Azithromycin reduces hemoglobin-induced innate neuroimmune activation.
Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to reduce innate immune activation in an in vitro model of microglial activation using the blood product hemoglobin (Hgb). We then utilized azithromycin in our in vivo model of IVH, using intraventricular blood injection into the lateral ventricle of post-natal day 5 rat pups. In both models, azithromycin modulated innate immune activation by several outcome measures including mitochondrial bioenergetic analysis, cytokine expression and flow cytometric analysis. This suggests that azithromycin, which is safe for neonates, could hold promise for modulating innate immune activation after IVH.


Lymphocyte ceruloplasmin and Behçet's disease.
Behçet's disease (BD) is a rare chronic inflammatory disorder of unknown aetiology. However, it has been postulated that a dysregulation of the prooxidant/antioxidant balance may be important to its pathogenesis. Ceruloplasmin (CP) is an acute phase protein expressed at the surface of peripheral blood lymphocytes (PBL) with antioxidant properties and with a relevant role in iron (Fe) metabolism. To study CP expression at the surface of PBL (PBLCP) in patients with BD. We measured serum CP and PBLCP obtained from BD patients (n=10) and respective controls (n=10) using nephelometry and flow cytometry techniques, respectively. Additionally, haematological parameters, biochemical Fe metabolism markers [serum Fe, serum ferritin, serum transferrin, total Fe binding capacity (TIBC), transferrin saturation] and non-specific markers of inflammation [serum C reactive protein (CRP), beta2-microglobulin] were measured in all individuals. Despite the absence of significant differences between the two study groups when comparing serum CP, a significant difference in PBLCP was found in BD patients mainly due to a significant decrease of CP expression at the surface of CD3-CD56+ lymphocytes. Also, a significant decrease of PBLCP was observed in patients treated with azathioprine compared to patients that were not being treated with this drug. According to this study, we suggest that the significant decrease of PBLCP observed in BD patients might be due to azathioprine treatment and not directly related to the pathophysiology of BD.


PFAS Electroanalysis in Low-Oxygen River Water Using Electrogenerated Dioxygen.
Per- and polyfluoroalkyl substances (PFAS), nicknamed "forever chemicals" due to the strength of their carbon-fluorine bonds, are a class of potent micropollutants that cause deleterious health effects in mammals. The current state-of-the-art detection method requires the collection and transport of water samples to a centralized facility where chromatography and mass spectrometry are performed for the separation, identification, and quantification of PFAS. However, for efficient remediation efforts to be properly informed, a more rapid in-field testing method is required. We previously demonstrated the development and use of dioxygen as the mediator molecule. The use of dioxygen is predicated on the assumption that there will be consistent ambient dioxygen levels in natural waters. This is not always the case in hypoxic groundwater and at high altitudes. To overcome this challenge and further advance the strategies that will enable in-field electroanalysis of PFAS, we demonstrate, as a proof of concept, that dioxygen can be generated in solution through the hydrolysis of water. The electrogenerated dioxygen can then be used as a mediator molecule for the indirect detection of PFOS via molecularly imprinted polymer (MIP)-based electroanalysis. We demonstrate that calibration curves can be constructed with high precision and sensitivity (LOD < 1 ppt or 1 ng/L). Our results provide a foundation for enabling in-field hypoxic PFAS electroanalysis.


