A comparison of tablet-based and paper-based venous insufficiency epidemiologic and economic study quality of life/symptom questionnaire for assessment of chronic venous disease.
To comparatively evaluate performances of tablet-based versus paper-based Venous Insufficiency Epidemiologic and Economic Study-Quality of Life/Symptom (VEINES-QOL/Sym) questionnaire. We prospectively evaluated 78 consecutive patients who completed tablet-based and paper-based VEINES-QOL/Sym questionnaires and compared their scores, completion time, data entry time, and ease of use. We used Student's t-test and Wilcoxon test for quantitative variables, Bland-Altman test and kappa coefficient for agreement between questionnaires and patients, respectively. Spearman's correlation coefficient was used to assess correlations. Most participants (83.3%) found it easier to use the tablet device. Less time was needed to complete the tablet-based (median, 4.75; IQR, 3-7 min) than the paper-based (median, 8.3; IQR, 6.3-11.3 min) questionnaire (p < .001). Better educated patients took less time to complete paper-based (p = .003) and tablet-based (p = .001) questionnaires and considered the latter easier to use (p = .010). The tablet-based VEINES-QOL/Sym proved to be an easy-to-use and time-saving tool.


Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates.
Herein, we present an efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates. Each step of the synthesis was optimized to provide excellent yields. Moreover, the absolute configuration of the obtained compounds was determined by X-ray analysis, which proved the stereochemistry that was proposed based on NMR studies.


Surface antigens on normal and leukaemic human cells detected by monoclonal antibodies.
Surface antigens were analyzed on normal human marrow and chronic myeloid leukaemic cells using 4 monoclonal mouse anti-human antibodies. The fluorescence-activated cell sorter was used to quantify the binding of each antibody to different subpopulations of cells, and sorted fractions were cultured in agar-medium to assay for granulocyte-macrophage and eosinophil precursors. All cells in the granulocyte series including colony-forming cells bound a similar quantity of an antibody to the human leucocyte common antigen. This antibody did not bind to cells in the erythroid series. A monoclonal antibody to antigen present on brain, lymphocytes and granulocytes (and almost certainly homologous to the W3/13 antigen of the rat) bound to the cells in the order: blast greater than promyelocytes and myelocytes greater than granulocytes. The third monoclonal antibody was directed against a determinant of the leucocyte common antigen present predominantly on B lymphocytes and absent from the myeloid series. The fourth antibody, directed against the human homologue of Thy-1, reacted with less than 1% of marrow cells, none of which appeared to be granulocyte or eosinophil progenitors. The leucocoyte common antigen and the brain-lymphocyte-granulocyte-antigen were also present on colony- and cluster-forming cells from a patient with chronic myeloid leukemia. Using the low angle and wide angle light scatter properties of CML blood cells, 7-fold enrichment was obtained for progenitor cells from chronic myeloid leukaemia. With the monoclonal antibodies up to 4-fold enrichment was obtained.


Methotrexate for ankylosing spondylitis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. Methotrexate (MTX), a widely used disease-modifying antirheumatic drug (DMARD), is effective for rheumatoid arthritis (RA), and so might work for AS. This is an update of a Cochrane review first published in 2004, and previously updated in 2006. To evaluate the benefits and harms of MTX for treating AS. We searched CENTRAL (The Cochrane Library Issue 6, 2012), MEDLINE (2005 to June 25, 2012), EMBASE (2005 to June 25, 2012), Ovid MEDLINE Scopus, World Health Organization International Clinical Trials Registry Platform and the reference sections of retrieved articles. Trials published in any language were acceptable. Randomized controlled trials (RCTs) and quasi-randomized controlled trials (qRCTs) examining the benefits and harms of MTX versus placebo, other medication, or no medication for treatment of AS. Two review authors independently extracted data and assessed risk of bias. We resolved any disagreements through discussions with a third review author. In the absence of significant heterogeneity, we combined results for continuous data using mean difference or standardized mean difference values. We calculated the risk ratio for dichotomous data. We identified three RCTs (no additional new studies), which included 116 participants. Of these three trials, one was a 12-month trial that compared naproxen plus MTX with naproxen alone. Also, there were two 24-week trials that compared different doses of MTX with placebo. We included the outcomes of response, physical function, pain, spinal mobility, peripheral joints/entheses pain, swelling and tenderness, changes in spine radiographs, and patient and physician global assessment. We judged only one trial to be at low risk of bias. Across these three trials, we did not identify any statistically significant differences favoring MTX treatment over no MTX treatment apart from one exception. The response rate in one trial showed a statistically significant absolute benefit of 36% and a number to treat for benefit (NNT) of three in the MTX group compared to the placebo group (RR 3.18, 95% CI 1.03 to 9.79). This response rate was based on a composite index that included assessments of morning stiffness, physical well-being, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire for spondyloarthropathies (HAQ-S), and physician and patient global assessment. We did not identify any outcome that showed a statistically significant difference between the MTX treated and no MTX treatment groups when endpoint results were compared. Furthermore, no serious side effects were reported in any of the included trials. There is not enough evidence to support any benefit of MTX in the treatment of AS. High-quality RCTs of larger sample sizes are needed to clarify the effect(s) of MTX on AS.


Embryonal adenoma of the kidney. A rare embryonal adenoma of the kidney.
We report the case of a 47-year-old man who underwent partial nephrectomy for an embryonal adenoma which was characterized by a monomorphous appearance. No adjuvant therapy was given and at the 5-year follow-up the patient is in perfect health and no relapse has been observed.


Photochemical reactivity of polyenes: from dienes to rhodopsin, from microseconds to femtoseconds.
In reviewing the photochemistry of polyenes (from dienes and trienes to the visual retinyl chromophore), we categorize condensed-phase photochemical reactivity of molecules into two groups: those from thermally equilibrated excited species and those from unequilibrated excited species. Classical theories on radiationless transitions are useful for rationalizing the reactivity of molecules belonging to the first set only. The second group includes many of the exciting ultrafast photochemical reactions reported recently for polyenes (including dienes and trienes), in some cases with rates faster than vibrational relaxation. Much of the excited singlet-state reactions of polyenes, including the Hula-twist mechanism of photoisomerization, have been integrated with concepts introduced in other ultrafast spectroscopic/photochemical studies. Taking into consideration the special environment of the retinyl chromophore in rhodopsin, we propose a new mechanism for the phototrigger that accounts for its unusually fast rate of isomerization.


Prediction of Protein Coding Regions Using a Wide-Range Wavelet Window Method.
Prediction of protein coding regions is an important topic in the field of genomic sequence analysis. Several spectrum-based techniques for the prediction of protein coding regions have been proposed. However, the outstanding issue in most of the proposed techniques is that these techniques depend on an experimentally-selected, predefined value of the window length. In this paper, we propose a new Wide-Range Wavelet Window (WRWW) method for the prediction of protein coding regions. The analysis of the proposed wavelet window shows that its frequency response can adapt its width to accommodate the change in the window length so that it can allow or prevent frequencies other than the basic frequency in the analysis of DNA sequences. This feature makes the proposed window capable of analyzing DNA sequences with a wide range of the window lengths without degradation in the performance. The experimental analysis of applying the WRWW method and other spectrum-based methods to five benchmark datasets has shown that the proposed method outperforms other methods along a wide range of the window lengths. In addition, the experimental analysis has shown that the proposed method is dominant in the prediction of both short and long exons.


Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation.
Linalool, a natural compound that exists in the essential oils of several aromatic plants species, has been reported to have anti-inflammatory effects. However, the effects of linalool on cigarette smoke (CS)-induced acute lung inflammation have not been reported. In the present study, we investigated the protective effects of linalool on CS-induced acute lung inflammation in mice. Linalool was given i.p. to mice 2h before CS exposure daily for five consecutive days. The numbers of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) were measured. The production of TNF-α, IL-6, IL-1β, IL-8 and MCP-1 were detected by ELISA. The expression of NF-κB was detected by Western blotting. Our results showed that treatment of linalool significantly attenuated CS-induced lung inflammation, coupled with inhibited the infiltration of inflammatory cells and TNF-α, IL-6, IL-1β, IL-8 and MCP-1 production. Meanwhile, treatment of linalool inhibited CS-induced lung MPO activity and pathological changes. Furthermore, linalool suppressed CS-induced NF-κB activation in a dose-dependent manner. In conclusion, our results demonstrated that linalool protected against CS-induced lung inflammation through inhibiting CS-induced NF-κB activation.


Ultrasonography of the equine larynx.
Nasopharyngeal and laryngeal evaluation is important when examining horses with upper airway signs for poor performance. Currently endoscopy is the most common method to evaluate the equine upper airway. Ultrasonography of the equine larynx has not previously been described. Using six cadaveric specimens and four standing horses, the ultrasonographic appearance of the equine larynx was established. A scanning technique, including useful acoustic windows and the normal ultrasonographic appearance at each site, is described. Ultrasound allowed visualization of portions of the hyoid apparatus, laryngeal cartilages, associated soft tissues, and intrinsic and extrinsic laryngeal musculature, that are not seen using endoscopy. Additionally, real-time ultrasound allowed observation of the movement of the vocal folds and the arytenoid cartilages during respiration. In three horses with arytenoid chondritis, ultrasonography aided in the diagnosis and localization of arytenoid abcessation and perilaryngeal inflammation. The establishment of this technique will serve as the basis for future investigations in the evaluation of clinical patients with upper airway abnormalities.


