline organization of the biofilm matrix may represent antibacterial strategies.


Is The Allergen Really Needed in Allergy Immunotherapy?
Immunotherapy for type I allergies is well established and is regarded to be the most efficient treatment option besides allergen avoidance. As of today, different forms of allergen preparations are used in this regard, as well as different routes of application. Virus-like particles (VLPs) represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances activation of innate as well as adaptive immune responses. CpG motifs represent intensively investigated and potent direct stimulators of plasmacytoid dendritic cells and B cells, while T cell responses are enhanced indirectly through increased antigen presentation and cytokine release. This article will focus on the function of VLPs loaded with DNA rich in nonmethylated CG motifs (CpGs) and the clinical experience gained in the treatment of allergic rhinitis, demonstrating clinical efficacy also if administered without allergens. Several published studies have demonstrated a beneficial impact on allergic symptoms by treatment with CpG-loaded VLPs. Subcutaneous injection of VLPs loaded with CpGs was tested with or without the adjuvant alum in the presence or absence of an allergen. The results encourage further investigation of VLPs and CpG motifs in immunotherapy, either as a stand-alone product or as adjuvants for allergen-specific immunotherapy.


Inhibition of DNA repair by deoxyadenosine in resting human lymphocytes.
Profound lymphopenia is characteristic of immunodeficient children who lack adenosine deaminase (ADA). When ADA is inactive, deoxyadenosine (dAdo) is phosphorylated by immature T lymphoblasts and inhibits cell division. However, dAdo also causes the slow accumulation of DNA strand breaks in nondividing, mature human peripheral blood lymphocytes. To explore the basis for this phenomenon, we have assessed the effects of dAdo and other deoxynucleosides on the repair of gamma-radiation induced DNA strand breaks in resting normal lymphocyte cultures. As measured by a sensitive DNA unwinding assay, most DNA strand breaks were rejoined within 2 hr after exposure of lymphocytes to 500 rad. In medium supplemented with deoxycoformycin, a tight binding ADA inhibitor, dAdo retarded DNA rejoining in a dose and time dependent manner. The inhibition required dAdo phosphorylation. Over an 8-hr period, 10 microM dAdo gradually rendered peripheral blood lymphocytes incompetent for DNA repair. Among several other compounds tested, 2-chlorodeoxyadenosine, an ADA resistant dAdo congener with anti-leukemic and immunosuppressive activity, was the most powerful inhibitor of DNA repair, exerting significant activity at concentrations as low as 100 nM. Both dAdo and 2-chlorodeoxyadenosine blocked unscheduled DNA synthesis in irradiated resting lymphocytes, as measured by [3H]thymidine uptake. On the basis of this and other data, we suggest that quiescent peripheral blood lymphocytes break and rejoin DNA at a slow and balanced rate. The accumulation of dATP progressively retards the DNA repair process and thereby fosters the time-dependent accretion of DNA strand breaks. By inhibiting DNA repair, dAdo, 2-chlorodeoxyadenosine and related compounds may substantially potentiate the toxicity of DNA damaging agents to normal and malignant lymphocytes.


In vivo modulation of endothelial F-actin microfilaments by experimental alterations in shear stress.
F-actin microfilament reorganization in response to alterations in shear stress has not been experimentally tested in vivo. In the current study, we analyzed changes in F-actin distribution in endothelial cells around the site of a coarctation performed in the midabdominal aorta of rabbits. The coarctation caused a 60% decrease in luminal diameter and produced three distinct zones: 1) a high shear region immediately upstream of the coarct (Zone I); 2) a region of low, fluctuating shear immediately downstream of the coarct (Zone II); and 3) an annular vortex characterized by high shear extending 0.5 to 3 mm downstream of the coarct (Zone III). Endothelial cells of control abdominal aortas were ellipsoid in shape and aligned in the direction of blood flow. They displayed a prominent circumferential band of microfilaments and short, thin stress fibers. Near coarctations, cells of Zone I were much more elongate, and stress fibers were markedly thicker and longer than in control abdominal aortas. In Zone II, cells were polygonal in shape and showed a prominent peripheral band of microfilaments and central stress fibers. Zone III cells were similar in shape to control abdominal aortic endothelial cells but showed very striking central stress fibers. These findings indicate that in vivo F-actin microfilament distribution can be modulated by experimentally altering flow conditions. F-actin redistribution in response to elevated shear stresses may increase cell-substrate adhesion and thus maintain endothelial integrity.


Participatory Action Research and Photovoice: Applicability, Relevance, and Process in Nursing Education Research.
Participatory action research (PAR) is a philosophy and approach to qualitative research. The purpose of this article is to generate a clearer understanding of PAR and its relevance to the discipline and profession of nursing. The authors provide a description of the principles and process of implementing PAR methodology, using photovoice as an innovative, participant-directed data collection method in rural nursing preceptorship. Participants were undergraduate nursing students and faculty advisors assigned to rural communities during the final clinical preceptorship. Participants described opportunities and challenges experienced during the preceptorship and how these experiences influenced their learning and overall preceptorship experience.


Efficacy and tolerability of lithium for the treatment of acute mania in children with bipolar disorder: A systematic review: A report from the ISBD-IGSLi joint task force on lithium treatment.
To assess the efficacy and tolerability of lithium for the treatment of acute mania in children and adolescent diagnosed with bipolar disorder. A systematic literature search up to August 2017 was conducted for clinical trials that included lithium in males and females up to 18 years of age with a diagnosis of bipolar disorder and experiencing a manic or mixed episode according to standardized diagnostic criteria. The protocol was registered in PROSPERO (CRD42017055675). Four independent studies described in seven manuscripts met the inclusion criteria. Overall, 176 patients were treated with lithium either as a monotherapy or adjunct to risperidone. Efficacy results suggest that lithium may be superior to placebo (standardized mean difference [SMD] -0.42, 95% confidence interval [CI] -0.88 to 0.04), comparable to sodium divalproex (SMD -0.07, 95% CI: -0.31 to 0.18), but significantly less effective than risperidone for treating protracted manic/mixed episodes and comorbid attention-deficit hyperactivity disorder (ADHD) in prepubertal children (SMD 0.85, 95% CI: 0.54 to 1.15). Lithium was not associated with serious adverse events, and was generally well tolerated with common side effects similar to those reported in adults. Limited data suggests that lithium may be an effective and tolerable treatment for some forms of paediatric mania. However, lithium is clearly inferior in efficacy to risperidone in prepubertal patients diagnosed with protracted manic/mixed episodes and comorbid ADHD. There is a lack of data concerning the efficacy and tolerability of lithium as an acute treatment for classical mania in adolescents and important clinical issues remain unaddressed.


Analysis of single nucleotide polymorphism in adolescent idiopathic scoliosis in Korea: for personalized treatment.
The incidence of adolescent idiopathic scoliosis (AIS) has rapidly increased, and with it, physician consultations and expenditures (about one and a half times) in the last 5 years. Recent etiological studies reveal that AIS is a complex genetic disorder that results from the interaction of multiple gene loci and the environment. For personalized treatment of AIS, a tool that can accurately measure the progression of Cobb's angle would be of great use. Gene analysis utilizing single nucleotide polymorphism (SNP) has been developed as a diagnostic tool for use in Caucasians but not Koreans. Therefore, we attempted to reveal AIS-related genes and their relevance in Koreans, exploring the potential use of gene analysis as a diagnostic tool for personalized treatment of AIS therein. A total of 68 Korean AIS and 35 age- and sex-matched, healthy adolescents were enrolled in this study and were examined for 10 candidate scoliosis gene SNPs. This study revealed that the SNPs of rs2449539 in lysosomal-associated transmembrane protein 4 beta (LAPTM4B) and rs5742612 in upstream and insulin-like growth factor 1 (IGF1) were associated with both susceptibility to and curve severity in AIS. The results suggested that both LAPTM4B and IGF1 genes were important in AIS predisposition and progression. Thus, on the basis of this study, if more SNPs or candidate genes are studied in a larger population in Korea, personalized treatment of Korean AIS patients might become a possibility.