Development and evaluation of RT-qPCR assays for two neglected orthobunyaviruses: Oya virus and Ebinur Lake virus.
Oya virus (OYAV) and Ebinur lake virus (EBIV) belong to the genus Orthobunyavirus within the Peribunyaviridae family, and both are recognized as the novel virus with potential threat to the animal or public health. Given their potential to cause outbreaks and their detection in diverse samples across different regions, the need for a reliable and efficient molecular detection method for OYAV and EBIV becomes imperative. The S-segment of OYAV and EBIV was used for designing specific primer and probe sets, which were employed in a real-time reverse transcription quantitative PCR (RT-qPCR) assay. The analytical performance of these assays, encompassing specificity, sensitivity, reproducibility, and fitness for purpose, was thoroughly evaluated across various sample matrices. The developed RT-qPCR assays were very specific to their respective targets. Both assays were highly reproducible (%CV<3) and sensitive with the 95% limit of detection (LOD) of 0.80 PFU/mL for OYAV primer probe set and 0.37 PFU/mL for EBIV primer probe set. Furthermore, the assays fitness for purpose was good as it could detect the specific viruses in virus-spiked serum samples, virus-inoculated mosquito samples, field caught mosquitoes and biting midge samples. Our study has successfully developed specific, sensitive, and reliable RT-qPCR assays for the detection of OYAV and EBIV. These assays hold great promise for their potential application in clinical and field samples in the future.


Mass invariance of population nitrogen flux by terrestrial mammalian herbivores: an extension of the energetic equivalence rule.
According to the energetic equivalence rule, energy use by a population is independent of average adult body mass. Energy use can be equated with carbon flux, and it has been suggested that population fluxes of other materials, such as nitrogen and phosphorus, might also be independent of body mass. We compiled data on individual nitrogen deposition rates (via faeces and urine) and average population densities of 26 species of mammalian herbivores to test the hypothesis of elemental equivalence for nitrogen. We found that the mass scaling of individual nitrogen flux was opposite to that of population density for the species in our dataset. By computing the product of individual nitrogen flux and average population density for each species in our dataset, we found that population-level nitrogen flux was independent of species mass, averaging c. 3.22 g N ha(-1) day(-1). Results from this analysis can be used to understand the influence of mammalian herbivore communities on nitrogen cycling in terrestrial ecosystems.


Pathways of methanol conversion in a thermophilic anaerobic (55 degrees C) sludge consortium.
The pathway of methanol conversion by a thermophilic anaerobic consortium was elucidated by recording the fate of carbon in the presence and absence of bicarbonate and specific inhibitors. Results indicated that about 50% of methanol was directly converted to methane by the methylotrophic methanogens and 50% via the intermediates H(2)/CO(2) and acetate. The deprivation of inorganic carbon species [Sigma(HCO(3)(-)+CO(2))] in a phosphate-buffered system reduced the rate of methanol conversion. This suggests that bicarbonate is required as an electron (H(2)) sink and as a co-substrate for the efficient and complete removal of the chemical oxygen demand. Nuclear magnetic resonance spectroscopy was used to investigate the route of methanol conversion to acetate in bicarbonate-sufficient and bicarbonate-depleted environments. The proportions of [1,2-(13)C]acetate, [1-(13)C]acetate and [2-(13)C]acetate were determined. Methanol was preferentially incorporated into the methyl group of acetate, whereas HCO(3)(-) was the preferred source of the carboxyl group. A small amount of the added H(13)CO(3)(-) was reduced to form the methyl group of acetate and a small amount of the added (13)CH(3)OH was oxidised and found in the carboxyl group of acetate when (13)CH(3)OH was converted. The recovery of [(13)C]carboxyl groups in acetate from (13)CH(3)OH was enhanced in bicarbonate-deprived medium. The small amount of label incorporated in the carboxyl group of acetate when (13)CH(3)OH was converted in the presence of bromoethanesulfonic acid indicates that methanol can be oxidised to CO(2 )prior to acetate formation. These results indicate that methanol is converted through a common pathway (acetyl-CoA), being on the one hand reduced to the methyl group of acetate and on the other hand oxidised to CO(2), with CO(2) being incorporated into the carboxyl group of acetate.


