NK-lysin antimicrobial peptide-functionalized nanoporous alumina membranes as biosensors for label-free bacterial endotoxin detection.
We report an NK-lysin peptide-functionalized nanoporous anodized aluminum oxide (NAAO) based biosensor to detect bacterial endotoxin. Bovine NK-lysin-derived peptides show antimicrobial activity against bacterial pathogens, and bactericidal activity is primarily due to the membranolysis activity. Antimicrobial activity of NK-lysin NK2A was confirmed against a Gram-negative Mannheimia haemolytica and a Gram-positive Staphylococcus aureus. Electron microscopic examination showed the localization of NK2A conjugated silver nanoparticles, but not unconjugated silver nanoparticles used as control, to the bacterial outer membrane and cell wall. NK2A functionalized NAAO membranes were used in a previously developed four-electrode electrochemical configuration to detect the presence of Gram-negative bacterial lipopolysaccharides (LPS) and Gram-positive bacterial lipoteichoic acid (LTA) molecules. NK2A-functionalized NAAO biosensor could detect LPS with a detection limit of 10 ng/mL within an appreciable signal/noise ratio. Biosensors functionalized with a scrambled amino acid version of NK2A (Sc-NK2A) that lacks antimicrobial activity could not detect the presence of LPS. However, both NK2A and Sc-NK2A functionalized biosensors showed sensing signals with Gram-positive bacterial lipoteichoic acids. These results suggest that the specific binding of NK2A-LPS on the NAAO membrane surface is responsible for the observed biosensor signals. These findings suggest that NK2A-functionalized biosensors can be used for rapid and sensitive label-free LPS detection.


[Glucocorticoids].
The established evidence of the rapid effects, along with the growing recognition of their disease-modifying properties has led us to reconsider the potential of glucocorticoids in the treatment of rheumatoid arthritis. Given their acceptable safety profile, especially when used at low dosages, several glucocorticoid-based therapeutic approaches have been explored in order to optimize their clinical benefits, while limiting the adverse effects. Encouraging results on the clinical and sub-clinical effects of low dosages are going to lead to a shift in usual daily practice. Optimizing the use of key non-biologic drugs including glucocorticoids may prolong disease control, thereby delaying the need for costly biologic therapies.


Role for limited neck exploration in young adults with apparently sporadic primary hyperparathyroidism.
The risk of multiglandular disease (MGD) dictates the extent of exploration in patients with primary hyperparathyroidism (PHPT). Historically, young patients with PHPT were more likely to have MGD, but the existing literature is sparse and conflicting. We hypothesized that young adults (ages 16-40 years) without familial PHPT have a disease process similar to that in older patients. A 22-year retrospective chart review was performed on patients who underwent neck exploration for PHPT at our tertiary care center. Altogether, 708 charts were reviewed for demographics, family history, laboratory values, operative findings, pathology, and outcomes. As a group, young adults comprised 14.0% of the total population and were more likely to have preexisting familial disorders of PHPT (p < 0.01), therapeutic failure (p < 0.01), failure to identify an abnormal parathyroid at operation (p < 0.01), and higher reoperative rates (p = 0.02); they were less likely to have single-gland disease (p = 0.04). Young adults without a family history of the disease demonstrated no disease differences except for a higher rate of symptoms (p < 0.01). Additional analysis found that patients with a family history of hypercalcemia, a sole family member with PHPT, or nephrolithiasis ("possible" family history) were more likely to have MGD (relative risk 2.0). In this largest single-institution study of young adults with sporadic PHPT, we conclude that sporadic PHPT in young adults represents a disease entity similar to that in older patients, with no increased risk for MGD, and hence they can be managed with a similar surgical approach. Further studies are needed to assess the role of a "possible" family history as a risk factor for MGD.


Effects of aerobic, resistance, and mixed exercises on quality of life in patients with cancer: A systematic review and meta-analysis.
Quality of life has multiple aspects, but little is known about the effects of exercise on each domain of it. This systematic review aimed to determine the effects of aerobic, resistance, and mixed exercise on multiple aspects of quality of life in patients with cancer through a meta-analysis. Randomized controlled trials with quality of life were collected, and 20 studies were analyzed. Subgroup analyses were performed according to exercise types. Exercise improved global, physical, role, and emotional quality of life, but not cognitive and social quality of life. Aerobic, resistance, and mixed exercises improved global, physical, role, emotional, and social quality of life; global, physical and role quality of life; and only physical quality of life, respectively. According to exercise type, aerobic and resistance exercises improved global, physical, and role quality of life, whereas aerobic exercise only improved emotional quality of life.


Natural products isolation in modern drug discovery programs.
Natural products play a vital role in drug discovery. They have served as the basic reference and initiators in drug discovery programs. Natural products as pure compounds have been involved in western medicine as drugs or lead compounds for drug discovery and development. In traditional medicine, they have been involved for a very long time as medicinal extracts, infusions, decoctions, or other therapeutic preparations. Modern drug discovery programs require an arsenal of drug candidate molecules in pure form whose activities (usually against cells or enzymes) are rapidly determined using high-throughput screening (HTS) and activities are expected in micro- (μM) to nanomolar (nM) levels. The difficulty in meeting today's standards for drug candidate molecules poses the question: are natural products still relevant in modern drug discovery programs? This and other issues, including the spectroscopic investigation of crude extracts, are discussed.


Diagnostic Relevance of microRNAs in Other Body Fluids Including Urine, Feces, and Saliva.
Beside blood-borne circulating miRNAs, miRNAs have been identified in other body fluid and excrements including stool, bile, saliva, and urine. Given the direct link of these body fluids to certain organs, their analysis for potential diagnostic miRNA markers is plausible. Several independent findings underline the potential utility of stool-derived miRNAs in the diagnosis of colorectal and pancreatic cancer. Given the difficulties in the diagnosis of cholangiocellular cancer, biliary miRNAs might be envisaged as useful markers. Several miRNAs have been identified in the saliva that could be associated with diseases, including tumors of the oral cavity. The urinary pool of miRNAs could be exploited for the diagnosis of urinary tract diseases and some appear to enable early diagnosis. In this chapter, we present findings supporting the potential diagnostic utility of fecal, biliary, salivary, and urinary miRNAs focusing mostly on tumors.


Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats.
The effects of Prostaglandin E2 (PGE2) and Risedronate (Ris) both separately and in combination (PGE2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2 with an antiresorptive agent is more effective anabolically than PGE2 alone. Nine-month-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 micrograms Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 micrograms Ris/kg twice a week (PGE2 + 1 Ris or PGE2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double-fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = basal > PGE2 > 1 microgram Ris = 5 micrograms Ris = aging. The density of the PS was ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = PGE2 = 5 micrograms Ris = 1 microgram Ris > basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphosphonate. Bone mass in the SS was ranked as follows: PGE2 + 5 Ris = PGE2 + 1 Ris = PGE2 > 5 micrograms Ris = 1 microgram Ris = aging = basal.(ABSTRACT TRUNCATED AT 250 WORDS)


Discovery of Chromane-6-Sulfonamide Derivative as a Potent, Selective, and Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor γt Inverse Agonist.
Interleukin-17 (IL-17) is a proinflammatory cytokine that plays a dominant role in inflammation, autoimmunity, and host defense. RORγt is a key transcription factor mediating T helper 17 (Th17) cell differentiation and IL-17 production, which is able to activate CD8+ T cells and elicit antitumor efficacy. A series of sulfonamide derivatives as novel RORγt inverse agonists were designed and synthesized. Using GSK2981278 (phase II) as a starting point, we engineered structural modifications that significantly improved the activity and pharmacokinetic profile. In animal studies, oral administration of compound d3 showed a robust and dose-dependent inhibition of the IL-17A cytokine expression in a mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that the compound d3 occupied the active pocket suitably. Thus, compound d3 was selected as a clinical compound for the treatment of Th17-driven autoimmune diseases.


Type II diabetes promotes a myofibroblast phenotype in cardiac fibroblasts.
Cardiovascular disease is the leading cause of death for individuals diagnosed with type II diabetes mellitus (DM). Changes in cardiac function, left ventricular wall thickness and fibrosis have all been described in patients and animal models of diabetes; however, the factors mediating increased matrix deposition remain unclear. The goal of this study was to evaluate whether cardiac fibroblast function is altered in a rat model of type II DM. Cardiac fibroblasts were isolated from 14 week old Zucker diabetic and lean control (LC) adult male rat hearts. Fibroblasts were examined for their ability to remodel 3-dimensional collagen matrices, their adhesion, migration and proliferation on collagen and changes in gene expression associated with collagen remodeling. Cardiac fibroblasts from diabetic animals demonstrated significantly greater ability to contract 3-dimensional collagen matrices compared to cardiac fibroblasts from LC animals. The enhanced contractile behavior was associated with an increase in diabetic fibroblast proliferation and elevated expression of α-smooth muscle actin and type I collagen, suggesting the transformation of diabetic fibroblasts into a myofibroblast phenotype. Cardiac fibrosis is a common complication in diabetic cardiomyopathy which may contribute to the observed cardiac dysfunction associated with this disease. Identifying and understanding the changes in fibroblast behavior which contribute to the increased deposition of collagen and other matrix proteins may provide novel therapeutic targets for reducing the devastating effects of diabetes on the heart.


Non-eicosanoid functions of essential fatty acids: regulation of adenosine-related functions in cultured neuroblastoma cells.
Studies have demonstrated that augmenting the omega 6 polyunsaturated-fatty-acid (PUFA) content of N1E-115 neuroblastoma cells by media supplementation with linoleic acid results in greater than or equal to 2-fold increases in basal levels of intracellular cyclic AMP (cAMP). Data suggested some involvement of increased production of adenosine from endogenous metabolites; however, increases in adenosine were not related to increased activity of 5'-nucleotidase or decreased uptake of extracellular adenosine. PUFA-dependent elevations in basal cAMP were evident within 1 min of exposure to a phosphodiesterase inhibitor; this phenomenon did not appear to be due to PUFA-dependent changes in Ca2+ uptake or to increases in sensitivity of adenylate cyclase to Ca2+. Forskolin-stimulated cAMP formation was 3-fold higher in PUFA-enriched cells than in control cells, which suggested a direct effect on the functioning of the catalytic unit. Linoleic acid supplementation resulted in a 2-fold increase in the maximum amounts of cAMP produced in response to the stable adenosine analogue, 5'-N'ethylcarboxy-amidoadenosine (NECA). The altered stimulatory response did not involve eicosanoid formation, but may have been related to an increase in the number of stimulatory adenosine receptors, as judged by binding of [3H]NECA. These studies indicate that membrane PUFA modulate adenosine-related functions in neuroblastoma cells, and suggest that a complex series of mechanisms is involved in this regulation.