Evaluation of age effects on doxorubicin-induced toxicity in mesenchymal stem cells.
Background: Doxorubicin, by aggregating in bone marrow, causes genotoxic effects, and thus reduces the repair ability of cells. The present study was conducted as an in vitro evaluation of age effects on the cytotoxicity induced by doxorubicin in mesenchymal stem cells (MSCs). Methods: The MSCs of female BALB/c mice aged 1, 8, and 16 months were separated, characterized, and subsequently evaluated in cellular growth media. After 24 hours, exposure of the MSCs of the 3 groups of mice to doxorubicin (25, 50, 100, 200, 400, 800, 1200 nM) and cytotoxicity were assessed, and the sublethal dose was determined using flow cytometry technique and lactate dehydrogenase (LDH) release assay. Results: The IC50 values determined by flow cytometry for the separated MSCs of 1 young, 8 middle- aged, and 16 old mice were and respectively. Interestingly, the results of these 2 methods in determining cytotoxicity were in agreement, and a concentration of approximately 25 nM was considered to be the shared sublethal dose for different ages. Conclusion: The results indicated that MSCs of middle-aged mice were more resistant to the toxic effects of the drug. Besides, MSCs separated from the old mice were the most sensitive to chemotherapy and its side effects such as disruptions of cell proliferation and viability. These disruptions can be ascribed to the alteration of function and physiological processes with age. Determining proper concentration of doxorubicin drug to destruct cancerous cells based on age and individual sensitivity can minimize the amount of toxicity.


Preparation and, in vitro, preclinical and clinical studies of aceclofenac spherical agglomerates.
Aceclofenac agglomerates were prepared by spherical crystallization technique using a three solvent system comprising acetone: dichloromethane (DCM): water (bridging liquid, good solvent and bad solvent, respectively). Hydroxypropyl methylcellulose-50cps (HPMC) in different concentrations was used as hydrophilic polymer. The effect of speed of rotation and amount of bridging liquid on spherical agglomeration were studied. The agglomerates were subjected to various physicochemical evaluations such as practical yield, drug content, particle size, loss on drying, porosity, IR spectroscopy, differential scanning calorimetry, X-ray diffraction studies, relative crystallinity, scanning electron microscopy, micromeritic properties, solubility and dissolution studies. The agglomerates showed improved micromeritic properties as well as dissolution behaviour in comparison to conventional drug crystals. The optimized agglomerates (F-9) showed good sphericity as well as high drug release, and hence they were compressed into tablets by direct compression. The tablets were found within the limits with respect to various physicochemical parameters. The dissolution rate of prepared tablets was better than that of marketed tablet and pure drug. The optimized agglomerates and tablet formulations were found to be stable for 6 months under accelerated conditions. The in vivo studies (preclinical pharmacokinetics, pharmacodynamics and toxicity studies, and clinical pharmacokinetics) of optimized agglomerates were carried out. The results of preclinical studies revealed that the agglomerates provided improved pharmacodynamic and pharmacokinetic profiles of drug besides being nontoxic. The results of pharmacokinetic studies of optimized tablet in human subjects indicated improved pharmacokinetic parameters of drug in comparison with that of marketed tablet.


Interdisciplinary craniofacial teams compared with individual providers: is orofacial cleft care more comprehensive and do parents perceive better outcomes?
The primary objective was to examine whether children with orofacial clefts received more comprehensive care and whether their parents perceived better outcomes if the care was delivered by interdisciplinary teams compared with individual providers. Data about services received and outcomes were collected from mothers of children with orofacial clefts. Mothers of children born between 1998 and 2003 with orofacial clefts from Arkansas, Iowa, and New York who participated in the National Birth Defects Prevention Study were eligible. Services and treatments received and maternal perception of cleft care, health status, aesthetics, and speech were evaluated by team care status. Of 253 children, 24% were not receiving team care. Of those with cleft lip and palate, 86% were enrolled in team care. Compared with children with team care, those without had fewer surgeries and were less likely to have seen a dentist, received a hearing test, or had a genetic consultation. Mothers of children lacking team care were twice as likely to give lower ratings for overall cleft care; maternal perceptions of global health, facial appearance, and speech did not differ by team care status. Recommended care tended to be received more often among those with team care. A larger, longitudinal study might answer questions about whether team care provides the best care and the role that type and severity of the condition and racial/ethnic differences play in the services received and outcomes experienced.


Thr202Ala in thyA is a marker for the Latin American Mediterranean lineage of the Mycobacterium tuberculosis complex rather than para-aminosalicylic acid resistance.
Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not always clear-cut, and phylogenetic SNPs have been misclassified as resistance markers in the past. In the present study, we investigated the utility of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para-aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug-resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were investigated for the presence of Thr202Ala. In both strain collections, the Thr202Ala SNP was found exclusively in strains of the Latin American Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM strains (not containing the SNP), as well as the results of growth curve analyses performed in liquid 7H9 medium in the presence of increasing PAS concentrations (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but, instead, represents a phylogenetic marker for the LAM lineage of the M. tuberculosis complex. These findings challenge some of the previous understanding of PAS resistance and, as a consequence, warrant further in-depth investigations of the genetic variation in PAS-resistant clinical isolates and spontaneous mutants.


TGF-Beta suppresses VEGFA-mediated angiogenesis in colon cancer metastasis.
The FET cell line, derived from an early stage colon carcinoma, is non-tumorigenic in athymic nude mice. Engineered FET cells that express TGF-α (FETα) display constitutively active EGFR/ErbB signaling. These cells readily formed xenograft tumors in athymic nude mice. Importantly, FETα cells retained their response to TGF-beta-mediated growth inhibition, and, like the parental FET cells, expression of a dominant negative TGF-beta type II receptor (DNRII) in FETα cells (FETα/DNRII) abrogated responsiveness to TGF-beta-induced growth inhibition and apoptosis under stress conditions in vitro and increased metastatic potential in an orthotopic model in vivo, which indicates metastasis suppressor activity of TGF-beta signaling in this model. Cancer angiogenesis is widely regarded as a key attribute for tumor formation and progression. Here we show that TGF-beta signaling inhibits expression of vascular endothelial growth factor A (VEGFA) and that loss of autocrine TGF-beta in FETα/DNRII cells resulted in increased expression of VEGFA. Regulation of VEGFA expression by TGF-beta is not at the transcriptional level but at the post-transcriptional level. Our results indicate that TGF-beta decreases VEGFA protein stability through ubiquitination and degradation in a PKA- and Smad3-dependent and Smad2-independent pathway. Immunohistochemical (IHC) analyses of orthotopic tumors showed significantly reduced TGF-beta signaling, increased CD31 and VEGFA staining in tumors of FETα/DNRII cells as compared to those of vector control cells. These results indicate that inhibition of TGF-beta signaling increases VEGFA expression and angiogenesis, which could potentially contribute to enhanced metastasis of those cells in vivo. IHC studies performed on human colon adenocarcinoma specimens showed that TGF-beta signaling is inversely correlated with VEGFA expression, indicating that TGF-beta-mediated suppression of VEGFA expression exists in colon cancer patients.