Comparison of emergency department utilization trends between the COVID-19 pandemic and control period.
Infectious disease pandemics has a great impact on the use of medical facilities. The purpose of this study was to analyze the effects of coronavirus disease 2019 (COVID-19) on the use of emergency medical facilities in the Republic of Korea. This single-center, retrospective observational study was conducted in a tertiary teaching hospital located in Incheon Metropolitan City, Republic of Korea. We set the pandemic period as February 19, 2020 to April 18, 2020, and the control period was set to the same period in 2018 and 2019. All consecutive patients who visited the emergency department (ED) during the study period were included. Patients were divided into 3 groups according to age (pediatric patients, younger adult patients and older adult patients). The total number, demographics, clinical data, and diagnostic codes of ED patients were analyzed. The total number of ED patients in the pandemic period was lower than that in the control period, which was particularly pronounced for pediatric patients. The proportion of patients who used the 119 ambulances increased in all 3 groups (P = .002, P < .001, and P = .001), whereas the proportion of patients who visited on foot was decreased (P = .006, P < .001, and P = .027). In terms of diagnostic codes, a significant decrease was observed in the proportion of certain infectious or parasitic diseases (A00-B99), and respiratory diseases (J00-J99) in the pediatric and younger adult patient groups (P < .001 and P < .001, respectively). The COVID-19 pandemic reduced the number of ED patients; however, the proportion of patients using ambulances increased. In particular, the proportion of patients with diagnostic codes for infectious and respiratory diseases significantly decreased during the pandemic period.


[Evaluation of bladder tumor staging by submucosonography].
Submucosonography to stage tumors of the esophagus and stomach is well reported. Here we report our experience with a modified procedure to evaluate the stage of bladder tumor cystoscopically and compare the results of staging by other methods. The evaluation was carried out on accuracy 10 patients (10 bladder tumors). A water soluble contrast medium (CM: lohexol 33 mg/ml) was injected into the submucosa of the bladder cystoscopically. Usually the injected point was one centimeter to the urethral margin of the tumor and up to three points were selected. Within 30 minutes after the injection, the lateral and frontal X-ray pictures were taken. The accuracies of staging by submucosonography were compared with the results of other methods, i.g., ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI). By submucosonography, three categories depending on the diffusion of CM were classified as follows. Type I: (diffuse type) without disturbance of diffusion. Type II: (borderline type) between type I and III. Type III: (defect type) local disturbance of diffusion. Overall accuracies of each were 70.0% (submucosonography), 62.5% (US), 44.4% (CT), 66.7% (MRI) respectively. The accuracies of submucosonography were high in stage Ta, above stage T2 and low in stage T1.


Computer-Assisted Qualitative Data Analysis Software, Phenomenology, and Colaizzi's Method.
Technology is widely used to support qualitative research. Computer-Assisted Qualitative Data Analysis Software (CAQDAS) encompasses complementary technologies to support qualitative analysis. Advantages of CAQDAS include efficient management of data and transparency in analysis. Disadvantages include heavy emphasis on coding as a distractor from analysis and considerable time to learn the program. In this methods article, we, as less experienced, qualitative researchers describe our experiences using NVivo, a CAQDAS program, in a descriptive phenomenological study using Colaizzi's method. Over 1 year, 24 postpartum women were given a secure research link to record their experiences with pain and depression during the third trimester of pregnancy. Although NVivo analysis was helpful, the philosophy of phenomenology, reflexivity, and Colaizzi's method directed researchers away from NVivo for the final summation. Recommendations for future use of CAQDAS used concurrently with Colaizzi's method include the use of word clouds and other visualizations for bracketing and triangulation.


Naturally occurring primary deficiencies of the immune system.
Naturally occurring genetic disorders of the immune system provide many models for the study of its development and function. In a way, their analysis complements the information provided by the generation of genetic defects in mice created using homologous recombination techniques. In this review, the recent findings made in three areas are focused upon deficiencies in T cell differentiation and in T lymphocyte activation, and on the control process of peripheral immune response.


Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.
Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.


Ecto-5'-nucleotidase/CD73 enhances endothelial barrier function and sprouting in blood but not lymphatic vasculature.
CD73/ecto-5'-nucleotidase is a key enzyme in the regulation of purinergic signaling and inflammatory reactions. It hydrolyzes extracellular AMP into adenosine, which dampens immune cell activation, and reduces leukocyte trafficking. By comparing CD73 expression and function in mononuclear and endothelial cells (ECs) of blood and lymph, we show that extracellular purines and CD73 activity have differential effects in these two vascular systems. We found that CD8-positive T lymphocytes and CD19-positive B lymphocytes in human lymph expressed high levels of CD73 and other purinergic enzymes and adenosine receptors. Soluble CD73 was less abundant in human lymph than in serum, whereas CD73 activity was higher in afferent lymphatic ECs than in blood ECs. Adenosine signaling improved barrier function and induced sprouting of human blood, but not lymphatic, ECs in vitro. Similarly, using CD73-deficient mice we found that CD73 controls only blood vascular permeability at selected lymphoid organs under physiological conditions. Thus, both vascular and lymphatic arms of the immune system synthesize the components of purinergic signaling system, but surprisingly they use CD73 differentially to control endothelial permeability and sprouting.


Quantification of the production of hydrogen peroxide H2O2 during accelerated wine oxidation.
Understanding how wines react towards oxidation is of primary importance. Here, a novel approach was developed based on the quantitative determination of the key intermediate H2O2 produced during accelerated oxidation by ambient oxygen. The assay makes use of the conversion of the non-fluorescent Amplex Red substrate into a fluorescent product in presence of H2O2. The total production of H2O2 during 30min was quantified with low within-day and between-day variabilities. Polymerized pigments, but not total polyphenols, played a major role in the determination of H2O2 levels, which were lower in white wines than red wines. H2O2 amounts also increased with temperature and the addition of metal ions, but did not depend on the concentration of many other wine constituents such as SO2. H2O2 levels did not correlate with anti-oxidant properties. We believe that this novel methodology might be generically used to decipher the oxidation mechanisms in wines and food products.


Considering the inferior surface area of lower lumbar vertebrae: determining weight transmission pattern at the lumbosacral junction.
The biomechanical function of the lumbosacral junction (LSJ) is obscure, but its medical significance is not, as it is the most common site of low back pain. In this study, we analyzed the difference between the mean values of the surface areas of the inferior body and total inferior facet areas of the fourth and fifth lumbar vertebrae. We aimed to define the function of the LSJ during weight transmission and clarify its mechanical significance. Vertebral columns of 45 adult male human cadavers from five anatomy departments in Nigeria were cut at the L3-L4 intervertebral disc and macerated. Using the graph paper method, the mean values of the surface area of the inferior body and total facet area of the fourth and fifth lumbar vertebrae were 1356 ± 26 and 329 ± 6 and 1277 ± 27 and 418 ± 8 mm2, respectively. The relationships between the fourth and fifth lumbar vertebrae paired variables were highly significant (P < 0.001). A sudden reduction in the surface area of the inferior body of the fifth lumbar vertebra was compensated for by a corresponding increase in its total inferior facet area, which indicated that corresponding weight was diverted from the anterior column to the posterior column at the LSJ. This pattern of weight transmission may be a beneficial functional adaptation in man to protect the relatively large intervertebral disc of the LSJ in bipedal posture, or it may predispose the LSJ synovial zygapophyseal joints to mechanical stress.


A Peri-Ictal EEG-Based Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP) Derived From Brain Network Analysis.
Sudden unexpected death in epilepsy (SUDEP) is the leading seizure-related cause of death in epilepsy patients. There are no validated biomarkers of SUDEP risk. Here, we explored peri-ictal differences in topological brain network properties from scalp EEG recordings of SUDEP victims. Functional connectivity networks were constructed and examined as directed graphs derived from undirected delta and high frequency oscillation (HFO) EEG coherence networks in eight SUDEP and 14 non-SUDEP epileptic patients. These networks were proxies for information flow at different spatiotemporal scales, where low frequency oscillations coordinate large-scale activity driving local HFOs. The clustering coefficient and global efficiency of the network were higher in the SUDEP group pre-ictally, ictally and post-ictally (p < 0.0001 to p < 0.001), with features characteristic of small-world networks. These results suggest that cross-frequency functional connectivity network topology may be a non-invasive biomarker of SUDEP risk.


Continuation of Gender Disparities in Pay Among Academic Emergency Medicine Physicians.
The objective was to identify the effects of gender and other predictors of change in the salary of academic emergency physicians over a four sequential time period of survey administration, across a sample of physicians within different emergency departments (EDs) and within states representing the four main geographical regions of the United States. This was a successive cross-sectional observational study of EDs in the United States using an annual salary survey distributed to all Association of Academic Chairs in Emergency Medicine (AACEM) and Academy of Administrators in Academic Emergency Medicine (AAAEM) members in 2013, 2015, 2016, and 2017 with a sample size of 7,102 respondents over all time periods. The primary variable of interest was the adjusted base salary, calculated to be the full-time effort of the physician without any enhancements (e.g., without stipend, release time, extra hours). Institutional predictive variables included U.S. region that ED was in and if the site was an academic or community academic hybrid ("community") ED. Individual level variables included gender, academic rank, years at academic rank, years at rank within the ED, and primary duty (clinical or other). A series of Wilcoxon tests were conducted to determine if the unadjusted difference in salaries by gender for each year of the survey were significantly different. The effects of relative change in adjusted base salary over time were assessed using a mixed-effects regression model, with institutional- and individual-level predictors included in the model. Data were provided by 81 departments across the four geographic regions of the United States (Northeast, South, West, and Midwest). Most of the survey respondents across the four time periods of administration were male (65%) and reported primary clinical appointments at an academic ED (94%). Overall salaries increased across the four time points of the data with an overall relative 10.8% (95% confidence interval [CI] = 9.6%-12%) change in median salary between 2013 and 2017; the relative percentage change for female respondents was 10.6% (95% CI = 9.4%-11.85%) and 11.1% (95% CI = 10.2%-12%) for males. Within survey years, not adjusting for academic rank, the median salary increase for males was higher ($226,746 in 2013 to $252,000 in 2017) than females ($217,000 in 2013 to $240,000 in 2017), with significance at all four time points (Z = 6.33, p < 0.001), with a median average salary gap of $12,000 in 2017. In the predictive model that adjusted for covariates, gender significantly predicted median adjusted salary, with males earning significantly more than females (F(1) = 22.5, p < 0.001). Despite previously published data showing an inappropriate gender salary gap in emergency medicine, this gap has remained essentially unchanged over the past 4 years.