Cyclic 3',5'AMP phosphodiesterase in Physarum polycephalum. II. Kinetic properties.
Some kinetic characteristics of soluble and particulate cyclic 3',5'-AMP phosphodiesterases from Physarum polycephalum are presented. The nature of enzyme inhibition by various agents is reported. The relationship between various enzyme inhibitors and their reported chemotactic properties in Physarum is examined. The results suggest that the chemoattractant effect of several inhibitors may be related to their ability to inhibit the particulate and extracellular phosphodiesterases, but is unrelated to inhibition of the intracellular enzyme.


Association between radiographic and functional outcome in vertebral osteomyelitis SPONDIMMO, a 6-month prospective multicenter cohort.
This study aimed to describe radiographic and functional evolution over 6 months in a large cohort of VO patients. We prospectively recruited patients with VO from 2016 to 2019 in 11 French centers. X-rays were performed at baseline, 3 months, and 6 months to assess progression using structural and static criteria. Functional impairment was evaluated using the Oswestry Disability Index (ODI) at 3 months and 6 months. Two hundred and twenty-two patients were included. Mean age was 67.8±14 years, mostly men (67.6%). After 3 months, there was a significant increase in vertebral fusion (16.4% vs 52.7%), destruction of vertebral bodies (10.1% vs 22.8%), and of all the static features (frontal angulation (15.2% vs 24.4%), segmental (34.6% vs 56%) and regional (24.5% vs 41%) kyphosis). From 3 to 6 months, among the different X-ray abnormalities, only the complete fusion progressed significantly (16.6% vs 27.2%). Median ODI showed significant improvement from 3 to 6 months (24, IQR [11.5-38] vs 16, IQR [6-34]). At 6 months, 14.1% of the patients had a severe disability, 2% a major disability. The persistence of vertebral destruction at 6 months was associated with a higher ODI (16, IQR [7.5-30.5] vs 27, IQR [11.5-44.5]). No differences in radiological progression were observed with immobilization using a rigid brace. Our study demonstrates structural and static radiographic progression after 3 months. Only the complete fusion progressed over the long-term. Functional impairment was associated with persistence of vertebral destruction.


Mental healthcare utilisation by patients before and after receiving paliperidone palmitate treatment: mirror image analyses.
To compare mental healthcare use and healthcare professional (HCP) contacts for patients before and after initiation of paliperidone palmitate. The South London and Maudsley NHS Foundation Trust (SLAM) Biomedical Research Centre Clinical Record Interactive Search. We identified all adults with a diagnosis of schizophrenia (International Classification of Diseases 10th Revision: F20.x), who had received paliperidone palmitate prescription for at least 365 days and had at least 1 year of recorded treatment from SLAM, prior to the first recorded receipt of paliperidone palmitate. Inpatient and community mental healthcare service use, such as inpatient bed days, number of active days in the service, face-to-face and telephone HCP use in the 12 months before and after paliperidone palmitate initiation. We identified 664 patients initiated on paliperidone palmitate. Following initiation, inpatient bed days were lower, although patients remained active on the service case load longer for both mirror approach 1 (mean difference of inpatient bed days -10.48 (95% CI -15.75 to -5.22); days active 40.67 (95% CI 33.39 to 47.95)) and mirror approach 2 (mean difference of inpatient bed days -23.96 (95% CI -30.01 to -17.92); mean difference of days active 40.69 (95% CI 33.39 to 47.94)). The postinitiation period was further characterised by fewer face-to-face and telephone contacts with medical and social work HCPs, and an increased contact with clinical psychologists. Our findings indicate a change in the profile of HCP use, consistent with a transition from treatment to possible rehabilitation.


The surfactant Dioctyl Sodium Sulfosuccinate (DOSS) exposure causes adverse effects in embryos and adults of zebrafish (Danio rerio).
Dioctyl Sodium Sulfosuccinate (DOSS, CAS 577-11-7) is a chemical emulsifying surfactant that is widely used in the food and the cosmetic industry, and it is also the major component of the crude oil chemical dispersant Corexit™. Despite of its wide use, the studies related to its negative effect have been evaluated mainly in marine environments showing that DOSS is highly bioactive, extremely low volatile, and potential to persist in the environment longer than other dispersant components. Up to date, there is no available information of DOSS concentration in freshwater environments, little is known about its downstream fate after excretion and its effect on freshwater organisms. The objective of this study was to evaluate the effect of DOSS at different concentrations in embryos and adults of zebrafish Danio rerio in an acute-static bioassays of 96 h. The median lethal concentration in embryos was 33.3 mg/L. Malformations started to be observed at 10 mg/L. In adults, the gene expression analysis in gill tissues showed a deregulation in genes associated with the antioxidant system and the nucleotide excision repair mechanism. Additionally, Micronuclei (DNA damage) in erythrocytes, and fat degeneration in liver, hypertrophy and hyperplasia in gills, and hyaline drops in kidney tissues were also observed. In conclusion, the concentrations of DOSS evaluated here would be of health relevance to fish based on morphological alterations in embryos and changes in the gene expression profile, DNA damage and tissue impairment in adults.


Total Synthesis and Monoamine Oxidase Inhibitory Activities of (±)-Entonalactam A and Its Derivatives.
The first total synthesis of isoindolinone (±)-entonalactam A (6), originally obtained from the fungus Entonaema sp., was achieved in 14 steps from commercially available 5-bromovanillin via benzophenone intermediates. Isoindolinone, phthalide, and benzophenone analogues of natural products were also synthesized. The monoamine oxidase (MAO) A and B inhibitory activities were tested. The isoindolinone derivative 30 exhibited inhibition of both MAO-A and -B (IC50 = 17.8 and 15.8 μM, respectively).


Full body illusion and cognition: A systematic review of the literature.
In recent years, an increasing number of studies employed the full body illusion paradigm (i.e., the experimentally induced illusory ownership over a fake/virtual body) to investigate the role of body ownership in higher-level cognition. However, to date, no systematic review of this topic is present. To fill this gap, here we identified 102 papers classifiable in 4 cognitive domains and 12 subdomains. Overall, they manipulated the identity of the fake body, and/or its spatial perspective, and/or the kind of multisensory stimulation, and/or its spatiotemporal congruency. The effects were measured through implicit and/or explicit indices. In summary, results showed that participants' behavior shifted away from the self and/or towards that of the embodied fake/virtual body. The findings have been interpreted within various exploratory frameworks, with the most common being the Proteus effect, the cortical body matrix and the inverse model of motor control. Future studies should focus on building a unitary theoretical explanation of the effects, gaining solid neural evidence, creating standard experimental procedures, and exploring the practical applications.


Sex differences in the human group mean SEP.
The following results were obtained with SEPs recorded from strictly age-matched normal human subjects, 100 males and 100 females, 22.29 +/- 1.90 years. (1) The sex factor on the wave form of SEP was confirmed highly significant by MANOVA. (2) It was confirmed that the group mean SEP of each sex each converges to a given wave form which significantly differed from each other. (3) The differences in the wave form of the group mean SEP between sexes were established. The group mean SEP for females consisted of the 12 components, N1, P1, N2, P2, N3, P3, N4, P4, N5, P5, N6 and P6, and was approximately tetraphasic within 500 msec in latency, while that for males consisted of the same components except for N4 and P4. The baseline amplitude of the wave form of the group mean SEP, smaller in males than in females, differed significantly between sexes, corresponding to the most remarkable difference in its wave form, in the descending slope from the highest positive peak P2 to the deep negative trough N6, where there was a high convex arch with P4 (80 msec) in females, a low hollow slope without the peak in males. The latencies of the components tended to be longer in males than in females. (4) With scaled SEPs, which were converted from SEPs by amplitude scaling, results were similar to those with SEPs, and the sex difference in the scaled group mean SEP was also verified to be significant. These results indicate the further possibility of data reduction by amplitude scaling.


Comparison of physical and biological properties of a flowable fiber reinforced and bulk filling composites.
To evaluate in vitro the mechanical, biological, and polymerization behavior of a flowable bulk-fill composite with fibers as a dispersed phase. EverX Flow™ (GC Corporation) (EXF), one conventional bulk-fill composite (Filtek™ Bulk Fill Posterior Restorative, 3 M (FBF)), and one flowable bulk composite without fibers (SDR® flow+, Dentsply (SDR)) were tested. Samples were characterized in terms of flexural strength (ISO 4049), fracture toughness (ISO 20795-1), and Vickers hardness. Polymerization stress and volumetric shrinkage were evaluated. The in vitro biological assessment was achieved on cultured primary Human Gingival Fibroblast cells (HGF). The cell metabolic activity was evaluated using Alamar Blue assay at 1, 3, and 5 days of contact to the 3 tested composite extracts (ISO 10993) and cell morphology was evaluated by confocal microscopy. Data were submitted to One-Way analysis of variance (ANOVA) and independent t-test (α = 0.05). FBF showed statistically higher Vickers hardness and flexural modulus than EXF and SDR. However, EXF showed statistically higher KIC than FBF and SDR. EXF had the statistically highest shrinkage stress values and FBF the lowest. Archimedes volumetric shrinkage showed significantly lower values for FBF as compared to the other two composites. Slight cytotoxic effect was observed for the three composites at day one. An enhancement of metabolic activity at day 5 was observed in cells treated with EXF extracts. EXF had a significantly higher fracture toughness validating its potential use as a restorative material in stress bearing areas. EXF showed higher shrinkage stress values, and less cytotoxic effect. Fiber reinforced flowable composite is mainly indicated for deep and large cavities, signifying the importance for assessing its shrinkage stress and biological behavior.