The Changing Climate: Managing Health Impacts.
Concentrations of greenhouse gases continue to accumulate in the atmosphere at increasing rates, heating the Earth's surface and destabilizing climate. Health impacts from climate change may include increased morbidity and mortality from worsening cardiopulmonary health, worsening allergies, and greater risk of infectious disease and mental illness, including anxiety, depression, and posttraumatic stress disorder from extreme weather events. Family physicians should advise patients to minimize exposure to air pollution, which is potentiated by rising temperatures. Use of self-monitoring devices, tracking local weather information, and awareness of events such as wildfires can alert patients to poor ambient air quality. Vulnerable individuals should avoid intense outdoor exercise and stay indoors or wear protective N95 masks when air quality is in the harmful range. Physicians can teach patients to recognize early symptoms of heat illness and advise adequate hydration and cooling on hot days. Physicians should become aware of the signs and symptoms of vectorborne illnesses to ensure early treatment and limit spread. Physicians should be aware of the climate and health benefits of active transport and plant-based diets when counseling their patients. Physicians can have a positive impact on climate change awareness and policy by incorporating counseling, public health precepts, and advocacy into their practice.


Brain metastases from prostate cancer: A single-center experience.
Metastases from prostate cancer to the brain are very unusual and very few case series have been reported in the literature. Present study was performed to assess the proportion of brain metastasis from prostate cancer among other brain metastasis in men, to evaluate the distribution, pattern and magnetic resonance imaging (MRI) appearance of these metastatic lesions, and prognosis of brain metastasis in patients with prostate cancer. Between January 2010 and November 2016, 339 males who had received radiotherapy at our department were retrospectively reviewed. After the first evaluation of patients data, we reviewed only the patients with brain metastases from prostate cancer. We evaluated MRI characteristics of metastatic brain lesions and characteristics of the patients, tumor and treatment modalities. Ten of 339 patients (2.9%) had brain metastases from prostate cancer. Sixty percent of the patients had pure intraparenchymal metastasis, 20% of the patients had pure extensive dural metastasis and 20% of them had both. Seventy-five percent of the patients with intraparenchymal metastasis had multiple metastatic lesions. The median prostate specific antigen (PSA) level was 49.40 ng/mL and the Gleason score was ≥7 in all patients. Sixty percent of the patients had distant metastasis at the time of the diagnosis of prostate cancer. Median survival time in patients with brain metastasis was 4.5 months. Lesions of brain metastasis from prostate cancer had a large variety of imaging presentation and it is very difficult to distinguish them from the other brain metastasis originating from other types of cancer. Presence of a disseminated disease, high PSA level and high Gleason score can be useful parameters for the prediction of brain metastasis from prostate cancer.


Phytoremediation Using Bamboo to Reduce the Risk of Chromium Exposure from a Contaminated Tannery Site in Kenya.
This study examines an intervention strategy to reduce the risk of chromium (Cr) exposure. It follows a previous Cr exposure investigation, which revealed that large volumes of Cr-contaminated waste were burnt on site. The study site had a long history of land-based waste disposal since 1994. The potential for phytoremediation using bamboo species to restore Cr-contaminated soil was evaluated. Chromium levels and physico-chemical properties of the tannery and control soils were analyzed before transplanting six different bamboo species. Translocation, bio-concentration and bioaccumulation factors of the species were assessed for phytoremediation capabilities. Chromium levels in the tannery soils ranged from 1337.0 to 3398.0 mg/kg dw. The chromium levels were significantly higher (P < 0.05) than those of the control soils (0.20 to 2.34 mg/kg dw) and markedly exceeded the recommended limit of 100 mg/kg dw. The physicochemical properties of the tannery soils were also significantly varied (P < 0.05) compared to the control soils. In all cases, the species grown in the tannery soils were tolerant to a wide range of prevailing conditions. All of the bamboo species in the present study had a 100% survival rate in the tannery soils, except for D. birmanicus, which had a survival rate of 83.3%. Moreover, growth performance of the species in the tannery and control soils as evaluated by height and clump diameters did not vary significantly (P > 0.05). However, Cr levels in the tannery differed significantly (P < 0.05) among the species and rhizosphere soils. D. asper, B. vulgaris, D. membranaceus and B. blumeana had a bio-concentration factor (BCF) > 1 and translocation factor (TF) < 1, indicating that they are suitable for phytostablization. On the contrary, B. bambos had a bioaccumulation factor (BAF) < 1 and TF > 1, indicating potential for phytoextraction, while D. birmanicus showed no potential for phytoextraction or phytostabilization. The present study identified D. asper, B. vulgaris, D. membranaceus and B. blumeana as suitable for restoration of Cr-contaminated tannery sites. Close monitoring of toxic metals is necessary during application of these species. Further studies are also recommended using a wide variety of bamboo species to optimize their application in phytoremediation.


Global Myocardial Work Is Superior to Global Longitudinal Strain to Predict Significant Coronary Artery Disease in Patients With Normal Left Ventricular Function and Wall Motion.
Noninvasive detection of functionally significant coronary artery disease (CAD) by echocardiography remains challenging, with the need to perform stress imaging to detect ischemia. The aim of this study was to determine whether global myocardial work (MW), derived from noninvasive left ventricular (LV) pressure-strain loops at rest, can predict significant CAD in patients without regional wall motion abnormalities and preserved LV ejection fraction (EF). One hundred and fifteen patients referred for coronary angiography who had EF ≥ 55%, no resting regional wall motion abnormalities, and no chest pain were assessed using echocardiography. Global MW was derived from noninvasive LV pressure-strain loops constructed from speckle-tracking echocardiography indexed to brachial systolic blood pressure. Global constructive work represented the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation. Global wasted work represented energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation. Global MW efficiency was derived from the percentage ratio of constructive work to the sum of constructive work and wasted work. Patients with significant CAD demonstrated a significantly reduced global MW (P < .001) compared with those without CAD. Global longitudinal strain was significantly reduced (P < .001) in patients with multivessel CAD but not those with single-vessel CAD (P = .47). Receiver operating characteristic curve analysis demonstrated that global MW was the most powerful predictor of significant CAD (area under the curve = 0.786) and was superior to global longitudinal strain (area under the curve = 0.693). The optimal cutoff global MW value to predict significant CAD was 1,810 mm Hg% (sensitivity, 92%; specificity, 51%). Noninvasive global MW derived using LV pressure-strain loops at rest is a more sensitive index than global longitudinal strain to detect significant CAD in patients with no regional wall motion abnormalities and normal EF. This is a potential valuable clinical tool to assist in the early diagnosis of CAD.