Quantitative Analysis of Aloins and Aloin-Emodin in Aloe Vera Raw Materials and Finished Products Using High-Performance Liquid Chromatography: Single-Laboratory Validation, First Action 2016.09.
A single-laboratory validation study is described for a method of quantitative analysis of aloins (aloins A and B) and aloe-emodin in aloe vera raw materials and finished products. This method used HPLC coupled with UV detection at 380 nm for the aloins and 430 nm for aloe-emodin. The advantage of this test method is that the target analytes are concentrated from the sample matrix (either liquid or solid form) using stepwise liquid-liquid extraction (water-ethyl acetate-methanol), followed by solvent evaporation and reconstitution. This sample preparation process is suitable for different forms of products. The concentrating step for aloins and aloe-emodin has enhanced the method quantitation level to 20 parts per billion (ppb). Reversed-phase chromatography using a 250 × 4.6 mm column under gradient elution conditions was used. Mobile phase A is 0.1% acetic acid in water and mobile phase B is 0.1% acetic acid in acetonitrile. The HPLC run starts with a 20% mobile phase B that reaches 35% at 13 min. From 13 to 30 min, mobile phase B is increased from 35 to 100%. From 30 to 40 min, mobile phase B is changed from 100% back to the initial condition of 20% for re-equilibration. The flow rate is 1 mL/min, with a 100 μL injection volume. Baseline separation (Rs > 2.0) for aloins A and B and aloe-emodin was observed under this chromatographic condition. This test method was validated with raw materials of aloe vera 5× (liquid) and aloe vera 200× (powder) and finished products of aloe concentrate (liquid) and aloe (powder). The linearity of the method was studied from 10 to 500 ppb for aloins A and B and aloe-emodin, with correlation coefficients of 0.999964, 0.999957, and 0.999980, respectively. The test method was proven to be specific, precise, accurate, rugged, and suitable for the intended quantitative analysis of aloins and aloe-emodin in raw materials and finished products. The S/N for aloins A and B and aloe-emodin at 10 ppb level were 12, 10, and 8, respectively, indicating our conservative LOD level at 10 ppb (the typical LOD level S/N is about 3). The S/N for aloins A and B and aloe-emodin at the 20 ppb level were 17, 14, and 16, respectively, indicating our conservative LOQ level at 20 ppb (the typical LOQ level S/N is about 10). The stock standard solution of a mixture of aloins and aloe-emodin and a working standard solution were found to be stable for at least 19 days when stored refrigerated at 2-8°C, with a recovery of 100 ± 5%.


[Influence of carbodiimide-ethanol solution surface treatment on dentin microtensile bond strength].
To evaluate the microtensile bond strength changes and patterns of fractures of the bonding interface after dentine surface treatment with carbodiimide-ethanol solution. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) dissolved in ethanol was diluted into different concentrations of 2, 1, 0.3, 0.1 and 0.01 mol/L EDC-ethanol solutions. Twenty-eight caries-free extracted human third molars were ground metallurgically to prepare flat occlusal mid-coronal dentin surfaces and etched with 35% (mass fraction) phosphoric acid gel. Then they were treated with EDC-ethanol solution for 60 s before the bonding procedure and randomly divided into five experimental groups corresponding to the tested EDC-ethanol concentrations. The ethanol treated and no pre-treated surfaces were used as controls. Single Bond 2 adhesive was applied and resin composite disk was stacked on the treated dentine surface. The teeth with resin composite disks were stored in water at room temperature for 24 h and then sectioned longitudinally to produce stick specimens for microtensile bond strength test. Fracture patterns were observed with a stereomicroscope. The dentin surfaces pre-treated with 2 mol/L [(22.17±13.31) MPa] and 1 mol/L [(45.31±17.80) MPa] EDC-ethanol solutions resulted in statistically significant lower bond strength value (P<0.05). Increasing numbers of fracture pattern at the resin-dentin interface were also found in this two groups with percentages of 81.2% and 41.3% respectively. No significant difference was observed in the groups with 0.3, 0.1, 0.01 mol/L EDC surface treatment (P>0.05). No significant difference of immediate bond strengths was found in the 0.3, 0.1, 0.01 mol/L groups compared with the control group. EDC-ethanol solution surface treatment with concentrations of 2 mol/L and 1 mol/L resulted in decreasing of the bonding strength.


Infectious Spondylitis with Bacteremia Caused by Roseomonas mucosa in an Immunocompetent Patient.
Roseomonas are a gram-negative bacteria species that have been isolated from environmental sources. Human Roseomonas infections typically occur in immunocompromised patients, most commonly as catheter-related bloodstream infections. However, Roseomonas infections are rarely reported in immunocompetent hosts. We report what we believe to be the first case in Korea of infectious spondylitis with bacteremia due to Roseomonas mucosa in an immunocompetent patient who had undergone vertebroplasty for compression fractures of his thoracic and lumbar spine.


Saline-induced natriuresis and renal blood flow in conscious dogs: effects of sodium infusion rate and concentration.
This study focused on static and dynamic changes in total renal blood flow (RBF) during volume expansion and tested whether a change in RBF characteristics is a necessary effector mechanism in saline-induced natriuresis. The aortic flow subtraction technique was used to measure RBF continuously. Identical amounts of NaCl (2.4 mmol kg(-1)) were given as slow isotonic (Iso, 120 min), slow hypertonic (Hyper, 120 min), and rapid isotonic loads (IsoRapid, 30 min). During Iso and IsoRapid, arterial blood pressure increased slightly (6-7 mmHg), and during Hyper it remained unchanged. Iso and Hyper increased sodium excretion (4 +/- 1 to 57 +/- 27 and 10 +/- 4 to 79 +/- 28 micromol min(-1), respectively) and decreased plasma renin activity (by 38% and 29%), angiotensin II (by 56% and 58%) and aldosterone (by 47% and 65%), while RBF remained unchanged. IsoRapid caused a similar increase in sodium excretion (to 72 +/- 19 micromol min(-1)), a similar decrease in renin system activity, but a 15% elevation of RBF (282 +/- 22 to 324 +/- 35 mL min(-1)). Selected frequency domain parameters of RBF autoregulation did not change in response to any load. In response to slow saline loading simulating daily sodium intake, the rate of sodium excretion may increase 10-20-fold without any change in mean arterial blood pressure or in RBF. Regulatory responses to changes in total body NaCl levels appears, therefore, to be mediated primarily by neurohumoral mechanisms and may occur independent of changes in arterial pressure or RBF.


RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal bodies.
Cajal bodies (CBs) are subnuclear organelles of animal and plant cells. A role of CBs in the assembly and maturation of small nuclear ribonucleoproteins (snRNP) has been proposed but is poorly understood. Here we have addressed the question where U4/U6.U5 tri-snRNP assembly occurs in the nucleus. The U4/U6.U5 tri-snRNP is a central unit of the spliceosome and must be re-formed from its components after each round of splicing. By combining RNAi and biochemical methods, we demonstrate that, after knockdown of the U4/U6-specific hPrp31 (61 K) or the U5-specific hPrp6 (102 K) protein in HeLa cells, tri-snRNP formation is inhibited and stable U5 mono-snRNPs and U4/U6 di-snRNPs containing U4/U6 proteins and the U4/U6 recycling factor p110 accumulate. Thus, hPrp31 and hPrp6 form an essential connection between the U4/U6 and U5 snRNPs in vivo. Using fluorescence microscopy, we show that, in the absence of either hPrp31 or hPrp6, U4/U6 di-snRNPs as well as p110 accumulate in Cajal bodies. In contrast, U5 snRNPs largely remain in nucleoplasmic speckles. Our data support the idea that CBs may play a role in tri-snRNP recycling.


Genetic factors and lithium response in manic-depressive illness.
The relationship between success in lithium treatment and the presence of affective illness in the families of manic-depressive patients was investigated in a double-blind study of lithium prophylaxis. Of a total of 89 outpatients who were followed for periods of up to 48 months, 43 were randomly assigned to lithium and 46 to placebo. 56% of the lithium-treated patients remained asymptomatic, as compared to 28% of the placebo patients. Of the 24 successfully treated lithium cases, 16 (66%) had at least one first-degree relative with bipolar illness, while only 4 of the 19 lithium failures (21%) had a first-degree relative with bipolar illness. No relationship was found between response to lithium and the presence of unipolar illness in the patients' families.


Exosomes from Bone Marrow Mesenchymal Stem Cells with Overexpressed Nrf2 Inhibit Cardiac Fibrosis in Rats with Atrial Fibrillation.
Even though nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling has been associated with the pathogenesis of multiple heart conditions, data on roles of Nrf2 within atrial fibrillation (AF) still remain scant. The present investigation had the aim of analyzing Nrf2-overexpressing role/s upon bone mesenchymal stem cell- (BMSC-) derived exosomes in rats with AF. Exosomes were collected from control or Nrf2 lentivirus-transduced BMSCs and then injected into rats with AF through the tail vein. AF duration was observed using electrocardiography. Immunohistochemical staining was then employed for assessing Nrf2, HO-1, α-SMA, collagen I, or TGF-β1 expression profiles within atrial myocardium tissues. Conversely, Masson staining was utilized to evaluate atrial fibrosis whereas apoptosis within myocardia was evaluated through TUNEL assays. In addition, TNF-α, IL-1β, IL-4, or IL-10 serum expression was assessed through ELISA. Results of the current study showed significant downregulation of Nrf2/HO-1 within AF rat myocardia. It was found that injection of the control or Lv-Nrf2 exosomes significantly alleviated and lowered AF timespans together with reducing cardiomyocyte apoptosis. Moreover, injection of Lv-Nrf2 exosomes essentially lowered AF-driven atrial fibrosis and also inhibited inflammatory responses in the rats with AF. Delivery of BMSC-derived exosomes using overexpressed Nrf2 inhibited AF-induced arrhythmias, myocardial fibrosis, apoptosis, and inflammation via Nrf2/HO-1 pathway triggering.