Postillumination adenosine triphosphate synthesis in Rhodospirillum rubrum chromatophores. I. Conditions for maximal yields.
The very low level of postillumination ATP synthesis in chromatophores was markedly stimulated when permeant anions (thiocyanate or perchlorate) or permeant cations (potassium in the presence of valinomycin) were added to the light stage. Although these compounds stimulated also light-induced proton uptake in chromatophores the pH dependence of both photoreactions was different. Proton uptake peaked at pH 6.5 while the amount of postillumination ATP was maximal when the light stage was carried out around pH 7.7. The increased yield of ATP at the more alkaline pH could not be explained by a slower decay of the high energy state at this pH, since the decay rate was faster at pH 7.7 than at pH 6.5. The proton concentration gradient which is maintained across the chromatophore membrane in the light was also found to increase when the external pH was raised from 6.0 to 8.0. Only a minimal amount of postillumination ATP was formed when this gradient was below 2.1 pH units, but above this value the ATP yield rose steeply as a function of the increasing pH gradient. In light of these results it is suggested that in order to obtain a high yield of postillumination ATP synthesis in chromatophores two conditions are required: the particles have to be loaded with a sufficient number of protons and a light-induced pH gradient above a certain threshold value has to be maintained across their membrane. The low yield of postillumination ATP in chromatophores and the increase obtained by adding permeating ions, is thus explained by similar variations in the extent of the pH gradient, which exceeded the threshold value only in the presence of the permeating ions.


Measuring outcomes in adult brachial plexus reconstruction.
The focus of this article is on evaluating the various outcome measures of surgical interventions for adult brachial plexus injuries. From a surgeon's perspective, the goals of surgery have largely focused on the return of motor function and restoration of protective sensation. From a patient's perspective, alleviation of pain, cosmesis, return to work, and emotional state are also important. The ideal outcome measure should be valid, reliable, responsive, unbiased, appropriate, and easy. The author outlines pitfalls and benefits of current outcome measures and offers thoughts on possible future measures.


Thickness of the buffer layer in the 'reaction front' model of solid-state digestion.
Conventional models of anaerobic digestion assume dispersed reaction, in the aqueous phase and at solid-liquid interfaces. However, a second, localized mechanism might operate in a bed of nutrient-rich wastes, such as occurs in many landfills and some waste digesters. A 'reaction front' (comprising two distinct reaction zones separated by a buffer zone) might develop around 'seed bodies' (local concentrations of methanogenic inoculum) then propagate through the waste. The initial conditions, notably the mode of seeding, would determine whether which mechanism is dominant. This paper presents a method of predicting the thickness of such a front and indicates a thickness of the order of 3.5 cm. This would suggest that the seed material must be present in the form of 'seed bodies' of over 7 cm diameter or layers over 7 cm thick. The probability of the formation of a reaction front is discussed, as are the implications for operational practice.


Study of glycol chitosan-carboxymethyl β-cyclodextrins as anticancer drugs carrier.
Efficient target delivery system for insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. Herein, glycol chitosan-carboxymethyl β-cyclodextrins (G-chitosan-CM-dextrins) was synthesized for delivering different hydrophobic anticancer drugs. Surface plasmon resonance and UV-vis spectroscopy results showed that all the three anticancer drugs (5-fluorouracil, doxorubicin, and vinblastine) could be successfully loaded into the cavities of the covalently linked CM-dextrins. Moreover, the free carboxymethyl groups could enhance the binding interactions between the covalently linked CM-dextrins and anticancer drugs. Release behaviors with pH changes of the three drugs were also explored, result showed different drugs would be released by different ways, as for doxorubicin, pH sensitive release has been realized. The obtained G-chitosan-CM-dextrins carrier has both mucoadhesive property of G-chitosan and hydrophobic cavities of β-cyclodextrins. Therefore, the new synthesized G-chitosan-CM-dextrins carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy.


Quantifying the Generality of Strength Adaptation: A Meta-Analysis.
Isotonic exercise is the most common mode of strength training. Isotonic strength is often measured in the movement that was exercised, but isometric and isokinetic movements are also commonly used to quantify changes in muscular strength. Previous research suggests that increasing strength in one movement may not lead to an increase in strength in a different movement. Quantifying the increase in strength in a movement not trained may be important for understanding strength training adaptations and making recommendations for resistance exercise and rehabilitation programs. To quantify changes in non-specific strength relative to a control. A systematic review and random effects meta-analysis was conducted investigating the effects of isotonic strength training on isotonic and isokinetic/isometric strength. This systematic review was conducted in Google scholar, PubMed, Academic Search Premier, and MENDELEY. To be included in this review paper the article needed to meet the following criteria: (1) report sufficient data for our variables of interest (i.e., changes in isotonic strength and changes in isokinetic or isometric strength); (2) include a time-matched non-exercise control; (3) be written in English; (4) include healthy human participants over the age of 18 years; (5) the participants had to train and test isotonically; (6) the participants had to be tested isokinetically or isometrically on a device different from that they trained on; (7) the non-specific strength task had to test a muscle involved in the training (i.e., could not have trained chest press and test handgrip strength); and (8) the control group and the experimental group had to perform the same number of strength tests. We completed two separate searches. In the original search a total of 880 papers were screened and nine papers met the inclusion criteria. In the secondary search a total of 2594 papers were screened and three additional papers were added (total of 12 studies). The overall effect of resistance training on changes in strength within a movement that was not directly trained was 0.8 (Cohen's d) with a standard error of 0.286. This overall effect was significant (t = 2.821, p = 0.01) and the 95% confidence interval (CI) is 0.22-1.4. The overall effect of resistance training on strength changes within a movement that was directly trained was 1.84 (Cohen's d) with a standard error of 0.296. This overall effect was significant (t = 6.221, p < 0.001) and the 95% CI is 1.23-2.4. The results of our meta-analysis suggest that strength increases in both the specific and non-specific strength tests. However, the smaller effect size associated with non-specific strength suggests that it will be difficult for a single study to meaningfully investigate the transfer of strength training adaptions.


Alcohol use in the perspective of cultural ecology.
Examination of the use of alcohol in traditional agrarian society reveals that drinking and the drinking context is for the most part integrative, conflict-reducing, and reinforcing of corporate identity. With acculturation and modernization, and the introduction of full-scale cash-based economies, alcohol use is more frequently a social and pathological and serves individual as opposed to jointly shared objectives. Analysis of these issues is accomplished through a review of the cultural ecological perspectives on drinking and culture in a variety of societies around the world.


Overexpression of epithelial growth factor receptor (EGFR) predicts better response to neo-adjuvant chemotherapy in patients with triple-negative breast cancer.
Triple negative breast cancer (TNBC) occurs in approximately 10% to 25% of all patients with breast cancer and is associated with poor prognosis. Neo-adjuvant chemotherapy has been reported to produce a higher pathologic complete response (pCR) rate in TNBC. If pCR is achieved, patients with TNBC had a similar survival with non-TNBC patients. The aim of our study was to investigate the protein expression of epithelial growth factor receptor (EGFR) and response to neo-adjuvant chemotherapy and clinical outcome in patients with TNBC compared with non-TNBC. A total of 198 locally advanced breast cancer patients who received neo-adjuvant chemotherapy were studied. Immunohistochemistry (IHC) was carried out to detect the protein expression of EGFR in tumor samples. Clinical and pathological parameters, pCR rate and survival data were compared between 40 TNBCs and 158 non-TNBCs. In 198 cases who received neo-adjuvant chemotherapy, significant differences exist in surgical therapy (P=0.005) and pCR rate (P=0.012) between patients with TNBCs and non-TNBCs. Overexpression of EGFR was significantly associated with pCR rate in patients with TNBCs (P < 0.001). Survival analysis revealed that patients with TNBCs had worse DFS and OS than those with non-TNBCs (P = 0.001, P < 0.001 respectively). Furthermore, for patients with non-TNBCs, those who achieved pCR had better DFS and OS than those who achieved RD (both P < 0.001). Our results suggested that patients with TNBCs had increased pCR rates compared with non-TNBC. Overexpression of EGFR predicted better response to neo-adjuvant chemotherapy in patients with TNBCs.


Total hip replacement but not clinical osteoarthritis can be predicted by the shape of the hip: a prospective cohort study (CHECK).
To investigate the association between baseline hip shape and both clinical hip osteoarthritis (OA) and total hip replacement (THR) at 5-year follow-up. Individuals from the Cohort Hip and Cohort Knee (CHECK) study, with early symptomatic OA, having standardized anteroposterior pelvic radiographs at baseline and 5-year follow-up (n = 723) were included. Hip shape on the radiographs was assessed using statistical shape modeling (SSM). Hips fulfilling the American College of Rheumatology (ACR) criteria at follow-up were classified as clinical OA. The association between each mode of shape variation and both outcome measures was calculated by Generalized Estimating Equations (GEE). The included individuals comprised 575 females and 148 males (mean age 55.9 ± 5.2 years). At baseline, 8% fulfilled the ACR criteria, 76% had no radiographic hip OA [Kellgren & Lawrence (K&L) = 0] and 24% had doubtful OA (K&L = 1). At follow-up, 147 hips (10.4%) fulfilled the ACR criteria and 35 hips (2.5%) had received THR. Five shape variants (modes) at baseline associated significantly with THR within 5 years. When combined in one GEE model, these shape variants resulted in a predictive power indicated by an area under the curve of 0.81. No shape variants associated with the presence of clinical OA at follow-up. The shape of the hip as quantified by an SSM has a good predictive value for THR, whereas variation in shape cannot predict clinical OA. Minor shape variants may be used as a radiographic biomarker to predict the future risk of THR.