Nasogastric feeding tube placement in patients with esophageal cancer: application of ultrathin transnasal endoscopy.
Patients with esophageal cancer often present with dysphagia and malnutrition. Obstructive symptoms may improve after radiotherapy and chemotherapy. Nutrition support via a nasogastric tube (NG) or gastrostomy is very important during treatment. The newly developed ultrathin endoscope (Olympus, GIF-N230, outer diameter: 6 mm) has a smaller diameter than the standard endoscope and can be introduced into the esophagus via the nasal cavity. This article reports on the use of an ultrathin endoscope for NG placement for patients with esophageal cancer who presented with dysphagia and failed traditional NG tube placement. A consecutive series of 40 patients with esophageal cancer were referred to our hospital from November 2001 to October 2002 for endoscopic placement of NG tubes due to failure of traditional methods of NG placement. An ultrathin endoscope was used to advance the guidewire into the stomach via the nasal cavity. After withdrawal of the scope, the NG tube was inserted over the guidewire under fluoroscopy. A total of 71 procedures were performed in 40 patients (37 males, 3 females), age 57 +/- 15 years (range, 37-91 y). Seventy procedures (99%) were successful in completing NG tube placement by using an ultrathin transnasal endoscope. Only one procedure failed because the esophageal lumen was completely occluded and the guidewire was not able to be passed through the obstructed site. The average duration that the NG tube was left in place was 49 +/- 35 days (range, 2-144 days). No procedure-related complications, such as bleeding or perforation, occurred. Using ultrathin transnasal endoscopy to place an NG tube for esophageal cancer patients is effective and safe. It simplifies the procedures and increases the success rate.


Functional Analyses of Resurrected and Contemporary Enzymes Illuminate an Evolutionary Path for the Emergence of Exolysis in Polysaccharide Lyase Family 2.
Family 2 polysaccharide lyases (PL2s) preferentially catalyze the β-elimination of homogalacturonan using transition metals as catalytic cofactors. PL2 is divided into two subfamilies that have been generally associated with secretion, Mg(2+) dependence, and endolysis (subfamily 1) and with intracellular localization, Mn(2+) dependence, and exolysis (subfamily 2). When present within a genome, PL2 genes are typically found as tandem copies, which suggests that they provide complementary activities at different stages along a catabolic cascade. This relationship most likely evolved by gene duplication and functional divergence (i.e. neofunctionalization). Although the molecular basis of subfamily 1 endolytic activity is understood, the adaptations within the active site of subfamily 2 enzymes that contribute to exolysis have not been determined. In order to investigate this relationship, we have conducted a comparative enzymatic analysis of enzymes dispersed within the PL2 phylogenetic tree and elucidated the structure of VvPL2 from Vibrio vulnificus YJ016, which represents a transitional member between subfamiles 1 and 2. In addition, we have used ancestral sequence reconstruction to functionally investigate the segregated evolutionary history of PL2 progenitor enzymes and illuminate the molecular evolution of exolysis. This study highlights that ancestral sequence reconstruction in combination with the comparative analysis of contemporary and resurrected enzymes holds promise for elucidating the origins and activities of other carbohydrate active enzyme families and the biological significance of cryptic metabolic pathways, such as pectinolysis within the zoonotic marine pathogen V. vulnificus.


Dynamics of Transforming Growth Factor (TGF)-β Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines.
Human immunodeficiency virus type 1 (HIV-1) infection triggers rapid induction of multiple innate cytokines including type I interferons, which play important roles in viral control and disease pathogenesis. The transforming growth factor (TGF)-β superfamily is a pleiotropic innate cytokine family, some members of which (activins and bone morphogenetic proteins (BMPs)) were recently demonstrated to exert antiviral activity against Zika and hepatitis B and C viruses but are poorly studied in HIV-1 infection. Here, we show that TGF-β1 is systemically induced with very rapid kinetics (as early as 1-4 days after viremic spread begins) in acute HIV-1 infection, likely due to release from platelets, and remains upregulated throughout infection. Contrastingly, no substantial systemic upregulation of activins A and B or BMP-2 was observed during acute infection, although plasma activin levels trended to be elevated during chronic infection. HIV-1 triggered production of type I interferons but not TGF-β superfamily cytokines from plasmacytoid dendritic cells (DCs) in vitro, putatively explaining their differing in vivo induction; whilst lipopolysaccharide (but not HIV-1) elicited activin A production from myeloid DCs. These findings underscore the need for better definition of the protective and pathogenic capacity of TGF-β superfamily cytokines, to enable appropriate modulation for therapeutic purposes.


Antitumor Effects of N-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells.
Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. N-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G0/G1 and subG1 phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer.


Modulation of iridium(III) phosphorescence via photochromic ligands: a density functional theory study.
The photochromic iridium(iii) complex (Py-BTE)(2)Ir(acac) synthesized by Tan et al. [W. Tan et al., Org. Lett. 2009, 11, 161-164] has shown distinct photo-reactivity and photo-controllable phosphorescence. We here present a density functional theory study on the (Py-BTE)(2)Ir(acac) complex to explore the mechanism at the molecular level and to help further design of photochromic iridium(iii) complexes with the desirable properties. The hybrid functional PBE0, with 25% Hartree-Fock exchange, is found to give an optimal structure compared with X-ray crystallographic data. The absorption bands are well reproduced by using time-dependent density functional theory calculations, lending the possibility to assign the metal-to-ligand and intra-ligand charge transfer transitions. The radiative and nonradiative deactivation rate constants, k(r) and k(nr), are rationalized for both the open-ring and closed-ring forms of the complex. The very large k(nr) and small k(r) make the closed-ring form of the complex non-emissive. The triplet reactivity of the Py-BTE ligand is also studied by performing density functional theory calculations on the potential energy surfaces of the ground state and the lowest triplet state.


An observational study of patient characteristics and mortality following hypoglycemia in the community.
Characterize patients with diabetes with severe hypoglycemia requiring emergency services intervention at home and investigate 12-month mortality. Emergency services call-outs for hypoglycemia were recorded between 2005 and 2013 in an area covering 34 000 patients with diabetes. Patient characteristics were documented together with capillary blood glucose (CBG), glycated hemoglobin (HbA1c), and treatment for hypoglycemia; 12-month mortality and variables influencing survival were analyzed. In 1835 episodes among 1156 patients, 45% had type 1 diabetes (68.2% males) and 44% had type 2 diabetes (49.4% males), with a minority unclassified. CBG at presentation (mean±SD) was 1.76±0.72 mmol/L in patients with type 1 diabetes and 1.96±0.68 mmol/L in patients with type 2 diabetes (p<0.0001), with a higher HbA1c in the former group (8.3±1.52% (67.5±16.4 mmol/mol) and 7.8±1.74% (61.6±19.0 mmol/mol), respectively; p<0.0001). A third of patients with type 2 diabetes were not on insulin therapy and displayed lower HbA1c compared with insulin users. Glucagon was used in 37% of patients with type 1 diabetes and 28% of patients with type 2 diabetes (p<0.0001). One-year mortality was 4.45% in type 1 diabetes and 22.1% in type 2 diabetes. Age and type of diabetes were predictive of mortality in multivariable analysis, whereas CBG levels/frequency of hypoglycemia had no effect. Severe hypoglycemia in the community is common with a male predominance in type 1 diabetes. Severe hypoglycemia in non-insulin treated patients with type 2 diabetes is associated with lower HbA1c compared with insulin users. Severe hypoglycemia appears to be associated with increased mortality at 12 months, particularly in type 2 diabetes.