INVESTIGATION OF A MIXTURE CONTAINING ALPRAZOLAM, CODEINE AND PARACETAMOL USING THIN-LAYER AND HIGH PERFORMANCE LIQUID CHROMATOGRAPHY METHODS.
The increasing drug consumption in Lithuania and all over the world makes us think about the negative consequences - the risk of toxicity. Fast and accurate identification of material that caused the poisoning reduces the probability in death cases and makes easier to determine the main cause of death. The results have shown that the most appropriate systems of solvents for qualitative analysis by TLC method of the mixture consisting of alprazolam, codeine and paracetanol are: system "D" (trichloromethane : acetone : conc. ammonia = 55 : 40 : 5 (v/v/v)) and system "F" (trichloromethane : diethyl ether: isobutanol : conc. ammonia = 50 : 30 : 15 : 5 (v/v/v/v)). For qualitative analysis of the mixture consisting of alprazolam, codeine and paracetamol by HPLC method the chromatographic column ACE C18 (25 cm x 4.6 mm x 5 µm), gradient elution mode (mixture of 3% acetic acid and methanol and the flow rate 1 mL/min have been used. The injection volume was 10 pL. Photodiode array detector (210 - 240 nm range) has been used. UV absorption spectra of materials measured using photodiode array detector have been identical to those presented in the scientific literature.


Infrared predissociation spectroscopy of cluster cations of protic molecules, (NH3)n+, n=2-4 and (CH3OH)n+, n=2,3.
Infrared predissociation spectroscopy is carried out for the structure investigation of unprotonated cluster cations of protic molecules such as ammonia and methanol, which are generated through vacuum-ultraviolet one-photon ionization of their jet-cooled neutral clusters. The observed spectral features show that the cluster cations have the proton-transferred type structures, where a pair of a protonated cation and a neutral radical, NH(4) (+)...NH(2) or CH(3)OH(2) (+)...OCH(3), is formed. Theoretical calculations at the MP2 and B3LYP levels support the formation of the proton-transferred type structures for the cluster cations, and indicate that they are formed by proton-transfer following the photoionization of the neutral clusters.


Acute viral hepatitis in Auckland.
A community survey was undertaken in order to determine the seroepidemiologic pattern of acute viral hepatitis in Auckland. As hospital records and Health Department notifications underestimate the problem, all patients with a serum alanine transpeptidase (ALT) level of greater than 200 mu/l (X 5 normal) were investigated for viral liver disease. Over a four month period a total of 303 cases of acute viral hepatitis were identified, 49 (16.2%) were hepatitis A, 11 with coincident hepatitis B, 88 (29%) were hepatitis B, 80 (26.4%) nonA nonB hepatitis, 81 (26.7%) Epstein Barr virus hepatitis and 5 (1.6%) cytomegalovirus hepatitis. Hepatitis A and hepatitis B occurred with increased frequency among Maoris and Polynesians, while Epstein Barr virus, cytomegalovirus and nonA nonB hepatitis occurred more frequently among Europeans. The incidence of acute symptomatic viral hepatitis (excluding cytomegalovirus and Epstein Barr virus infections) was 78 cases/10(5)/per year for the Auckland region in this survey.


Puerarin promotes the proliferation and differentiation of MC3T3-E1 cells via microRNA-106b by targeting receptor activator of nuclear factor-κB ligand.
Puerarin, an isoflavone-C-glucoside extracted from the root of Pueraria Labata (Willd.) Ohwi, is one of the most important crude herbs used in Chinese medicine for various medicinal purposes. Accumulating evidence has indicated that puerarin suppresses bone resorption and promotes bone formation. However, the molecular mechanism involved in puerarin-associated bone formation is unclear. The present study aimed to investigate the molecular mechanism of puerarin-induced osteoblast proliferation and differentiation. The study showed that puerarin treatment differentially affected cell proliferation in a time-dependent manner. Notably, at a concentration of 20 µM, puerarin significantly promoted cell proliferation in comparison with the control (P<0.01). Furthermore, puerarin promoted MC3T3-E1 cell differentiation at an appropriate concentration. In addition, miR-106b was significantly upregulated in MC3T3-E1 cells following treatment with 20 µM puerarin (P<0.01), and a known target for miR-106b, receptor activator of nuclear factor-κB ligand (RANKL) was demonstrated using the luciferase reporter assay. Furthermore, inhibition of miR-106b significantly reversed the promotion of cell differentiation induced by puerarin in MC3T3-E1 cells (P<0.01). In conclusion, the present study demonstrated that puerarin exerts its role in MC3T3-E1 osteogenesis through miR-106b by targeting RANKL. The findings suggest that puerarin may be considered a promising anti-osteoporotic agent for the treatment of osteoporosis.


A small dynamic leaf-level model predicting photosynthesis in greenhouse tomatoes.
The conversion of supplemental greenhouse light energy into biomass is not always optimal. Recent trends in global energy prices and discussions on climate change highlight the need to reduce our energy footprint associated with the use of supplemental light in greenhouse crop production. This can be achieved by implementing "smart" lighting regimens which in turn rely on a good understanding of how fluctuating light influences photosynthetic physiology. Here, a simple fit-for-purpose dynamic model is presented. It accurately predicts net leaf photosynthesis under natural fluctuating light. It comprises two ordinary differential equations predicting: 1) the total stomatal conductance to CO2 diffusion and 2) the CO2 concentration inside a leaf. It contains elements of the Farquhar-von Caemmerer-Berry model and the successful incorporation of this model suggests that for tomato (Solanum lycopersicum L.), it is sufficient to assume that Rubisco remains activated despite rapid fluctuations in irradiance. Furthermore, predictions of the net photosynthetic rate under both 400ppm and enriched 800ppm ambient CO2 concentrations indicate a strong correlation between the dynamic rate of photosynthesis and the rate of electron transport. Finally, we are able to indicate whether dynamic photosynthesis is Rubisco or electron transport rate limited.


Identification of carbohydrate degrading bacteria in sub-tropical regions.
Several bacteria from the islands of Puerto Rico, Vieques and Trinidad were isolated for their carbohydrate degrading activities. These terrestrial and marine bacterium were collected from pineapple agricultural lands, tropical rain forests, coastlands and mangrove swamps. Organisms were screened for activity using chromogenic substrates (AZCL Megazyme International Ltd., Ireland). The media composition for the effective culturing of some of the marine organisms has also been standardized. Gram-negative organisms were identified by sequence analysis of the PCR- amplified partial small subunit rRNA gene. Results indicate that the majority of the marine organisms tested belong to the genera Vibrio and Pseudoalteromonas and in the terrestrial environments Chryseobacterium predominated. These experiments reveal that sub-tropical environments are potentially good sources of microorganisms with novel carbohydrase activities.


Minimally invasive management of hepatic cysts: indications and complications.
Liver cysts are divided into congenital and acquired. Congenital cystic lesions include polycystic liver disease, simple cysts, duct related and ciliated hepatic foregut cysts. Acquired cystic lesions are divided into infectious and non-infectious. The infectious cysts are the hydatid cyst, the amoebic abscess, and the pyogenic abscess, whereas the non-infectious cysts are neoplastic cysts and false cysts. While modern medicine provides a lot of minimally invasive therapeutic modalities, there has emerged a pressing need for understanding the various types of liver cysts, the possible minimal therapeutic options along with their indications and complications. We aim is to clarify the role of minimally invasive techniques in the management of hepatic cysts. A literature review was performed using the MEDLINE database. The search terms were: liver cyst, minimally invasive, laparoscopic, percutaneous, drainage and fenestration. We reviewed 82 English language publications articles, published until October 2017. Minimally invasive management of liver LC is an emerging field including many therapeutic modalities ranging from the percutaneous aspiration of pyogenic abscesses to laparoscopic hepatectomy for hepatic cystadenomas. The most used techniques are percutaneous drainage, laparoscopic fenestration, and laparoscopic hepatectomy. The application of the various minimally invasive approaches, as well as their indication and complications, depend on the type of the cystic lesion, its size and its position in the liver. Percutaneous drainage is mostly used in simple cysts, hydatid cysts, pyogenic abscesses and bilomas. Laparoscopic fenestration is mostly used in simple cysts and polycystic liver disease. Finally, laparoscopic hepatectomy is mostly used in polycystic liver disease, hydatid cysts, and cystadenomas.


Information and human freedom: nursing implications and ethical decision-making in the 21st century.
With globalization and the increasing volume of healthcare information available to people, questions surface as nurses contemplate and envision what role and how our nursing theory-guided discipline ought to be lived with colleagues of other disciplines, each other, and those we serve in the 21(st) century. This column begins a path of ethical exploration and possible implications for the opportunities and challenges associated with the information age in nursing research, practice, and education. Discussion focuses on the disciplinary responsibilities for information giving and receiving; coming to know, human freedom, and decision-making in the human-universe-health process.


Racial and ethnic disparities in immunizations: recommendations for clinicians.
There continue to be significant racial and ethnic disparities in rates of childhood and adult immunizations in the United States. The causes are multifactorial, including inequities in education, income, and socioeconomic status; structural and systemic barriers in the health care delivery system; and beliefs, preferences, and practice patterns of the recipients and providers of care. Elimination of these disparities is a targeted priority in Healthy People 2010. The individual clinician can contribute to the narrowing of this gap by being informed of and using available national and regional resources, implementing national standards for culturally and linguistically appropriate health care services, and using every clinical encounter to assure that vaccination is offered and provided. Specific action steps are suggested.