Biosynthesis and preparation of fiveAlternaria metabolites.
Metabolites ofAlternaria alternata were produced on rice as a solid substrate, chosen out of 6 substrates as the most useful. Optimal methods of extraction, purification, and separation of 5 metabolites were elaborated, using liquid - liquid partition, column chromatography, and preparative TLC. Alternariol, alternariol methyl ether, and copper salt of tenuazonic acid were obtained as crystals, altertoxin and altenuene as a film.


Interplay between 3'-UTR polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the risk of ischemic stroke.
Stroke incidence is a multifactorial disease and especially hyperhomocysteinemia is associated with a higher risk of stroke. Previous studies have reported a folate metabolism disorder associated with the MTHFR gene. We investigated four single nucleotide polymorphisms in the MTHFR 3'-UTR [2572 C > A (rs4846049), 4869 C > G (rs1537514), 5488 C > T (rs3737967), and 6685 T > C (rs4846048)] to elucidate associations between ischemic stroke prevalence and prognosis. We examined 511 consecutive patients with ischemic stroke. Additionally, we selected 411 sex-/age-matched control subjects from patients presenting at our hospitals during the same period. The MTHFR 2572 C > A and 6685 T > C were significantly associated with ischemic stroke prevalence in the cardioembolism subgroup (MTHFR 2572CC vs. CA + AA: AOR, 2.145; 95% CI, 1.203-3.827; P = 0.010; MTHFR 6685TT vs. CC: AOR, 10.146; 95% CI, 1.297-79.336; P = 0.027). The gene-environment combined effect was significant, with MTHFR 2572CA + AA and folate levels ≤3.45 ng/mL correlating with ischemic stroke incidence. In addition, the total homocysteine (tHcy) levels in subjects with MTHFR 2572AA were elevated compared to tHcy levels in subjects with MTHFR 2572CC. Therefore, we suggest that MTHFR 2572 C > A and 6685 T > C are associated with ischemic stroke pathogenesis. The combined effects of the MTHFR 3'-UTR polymorphisms and tHcy/folate levels may contribute to stroke prevalence.


Self-efficacy contributes to individual differences in subjective improvements using CPAP.
Continuous positive airway pressure (CPAP) improves depressive symptoms and daytime sleepiness in patients with obstructive sleep apnea (OSA). However, there is variability in response to CPAP. This study examined individual differences in the daily associations between CPAP use and improvements in affect and sleepiness patients beginning CPAP. This observational repeated measures study involved 31 CPAP-naïve patients diagnosed with obstructive sleep apnea at an academic sleep disorders center. Patients completed pre-treatment assessments of OSA knowledge, expectations for CPAP, and treatment self-efficacy as well as a repeated daily assessment of positive affect and negative affect, sleepiness/fatigue, and CPAP adherence for 10 days beginning the first week of treatment. Data were analyzed using multilevel modeling. Nightly CPAP adherence predicted improvements in next-day positive affect, negative affect, and sleepiness/fatigue. The apnea-hypopnea index (AHI), treatment self-efficacy, and outcome expectancies were significant moderators of day-to-day improvement. Higher self-efficacy and lower AHI were associated with a stronger relationship between adherence and next-day improvements in positive affect and sleepiness. Very high-outcome expectances were associated with a weaker relationship between adherence and next-day improvements in sleepiness. Subjective sleepiness at pre-treatment did not give moderate improvements in next-day affect. Although CPAP use predicted daily improvements in affect and sleepiness for the majority of patients, patients with lower AHI, greater treatment self-efficacy, and moderate outcome expectancies reported stronger daily benefits from CPAP. For patients with high-treatment efficacy, adherence may be reinforced by a stronger link between adherence and daily improvements.


Fluoropyrimidine therapy: hyperbilirubinemia as a consequence of hemolysis.
Hemolytic anemia has been noted during treatment with a variety of chemotherapeutic agents. We observed mild compensated hemolytic anemia in a patient receiving capecitabine during a randomized, controlled trial of adjuvant therapy. In order to investigate the hypothesis that hemolysis is the underlying cause of the hyperbilirubinemia sometimes observed during capecitabine treatment, we evaluated factors associated with hemolysis in ten patients. Factors were also analyzed in ten patients receiving 5-fluorourocil/leucovorin (5-FU/LV). Twenty chemotherapy-naïve patients undergoing surgery for Dukes' C colon cancer were included in the phase III, 'X-ACT' trial, and randomized to receive 24-week adjuvant treatment with either oral capecitabine (eight cycles of 1,250 mg/m2 twice daily for 14 days, followed by a 7-day rest period) (n=10) or 5-FU/LV administered according to the Mayo Clinic regimen (six cycles of LV 20 mg/m2 followed by 5-FU 425 mg/m2, administered as an i.v. bolus on days 1-5 every 28 days) (n=10). Ten patients randomized in each treatment arm were evaluated. Hemolytic parameters evaluated included bilirubin, lactate dehydrogenase, haptoglobin, and reticulocytes. Seven patients receiving capecitabine and three patients receiving 5-FU/LV experienced grade 1/2 elevations of bilirubin during the 24-week treatment period. In most cases, hyperbilirubinemia was associated with concomitant alterations in other hemolytic parameters. Five episodes of grade 1 compensated hemolytic anemia were reported in four capecitabine-treated patients, all of which were associated with hyperbilirubinemia. Adjuvant treatment with capecitabine or 5-FU/LV in a small sample of patients with Dukes' C colon cancer was associated with alterations in hemolytic parameters. These alterations, in particular hyperbilirubinemia, were associated in some patients with low-grade compensated hemolytic anemia. All changes were clinically insignificant, fully reversible, and may represent a fluoropyrimidine class effect. Further studies are indicated to evaluate the incidence and implications of this effect.


Glaucoma therapy escalation in eyes with pseudophakic corneal edema after penetrating keratoplasty and Descemet's stripping automated endothelial keratoplasty.
The purpose of this study was to determine and compare the prevalence of glaucoma therapy escalation (GTE) after penetrating keratoplasty (PKP) and Descemet's stripping automated endothelial keratoplasty (DSAEK) in eyes with a surgical indication of pseudophakic corneal edema. A retrospective review was conducted of the medical records of all patients who underwent PKP or DSAEK to treat pseudophakic corneal edema at a tertiary eye care center from January 1 2003 to December 31, 2006. Eyes that were treated with PKP from January 1, 2003 to December 31, 2004 and with DSAEK from January 1, 2005 to December 31, 2006 were included in the statistical analysis. Inclusion criteria included satisfactory preoperative control of intraocular pressure (IOP) and follow-up of at least 12 months. The main outcome measure was GTE, which was defined as a sustained requirement for escalation of topical medical therapy or the need to provide surgical intervention to maintain a satisfactory postoperative IOP. Among 54 eyes that met the inclusion criteria, GTE occurred in 7 (35.0%) of 20 eyes after PKP and in 14 (41.2%) of 34 eyes after DSAEK (P = 0.78) during a mean follow-up period of 27.6 and 28.6 months, respectively. Surgical escalation occurred in 2 (10.0%) eyes after PKP and 2 (5.9%) eyes after DSAEK (P = 0.62), and was associated with late-onset endothelial graft failure in all four eyes. Glaucoma therapy escalation is relatively common and occurs with comparable frequency in eyes with pseudophakic corneal edema after PKP and DSAEK.


Evaluation and prediction of water conservation of the Yellow river basin in Sichuan Province, China, based on Google Earth Engine and CA-Markov.
The Yellow River Basin in China has the world's most serious soil erosion problem. The Yellow River Basin in Sichuan Province (YRS), as the upper reaches of the Yellow River, and its water conservation (WC) capacity greatly affects the ecological environment of the downstream basin. In recent years, YRS has received more and more attention, and numerous policies have been developed to improve local WC. However, there is a vacancy in the long-term research of WC in the YRS due to the lack of in-situ data. This study quantitatively evaluated the WC of YRS from 2001 to 2020 through Google Earth Engine (GEE) and analyzed the spatio-temporal variations of WC and land cover (LC). CA-Markov predicted the LC and WC in 2025 under three scenarios to assess the contribution of different scenarios to WC. The WC in YRS fluctuated from 1.93 to 6.77 billion m3. The climate is the dominant factor of WC change, but the effect of LC on WC is also evident. The WC capacity increases with vegetation coverage and height. The WC capacity of forests per km2 exceeds 600 mm, while that of grasslands is about 250 mm, and barren can cause around 300 mm of WC loss. In 2025, the WC in YRS may exceed 7.5 billion m3, but the past ecological management mode should be transformed. Improving the quality of land use and converting grasslands to forests is better than reducing cropland to improve WC.


Enzyme-Free Electrochemical Biosensor Based on Localized DNA Cascade Displacement Reaction and Versatile DNA Nanosheets for Ultrasensitive Detection of Exosomal MicroRNA.
MicroRNA existing in exosomes (exo-miRNA) is a crucial and reliable biomarker for cancer screening and diagnosis. However, accurate detection of ultralow exo-miRNA amounts in real samples remains a challenge. Herein, a robust and ultrasensitive electrochemical biosensor was developed based on localized DNA cascade displacement reaction (L-DCDR) and versatile DNA nanosheets (DNSs) for enzyme-free analysis of exo-miRNA. The target activated L-DCDR repeatedly by consecutive toehold-mediated strand displacement, which released plentiful P strands to hybridize with capture probes immobilized on the electrode surface and DNS tags, generating an amplified electrochemical signal for the detection of exo-miRNA. The DNS could label-free load various electroactive molecules. The electrochemical biosensor revealed high sensitivity ranging from 0.1 fM to 1 nM with a limit of detection of 65 aM and good specificity. The constructed biosensor was demonstrated to be able to detect exo-miRNA derived from gastric cancer cell line (SGC-7901) and gastric cancer patients. In addition, the developed biosensor possessed several considerable advantages including simple substrate assembly, improved reaction rate, and high signal-to-noise ratio. Therefore, this strategy has great potential in bioanalysis and clinical diagnostics.