Hypohydration does not alter standing balance.
We examined the effect of body water deficits on standing balance and sought to determine if plasma hyperosmolality (P(osm)) and/or volume reduction (%ΔV(plasma)) exerted independent effects. Nine healthy volunteers completed three experimental trials which consisted of a euhydration (EUH) balance test, a water deficit session and a hypohydration (HYP) balance test. Hypohydration was achieved both by exercise-heat stress to 3% and 5% body mass loss (BML), and by a diuretic to 3% BML. Standing balance was assessed during quiet standing on a force platform with eyes open and closed. With eyes closed, hypohydration significantly decreased medial-lateral sway path and velocity by 13% (both p < .040). However, 95% confidence intervals for the mean difference between EUH and HYP were all within the coefficient of variation of EUH measures, indicating limited practical importance. Neither V(plasma) loss nor P(osm) increases were associated with changes in balance. We concluded that standing balance was not altered by hypohydration.


Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.
Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. To develop recommendations for the care of adults with EMPD. A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.


Internalized Homophobia, Depressive Symptoms, and Suicidal Ideation Among Lesbian, Gay, and Bisexual Adults in South Korea: An Age-Stratified Analysis.
Purpose: Little research on internalized homophobia (IHP) and mental health among lesbian, gay, and bisexual (LGB) individuals has been done in South Korea, a context in which LGB populations widely experience societal stigma. This study examined the association between IHP and depressive symptoms and suicidal ideation among Korean LGB adults and investigated whether the association differed by participants' age. Methods: Cross-sectional data from the "Rainbow Connection Project I - Korean Lesbian, Gay, & Bisexual Adults' Health Study" were used for this study (N = 2178). Descriptive analyses were conducted to explore the distribution of IHP, depressive symptoms, and suicidal ideation across all covariates. Multivariate analyses were also used to investigate the overall and age-stratified associations between IHP and depressive symptoms and suicidal ideation. Results: The prevalence of high IHP was greater among older LGB adults, whereas the prevalence of depressive symptoms and suicidal ideation was higher among younger LGB adults. LGB individuals with high IHP levels had significantly greater risk of depressive symptoms than those with low IHP levels. In the age-stratified analyses, the associations between IHP and depressive symptoms were statistically significant only among older LGB adults with high IHP levels. Regarding suicidal ideation, the overall association was statistically significant in the full sample, but not in the age-stratified analyses. Conclusion: These findings suggest that mental health interventions are needed for LGB adults who have high IHP levels, especially among older generations. Furthermore, greater efforts are needed to enact protective legislation for sexual minority individuals in South Korea.


Impact of obesity on complications and outcomes: a comparison of fusion and nonfusion lumbar spine surgery.
OBJECTIVE Prior studies have shown obesity to be associated with higher complication rates but equivalent clinical outcomes following lumbar spine surgery. These findings have been reproducible across lumbar spine surgery in general and for lumbar fusion specifically. Nevertheless, surgeons seem inclined to limit the extent of surgery, perhaps opting for decompression alone rather than decompression plus fusion, in obese patients. The purpose of this study was to ascertain any difference in clinical improvement or complication rates between obese and nonobese patients following decompression alone compared with decompression plus fusion for lumbar spinal stenosis (LSS). METHODS The Quality Outcomes Database (QOD), formerly known as the National Neurosurgery Quality and Outcomes Database (N2QOD), was queried for patients who had undergone decompression plus fusion (D+F group) versus decompression alone (D+0 group) for LSS and were stratified by a body mass index (BMI) ≥ 30 kg/m2 (obese) or < 30 kg/m2 (nonobese). Demographic, surgical, and health-related quality of life data were compared. RESULTS In the nonobese cohort, 947 patients underwent decompression alone and 319 underwent decompression plus fusion. In the obese cohort, 844 patients had decompression alone and 337 had decompression plus fusion. There were no significant differences in the Oswestry Disability Index score or in leg pain improvement at 12 months when comparing decompression with fusion to decompression without fusion in either obese or nonobese cohorts. However, absolute improvement in back pain was less in the obese group when decompression alone had been performed. Blood loss and operative time were lowest in the nonobese D+0 cohort and were higher in obese patients with or without fusion. Obese patients had a longer hospital stay (4.1 days) than the nonobese patients (3.3 days) when fusion had been performed. In-hospital stay was similar in both obese and nonobese D+0 cohorts. No significant differences were seen in 30-day readmission rates among the 4 cohorts. CONCLUSIONS Consistent with the prior literature, equivalent clinical outcomes were found among obese and non-obese patients treated for LSS. In addition, no difference in clinical outcomes as related to the extent of the surgical procedure was observed between obese and nonobese patients. Within the D+0 group, the nonobese patients had slightly better back pain scores at 2 years postoperatively. There may be a higher blood product requirement in obese patients following spine surgery, as well as an extended hospital stay, when fusion is performed. While obesity may influence the decision for or against surgery, the data suggest that obesity should not necessarily alter the appropriate procedure for well-selected surgical candidates.


Cosmetic dermatology training in residency: results of a survey from the residents' perspective.
Dermatologists are expected to be experts in the evaluation and treatment of their patient's cosmetic concerns. It has been reported that some dermatology residents do not feel adequately trained in this field. To assess how dermatology residents are being trained in cosmetic dermatology. A survey was e-mailed to 473 third-year dermatology residents. One hundred eighteen surveys were returned (24.9%), representing 45% of programs. Most residents have assigned reading (70.7%) and lectures (81.4%) in cosmetic dermatology. To learn technical skills, 79.7% participate in formal training sessions, and 73% have an apprenticeship model. Most residents have the opportunity to perform botulinum toxin injections, laser surgery, fillers, chemical peels, and sclerotherapy. More than 58% of programs have an encouraging or somewhat encouraging attitude toward teaching cosmetics, whereas 22% were somewhat discouraging or discouraging. Most residents (75.4%) plan to incorporate cosmetics into their practice. Residents do not feel less prepared (94.9%) or less interested (97.4%) in medical dermatology as a result of their cosmetic training. Residents are being trained in cosmetic dermatology through a variety of methods. Residency programs should periodically assess and adapt their curricula to ensure adequate training in this field.


Mesenchymal Stem Cell-Derived Exosomes: Hope for Spinal Cord Injury Repair.
Spinal cord injury (SCI) is a devastating medical condition with profound social and economic impacts. Although research is ongoing, current treatment options are limited and do little to restore functionality. However, recent studies suggest that mesenchymal stem cell-derived exosomes (MSC-exosomes) may hold the key to exciting new treatment options for SCI patients. MSCs are self-renewing multipotent stem cells with multi-directional differentiation and can secrete a large number of exosomes (vesicles secreted into the extracellular environment through endocytosis, called MSC-exosomes). These MSC-exosomes play a critical role in repairing SCI through promoting angiogenesis and axonal growth, regulating inflammation and the immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be utilized to transport genetic material or drugs to target cells, and their relatively small size makes them able to permeate the blood-brain barrier. In this review, we summarize recent advances in MSC-exosome themed SCI treatments and cell-free therapies to better understand this newly emerging methodology.