Dispersed dynamics of solvation in G-quadruplex DNA: comparison of dynamic Stokes shifts of probes in parallel and antiparallel quadruplex structures.
G-quadruplex DNA (GqDNA) structures play an important role in many specific cellular functions and are promising anti-tumor targets for small molecules (ligands). Here, we measured the dynamic Stokes shift of a ligand (Hoechst) bound to parallel c-Myc (mPu22) GqDNA over five decades of time from 100 fs to 10 ns, and compared it with the previously reported dynamics of DAPI bound to antiparallel human telomeric (hTelo22) GqDNA (Pal et al 2015 J. Phys. Chem. Lett. 6 1754). Stokes shift data from fluorescence up-conversion and time-correlated single photon counting experiments was combined to cover the broad dynamic range. The results show that the solvation dynamics of Hoechst in parallel mPu22 GqDNA follow a power law relaxation, added to fast 2 ps exponential relaxation, from 100 fs to 10 ns, with only a subtle difference of power law exponents in the two ligand-GqDNA systems (0.06 in Hoechst-mPu22 compared to 0.16 in DAPI-hTelo22). We measured steady-state fluorescence spectra and time-resolved anisotropy decays which confirm the tight binding of Hoechst to parallel mPu22 with a binding constant of ~1 × 105 M-1. The molecular docking of Hoechst in parallel GqDNA followed by a 50 ns molecular dynamics (MD) simulation on a Hoechst-GqDNA complex reveals that Hoechst binds to one of the outer G-tetrads by end-stacking near G13 and G4, which is different from the binding site of DAPI inside a groove of antiparallel hTelo22 GqDNA. Reconciling previous experimental and simulation results, we assign the 2 ps component to the hydration dynamics of only weakly perturbed water near mPu22 and the power law relaxation to the coupled motion of water and DNA (i.e. DNA backbone, unpaired bases and loops connecting G-tetrads) which come near the Hoechst inside parallel GqDNA.


Pregnancy in HIV-positive patients: effects on vaginal flora.
A high proportion of HIV-infected pregnant women present pathogenic organisms in their lower genital tract. This has been associated with the development of postpartum morbility, HIV transmission to the partner and offspring, and other gynaecological conditions, such as cervical dysplasia or cancer. Vaginal flora alterations can range from 47% in Western countries to 89% in Africa in pregnant HIV-positive patients, much higher than about 20% of the general population. Pathogen organism retrieval is high. As peripartum complications due to vaginal infections seem higher in HIV-positive patients, accurate investigation and treatment of such infections are strongly mandatory.


Relationship between intrinsic capacity and health-related quality of life among community-dwelling older adults: the moderating role of social support.
To examine how social support might moderate the relationship between intrinsic capacity and health-related quality of life (HRQoL) based on the buffering model of social support. This was a cross-sectional study with a sample of 1181 Chinese community-dwelling older adults aged ≥ 60 years in 2016. Social support was assessed using the Social Support Rating Scale. Intrinsic capacity was assessed using the revised integrated care for older people screening tool. HRQoL was measured by the 12-item Short Form Health Survey. Hierarchical linear regression analysis was implemented to test the moderating effect of social support. Support utilization attenuated the relationship between lower intrinsic capacity and poor physical HRQoL while subjective support attenuated the relationship between lower intrinsic capacity and poor mental HRQoL. However, objective support had no significant moderating effect on the relationship between intrinsic capacity and specific domains of HRQoL. The moderating effects of social support on the association between intrinsic capacity and HRQoL vary by support types. Effective interventions should target the perception and utilization of available support among older adults with lower intrinsic capacity to maintain their physical and mental HRQoL.


Thyroid and endostyle development in cyclostomes provides new insights into the evolutionary history of vertebrates.
The endostyle is an epithelial exocrine gland found in non-vertebrate chordates (amphioxi and tunicates) and the larvae of modern lampreys. It is generally considered to be an evolutionary precursor of the thyroid gland of vertebrates. Transformation of the endostyle into the thyroid gland during the metamorphosis of lampreys is thus deemed to be a recapitulation of a past event in vertebrate evolution. In 1906, Stockard reported that the thyroid gland in hagfish, the sister cyclostome group of lampreys, develops through an endostyle-like primordium, strongly supporting the plesiomorphy of the lamprey endostyle. However, the findings in hagfish thyroid development were solely based on this single study, and these have not been confirmed by modern molecular, genetic, and morphological data pertaining to hagfish thyroid development over the last century. Here, we showed that the thyroid gland of hagfish undergoes direct development from the ventrorostral pharyngeal endoderm, where the previously described endostyle-like primordium was not found. The developmental pattern of the hagfish thyroid, including histological features and regulatory gene expression profiles, closely resembles that found in modern jawed vertebrates (gnathostomes). Meanwhile, as opposed to gnathostomes but similar to non-vertebrate chordates, lamprey and hagfish share a broad expression domain of Nkx2-1/2-4, a key regulatory gene, in the pharyngeal epithelium during early developmental stages. Based on the direct development of the thyroid gland both in hagfish and gnathostomes, and the shared expression profile of thyroid-related transcription factors in the cyclostomes, we challenge the plesiomorphic status of the lamprey endostyle and propose an alternative hypothesis where the lamprey endostyle could be obtained secondarily in crown lampreys.


A plasmonic fluorescent ratiometric temperature sensor for self-limiting hyperthermic applications utilizing FRET enhancement in the plasmonic field.
Nanoparticle mediated photo-induced hyperthermia holds much promise as a therapeutic solution for the management of diseases like cancer. The conventional methods of temperature measurements do not measure the actual temperature generated in the vicinity of the nanoparticles during illumination. In contrast, nano temperature sensors built on hyperthermic nanoparticles can relay local temperatures around the nanoparticles during thermal induction. In this study, we present a core shell construct consisting of a plasmonic core and a silica shell encapsulating a FRET pair of organic dyes for such application. The plasmonic core imparts photo-induced hyperthermic properties to the nanoconstruct, while the fluorescent shell enables ratiometric sensing of temperature. We see that even at a low dye encapsulation concentration, the shell displays a linear ratiometric fluorescence response to temperature and high energy transfer between the dye pair. Interestingly, Monte Carlo simulations, without considering the plasmonic core, show that the energy transfer in the system should be much smaller than that observed, confirming plasmon enhancement in the FRET energy transfer. We also show the ratiometric temperature measurement using these particles during photoinduced hyperthermia. This study suggests the use of plasmonic nanoparticles in the next generation "self-limiting" photothermal therapy.


Asymmetry of the Electrostatic Environment as the Origin of the Symmetry Breaking Effect of the Nitrate Ion in Aqueous Solution.
Elucidating the mechanism of how vibrational modes are affected by intermolecular interactions is important for a better understanding of the nature of the former as probes of the latter. Here, such an analysis is carried out for the N-O stretching modes of the nitrate ion interacting with water, with an emphasis on the symmetry breaking effect. On the basis of theoretical calculations on the structural, vibrational, and electrostatic properties of molecular clusters and spectral simulations for an aqueous solution, a transparent view is demonstrated on the mechanism that modulations of spatially local electrostatic environment give rise to structural and spectroscopic symmetry breaking effect. The electrostatic interaction model constructed here is a seven-parameter model; the use of a single electrostatic parameter, such as the electric field on a single atomic site, is found to be insufficient for quantitative evaluation. It is also shown that the frequency modulations of the N-O stretching modes in aqueous solution occur on a time scale much shorter than 0.1 ps.


Anomalous pseudocapacitive behavior of a nanostructured, mixed-valent manganese oxide film for electrical energy storage.
While pseudocapacitors represent a promising option for electrical energy storage, the performance of the existing ones must be dramatically enhanced to meet today's ever-increasing demands for many emerging applications. Here we report a nanostructured, mixed-valent manganese oxide film that exhibits anomalously high specific capacitance (∼2530 F/g of manganese oxide, measured at 0.61 A/g in a two-electrode configuration with loading of active materials ∼0.16 mg/cm(2)) while maintaining excellent power density and cycling life. The dramatic performance enhancement is attributed to its unique mixed-valence state with porous nanoarchitecture, which may facilitate rapid mass transport and enhance surface double-layer capacitance, while promoting facile redox reactions associated with charge storage by both Mn and O sites, as suggested by in situ X-ray absorption spectroscopy (XAS) and density functional theory calculations. The new charge storage mechanisms (in addition to redox reactions of cations) may offer critical insights to rational design of a new-generation energy storage devices.


The mechanisms of air pollution and particulate matter in cardiovascular diseases.
Clinical and epidemiological studies demonstrate that short- and long-term exposure to air pollution increases mortality due to respiratory and cardiovascular diseases. Given the increased industrialization and the increased sources of pollutants (i.e., cars exhaust emissions, cigarette smoke, industry emissions, burning of fossil fuels, incineration of garbage), air pollution has become a key public health issue to solve. Among pollutants, the particulate matter (PM) is a mixture of solid and liquid particles which differently affects human health depending on their size (i.e., PM10 with a diameter <10 μm reach the lung and PM2.5 with a diameter <2.5 μm penetrate deeper into the lung). In particular, the acute exposure to PM10 and PM2.5 increases the rate of cardiovascular deaths. Thus, appropriate interventions to reduce air pollution may promote great benefits to public health by reducing the risk of cardiovascular diseases. Several biological mechanisms have been identified to date which could be responsible for PM-dependent adverse cardiovascular outcomes. Indeed, the exposure to PM10 and PM2.5 induces sustained oxidative stress and inflammation. PM2.5 is also able to increase autonomic nervous system activation. Some potential therapeutic approaches have been tested both in pre-clinical and clinical studies, based on the intake of antioxidants from dietary or by pharmacological administration. Studies are still in progress to increase the knowledge of PM activation of intracellular pathways and propose new strategies of intervention.