Open Source Antibiotics: Simple Diarylimidazoles Are Potent against Methicillin-Resistant Staphylococcus aureus.
Antimicrobial resistance (AMR) is widely acknowledged as one of the most serious public health threats facing the world, yet the private sector finds it challenging to generate much-needed medicines. As an alternative discovery approach, a small array of diarylimidazoles was screened against the ESKAPE pathogens, and the results were made publicly available through the Open Source Antibiotics (OSA) consortium (https://github.com/opensourceantibiotics). Of the 18 compounds tested (at 32 μg/mL), 15 showed >90% growth inhibition activity against methicillin-resistant Staphylococcus aureus (MRSA) alone. In the subsequent hit-to-lead optimization of this chemotype, 147 new heterocyclic compounds containing the diarylimidazole and other core motifs were synthesized and tested against MRSA, and their structure-activity relationships were identified. While potent, these compounds have moderate to high intrinsic clearance and some associated toxicity. The best overall balance of parameters was found with OSA_975, a compound with good potency, good solubility, and reduced intrinsic clearance in rat hepatocytes. We have progressed toward the knowledge of the molecular target of these phenotypically active compounds, with proteomic techniques suggesting TGFBR1 is potentially involved in the mechanism of action. Further development of these compounds toward antimicrobial medicines is available to anyone under the licensing terms of the project.


The Bright Fluorescent Protein mNeonGreen Facilitates Protein Expression Analysis In Vivo.
The Green Fluorescent Protein (GFP) has been tremendously useful in investigating cell architecture, protein localization, and protein function. Recent developments in transgenesis and genome editing methods now enable working with fewer transgene copies and, consequently, with physiological expression levels. However, lower signal intensity might become a limiting factor. The recently developed mNeonGreen protein is a brighter alternative to GFP in vitro The goal of the present study was to determine how mNeonGreen performs in vivo in Caenorhabditis elegans-a model used extensively for fluorescence imaging in intact animals. We started with a side-by-side comparison between cytoplasmic forms of mNeonGreen and GFP expressed in the intestine, and in different neurons, of adult animals. While both proteins had similar photostability, mNeonGreen was systematically 3-5 times brighter than GFP. mNeonGreen was also used successfully to trace endogenous proteins, and label specific subcellular compartments such as the nucleus or the plasma membrane. To further demonstrate the utility of mNeonGreen, we tested transcriptional reporters for nine genes with unknown expression patterns. While mNeonGreen and GFP reporters gave overall similar expression patterns, low expression tissues were detected only with mNeonGreen. As a whole, our work establishes mNeonGreen as a brighter alternative to GFP for in vivo imaging in a multicellular organism. Furthermore, the present research illustrates the utility of mNeonGreen to tag proteins, mark subcellular regions, and describe new expression patterns, particularly in tissues with low expression.


Role of complexes formation between drugs and penetration enhancers in transdermal delivery.
The use of chemical penetration enhancers (CPE) is growing due to their ability to improve drug delivery through the skin. A possible mechanism of penetration enhancement could involve the complex formation between drug and components in the pharmaceutical formulation, thus altering the physicochemical properties of the active substance. Here, modelling studies indicate that hydrocarbon and oxygen-containing terpenes (penetration enhancers) could form complexes with drugs. Satisfactory correlations have been obtained between the predicted molecular properties of enhancers and their enhancement effects.


Regulation of glutamine synthetase activity in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 by the nitrogen source: effect of ammonium.
Glutamine synthetase activity from Synechocystis sp. strain PCC 6803 is regulated as a function of the nitrogen source available in the medium. Addition of 0.25 mM NH4Cl to nitrate-grown cells promotes a clear short-term inactivation of glutamine synthetase, whose enzyme activity decreases to 5 to 10% of the initial value in 25 min. The intracellular levels of glutamine, determined under various conditions, taken together with the results obtained with azaserine (an inhibitor of transamidases), rule out the possibility that glutamine per se is responsible for glutamine synthetase inactivation. Nitrogen starvation attenuates the ammonium-mediated glutamine synthetase inactivation, indicating that glutamine synthetase regulation is modulated through the internal balance between carbon-nitrogen compounds and carbon compounds. The parallelism observed between the glutamine synthetase activity and the internal concentration of alpha-ketoglutarate suggests that this metabolite could play a role as a positive effector of glutamine synthetase activity in Synechocystis sp. Despite the similarities of this physiological system to that described for enterobacteria, the lack of in vivo 32P labeling of glutamine synthetase during the inactivation process excludes the existence of an adenylylation-deadenylylation system in this cyanobacterium.


Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma.
Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN blocks the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. We have used a mouse model for asthma to determine the effect of PI3K inhibitors and PTEN on allergen-induced bronchial inflammation and airway hyperresponsiveness. PI3K activity increased significantly after allergen challenge. PTEN protein expression and PTEN activity were decreased in OVA-induced asthma. Immunoreactive PTEN localized in epithelial layers around the bronchioles in control mice. However, this immunoreactive PTEN dramatically disappeared in allergen-induced asthmatic lungs. The increased IL-4, IL-5, and eosinophil cationic protein levels in bronchoalveolar lavage fluids after OVA inhalation were significantly reduced by the intratracheal administration of PI3K inhibitors or adenoviruses carrying PTEN cDNA (AdPTEN). Intratracheal administration of PI3K inhibitors or AdPTEN remarkably reduced bronchial inflammation and airway hyperresponsiveness. These findings indicate that PTEN may play a pivotal role in the pathogenesis of the asthma phenotype.


Ramifications of Heat Stress on Rabbit Production and Role of Nutraceuticals in Alleviating Its Negative Impacts: An Updated Review.
Heat stress has become a widespread concern worldwide, which is a major environmental stress that causes substantial economic loss in the rabbit industry. Compared to other agricultural animals, rabbits are more sensitive to heat stress as they have fewer sweat glands and a thicker coat of fur, increasing the heat dissipation complexity. Thus, heat stress hurts rabbits' productivity, meat quality, reproductive performance, antioxidative properties, immune responsiveness, intestinal histomorphology, and microbiome. Nutraceuticals include vitamins, minerals, antioxidants, organic acids, fatty acids, probiotics, prebiotics, synbiotics, enzymes, and medicinal plants due to the possible impacts on maintaining common biological situations, strengthening immune response, and preventing illness, which ultimately led to an increase in productivity. Nutraceuticals have recently attracted a lot of attention to alleviate the adverse impacts of heat stress in rabbit farms. The objective of the current review is to provide acquaintance with the recent findings about the impact of heat stress on rabbit productivity and the advantages of dietary supplementation of nutraceuticals in mitigating it.


Combined intravesical sodium hyaluronate/chondroitin sulfate therapy for interstitial cystitis/bladder pain syndrome: a prospective study.
The aim of this study was to verify the efficacy and safety of intravesical treatment combining sodium hyaluronate (HA) and chondroitin sulfate (CS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Between February 2010 and May 2011, 20 consecutive women with IC/BPS were treated with intravesical instillations containing sodium HA (1.6%; 800 mg/50 ml) and sodium CS (2%; 1 g/50 ml) weekly for the first month, biweekly for the second month, and then monthly for at least 3 months. Before and after treatment, all patients filled in the Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI), the Patient Health Questionnaire 9 and the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF). Treatment efficacy was assessed by comparing the pre- and post-treatment mean scores of the three questionnaires using Student's t test (p value <0.05 was considered significant). Statistically significant mean decreases in ICSI (from 13.0 to 9.3; p = 0.0003), ICPI (from 11.35 to 8.85; p = 0.0078) and PUF (from 20.0 to 15.75; p = 0.0007) questionnaire scores were seen. No cases of side effects or complications were observed. The mean follow up was 5 months. Despite the limitations of this study, the outcomes confirmed the role of combination therapy with HA and CS as a safe and effective option for the treatment of IC/BPS. Further randomized controlled studies with a higher number of patients and a longer follow-up period are needed to confirm these results.