Overdentures on implants placed in bone augmented with fresh frozen bone.
In the last decade several studies have been performed to evaluate the clinical outcome of one or two stage loaded implants supporting overdentures. Since fresh frozen bone (FFB) has an ever-increasing number of clinical applications and few reports are available on implants inserted into FFB, we performed a retrospective study on fixtures inserted in FFB and bearing overdentures. In the period between December 2003 and December 2006, 17 patients (14 females and 3 males with a median age of about 56 years) were grafted and 60 implants inserted thereafter. A total of 17 overdentures were delivered: 8 in the mandible and 9 in the maxilla. Multiple implant systems were used: 22 Double etched, 7 SLA, 9 Anodic oxidized, and 22 CaPo4 ceramic-blasted. Implant diameter ranged from 3.25 to 4.3 mm and length from 11.5 to 16.0 mm. Implants were inserted to replace 23 incisors, 9 cuspids, 20 premolars and 8 molars. No implants were lost (i.e., survival rate=100%) and no differences were detected among the studied variables. Kaplan Meier algorithm and Cox regression did not reveal any statistical differences among the studied variables also as regards the success rate. Implants inserted FFB and bearing overdentures have a high survival rate and success rates, which are comparable to those of implants inserted in non-grafted bone. FFB bone is a reliable material for alveolar ridge augmentation. No difference was detected among removable prostheses supported by two or more implants.


Increased expression of inhibitor of apoptosis proteins in atherosclerotic plaques of symptomatic patients with carotid stenosis.
Vascular remodeling and atheromatous lesion formation are determined in part by the balance between apoptosis and survival of vascular smooth muscle cells (VSMCs). In the chronic stages, apoptosis of VSMCs in the atherosclerotic plaques contributes to the weakening and potential rupture of the plaque causing pathologies such as acute coronary syndrome. The higher incidence of apoptosis in the plaques of symptomatic than in asymptomatic patients has been demonstrated, but the expression of survival proteins, including the inhibitor of apoptosis proteins (IAPs), has not been thoroughly examined. The aim of this study was to investigate the immunohistochemical expression of cellular inhibitor of apoptosis protein-2 (cIAP2), x-linked inhibitor of apoptosis protein (XIAP), and survivin in normal carotid arteries, and carotid endarterectomy specimens of symptomatic and asymptomatic patients with carotid stenosis. The results demonstrated stronger immunopositivity to smooth muscle myosin heavy chain antigen (SM-MHC) (sm2), proliferating cell nuclear antigen (PCNA), and p50 subunit of NF-kappabeta in the asymptomatic plaques than in symptomatic plaques. Furthermore, there was higher expression of cIAP2, XIAP, and survivin in the symptomatic than in the asymptomatic plaques and this paralleled caspase-3 expression. The increased expression of IAPs in symptomatic plaques could be due to endogenous defense mechanism to protect against the pro-apoptotic effect of the inflammatory stimuli that are released in the plaques. This could be involved in the stabilization of symptomatic atheromatous plaques and may prove a potential therapeutic target.


Neighborhood disparities in prevalence of childhood obesity among low-income children before and after implementation of New York City child care regulations.
New York City Article 47 regulations, implemented in 2007, require licensed child care centers to improve the nutrition, physical activity, and television-viewing behaviors of enrolled children. To supplement an evaluation of the Article 47 regulations, we conducted an exploratory ecologic study to examine changes in childhood obesity prevalence among low-income preschool children enrolled in the Nutrition Program for Women, Infants, and Children (WIC) in New York City neighborhoods with or without a district public health office. We conducted the study 3 years before (from 2004 through 2006) and after (from 2008 through 2010) the implementation of the regulations in 2007. We used an ecologic, time-trend analysis to compare 3-year cumulative obesity prevalence among WIC-enrolled preschool children during 2004 to 2006 and 2008 to 2010. Outcome data were obtained from the New York State component of the Centers for Disease Control and Prevention's Pediatric Nutrition Surveillance System. Early childhood obesity prevalence declined in all study neighborhoods from 2004-2006 to 2008-2010. The greatest decline occurred in Manhattan high-risk neighborhoods where obesity prevalence decreased from 18.6% in 2004-2006 to 15.3% in 2008-2010. The results showed a narrowing of the gap in obesity prevalence between high-risk and low-risk neighborhoods in Manhattan and the Bronx, but not in Brooklyn. The reductions in early childhood obesity prevalence in some high-risk and low-risk neighborhoods in New York City suggest that progress was made in reducing health disparities during the years just before and after implementation of the 2007 regulations. Future research should consider the built environment and markers of differential exposure to known interventions and policies related to childhood obesity prevention.


Aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during West Nile virus infection.
West Nile virus (WNV) is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC) signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-beta and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively), whilst transiently enhancing interleukin-10 (IL-10) expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively) in the skin and draining lymph nodes. These results suggest that mosquito saliva dysregulates APC antiviral signaling, and reveal a possible mechanism for the observed enhancement of WNV disease mediated by mosquito saliva via a reduction of T lymphocyte and antiviral activity at the inoculation site, an elevated abundance of susceptible cell types, and a concomitant increase in immunoregulatory activity of IL-10.


Effect of 3'-4'-dihydroxyflavonol on lipid per oxidation in experimental renal ischemia-reperfusion in rats.
This study aimed to examine the affects of 3'-4'-dihydroxyflavonol (DiOHF) on lipid peroxidation in experimental renal ischemia-reperfusion. The research was conducted on Wistar-albino type male rat. The experimental groups were formed as 1.Control; 2.Sham; 3.Ischemia; 4.Ischemia+reperfusion; 5.DiOHF+Ischemia; 6.Ischemia+ DiOHF + reperfusion. The highest tissue glutathione levels were found in groups 5 and 6. Groups 1 and 2, which were control and sham groups respectively, had the lowest tissue GSH values. Ischemia group was found to have the highest tissue malondialdehyde (MDA) level. Tissue MDA levels in group 4 were lower than those in group 3, however, higher than the levels in all other groups. Erythrocyte GSH levels in groups 5 and 6 were higher than the levels in all other groups. Group 4 has highest plasma MDA values. Plasma MDA levels in group 3 were lower than the levels in Group 4, but higher than those in other groups. The results of the study indicate that intraperitoneal DiOHF administration inhibits lipid per oxidation that intensifies in the case of renal ischemia-reperfusion injury in rats.


Cost-Effectiveness of a Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
The use of a bronchial genomic classifier has been shown to improve the diagnostic accuracy of bronchoscopy for suspected lung cancer by identifying patients who may be more suitable for radiographic surveillance as opposed to invasive procedures. Our objective was to assess the cost-effectiveness of bronchoscopy plus a genomic classifier versus bronchoscopy alone in the diagnostic work-up of patients at intermediate risk for lung cancer. A decision-analytic Markov model was developed to project the costs and effects of two competing strategies by using test performance from the Airway Epithelial Gene Expression in the Diagnosis of Lung Cancer-1 and Airway Epithelial Gene Expression in the Diagnosis of Lung Cancer-2 studies. The diagnostic accuracy of noninvasive and invasive follow-up, as well as associated adverse event rates, were derived from published literature. Procedure costs were based on claims data and 2016 inpatient and outpatient reimbursement amounts. The model projected the number of invasive follow-up procedures, 2-year costs and quality-adjusted life-years (QALYs) by strategy, and resulting incremental cost-effectiveness ratio discounted at 3% per annum. Use of the genomic classifier reduced invasive procedures by 28% at 1 month and 18% at 2 years, respectively. Total costs and QALY gain were similar with classifier use ($27,221 versus $27,183 and 1.512 versus 1.509, respectively), resulting in an incremental cost-effectiveness ratio of $15,052 per QALY. Our analysis suggests that the use of a genomic classifier is associated with meaningful reductions in invasive procedures at about equal costs and is therefore a high-value strategy in the diagnostic work-up of patients at intermediate risk of lung cancer.