Changes in glycosylation patterns of monoterpenes during grape berry maturation in six cultivars of Vitis vinifera.
Plants conjugate monoterpenoids to sugars, rendering them non-volatile. Hydrolysis of these glycosidic precursors frees the volatile aroma compounds. Here, we profile intact monoterpenyl glycosides in six Vitis vinifera grape berry cultivars. Relative concentrations of twenty-six monoterpenyl glycosides, including nine new putatively identified compounds, were analyzed by UHPLC-QTOF MS/MS at three times during grape maturation (pre-véraison, véraison, and post-véraison). Total glycoside content reached a maximum in Muscat cultivars post-véraison but remained relatively constant in all other cultivars. Three types of monoterpenyl glycosides predominated in all samples: malonylated monoterpenol glucosides, monoterpenol hexose-pentoses, and monoterpendiol hexose-pentoses. The two Muscat cultivars were not differentiated at the earlier developmental stages but could be differentiated post-véraison. In contrast, similarities between Chardonnay and Pinot noir glycoside profiles developed post-véraison. Overall monoterpene glycoconjugation patterns may align with underlying genetic relationships among cultivars. By understanding monoterpene glycoconjugation in wine grapes, scientists and winemakers can better understand grape and wine aromas.


Modulation of multiply scattered coherent light by ultrasonic pulses: an analytical model.
We present an analytical solution for the acousto-optical modulation of multiply scattered light in a medium irradiated with a train of ultrasound pulses. Previous theory is extended to cases where the ultrasound-induced optical phase increments between the different scattering events are strongly correlated, and it is shown that the approximate similarity relation still holds. The relation between the ultrasound induced motions of the background fluid and the optical scatterers is generalized, and it is shown that correlation exists between the optical phase increments that are due to the scatterer movement and the optical phase increments that are due to the modulation of the optical index of refraction. Finally, it is shown that compared with the spectrum of ultrasound pulses, the power spectral density of acousto-optically modulated light is strongly attenuated at the higher ultrasound frequencies.


The combination of IGF1 and FGF2 and the induction of excessive ocular growth and extreme myopia.
Different growth factors have been shown to influence the development of form-deprivation myopia and lens-induced ametropias. However, growth factors have relatively little effect on the growth of eyes with unrestricted vision. We investigate whether the combination of insulin-like growth factor 1 (IGF1) and fibroblast growth factor 2 (FGF2) influence ocular growth in eyes with unrestricted vision. Different doses of IGF1 and FGF2 were injected into the vitreous chamber of postnatal chicks. Measurements of ocular dimensions and intraocular pressure (IOP) were made during and at the completion of different treatment paradigms. Histological and immunocytochemical analyses were performed to assess cell death, cellular proliferation and integrity of ocular tissues. Treated eyes had significant increases in equatorial diameter and vitreous chamber depth. With significant variability between individuals, IGF1/FGF2-treatment caused hypertrophy of lens and ciliary epithelia, lens thickness was increased, and anterior chamber depth was decreased. Treated eyes developed myopia, in excess of 15 diopters of refractive error. Shortly after treatment, eyes had increased intraocular pressure (IOP), which was increased in a dose-dependent manner. Seven days after treatment with IGF1 and FGF2 changes to anterior chamber depth, lens thickness and elevated IOP were reduced, whereas increases in the vitreous chamber were persistent. Some damage to ganglion cells was detected in peripheral regions of the retina at 7 days after treatment. We conclude that the extreme myopia in IGF1/FGF2-treated eyes results from increased vitreous chamber depth, decreased anterior chamber depth, and changes in the lens. We propose that factor-induced ocular enlargement and myopia result from changes to the sclera, lens and anterior chamber depth.


The impact of COVID-19 on people with diabetes in Brazil.
The present study aims at identifying main barriers faced by people living with diabetes in Brazil during the COVID-19 pandemic. In a convenience sampling study, data were collected from 1701 individuals, aged 18 or above; 75.54% female participants; 60.73% T1D and 30.75% T2D, between April 22nd and May 4th, using an anonymous and untraceable survey containing 20 multiple choice questions (socio-demographic; health status and habits of life during COVID-19 pandemic). Relationship between variables was established using the multiple correspondence analysis technique. 95.1% of respondents reduced their frequency of going outside of their homes; among those who monitored blood glucose at home during the pandemic (91.5%), the majority (59.4%) experienced an increase, a decrease or a higher variability in glucose levels; 38.4% postponed their medical appointments and/or routine examinations; and 59.5% reduced their physical activity. T1D, the youngest group, was more susceptible to presenting COVID-19 symptoms despite not being testing; whilst the T2D group had higher frequency of comorbidities that are additional risk factors for COVID-19 severity. This study provides a first hand revelation of the severity of COVID-19 on individuals with diabetes in Brazil. Their habits were altered, which impacted their glycemia, potentially increasing the risk of poor outcomes and mortality if infected by SARS-CoV-2, and of acute and chronic diabetes complications.


The effect of microwave-assisted for photo-catalytic reaction in aqueous nano TiO2 particles dispersions.
In this study, the photo-catalytic degradation of methylene blue in TiO2 particles-dispersed aqueous solution was carried out by irradiating microwave and UV light simultaneously. The results of photocatalytic degradation of methylene blue showed that the decomposition rate increased with the microwave intensity, UV intensity, TiO2 particle dosages and the circulating fluid velocity. From the result of microwave-assisted photo-catalytic degradation of methylene blue, decomposition rate were shown gradually increased according to the increase of pH. The photo-catalytic degradation rate constant obtained under simultaneous irradiation of microwave and UV light case was about 1.5 times higher than irradiation of UV light only case. This result suggests that there is a synergy effect when the constituent techniques are applied together and that the additional irradiation of microwave can play a very important role in photo-catalysis of organic water pollutants.


[An analysis of the indices of ambulatory circadian blood pressure monitoring in patients with arterial hypertension].
The authors have found that more accurate prognosis of left ventricular myocardial hypertrophy (LVMH) may be made basing on fluctuations and variability of arterial pressure throughout the day: significant fluctuations of arterial pressure at night and pronounced variability of systolic arterial pressure in the day time and at night are indicative of essential hypertension instability and may contribute to LVMH progression. Of still greater prognostic significance is assessment of 24-h arterial pressure rhythm by the degree of a night fall (DNF) in diastolic arterial pressure (DAP). A disturbed 24-h rhythm of arterial pressure (a fall in DNF of DAP) is a predictor of LVMH development.


Extended working hours and health.
Statistical analyses of the relation between the amount of working hours and impairments to health, based on data from a European survey on working conditions in 2000, clearly reveal that there is a substantial correlation between the number of working hours per week and the frequencies of health complaints. This applies to both musculo-skeletal disorders as well as to psycho-vegetative complaints. The relationship of the duration of the exposure to working conditions to health impairments is moderated by a great number of individual (e.g., age) and situational (e.g., shift-work) variables, showing additive or interactive effects for which selected examples have been presented. In general, however, there is a consistent functional relationship between the number or working hours and their effects on the workers that holds over a great variety of conditions. It is argued that requests for extending working hours should thus be handled with care.


RANK-RANKL signalling in cancer.
Oncogenic events combined with a favourable environment are the two main factors in the oncological process. The tumour microenvironment is composed of a complex, interconnected network of protagonists, including soluble factors such as cytokines, extracellular matrix components, interacting with fibroblasts, endothelial cells, immune cells and various specific cell types depending on the location of the cancer cells (e.g. pulmonary epithelium, osteoblasts). This diversity defines specific "niches" (e.g. vascular, immune, bone niches) involved in tumour growth and the metastatic process. These actors communicate together by direct intercellular communications and/or in an autocrine/paracrine/endocrine manner involving cytokines and growth factors. Among these glycoproteins, RANKL (receptor activator nuclear factor-κB ligand) and its receptor RANK (receptor activator nuclear factor), members of the TNF and TNFR superfamilies, have stimulated the interest of the scientific community. RANK is frequently expressed by cancer cells in contrast with RANKL which is frequently detected in the tumour microenvironment and together they participate in every step in cancer development. Their activities are markedly regulated by osteoprotegerin (OPG, a soluble decoy receptor) and its ligands, and by LGR4, a membrane receptor able to bind RANKL. The aim of the present review is to provide an overview of the functional implication of the RANK/RANKL system in cancer development, and to underline the most recent clinical studies.


High-fat diet overfeeding promotes nondetrimental liver steatosis in female mice.
High-fat diet (HFD) feeding or leptin-deficient mice are extensively used as models resembling features of human nonalcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild-type (WT) and ob/ ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia. Given that most published works have been done in male models, we used female mice with the aim of increasing the body of evidence regarding NAFLD in female subjects. HFD promoted liver lipid accumulation only in the hyperphagic strain. Nevertheless, a decrease of lipid droplet-associated cholesteryl ester (CE) in both WT and obese animals was observed. These changes were accompanied by an improvement in the profile of lipoproteins that transport cholesterol and liver function markers in plasma from ob/ ob mice and a lower hepatic index. Using primary hepatocytes from female mice, overaccumulation of CE induced by 0.4 mM oleic acid reversed in the presence of a specific Takeda G protein-coupled bile acid receptor agonist. Nevertheless, hepatocytes from male mice were not responsive. This study suggests that enterohepatic circulation of bile acids might be one of the factors that can affect sex dimorphism in NAFLD development, which underlines the importance of including female models in the NAFLD research field. NEW & NOTEWORTHY This work provides new insight into the use of high-fat diet as a model to induce nonalcoholic fatty liver disease in wild-type and ob/ ob female mice. We show that high-fat diet induces steatosis only in ob/ ob mice while, surprisingly, several health indicators improve. Noteworthy, experiments with primary hepatocytes from male and female mice show that they express Takeda G protein-coupled bile acid receptor and that it and bile acid enterohepatic circulation might be accountable for sex dimorphism in nonalcoholic fatty liver disease development.