Cloning, characterization and function analysis of DAX1 in Chinese loach (Paramisgurnus dabryanus).
The mechanisms of sex determination and differentiation have not been elucidated in most fish species. In this study, the full-length cDNAs of DAX1 was cloned and characterized in aquaculture fish Chinese loach (Paramisgurnus dabryanus), designated as Pd-DAX1. The cDNA sequence of Pd-DAX1 was 1261 bp, including 795 bp open reading frame (ORF) encoding 264 amino acids. Pd-DAX1 shares highly identical sequence with DAX1 homologues from different species. The expression profiles of Pd-DAX1 in different developmental stages and diverse adult tissues were analyzed by quantitative real-time RT-PCR and in situ hybridization (ISH). Pd-DAX1 was continuously expressed during embryogenesis, with the extensive distribution in the development of the central nervous system. Tissue distribution analysis revealed that Pd-DAX1 expressed widely in adult tissues, with the highest expression level found in testis, moderate level in ovary, showing a sex-dimorphic expression pattern. Pd-DAX1 mainly located in spermatogonia cells, spermatocytes, primary oocytes and previtellogenic oocyte cells, implying that Pd-DAX1 may involve in gametogenesis. These preliminary findings suggest that Pd-DAX1 gene is highly conserved during vertebrate evolution and involved in a wide range of developmental processes including embryogenesis, central nervous system development and gonad development.


Calicheamicin gamma 1I and DNA: molecular recognition process responsible for site-specificity.
Calicheamicin gamma 1I is a recently discovered diyne-ene-containing antitumor antibiotic that cleaves DNA in a double-stranded fashion, a rarity among drugs, at specific sequences. It is proposed that the cutting specificity is due to a combination of the complementarity of the diyne-ene portion of the aglycone with DNA secondary structures and stabilization by association of the thiobenzoate-carbohydrate tail with the minor groove.


Continued gefitinib treatment after disease stabilisation prolongs survival of Japanese patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.
This study aimed to investigate the survival outcome of patients with non-small-cell lung cancer (NSCLC) who had obtained disease stabilisation with gefitinib treatment and to clarify the effect of continued treatment with gefitinib on prognosis. We reviewed the clinical records of 365 Japanese patients with NSCLC who received gefitinib (250 mg/day). Of 324 (89%) patients assessable for response, 147 (45%) obtained disease stabilisation and 71 (22%) patients achieved an objective response. Overall survival in patients obtaining disease stabilisation was significantly longer than in patients with progressive disease (median survival time 12.1 versus 4.4 months; P <0.0001). In patients obtaining disease stabilisation, those who continued gefitinib treatment until disease progression tended to have longer overall and progression-free survival compared with those discontinuing gefitinib treatment (1-year survival rate 52.1% versus 36.6%, P = 0.08; 1-year progression-free survival rate 31.8% versus 5.2%, P = 0.001). Multivariate analysis showed discontinuing gefitinib was an independent risk factor for progression-free survival (hazard ratio 1.66; 95% confidence interval 1.07-2.56; P = 0.022) but not for overall survival. Our findings indicate the importance of achieving disease stabilisation with gefitinib treatment and continued gefitinib treatment in Japanese patients with disease stabilisation, although further studies are required to confirm these findings.


Degenerative, non-atherosclerotic cardiovascular disease in the elderly: a clinico-pathological survey.
Cardiovascular disease, the major cause of death in the elderly, is mostly ascribable to complications of coronary atherosclerosis: angina pectoris, myocardial infarction, and sudden death. However, other degenerative diseases involving several cardiac structures exist, and should be distinguished from age-related cardiac changes. Extensive dystrophic calcification determines aortic stenosis, and may affect either a normally tricuspid or a congenitally bicuspid valve. Surgical valve replacement is now a low risk option, even in elderly persons, whereas the efficacy of balloon valvuloplasty is questionable. Aortic incompetence in adults and aged persons is mostly the consequence of aortic tunica media atrophy with anular ectasia, in the setting of nearly normal aortic leaflets. Mitral valve prolapse is the main cause of mitral incompetence; spontaneous cordal rupture is a late complication in the natural history of this disease, thus warranting prompt surgical valve repair or replacement. The entire spectrum of cardiomyopathies is observed in the elderly: dilated, hypertrophic, restrictive, arrhythmogenic. Cardiac amyloidosis is by far the most frequent secondary form and leads to congestive heart failure by impairing ventricular compliance. Idiopathic fibrosis of the specialized AV junction or dystrophic calcification of central fibrous body are the usual substrates of AV block, which requires pace-maker implantation. Nonrheumatic atrial fibrillation, due to fibro-fatty degeneration of the atrial musculature or dilated left atrium, carries a high risk of thromboembolic complications and cerebral accidents; oral anticoagulants have proven to be effective in preventing stroke. Aortic dissecting aneurysm is a spontaneous laceration, and usually a complication of longstanding systemic hypertension; exceptionally, spontaneous dissection may primarily occur in the coronary arteries. In conclusion, longevity at present is mostly threatened by cardiovascular disease, among which the role of degenerative, non-atherosclerotic disorders may be greater than thought.


A two-dimensional layer in N,N'-bis[2-(hydroxymethyl)benzyl]ethylenediamine and a three-dimensional network in N,N'-bis[2-(hydroxymethyl)benzyl]ethylenediammonium bis(perchlorate).
In both title compounds, C(18)H(24)N(2)O(2), (Ia), and C(18)H(26)N(2)O(2)(2+) x 2 ClO(4)(-), (II), respectively, the two aryl rings are strictly parallel, with an inversion centre lying at the mid-point of each central CH(2)-CH(2) bond. Molecules in (Ia) are linked into two-dimensional layers by N-H...O hydrogen bonds. The component ions in (II) are joined together by a combination of N/O/C-H...O hydrogen bonds and C-H...pi and anion...pi interactions, forming a three-dimensional network. A structural understanding of (Ia) and (II) may provide some useful information about how and why their metal-organic complexes display various biological activities and function in catalytic processes.


Biomedical Ontologies to Guide AI Development in Radiology.
The advent of deep learning has engendered renewed and rapidly growing interest in artificial intelligence (AI) in radiology to analyze images, manipulate textual reports, and plan interventions. Applications of deep learning and other AI approaches must be guided by sound medical knowledge to assure that they are developed successfully and that they address important problems in biomedical research or patient care. To date, AI has been applied to a limited number of real-world radiology applications. As AI systems become more pervasive and are applied more broadly, they will benefit from medical knowledge on a larger scale, such as that available through computer-based approaches. A key approach to represent computer-based knowledge in a particular domain is an ontology. As defined in informatics, an ontology defines a domain's terms through their relationships with other terms in the ontology. Those relationships, then, define the terms' semantics, or "meaning." Biomedical ontologies commonly define the relationships between terms and more general terms, and can express causal, part-whole, and anatomic relationships. Ontologies express knowledge in a form that is both human-readable and machine-computable. Some ontologies, such as RSNA's RadLex radiology lexicon, have been applied to applications in clinical practice and research, and may be familiar to many radiologists. This article describes how ontologies can support research and guide emerging applications of AI in radiology, including natural language processing, image-based machine learning, radiomics, and planning.


Implementation methods of infection prevention measures in orthopedics and traumatology - a systematic review.
Prevention of hospital-acquired infections, in the clinical field of orthopedics and traumatology especially surgical site infections, is one of the major concerns of patients and physicians alike. Many studies have been conducted proving effective infection prevention measures. The clinical setting, however, requires strategies to transform this knowledge into practice. As part of the HYGArzt-Project ("Proof Of Effectivity And Efficiency Of Implementation Of Infection Prevention (IP) Measures By The Physician Responsible For Infection Prevention Matters In Traumatology/Orthopedics"), the objective of this study was to identify effective implementation strategies for IP (infection prevention) measures in orthopedics and trauma surgery. The systematic review was conducted following PRISMA guidelines. A review protocol was drafted prior to the literature search (not registered). Literature search was performed in MEDLINE, SCOPUS and COCHRANE between January 01, 1950 and June 01, 2019. We searched for all papers dealing with infection and infection control measures in orthopedics and traumatology, which were then scanned for implementation contents. All study designs were considered eligible. Exclusion criteria were language other than English or German and insufficient reporting of implementation methods. Analyzed outcome parameters were study design, patient cohort, infection prevention measure, implementation methods, involved personnel, reported outcome of the studies and study period. The literature search resulted in 8414 citations. 13 records were eligible for analysis (all published between 2001 and 2019). Studies were primarily prospective cohort studies featuring various designs and including single IP measures to multi-measure IP bundles. Described methods of implementation were heterogeneous. Main outcome parameters were increase of adherence (iA) to infection prevention (IP) measures or decrease in surgical site infection rate (dSSI%). Positive results were reported in 11 out of 13 studies. Successful implementation methods were building of a multidisciplinary team (considered in 8 out of 11 successful studies [concerning dSSI% in 5 studies, concerning iA in five studies]), standardization of guidelines (considered in 10/11 successful studies [concerning dSSI% in 5 studies, concerning iA in seven studies]), printed or electronic information material (for patient and/or staff; considered in 9/11 successful studies [concerning dSSI% 4/4, concerning iA 5/5]), audits and regular meetings, personal training and other interactive measures as well as regular feedback (considered in 7/11 successful studies each). Personnel most frequently involved were physicians (of those, most frequently surgeons) and nursing professions. Although evidence was scarce and quality-inconsistent, we found that adhering to a set of implementation methods focusing on interdisciplinary and interactive /interpersonal work might be an advisable strategy when planning IP improvement interventions in orthopedics and traumatology.


Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma.
Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.


PPG, APG, duplex: which noninvasive tests are most appropriate for the management of patients with chronic venous insufficiency?
Numerous noninvasive tests have been described for assistance in the diagnosis and treatment of patients with chronic venous insufficiency (CVI). These tests include venous duplex ultrasound examination in the supine and standing positions, photoplethysmography (PPG), and air plethysmography (APG). The goal of these studies is to provide accurate information describing the anatomic or the hemodynamic characteristics of the patient with CVI, precluding the need for invasive studies. These tests will be reviewed including the typical information obtained, the usefulness of this information, and the relevance for clinical management of patients with CVI. Based on the clinical class, recommendations for a noninvasive testing protocol are outlined.