Self-Reported Periodontitis and Complications in Type 1 Diabetes Patients: A Brazilian Nationwide Survey.
This study aimed to evaluate the possible association between periodontitis and systemic complications in a Brazilian type 1 diabetes population. A multicentre, sectional study was carried out in 28 public clinics located in 20 Brazilian cities. Data from 3,591 patients were obtained (56.0% females, 57.2% Caucasians), with an average age of 21.2 ± 11.7 years and whose mean duration of type 1 diabetes was 9.6 ± 8.1 years. Periodontitis was evaluated through self-report. Odds ratios (OR) and 95% confidence intervals were calculated to evaluate the association between periodontitis and systemic diabetes complications (chronic micro and macrovascular complications and hospitalizations by hyperglycemia and diabetic ketoacidosis). The prevalence of periodontitis was 4.7% (n=170). Periodontitis patients had mean age of 27.4 ± 12.9. This group was older (p<0.001), exhibited longer diabetes duration (p<0.0001) and had elevated total cholesterol (p<0.05), triglycerides (p<0.001) and lower HDL (p<0.05) values than patients without periodontitis. Systolic and diastolic blood pressures were significantly increased in periodontitis patients (p<0.01). Periodontitis patients had increased odds of microvascular complications (2.43 [1.74-3.40]) and of hospitalizations related to hyperglycemia (2.76 [1.72-4.42]) and ketoacidosis (2.72 [1.53-4.80]). In conclusion, periodontitis was associated to systemic complications in Brazilian type 1 diabetes patients.


The impact of cancer treatment on the diets and food preferences of patients receiving outpatient treatment.
Patients undergoing cancer treatment experience a multitude of symptoms that can influence their ability to complete treatment as well as their quality of life during and after treatment. This cross-sectional study sought to describe the dietary changes experienced by cancer patients and to identify associations between these changes and common treatment symptoms. A convenience sample of 1199 cancer patients aged 18 yr and older undergoing active treatment were recruited from 7 cancer centers to complete a self-administered paper-and-pencil survey. Descriptive analyses were conducted to estimate prevalence of dietary changes and chi-squared tests were used to examine associations between dietary changes and health outcomes. Approximately 40% of patients reported a decreased appetite since beginning treatment, and 67.2% of patients reported at least 1 chemosensory alteration. Increased taste sensitivities were more common than decreased taste sensitivities, with increased sensitivity to metallic being the most common taste sensitivity (18.6%). Patients also had increased sensitivities to certain smells including cleaning solutions (23.4%), perfume (22.4%), and food cooking (11.4%). Patients reported a wide range of food preferences and aversions. Patients who had less energy or lost weight since beginning treatment were more likely than others to report treatment-related dietary changes.


Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial.
Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune responses to both the pre-erythrocytic and blood stages of the P. falciparum life cycle. This was a Phase I/IIa study of a new combination malaria vaccine FFM ME-TRAP+PEV3A. PEV3A includes peptides from both the pre-erythrocytic circumsporozoite protein and the blood-stage antigen AMA-1. This study was conducted at the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK. The participants were healthy, malaria naïve volunteers, from Oxford. The interventions were vaccination with PEV3A alone, or PEV3A+FFM ME-TRAP. The main outcome measure was protection from malaria in a sporozoite challenge model. Other outcomes included measures of parasite specific immune responses induced by either vaccine; and safety, assessed by collection of adverse event data. We observed evidence of blood stage immunity in PEV3A vaccinated volunteers, but no volunteers were completely protected from malaria. PEV3A induced high antibody titres, and antibodies bound parasites in immunofluorescence assays. Moreover, we observed boosting of the vaccine-induced immune response by sporozoite challenge. Immune responses induced by FFM ME-TRAP were unexpectedly low. The vaccines were safe, with comparable side effect profiles to previous trials. Although there was no sterile protection two major observations support an effect of the vaccine-induced response on blood stage parasites: (i) Lower rates of parasite growth were observed in volunteers vaccinated with PEV3A compared to unvaccinated controls (p = 0.012), and this was reflected in the PCR results from PEV3A vaccinated volunteers. These showed early control of parasitaemia by some volunteers in this group. One volunteer, who received PEV3A alone, was diagnosed very late, on day 20 compared to an average of 11.8 days in unvaccinated controls. (ii). Morphologically abnormal parasites were present in the blood of all (n = 24) PEV3A vaccinated volunteers, and in only 2/6 controls (p = 0.001). We describe evidence of vaccine-induced blood stage efficacy for the first time in a sporozoite challenge study.


Performance of a CO2 sorbent for indoor air cleaning applications: Effects of environmental conditions, sorbent aging, and adsorption of co-occurring formaldehyde.
Indoor air cleaning systems that incorporate CO2 sorbent materials enable HVAC load shifting and efficiency improvements. This study developed a bench-scale experimental system to evaluate the performance of a sorbent under controlled operation conditions. A thermostatic holder containing 3.15 g sorbent was connected to a manifold that delivered CO2 -enriched air at a known temperature and relative humidity (RH). The air stream was also enriched with 0.8-2.1 ppm formaldehyde. The CO2 concentration was monitored in real-time upstream and downstream of the sorbent, and integrated formaldehyde samples were collected at different times using DNPH-coated silica cartridges. Sorbent regeneration was carried out by circulating clean air in countercurrent. Almost 200 loading/regeneration cycles were performed in the span of 17 months, from which 104 were carried out at reference test conditions defined by loading with air at 25°C, 38% RH, and 1000 ppm CO2 , and regenerating with air at 80°C, 3% RH and 400 ppm CO2 . The working capacity decreased slightly from 43-44 mg CO2 per g sorbent to 39-40 mg per g over the 17 months. The capacity increased with lower loading temperature (in the range 15-35°C) and higher regeneration temperature, between 40 and 80°C. The CO2 capacity was not sensitive to the moisture content in the range 6-9 g/m3 , and decreased slightly when dry air was used. Loading isothermal breakthrough curves were fitted to three simple adsorption models, verifying that pseudo-first-order kinetics appropriately describes the adsorption process. The model predicted that equilibrium capacities decreased with increasing temperature from 15 to 35°C, while adsorption rate constants slightly increased. The formaldehyde adsorption efficiency was 80%-99% in different cycles, corresponding to an average capacity of 86 ± 36 µg/g. Formaldehyde was not quantitatively released during regeneration, but its accumulation on the sorbent did not affect CO2 adsorption.


Evaluation of midwifery care: results from a survey in rural Guatemala.
In an effort to reduce infant and maternal morbidity and mortality in developing countries, the World Health Organization has promoted the training of traditional birth attendants (midwives) and their incorporation into the formal health care system. In this paper, we examine several aspects of the integration of traditional and biomedical maternity care that are likely to reflect the quality of care received by Guatemalan women. Specifically, we examine the extent to which women combine traditional and biomedical pregnancy care, the frequency with which midwives refer women to biomedical providers, the content and quality of care offered by midwives, and the effects of midwife training programs on referral practices and quality of care. The analysis is based on data from the 1995 Guatemalan Survey of Family Health. The results offer a mixed assessment of the efficacy of midwife training programs. For example, although trained midwives are much more likely than other midwives to refer their clients to biomedical providers, most pregnant women do not see a biomedical provider, and the quality of midwife care, as defined and measured in this study, is similar between trained and untrained midwives.