Systemic study on the biogenic pathways of yezo'otogirins: total synthesis and antitumor activities of (±)-yezo'otogirin C and its structural analogues.
A systematic study of the biomimetic pathways to yezo'otogirin C under aerobic and anaerobic conditions has been investigated, and both are found to be feasible pathways to the natural product depending on the physiological conditions. Because of the lower activation energy, the aerobic process would be more favorable when the in vivo oxygen level is high. In the course of this study, a highly efficient synthetic route to (±)-yezo'otogirin C has been established in four steps (31% overall yield) from a readily available compound without using any protecting groups. The natural product and its structural analogues exhibited antitumor activities against several human cancer cell lines and appeared to arrest cell cycles in different phases.


Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer.
Disparities in breast cancer survival have been observed between African American and white women. There are also known differences in mean baseline white blood cell (WBC) count among racial and ethnic groups. If the WBC count falls below conventionally defined treatment thresholds for patients undergoing adjuvant chemotherapy, reduced doses or treatment delays may occur, which could lead to race-based differences in treatment duration. We used the tumor registry at Columbia-Presbyterian Medical Center to identify 1178 women with newly diagnosed stage I and II breast cancer from whom we collected base-line information for 73 African American women and 126 age- and tumor stage-matched white women. Of these women, 43 African American and 93 white women underwent adjuvant chemotherapy. African American women had statistically significantly lower WBC counts than white women at diagnosis (6.2 x 10(9)/L for African American women versus 7.4 x 10(9)/L for white women, difference = 1.2, 95% confidence interval [CI] = 0.2 to 1.2; P =.02) and after treatment (5.3 x 10(9)/L for African American women versus 6.4 x 10(9)/L for white women, difference = 1.1, 95% CI = 0.2 to 2.5; P =.03). Overall, African American women required a statistically significantly longer duration of treatment than white women (19 weeks versus 15 weeks, respectively, difference = 4 weeks, 95% CI = 0.5 to 7.2 weeks; P =.03). The lower baseline WBC counts and longer duration of treatment for early-stage breast cancer in African American women compared with those in white women result in lower dose intensity of treatment for African American women, possibly contributing to observed racial differences in breast cancer survival.


Organic transformations on metal nanoparticles: controlling activity, stability, and recyclability by support and solvent interactions.
The different mechanisms by which the support and the solvent can influence the catalytic properties of a metal nanoparticle (NP) are reviewed. The use of a support not only significantly facilitates the recycling of NPs but also has many additional advantages varying from enhanced stabilization of the NP dispersion to the alteration of the electronic properties of the metal, shape selectivity effects, and even active participation in the reaction mechanism. The correct choice of solvent, on the other hand, can drastically influence properties such as the morphology of the particles and, in the case of alloys, determine the composition of the NPs. Judicious solvent selection also enhances recyclability and stability, and in some cases, the solvent plays a cocatalytic role. Despite the many beneficial effects of combining metal NPs with the correct support or solvent, many processes are not well understood. Further research should be conducted on elucidating the general mechanisms behind the support-NP or solvent-NP interactions.


Preoperative diagnosis of occult parathyroid hyperplasia by calcium infusion in patients with multiple endocrine neoplasia, type 2a.
Hereditary multiple endocrine neoplasia, type 2 (MEN 2) comprises medullary thyroid carcinoma (MTC) and bilateral pheochromocytoma; the syndrome includes two major variants, MEN 2a (normal appearance, parathyroid disease common) and MEN 2b (mucosal neuromas, Marfanoid habitus, parathyroid disease rate). Patients with MEN 2a may be normocalcemic, with normal basal serum immunoreactive parathyroid hormone (iPTH) levels, yet have parathyroid hyperplasia discovered during thyroid surgery. In an attempt to predict the presence of this occult parathyroid hyperplasia, we performed calcium infusion (15 mg Ca++/kg/4 hours) in six patients with MEN 2a, seven patients with MEN 2b, and eight normal subjects. iPTH was measured in samples taken at one hour intervals during the infusion with a sensitive radioimmunoassay (antiserum GP 1M [Arnaud]). The iPTH values (expressed as per cent of the basal value) in the normal, MEN 2a, and MEN 2b groups at the fourth hour were 38.0 +/- 3.8% (mean +/- SE), 79.2 +/- 7.2%, and 47.8 +/- 5.2%. These iPTH values for patients with MEN 2a were significantly different from normal (P less than 0.001) and from those of the patients with MEN 2b (P less than 0.001). All MEN 2a patients had parathyroid hyperplasia at cervical exploration; parathyroid histology in the MEN 2b patients was normal. Failure of iPTH suppressibility in the MEN 2a patients was not due either to the plasma calcitonin or to achieved serum calcium concentrations. The normal iPTH suppressibility in MEN 2b is consistent with the concept that the parathyroid disease in MEN 2a is genetically determined, and not secondary to MTC and high plasma calcitonin concentration. Calcium infusion combined with the measurement of serum iPTH levels may detect occult parathyroid hyperplasia in patients with MEN 2a, normocalcemia, and normal basal iPTH values. The identification and follow-up of similar patients should establish the natural history of this unusual parathyroid disease.


Pre-eruptive intracoronal resorption of a permanent first molar.
For the last 70 years, the phenomenon of pre-eruptive intracoronal resorption (PIR) has been described in the literature, including a number of case reports illustrating the challenges clinicians face in diagnosing and managing these resorptive defects. Pre-eruptively affected teeth can be difficult to access and posteruptively they are difficult to diagnose because the defects resemble caries. Many times, these defects are not detected until after eruption, when the majority are diagnosed as dental decay and teeth are often subjected to surgical tooth restoration. The purposes of this paper are to report a case of nonprogressive PIR that was detected early, treated with a preventive glass ionomer sealant, and monitored for 44 months, and to propose an alternative approach to management of nonprogressive defects that may help preserve tooth structure.


Applications of liquid chromatography-mass spectrometry in doping control.
This paper reviews liquid chromatographic-mass spectrometric (LC-MS) procedures for the screening, identification and quantification of doping agents in urine and other biological samples and devoted to drug testing in sports. Reviewed methods published approximately within the last five years and cited in the PubMed database have been divided into groups using the same classification of the 2004 World Anti-Doping Agency (WADA) Prohibited List. Together with procedures specifically developed for anti-doping analysis, LC-MS applications used in other fields (e.g., therapeutic drug monitoring, clinical and forensic toxicology, and detection of drugs illicitly used in livestock production) have been included when considered as potentially extensible to doping control. Information on the reasons for potential abuse by athletes, on the requirements established by WADA for analysis, and on the WADA rules for the interpretation of analytical findings are provided for the different classes of drugs.


Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis.
The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non-targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule-associated protein 1A/1B-light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy-dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.


Efficacy and Safety of High Specific Volume Polysaccharide-A New Type of Dietary Fiber for Treatment of Functional Constipation and IBS-C.
We investigated the efficacy and safety of a new type of dietary fiber (high specific volume polysaccharide) for use in treating constipation of different etiologies. Functional constipation patients and irritable bowel syndrome-constipation (IBS-C) patients were administrated high specific volume polysaccharide (HSVP) three times daily for a period of 2 wk to relieve their symptoms. Scores on a stool form scale, and patient reports of straining during a bowel movement, having sensations of an incomplete bowel movement or a blocked anorectum, and abnormal defecation intervals were recorded, graded, and scored by a functional constipation sample group. Similarly, a cohort of IBS-C patients reported their occurrence of abdominal discomfort or pain, abnormal stool formation, defecation frequency, and straining during a bowel movement. Additionally, both groups reported any adverse reactions associated with taking HSVP. All patients in both groups returned for follow-up visits, and no adverse reactions to treatment with HSVP were reported. In the functional constipation group, HSVP was effective for treating symptoms of constipation in 81.46% and 93.17% of patients after 7 and 14 d of dosing, respectively (both p<0.05). In the IBS-C group, symptoms of constipation were relieved in 71.67% and 88.34% of patients after 7 and 14 d of dosing, respectively (both p<0.05). High specific volume polysaccharide was shown be effective for treatment of functional constipation and IBS-C, without causing significant adverse events.


Self-regulation strategies of children with emotional disturbance.
Children with emotional disturbance frequently have difficulty regulating their classroom behaviors. Many have co-occurrence of other disabilities, such as sensory processing problems, which compound difficulties in school participation. This exploratory project evaluated the 8-week-long use of the Alert Program within the classroom setting for seven children with emotional disturbance. Five children with emotional disturbance served as a control group. Self-regulation, behavioral adjustments, and sensory processing skills as reported by the children and teachers were evaluated. Changes from pretest to posttest indicated that children who received the Alert Program demonstrated a small improvement on all measures while performance of the control group remained relatively constant or decreased. These preliminary results indicate programs that target self-regulation skills may be useful in helping to improve self-regulation of children with emotional disturbance.