Potentiation of acetaminophen hepatotoxicity by phenytoin, leading to liver transplantation.
We report the case of a 22-year-old man who developed fulminant hepatic failure 3 days after an intentional acetaminophen overdose. The patient had a history of a seizure disorder for which he was taking phenytoin. The acetaminophen level at presentation was in the "nontoxic" range. Emergent liver transplantation was performed 4 days after the ingestion. This is the first reported case of successful liver transplantation for acetaminophen-induced fulminant hepatic failure in the setting of phenytoin therapy.


The Noble-Mengert-Fish operation-revisited: a composite approach for persistent rectovaginal fistulas and complex perineal defects.
Our aims were to evaluate the full-thickness anterior rectal wall advancement flap in the treatment of primary and recurrent or persistent rectovaginal fistulas, evaluate the surgical exposure for composite repair of site-specific perineal defects, and categorize clinical manifestations of site-specific perineal defects caused by obstetric injury. This is a prospective study of all patients with fecal incontinence from rectovaginal septal defects and complex perineal obstetric injuries treated by the Noble-Mengert-Fish operation. Thirty-four patients were classified into groups on the basis of site-specific perineal defects. Anatomic success was 94.2%. Functional success was excellent in 76.5%, good in 14.7%, fair in 5.9%, and poor in 2.9%. The Noble-Mengert-Fish operation is effective for primary and recurrent or persistent rectovaginal fistulas. The circumanal surgical exposure permits concomitant repair of all perineal defects.


Teacher, teacher: when pharmacists embrace their role as educators.
When long-term care directors of nursing need education and information about medications and medication-related issues, they often turn to their consultant pharmacists. Working together, these practitioners ensure that nurses have the skills and tools they need to solve problems, maximize efficiency, maintain quality, and reduce errors.


Case 4: using octenilin Solution with the schülke WoundPad.
This case study demonstrates the use of a debridement pad with octenilin.


Velocity of oxygen uptake response at the onset of exercise: A comparison between children after cardiac surgery and healthy boys.
A comparison was carried out concerning maximal oxygen uptake, oxygen uptake adjustment at the onset of high-intensity exercise, and maximal blood lactate between 10 healthy prepubertal boys and 35 children after repair of cardiac malformations or after Fontan operation. Mean maximal oxygen uptake (VO2) was moderately reduced in children after repair of tetralogy of Fallot or after Mustard or Senning operations and severely reduced after Fontan operations. Conversely, mean half-time of VO2 response was moderately prolonged in children after repair of tetralogy of Fallot or after Senning and Mustard operations and considerably prolonged after Fontan operations. According to our results unfavorable kinetics of VO2 response to physical exercise are present in addition to reduced aerobic power in many of the operated children. Besides being less qualified for endurance performance, these children are also less prepared for short, high-intensity exercise.


Disease activity is associated with reduced left ventricular systolic myocardial function in patients with rheumatoid arthritis.
Disease activity has emerged as a new, independent risk factor for cardiovascular disease in patients with rheumatoid arthritis (RA). We tested if disease activity in RA was associated with lower left ventricular (LV) systolic function independent of traditional cardiovascular risk factors. Echocardiographic assessment was performed in 78 patients with RA having low, moderate or high disease activity (Simplified Disease Activity Index (SDAI) >3.3), 41 patients in remission (SDAI ≤3.3) and 46 controls, all without known cardiac disease. LV systolic function was assessed by biplane Simpson ejection fraction, stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS). Patients with active RA had higher prevalence of hypertension and diabetes compared with patients in remission and controls (both p<0.05). LV ejection fraction (endocardial function) was normal in all three groups, while mean scMWS and GLS (myocardial function) were reduced in patients with RA with active disease compared with patients with RA in remission (95±18% vs 105±17% and -18.9±3.1% vs -20.6±3.5%, respectively, both p<0.01). Patients with RA in remission had similar scMWS and GLS as the controls. In multivariable analyses, having active RA was associated with lower GLS (β=0.21) and scMWS (β=-0.22, both p<0.05), both reflecting lower LV systolic myocardial function, independent of cardiovascular risk factors and LV ejection fraction. Classification of RA disease activity by other disease activity composite scores yielded similar results. Active RA is associated with lower LV systolic myocardial function despite normal ejection fraction and independent of traditional cardiovascular risk factors.


Mechanistic studies on the biosynthesis of 6-ketoprostaglandin F1alpha.
The isolation, structure and biosynthesis of a novel metabolite of arachidonic acid formed during incubations of rat stomach homogenates is reported. This product was formed from unlabeled, tritium-labeled and deuterium-labeled arachidonic acid and the prostaglandin endoperoxides, G2 and H2, demonstrating its formation via the "prostaglandin endoperoxide synthetase" pathway. Its structure, 6-ketoprostaglandin F1alpha, was based on mass spectral interpretation of several derivatives (undeuterated and deuterated) and confirmed through chemical synthesis. 6-Ketoprostaglandin F1alpha is unique in being formed from a substrate of the "2" series of prostaglandins, i.e. arachidonic acid, yet belonging to the "1" series. A mechanism for its biosynthesis is proposed involving a specific cyclising enzyme which we term, 6(9)-oxycyclase.


Resistance of naturally secreted α-synuclein to proteolysis.
Recent evidence suggests that specific extracellular α-synuclein (α-syn) strains are implicated in the progression of Parkinson's disease (PD) pathology. It is plausible that deregulation in the normal processing of secreted α-syn may be a causative risk factor for PD. To date, the degradation mechanisms involved have received very little attention. Here, we sought to investigate factors that regulate extracellular α-syn levels. We show, for the first time, that cell-secreted α-syn forms are resistant to direct proteolysis by kallikrein-related peptidase 6 (KLK6), an extracellular enzyme known to cleave recombinant α-syn. This differential susceptibility appears to be partially due to the association of secreted α-syn with lipids. We further provide evidence that secreted α-syn can be cleaved by KLK6 indirectly through activation of a secreted metalloprotease, suggestive of the involvement of a proteolytic cascade in the catabolism of secreted α-syn. Our results clearly suggest that physiological modifications affect the biochemical behavior of secreted α-syn and provide novel insights into mechanisms and potential targets for therapeutic interventions.-Ximerakis, M., Pampalakis, G., Roumeliotis, T. I., Sykioti, V.-S., Garbis, S. D., Stefanis, L., Sotiropoulou, G., Vekrellis, K. Resistance of naturally secreted α-synuclein to proteolysis.


Motivation and Problem Solving (MAPS): Motivationally Based Skills Training for Treating Substance Use.
Over 10 years ago, Baer and colleagues proposed the integration of skills training and motivational strategies for the treatment of substance abuse. Since that time, several studies evaluating the efficacy of such hybrid approaches have been published, but few have been efficacious. Motivation and Problem Solving (MAPS) is a comprehensive, dynamic, and holistic intervention that incorporates empirically supported cognitive behavioral and social cognitive theory-based treatment strategies within an overarching motivational framework, and has been demonstrated to be effective in a randomized clinical trial focused on the prevention of postpartum smoking relapse. MAPS was designed to be applicable to not only relapse prevention but also the cessation of substance use, and is relevant for individuals regardless of their motivation to change. MAPS views motivation as dynamically fluctuating from moment to moment throughout the behavior change process, and comprehensively addresses multiple issues important to the individual and relevant to change through the creation of a wellness program. As a result, we believe that MAPS enhances the likelihood that individuals will successfully achieve and maintain abstinence from substance use, and that its comprehensive focus on addressing diverse and salient issues enhances both engagement in treatment and its applicability in modifying other health risk behaviors. The current paper introduces MAPS, distinguishes it from other hybrid and stage-based substance use treatments, and provides detailed information and clinical text regarding how MAPS is specifically and uniquely implemented to address key mechanisms relevant to quitting smoking and maintaining abstinence.


Treatment interruptions affect biochemical failure rates in prostate cancer patients treated with proton beam therapy: Report from the multi-institutional proton collaborative group registry.
To date, no studies examining the effect of treatment interruptions (TI) with proton beam therapy (PBT) have been published. The goal of our study was to determine the predictors of TI amongst patients with prostate cancer (PCa) treated with PBT and to determine whether TI are associated with biochemical failure (BF). We hypothesized that any correlation between TI and biochemical control would be more pronounced in high risk groups. Data for 4278 patients with PCa was obtained from the prospectively collected Proton Collaborative Group (PCG) data registry. Univariate and multivariate logistic regression analysis (MVA) was used to model possible predictors of BF. A subset analysis was performed for high risk patients treated with ADT and PBT. Finally, propensity score (PS) analysis was performed to account for any indication bias caused by lack of randomization. Total treatment duration (OR, 1.05 [1.04-1.06]; p < 0.001) increased the likelihood of TI on MVA. TI did not have a statistically significant correlation with BF (OR, 1.44 [0.86-2.39]; p = 0.162) amongst PS matched patients. However, on subset analyses of high risk group patients with PS matching, there was a trend towards worse BF in patients with TI (OR 3.85; 95%CI (0.96-15.44); p = 0.057). In the first analysis of its kind, the results suggest that TI in high risk PCa patients treated with PBT and ADT have worse BF rates. Interventions such as increased patient education, proper maintenance of proton facilities, and decreasing total treatment duration with alternative fractionation schedules may help avoid the unintended negative effects on tumor control due to TI. However, future analyses on a larger patient population is needed.


Noninvasive transcutaneous cardiac pacing in prehospital cardiac arrest.
This study evaluated the efficacy of prehospital external cardiac pacing in cardiac arrest patients. From October 1984 to June 1985, 91 patients were paced. Mean time from cardiac arrest to advanced life support (ALS) intervention in this metropolitan-rural ALS system was 14.5 minutes. Electrical capture occurred in 85 (93%), mechanical capture (pulses) occurred in ten (11%), and a measurable blood pressure occurred in three (3%) of the 91 patients. Despite a high rate of electrical capture, palpable pulses were produced only in 11%, and no patients survived to be discharged from the hospital. There was no difference in the frequency of electrical capture, palpable pulses, or outcome for patients receiving pharmacologic intervention before or after pacing. Likewise there was no difference in the frequency of electrical capture, palpable pulses, or outcome for patients receiving ALS therapy within or after ten minutes of their arrest. Although we found that external cardiac pacing was easily used in the prehospital setting, pacing did not result in any increase in survival in cardiac arrest patients.