Intervention to promote physician well-being, job satisfaction, and professionalism: a randomized clinical trial.
IMPORTANCE Despite the documented prevalence and clinical ramifications of physician distress, few rigorous studies have tested interventions to address the problem. OBJECTIVE To test the hypothesis that an intervention involving a facilitated physician small-group curriculum would result in improvement in well-being. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 74 practicing physicians in the Department of Medicine at the Mayo Clinic in Rochester, Minnesota, conducted between September 2010 and June 2012. Additional data were collected on 350 nontrial participants responding to annual surveys timed to coincide with the trial surveys. INTERVENTIONS The intervention involved 19 biweekly facilitated physician discussion groups incorporating elements of mindfulness, reflection, shared experience, and small-group learning for 9 months. Protected time (1 hour of paid time every other week) for participants was provided by the institution. MAIN OUTCOMES AND MEASURES Meaning in work, empowerment and engagement in work, burnout, symptoms of depression, quality of life, and job satisfaction assessed using validated metrics. RESULTS Empowerment and engagement at work increased by 5.3 points in the intervention arm vs a 0.5-point decline in the control arm by 3 months after the study (P = .04), an improvement sustained at 12 months (+5.5 vs +1.3 points; P = .03). Rates of high depersonalization at 3 months had decreased by 15.5% in the intervention arm vs a 0.8% increase in the control arm (P = .004). This difference was also sustained at 12 months (9.6% vs 1.5% decrease; P = .02). No statistically significant differences in stress, symptoms of depression, overall quality of life, or job satisfaction were seen. In additional comparisons including the nontrial physician cohort, the proportion of participants strongly agreeing that their work was meaningful increased 6.3% in the study intervention arm but decreased 6.3% in the study control arm and 13.4% in the nonstudy cohort (P = .04). Rates of depersonalization, emotional exhaustion, and overall burnout decreased substantially in the trial intervention arm, decreased slightly in the trial control arm, and increased in the nontrial cohort (P = .03, .007, and .002 for each outcome, respectively). CONCLUSIONS AND RELEVANCE An intervention for physicians based on a facilitated small-group curriculum improved meaning and engagement in work and reduced depersonalization, with sustained results at 12 months after the study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01159977.


Laboratory measurements of spectral reflection from ice clouds of various habits.
Spectral light from 550 to 650 nm reflected from the surface of an ice cloud produced in a temperature-controlled column is measured at seven different angles between 16.7 degrees and 29.9 degrees . Cloud optical depth (tau) is determined from the extinction of a 670 nm laser and is corrected for forward scattering using a Monte Carlo ray-tracing algorithm. Reflection measurements are compared to expectations from a plane-parallel radiative transfer model with input parameters based on the measured tau and a phase function for the observed ice crystal types. The plane-parallel radiative transfer model can be used to interpret the measured reflection for tau less than about 0.4 for this particular experiment, ideal for providing a validation data set to assist with the development of satellite bidirectional remote sensing.


An exploration of how nurse prescribing is being used for patients with respiratory conditions across the east of England.
There is a need to reduce symptoms, exacerbations and improve quality of life for patients with respiratory diseases. Across the world, increasing numbers of nurses are adopting the prescribing role and can potentially enhance service provision. Evidence suggests improved quality of care and efficiencies occur when nurses adopt the prescribing role. No evidence is available on the views of nurse prescribers who care for respiratory patients. The aim was to explore how nurse prescribing is being used for patients with respiratory conditions in different care settings across one strategic health authority, and whether this has benefited patients, healthcare professionals and the National Health Service. A qualitative study involving semi-structured interviews with a purposive sample of 40 nurses who prescribed for respiratory patients across the six counties in the East of England Strategic Health Authority. Data were collected in 2011 and subject to thematic analysis. Disease management, including treatment and prevention of exacerbations, emergency episodes and minor illness, optimising and co-ordinating care were key aspects of care provided. Findings are reported under three themes: access, adherence and risk management and impact on nurses. Prescribing enabled nurses overcome existing problems in service provision to improve access, efficiency and patient convenience, reducing hospital admissions and length of stay. It also enabled patient centered consultations, which encouraged self-management, improved adherence, helped manage expectations, and reduced inappropriate service use. While participants experienced increased job satisfaction, knowledge and confidence, concerns were raised about increased responsibility, support, governance and future commissioning of services in line with planned major changes to the National Health Service. This study provides new knowledge about how nurse prescribers provide care to patients with respiratory diseases. Despite a lack of consensus over the most effective model of respiratory care, prescribing was reported to have improved and extended points of access to treatment, and supported management of complex patients, particularly vulnerable groups. Given the high burden of chronic respiratory disease to patients and families this has important implications that need to be considered by those responsible for commissioning services in the United Kingdom and other countries.


The Acute Effects of Caffeinated Black Coffee on Cognition and Mood in Healthy Young and Older Adults.
Cognitive and mood benefits of coffee are often attributed to caffeine. However, emerging evidence indicates behavioural effects of non-caffeine components within coffee, suggesting the potential for direct or synergistic effects of these compounds when consumed with caffeine in regular brewed coffee. The current randomised, placebo-controlled, double-blind, counterbalanced-crossover study compared the effects of regular coffee, decaffeinated coffee, and placebo on measures of cognition and mood. Age and sex effects were explored by comparing responses of older (61⁻80 years, N = 30) and young (20⁻34 years, N = 29) males and females. Computerised measures of episodic memory, working memory, attention, and subjective state were completed at baseline and 30 min post-drink. Regular coffee produced the expected effects of decreased reaction time and increased alertness when compared to placebo. When compared to decaffeinated coffee, increased digit vigilance accuracy and decreased tiredness and headache ratings were observed. Decaffeinated coffee also increased alertness when compared to placebo. Higher jittery ratings following regular coffee in young females and older males represented the only interaction of sex and age with treatment. These findings suggest behavioural activity of coffee beyond its caffeine content, raising issues with the use of decaffeinated coffee as a placebo and highlighting the need for further research into its psychoactive effects.


Frequent neurocognitive deficits after recovery from mild COVID-19.
Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20-105 days (median, 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation. Additionally, Modified Telephone Interview for Cognitive Status scores did not correlate with depressed mood or fatigue. In two severely affected patients, we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained sub-clinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.


DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7.
G2/M checkpoints prevent mitotic entry upon DNA damage or replication inhibition by targeting the Cdc2 regulators Cdc25 and Wee1. Although Wee1 protein stability is regulated by DNA-responsive checkpoints, the vertebrate pathways controlling Wee1 degradation have not been elucidated. In budding yeast, stability of the Wee1 homologue, Swe1, is controlled by a regulatory module consisting of the proteins Hsl1 and Hsl7 (histone synthetic lethal 1 and 7), which are targeted by the morphogenesis checkpoint to prevent Swe1 degradation when budding is inhibited. We report here the identification of Xenopus Hsl7 as a positive regulator of mitosis that is controlled, instead, by an entirely distinct checkpoint, the DNA replication checkpoint. Although inhibiting Hsl7 delayed mitosis, Hsl7 overexpression overrode the replication checkpoint, accelerating Wee1 destruction. Replication checkpoint activation disrupted Hsl7-Wee1 interactions, but binding was restored by active polo-like kinase. These data establish Hsl7 as a component of the replication checkpoint and reveal that similar cell cycle control modules can be co-opted for use by distinct checkpoints in different organisms.