A comparison of fenfluramine and amphetamine in man.
dl-Fenfluramine hydrochloride (60, 120, 240 mg), d-amphetamine sulfate (20, 40 mg), and placebo were compared in 8 postaddict volunteers, each dose given orally in random sequence at weekly intervals using a double-blind crossover design. Fenfluramine had little effect on blood pressure and temperature, but caused a marked dilation of pupils, whereas amphetamine was a potent vasopressor and a weak mydriatic. While fenfluramine produced euphoria in some subjects, its overall effects were unpleasant, sedative, and qualitatively different from amphetamine. Three subjects given 240 mg of fenfluramine experienced brief but vivid hallucinogenic episodes characterized by olfactory, visual, and somatic hallucinations, abrupt polar changes in mood, time distortion, fleeting paranoia, and sexual ideation. These observations indicate that fenfluramine is a hallucinogenic agent with a pharmacologic profile in man that is not amphetamine-like.


Perilunate Dislocation Above the Age of 65 Years: Case Series and Review of Literature.
Perilunate and fracture dislocations predominantly follow a high-energy mechanism. Perilunate dislocations have an incidence of 0.5/105 individuals/year, occurring at a mean age of 26 years and are frequently seen in men. This study aimed to describe the characteristics of this injury in elderly population of patients using literature review and our experience with four cases aged >65 years. We treated four patients with perilunate dislocation aged >65 years. All the patients' medical records were reviewed retrospectively. A literature review for case studies of perilunate dislocation was conducted with the purpose of finding cases including patients aged >65 years. Three of our patients had injuries that were missed in the first visit in the emergency department. The mechanism of injury was high energy in only two patients. Two patients had posterior perilunate dislocation, while the other two had transradial perilunate dislocation. Three patients were available for follow-up. The overall outcome was satisfaction according the Mayo wrist score and minimal disability according to the Disabilities of the Arm, Shoulder and Hand score. All patients reported that pain was absent and they were able to return to their regular activities. The literature review found only seven papers documenting treatment of patients aged >65 years. Perilunate dislocation is extremely rare in the population aged >65 years. Although the rate of missed diagnosis in our cohort was extremely high, the overall satisfaction and return to function was high. This case series and literature review highlight the unique characteristics of this injury in the age group of patients aged >65 years. Although perilunate dislocation in patients aged >65 years is rare, clinicians should be aware of the presentation of this condition in the elderly.


Myxedema psychosis: A protocol for a systematic review and a pooled analysis.
Myxedema psychosis (MP) is a rare presentation of hypothyroidism. Although known for >70 years, a significant lack of systematic literature describing this condition exists. This limits the clinician's ability to identify and manage this entity properly. Hence, we aimed to systematically review the literature and summarize the presentation, diagnosis, management, and outcomes of this rare entity. Systematic review following PRISMA guidance. We will perform a comprehensive search of PubMed, Medline, Embase, Google Scholar (first 300 hits), and Cochrane databases for published observational studies, case series, and case reports. We will use descriptive statistics to provide summary estimates of demographics, common presenting features, laboratory test results, imaging findings, treatment administered, and outcomes. Moreover, continuous variables will be compared by the Wilcoxon Mann Whitney test, whereas categorical variables will be assessed by the χ test. Bivariate and multivariate regression will be performed to assess risk factors associated with poor outcome. A scoping review revealed that a meta-analysis might not be feasible owing to the paucity of systematic studies describing the condition. This is the first systematic review examining this rare entity. Thus, the result of which will be significant. We hope that this review will help in identifying relevant predictive clinical or laboratory characteristics. Additionally, it identifies the best treatment strategies. The findings of this review will help increase our knowledge of this condition so as to recognize this condition promptly. Also, it will assist in differentiating MP from masqueraders, such as Hashimoto encephalopathy (HE). The results of this review will be published in a peer-reviewed journal. This is the first systematic review exploring MP demographics, diagnosis treatment, and outcomes. The information gathered by this review will be necessary for patients, clinicians, researchers, and guideline makers. CRD42020160310.


The early effect of Medicare's prospective payment system on the use of medical intensive care services in three community hospitals.
To assess the impact of Medicare's prospective payment system (PPS) on patient care and outcome from the medical intensive care unit (MICU), we reviewed the medical records of 400 MICU patients from three community hospitals: 200 patients were admitted before the PPS and 200 were admitted after the PPS. We sampled Medicare patients, aged 65 years and over, and non-Medicare comparison patients, aged 50 to 64 years, collecting data on case mix, treatment intensity and discharge disposition, hospital and six-month mortality, length of stay, and number of intensive care unit beds. After the PPS, the number of intensive care unit beds decreased 31%, without changes in MICU patients' illness severity or treatment intensity. Hospital length of stay decreased 15% in the Medicare group and 43% in the comparison group. For both Medicare and comparison patients combined, MICU length of stay decreased 14% and patients after the PPS were less likely to be discharged to go home. There were no significant changes in in-hospital or six-month mortality. Thus, clinically meaningful decreases in length of stay among seriously ill patients did not result in a change in in-hospital or six-month mortality.


[Systematic analysis of diagnostic errors in patients with myocardial infarction handled by the Swedish Health and Social Care Inspectorate].
Systematic analysis of diagnostic errors in patients with myocardial infarction handled by the Swedish Health and Social Care Inspectorate Diagnostic errors in 51 patients with myocardial infarction handled by the Swedish Health and Social Care Inspectorate were analyzed. In more than half of the cases, the diagnostic errors occurred in health-care outside of hospitals. Diagnostic errors were more common when patients presented atypical symptoms, but atypical symptoms were equally common in male and female patients. Insufficient initial investigation, including lack of ECG registration, preceded a majority of the diagnostic errors. Wider indications for ECG and measurement of troponins in combination with increased awareness of atypical symptoms could possibly be remedies.


Antimicrobial susceptibility and sessile behaviour of bacteria isolated from a minimally processed vegetables plant.
In this study, 20 heterotrophic bacteria from a minimally processed vegetables (MPV) plant were tested for their susceptibilities to five antibiotics (tetracycline, erythromycin, ampicillin, levofloxacin and ciprofloxacin), their (co)aggregation abilities and their survival under gastric simulated conditions. Peracetic acid (PA) and sodium hypochlorite (SH), both at 50 ppm, were evaluated for their abilities to control biofilms of these bacteria. In general, the Gram-negative bacteria were found to be more resistant to the selected antibiotics. Two isolates, Rhanella aquatilis and Stenotrophomonas maltophilia, demonstrated multidrug resistance. Only Rhodococcus erythropolis presented aggregation potential, while no bacterium survived under the gastric conditions. The biofilm experiments showed PA as less efficient than SH in killing biofilms and neither of the disinfectants was able to fully eliminate the biofilms. Significant regrowth was observed for most of the biofilms. The results indicate that alternative and/or complementary disinfection strategies are required to guarantee food safety.


Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta).
Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after, and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between time points in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not resolved within the first 24 hours. Therefore, it is important to acknowledge the interference between BAL and CT in rhesus macaques.


Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents.
Historically known for its role in blood coagulation and bone formation, vitamin K (VK) has begun to emerge as an important nutrient for brain function. While VK involvement in the brain has not been fully explored, it is well-known that oxidative stress plays a critical role in neurodegenerative diseases. It was recently reported that VK protects neurons and oligodendrocytes from oxidative injury and rescues Drosophila from mitochondrial defects associated with Parkinson's disease. In this study, we take a chemical approach to define the optimal and minimum pharmacophore responsible for the neuroprotective effects of VK. In doing so, we have developed a series of potent VK analogues with favorable drug characteristics that provide full protection at nanomolar concentrations in a well-defined model of neuronal oxidative stress. Additionally, we have characterized key cellular responses and biomarkers consistent with the compounds' ability to rescue cells from oxidative stress induced cell death.


Brief descriptive epidemiology of primary malignant brain tumors from North-East India.
Brain tumors are a mixed group of neoplasms that originate from the intracranial tissues and the meninges with degrees of malignancy varying greatly from benign to aggressive. Not much is known about the epidemiology of primary malignant brain tumors (PMBTs) in our population in North-East India. In this analysis, an attempt was made to identify the age groups, gender distribution, topography and different histological types of PMBT with data from a hospital cancer registry. A total of 231 cases of PMBT were identified and included for the present analysis. Our analysis has shown that most of PMBT occur at 20-60 years of age, with a male to female ratio of 2.3:1. Some 70.5% of cases occurred in cerebral lobes except for the occipital lobe, and astrocytic tumors were the most common broad histological type. In our population the prevalence of PMBT is 1% of all cancers, mostly affecting young and middle aged patients. As brain tumors are rare, so case-control analytic epidemiological studies will be required to establish the risk factors prevalent in our population.


FG syndrome update 1988: note of 5 new patients and bibliography.
At the eve of its mapping, the pre-molecular picture of the FG syndrome is heavily biased towards the severe end of the phenotypic spectrum because present knowledge is largely based on propositi. It is an X-linked, incompletely recessive, complexly pleiotropic syndrome with considerably variable expressivity. Though a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome, severe malformations are uncommon and involve mostly the anus (60%) and non-colonic GI defects (33%), hypospadias (25%), cleft palate (6%), rarely a congenital heart defect. The complex CNS dysfunctions of congenital hypotonia and all of its sequelae, MR, and occasional seizures, must be attributed to a developmental CNS defect which is rarely demonstrated at pre-mortem, and which is known to involve agenesis of the corpus callosum in some 25% of appropriately studied patients (mostly propositi). Thus, the diagnosis is largely made on a specific constellation of minor anomalies and mild malformations in a hypotonic boy with severe constipation and a very characteristic facial appearance and behavioral phenotype. In about 1/3 of cases, carrier manifestations may be detected physically. New hemizygote manifestations seen in this review of 5 new patients include abnormal eruption of teeth, diastasis between upper central incisors, apparent gynecomastia, cleft lip, and nasolacrimal and helicine fistulae. Only a half hundred or so FG syndrome patients are known, but we suspect the syndrome is much more common than realized, and because of the unfortunate recurrence risk potential, deserves careful consideration in every appropriate case. RFLP mapping studies are urged in order to aid diagnosis of "mild" cases, and prenatal and carrier detection.