The prokaryotic complex iron-sulfur molybdoenzyme family.
Bacterial genomes encode an extensive range of respiratory enzymes that enable respiratory metabolism with a diverse group of reducing and oxidizing substrates under both aerobic and anaerobic growth conditions. An important class of enzymes that contributes to this broad diversity is the complex iron-sulfur molybdoenzyme (CISM) family. The architecture of this class comprises the following subunits. (i) A molybdo-bis(pyranopterin guanine dinucleotide) (Mo-bisPGD) cofactor-containing catalytic subunit that also contains a cubane [Fe-S] cluster (FS0). (ii) A four-cluster protein (FCP) subunit that contains 4 cubane [Fe-S] clusters (FS1-FS4). (iii) A membrane anchor protein (MAP) subunit which anchors the catalytic and FCP subunits to the cytoplasmic membrane. In this review, we define the CISM family of enzymes on the basis of emerging structural and bioinformatic data, and show that the catalytic and FCP subunit architectures appear in a wide range of bacterial redox enzymes. We evaluate evolutionary events involving genes encoding the CISM catalytic subunit that resulted in the emergence of the complex I (NADH:ubiquinone oxidoreductase) Nqo3/NuoG subunit architecture. We also trace a series of evolutionary events leading from a primordial Cys-containing peptide to the FCP architecture. Finally, many of the CISM archetypes and related enzymes rely on the tat translocon to transport fully folded monomeric or dimeric subunits across the cytoplasmic membrane. We have used genome sequence data to establish that there is a bias against the presence of soluble periplasmic molybdoenzymes in bacteria lacking an outer membrane.


Systemic glucocorticoids as an adjunct to treatment of postoperative pain after total hip and knee arthroplasty: A systematic review with meta-analysis and trial sequential analysis.
Postoperative analgesic effects of systemic glucocorticoids given as an adjunct to treatment are largely undetermined in alloplastic procedures. To investigate the beneficial and harmful effects of peri-operative systemic glucocorticoid treatment for pain after total hip arthroplasty (THA) or total knee arthroplasty (TKA). A systematic review of randomised clinical trials (RCTs) with meta-analyses, trial sequential analyses and GRADE. Primary outcome was 24 h intravenous (i.v.) morphine (or equivalent) consumption with a predefined minimal important difference (MID) of 5 mg. Secondary outcomes included pain at rest and during mobilisation (MID, VAS 10 mm), adverse and serious adverse events (SAEs). We searched EMBASE, Cochrane CENTRAL, PubMed and Google Scholar up to October 2021. RCTs investigating peri-operative systemic glucocorticoid versus placebo or no intervention, for analgesic pain management of patients at least 18 years undergoing planned THA or TKA, irrespective of publication date and language. We included 32 RCTs with 3521 patients. Nine trials were at a low risk of bias. Meta-analyses showed evidence of a reduction in 24 h cumulative morphine consumption with glucocorticoids by 5.0 mg (95% CI 2.2 to 7.7; P = 0.0004). Pain at rest was reduced at 6 h by 7.8 mm (95% CI 5.5 to 10.2; P < 0.00001), and at 24 h by 6.3 mm (95% CI 3.8 to 8.8; P < 0.00001). Pain during mobilisation was reduced at 6 h by 9.8 mm (95% CI 6.9 to 12.8; P < 0.00001), and at 24 h by 9.0 mm (95% CI 5.5 to 12.4, P < 0.00001). Incidence of adverse events was generally lower in the glucocorticoid treatment group. SAEs were rarely reported. The GRADE rated quality of evidence was low to very low. Peri-operative systemic glucocorticoid treatment reduced postoperative morphine consumption to an individually relevant level following hip and knee arthroplasty. Pain levels were reduced but were below the predefined MID. The quality of evidence was generally low. PROSPERO ID: CRD42019135034.


Anticoagulant effect of Feijoa sellowiana extracts generated by different biotechnological techniques.
Blood clotting has become one of the most dangerous side effects associated with Corona virus, as well as the high level of cholesterol and triglycerides in the blood. Therefore, it has become necessary to use medicinal plants that are biologically safe and containing anti-clotting compound. Feijoa sellowiana represents a prolific source diverse compounds that may have thrombolytic activity. Therefore, the main research point is the production and scaling up of a target contents that have anticoagulants by using biotechnological techniques; calli production, and bioreactors and assessed their activity through in-vivo study. Murashige and Skoog (MS) medium enriched with varying concentrations of benzyl adenine (BA) and naphthalene acetic acid (NAA) was used to cultivate calli and cell suspension cultures from F. sellowiana seeds. Bioreactors were employed to boost active constituent's production. Moreover, the bioreactor physical factors such as effect of controlled or uncontrolled pH medium were investigated. The leaves of the main plant were extracted by ethanol 70% and polar and non-polar extracts were also prepared. The ethanol extract of calli and cells resulting from bioreactors were also prepared. All prepared extracts were subjected to chemical analysis by HPLC, in-vitro antioxidant assays, in-vivo anticoagulant activity and histopathological examination. Calli and cell suspension cultures were produced by using MS medium fortified with 1 mg/L BA+ 0.1 mg/L NAA. It was found that culturing of cell cultures in a bioreactor with uncontrolled pH and aeration at the value of 0.5 L/min gave the maximum and economical fresh and dry weights of the plants. After evaluation of all extracts; it was found that the calli ethanol extract for each plant was the highest value of total phenolic and total flavonoid contents either quantitatively or qualitatively. All extracts of Feijoa had antioxidant activity. The IC50 of the DPPH of Feijoa calli extract was 13.45 μg/mL, it was also confirmed by FRAP and ABTs values. Feijoa calli extract decreased platelet aggregation by suppression of thrombin, extended aPTT, PT, bleeding and clotting times. It was safer than warfarin medication. From these findings the authors can conclude that Feijoa had highly anticoagulant activity and the calli production achieved the goal of the enhancement of the phenolic constituent and thus their activity.


Dexmedetomidine versus midazolam as adjuvants to intrathecal bupivacaine: A clinical comparison.
Trials are being carried out to identify an adjuvant to intrathecal bupivacaine that preferably potentiates postoperative analgesia. This prospective, randomized, double-blind study was aimed to compare the onset and duration of sensory and motor block, postoperative analgesia and adverse effects of dexmedetomidine or midazolam given with 0.5% hyperbaric bupivacaine for spinal anesthesia. A total of 80 patients, scheduled for vaginal hysterectomies, were randomly allocated to Group D (n = 40) to receive intrathecally 3.0 mL 0.5% hyperbaric bupivacaine +5 ug dexmedetomidine in 0.5 mL of normal saline; and Group M (n = 40) to receive 3 mL of 0.5% hyperbaric bupivacaine +2 mg midazolam in 0.4 mL (5 mg/mL) +0.1 mL normal saline. The onset, duration of sensory and motor block, time to first postoperative analgesia and side effects were noted. Power and Sample size (PS) version 22.214.171.124 was used for power and sample size calculation. Statistical analysis was performed using Microsoft (MS) Office Excel software with the Student's t-test and Chi-square test (level of significance P = 0.05). Duration of sensory, motor blockade and time to the first requirement of analgesia were significantly higher in Group D. Postoperative visual analog scale was significantly less in Group D than Group M. Both groups were similar with respect to sedation, hemodynamic variables and side-effects. Intrathecal dexmedetomidine was better adjuvant than midazolam as it produces significantly longer duration of sensory block, reduced doses of postoperative analgesic agents with comparable side-effects.


Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm.
The aim of this study was to investigate the efficacy and safety of bepridil (a multichannel blocker including several potassium channels) for conversion of long-lasting atrial fibrillation (AF). Bepridil restored sinus rhythm alone or in combination with aprindine in 69% of 32 patients with persistent AF lasting > or = 3 months. The time to conversion after starting bepridil was 30 +/- 12 days. An increase in fibrillation cycle length with bepridil was greater in responders (31 +/- 10%), but an increase in QTc did not differ between responders and nonresponders. Bepridil is effective and safe for terminating long-lasting persistent AF.


Dynamin-related protein 1 differentially regulates FcεRI- and substance P-induced mast cell activation.
The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro, but its functions in MCs activated by various stimuli in vivo have not yet been examined. We sought to analyze Drp1 function in both mouse and human MCs. We used human peripheral blood-derived cultured MCs and 2 genetic mouse models in which MCs were depleted of Drp1: Drp1fl/flMcpt5cre+/- mice and Drp1fl/flCpa3cre+/- mice. In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P-stimulated MC activation in vitro and in vivo. This was also true in human peripheral blood-derived cultured MCs in vitro after pharmacologic inhibition of Drp1. Drp1 differentially regulates MC activation by various stimuli. Promoting Drp1 activation might therefore represent a novel therapy for suppressing IgE-dependent MC activation. Further, inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P.


Prehospital management of burns requiring specialized burn centre evaluation: a single physician-based emergency medical service experience.
Emergency medical services regularly encounter severe burns. As standards of care are relatively well-established regarding their hospital management, prehospital care is comparatively poorly defined. The aim of this study was to describe burned patients taken care of by our physician-staffed emergency medical service (PEMS). All patients directly transported by our PEMS to our burn centre between January 2008 and December 2017 were retrospectively enrolled. We specifically addressed three "burn-related" variables: prehospital and hospital burn size estimations, type and volume of infusion and pain assessment and management. We divided patients into two groups for comparison: TBSA < 20% and ≥ 20%. We a priori defined clinically acceptable limits of agreement in the small and large burn group to be ±5% and ± 10%, respectively. We included 86 patients whose median age was 26 years (IQR 12-51). The median prehospital TBSA was 10% (IQR 6-25). The difference between the prehospital and hospital TBSA estimations was outside the limits of agreement at 6.2%. The limits of agreement found in the small and large burn groups were - 5.3, 4.4 and - 10.1, 11, respectively. Crystalloid infusion was reported at a median volume of 0.8 ml/kg/TBSA (IQR 0.3-1.4) during the prehospital phase, which extrapolated over the first 8 h would equal to a median volume of 10.5 ml/kg/TBSA. The median verbal numeric rating scale on scene was 6 (IQR 3-8) and 3 (IQR 2-5) at the hospital (p < 0.001). Systemic analgesia was provided to 61 (71%) patients, predominantly with fentanyl (n = 59; 69%), followed by ketamine (n = 7; 8.1%). The median doses of fentanyl and ketamine were 1.7 mcg/kg (IQR 1-2.6) and 2.1 mg/kg (IQR 0.3-3.2), respectively. We found good agreement in burn size estimations. The quantity of crystalloid infused was higher than the recommended amount, suggesting a potential risk for fluid overload. Most patients benefited from a correct systemic analgesia. These results emphasized the need for dedicated guidelines and decision support aids for the prehospital management of burned patients.


Establishing a threshold for surgery in recurrent acute rhinosinusitis: a productivity-based analysis.
Treatment of recurrent acute rhinosinusitis (RARS) has 2 effective modalities: medical therapy with exacerbations or surgery to reduce the frequency and severity of infections. However, it is unclear when one therapy should be recommended over the other. This study seeks to identify a threshold number of infections where the morbidity of surgery is offset by the morbidity of RARS. Health economic breakeven threshold analysis. Clinical otolaryngology practice. None. A model of productivity was constructed to simulate the first 1 to 3 years after surgery using literature reported rates of medical and surgical response rates, quality of life, and productivity. Based on lost productivity, the lost time for the postoperative period balances out when patients suffer from 4 episodes per year (range, 1.8-12.8). Because of possible confusion with upper respiratory tract infections (URTIs), the authors have adopted an approach similar to that adopted by the Rhinosinusitis Task Force (RTF). Given the average number of URTIs suffered by adults annually is 1.4 to 2.3, they suggest adding 2 to the threshold number of episodes similar to the RTF guideline for RARS. From a productivity perspective, surgical intervention may be a viable consideration if patients have suffered from 6 episodes per year. However, the effects of surgery are expected to last longer than the 19 months observed in the literature, implying that the breakeven threshold is likely lower than projected. Discussion with the patient must include a rational consideration of the burden of disease, overall patient quality of life, and risks of surgery.


Central core degeneration after tenotomy in soleus muscles of hyperthyroid rats.
Tenotomy of the rat soleus muscle is followed by a central degeneration of slow, fatigue-resistant muscle fibers. Previous experiments showed that fast, fatigable fibers of the gastrocnemius when transformed to slow, fatigue-resistant fibers by cross-reinnervation also develop lesions after tenotomy. The experiments described in this communication were carried out to discover whether the susceptibility of fibers to lesions was determined by their fiber type or the nature of their innervation. Rats were rendered hyperthyroid by the administration of sodium 3,3',5-triiodo-L-thyronine (T3) for 7 to 10 weeks. Tenotomy of the soleus muscles was then carried out and the experimental and contralateral muscles were removed and stained for myosin ATPase activity after a further 2 weeks. The hyperthyroid state of each animal was confirmed by the assay of succinate dehydrogenase activity of liver and the contralateral muscle. After acid preincubation, whole muscle fiber type counts of contralateral muscles showed a statistically significant change from a predominantly acid-stable population of fibers to acid-labile fibers. In addition, many fibers of intermediate staining properties were seen. When the experimental muscles were examined, all three varieties of fiber showed central degeneration. The nature of the fiber type change induced by T3 and the role that innervation might play in this is discussed. It was concluded that the susceptibility of fibers to the lesions that follow tenotomy is dependent on the nature of their innervation rather than their fiber type.


[Use of Virtual Reality as a Component of Acute and Chronic Pain Treatment].
Future or reality? Treating acute and chronic pain is a part of the daily routine of clinical anesthesiologists. Commonly used analgesics have unwanted side effects or may even be insufficient as in chronic pain treatment. Virtual Reality (VR) could be a promising new approach which offers noninvasive therapy options for the treatment of pain. In case of the opioid misuse the adjunctive treatment is mandatory. Various phenomena occur in VR, such as immersion, presence, embodiment and Proteus effect, which can cause a change in body awareness and behavior. Experimental and clinical studies already yielded some promising results for analgesic effects for acute and chronic pain conditions using VR simulation. Potential analgesic mechanisms include distraction, cognitive behavioral change, and distance from reality, leading to neurophysiological changes at the cortical level. The quality of the virtual environment, personalized avatars, as well as the possibility of interaction and multisensory input can increase immersion, which leads to a state of presence, and thus effective VR. VR can be used as an immersive extension or alternative to mirror therapy, especially for pain disorders such as complex regional pain syndrome (CRPS) or phantom limb pain. VR can be supplemented by gamification, which increases intrinsic motivation, well-being and adherence to therapy. In summary, VR could be an effective and realistic therapy option for acute and chronic pain in clinical and home settings in the future.


Area Deprivation and Risk of Death and CKD Progression: Long-Term Cohort Study in Patients under Unrestricted Nephrology Care.
Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care. We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1-4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of "goal-oriented" nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements. We enrolled 715 consecutive patients (age: 64 ± 15 years; 59.1% males; eGFR: 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At referral, demographic, clinical, and therapeutic features were similar across ADI tertiles; after 12 months, treatment intensification allowed better control of hypertension, proteinuria, hypercholesterolaemia, and anaemia with no difference across ADI tertiles. During the subsequent long-term follow-up (10.5 years [interquartile range 8.2-12.6]), 166 renal events and 249 deaths were registered. ADI independently associated with all-cause death (p for trend = 0.020) and non-cardiovascular (CV) mortality (p for trend = 0.045), while CV mortality did not differ (p for trend = 0.252). Risk of composite renal outcomes was similar across ADI tertiles (p for trend = 0.467). The same held true for eGFR decline (p for trend = 0.675). In CKD patients under regular nephrology care, ADI is not associated with CKD progression, while it is associated with all-cause death due to an excess of non-CV mortality.


Malignant paraganglioma of the mesentery: a case report and review of literature.
Paragangliomas represent only 10% of chromaffin tissue tumors and those arising from the mesentery seem to be a rare occurrence. We report a case of a 55 year old man in whom an abdominal mass was discovered fortuitously by ultrasonography during a routine health exam. He presented occasional heart palpitations and diaphoresis as well as a well-demarcated mass upon abdominal physical examination. CT scan revealed a solid polylobulated mass in the right lower quadrant. Exploration laparotomy revealed a voluminous multi-nodular tumoral mass, which contained hemorrhagic spots. Histopathological studies confirmed the presence of a paraganglioma. The excision of the mass as well as the surrounding intestine and mesentery also revealed two lymphatic metastases, the first among 14 documented cases to be described concerning mesenteric paragangliomas. One year follow up and CT scan revealed neither recurrence nor the presence of distant metastases.


Preservation of microbial communities enriched on lignocellulose under thermophilic and high-solid conditions.
Microbial communities enriched from diverse environments have shown considerable promise for the targeted discovery of microorganisms and enzymes for bioconversion of lignocellulose to liquid fuels. While preservation of microbial communities is important for commercialization and research, few studies have examined storage conditions ideal for preservation. The goal of this study was to evaluate the impact of preservation method on composition of microbial communities enriched on switchgrass before and after storage. The enrichments were completed in a high-solid and aerobic environment at 55 °C. Community composition was examined for each enrichment to determine when a stable community was achieved. Preservation methods included cryopreservation with the cryoprotective agents DMSO and glycerol, and cryopreservation without cryoprotective agents. Revived communities were examined for their ability to decompose switchgrass under high-solid and thermophilic conditions. High-throughput 16S rRNA gene sequencing of DNA extracted from enrichment samples showed that the majority of the shift in composition of the switchgrass-degrading community occurred during the initial three 2-week enrichments. Shifts in community structure upon storage occurred in all cryopreserved samples. Storage in liquid nitrogen in the absence of cryoprotectant resulted in variable preservation of dominant microorganisms in enriched samples. Cryopreservation with either DMSO or glycerol provided consistent and equivalent preservation of dominant organisms. A stable switchgrass-degrading microbial community was achieved after three 2-week enrichments. Dominant microorganisms were preserved equally well with DMSO and glycerol. DMSO-preserved communities required more incubation time upon revival to achieve pre-storage activity levels during high-solid thermophilic cultivation on switchgrass. Despite shifts in the community with storage, the samples were active upon revival under thermophilic and high-solid conditions. The results suggest that the presence of microorganisms may be more important than their relative abundance in retaining an active microbial community.


Botulinum toxin injection for postoperative diplopia testing in adult strabismus.
To investigate the use of botulinum toxin type A in identifying adult patients with constant strabismus who are at high risk of developing intractable diplopia after surgery. A retrospective review of adult patients with constant horizontal strabismus who had botulinum toxin injection to evaluate their risk of postoperative diplopia. These patients reported diplopia when prisms were used to neutralize the deviation. One hundred ninety-five adults were studied; their mean age was 40.3 +/- 14 years (range, 16 to 73 years). One hundred thirty-three (68%) had botulinum toxin injected into a lateral rectus muscle; 62 (32%) had injections in a medial rectus muscle. Only 14 (7%) developed diplopia; 9 (4.6%) of these had troublesome diplopia but 5 (2.6%) could cope with the double vision and elected to have surgery. Surgical correction was recommended to the remaining 181 (93%) who did not experience diplopia. Complications of botulinum toxin injection were ptosis (10 patients, 5.1%) and superior oblique muscle weakness (3 patients, 1.5%). Twenty-six patients (13.3%) had a poor response to the first injection and required a second injection with a double dose. Surgery did not result in intractable diplopia after 6 weeks in any patient with a negative botulinum toxin diplopia test. Botulinum toxin is a useful diagnostic tool for identifying patients with a low risk or no risk of postoperative diplopia despite a positive prism diplopia test.