Non-invasive characterization of the elastic protein resilin in insects using Raman spectroscopy.
Resilin is an extremely efficient elastic protein found in the moving parts of insects. Despite many years of resilin research, we are still only just starting to understand its diversity, native structures, and functions. Understanding differences in resilin structure and diversity could lead to the development of bioinspired elastic polymers, with broad applications in materials science. Here, to better understand resilin structure, we offer a novel methodology for identifying resilin-rich regions of the insect cuticle using non-invasive Raman spectroscopy in a model species, the desert locust (Schistocerca gregaria). The Raman spectrum of the resilin-rich semilunar process of the hind leg was compared with that of nearby low-resilin cuticle, and reference spectra and peaks assigned for these two regions. The main peaks of resilin include two bands associated with tyrosine at 955-962 and 1141-1203 cm-1 and a strong peak at 1615 cm-1, attributed to the α-Amide I group associated with dityrosine. We also found the chitin skeletal modes at ~485-567 cm-1 to be significant contributors to spectra variance between the groups. Raman spectra were also compared to results obtained by fluorescence spectroscopy, as a control technique. Principal component analysis of these resulting spectra revealed differences in the light-scattering properties of resilin-rich and resilin-poor cuticular regions, which may relate to differences in native protein structure and relative abundance.


[Surgical treatment of cataract].
Today, the most frequently performed of all operative interventions is considered to be surgery for cataract. Modern surgical techniques applied under local anesthesia, tiny incisions that close spontaneously, reliable biometric methods, and the availability of artificial lenses, all combine to produce excellent results. In view of the low complication rate, this procedure can be recommended even in very old patients.


Ecology and functional roles of biological soil crusts in semi-arid ecosystems of Spain.
Biological soil crusts (BSCs), composed of lichens, cyanobacteria, mosses, liverworts and microorganisms, are key biotic components of arid and semi-arid ecosystems worldwide. Despite they are widespread in Spain, these organisms have been historically understudied in this country. This trend is beginning to change as a recent wave of research has been identifying BSCs as a model ecological system. Many studies and research projects carried out in Spain have explored the role of BSCs on water, carbon and nitrogen fluxes, the interactions between BSCs and vascular plants, their dynamics after disturbances, and their response to global change, among other topics. In this article we review the growing body of research on BSCs available from semi-arid areas of Spain, highlighting its importance for increasing our knowledge on this group of organisms. We also discuss how it is breaking new ground in emerging research areas on the ecology of BSCs, and how it can be use to guide management and restoration efforts. Finally, we provide directions for future research on the ecology of BSCs in Spain and abroad.


Atrioesophageal Fistula Rates Before and After Adoption of Active Esophageal Cooling During Atrial Fibrillation Ablation.
Active esophageal cooling reduces the incidence of endoscopically identified severe esophageal lesions during radiofrequency (RF) catheter ablation of the left atrium for the treatment of atrial fibrillation. A formal analysis of the atrioesophageal fistula (AEF) rate with active esophageal cooling has not previously been performed. The authors aimed to compare AEF rates before and after the adoption of active esophageal cooling. This institutional review board (IRB)-approved study was a prospective analysis of retrospective data, designed before collecting and analyzing the real-world data. The number of AEFs occurring in equivalent time frames before and after adoption of cooling using a dedicated esophageal cooling device (ensoETM, Attune Medical) were quantified across 25 prespecified hospital systems. AEF rates were then compared using generalized estimating equations robust to cluster correlation. A total of 14,224 patients received active esophageal cooling during RF ablation across the 25 hospital systems, which included a total of 30 separate hospitals. In the time frames before adoption of active cooling, a total of 10,962 patients received primarily luminal esophageal temperature (LET) monitoring during their RF ablations. In the preadoption cohort, a total of 16 AEFs occurred, for an AEF rate of 0.146%, in line with other published estimates for procedures using LET monitoring. In the postadoption cohort, no AEFs were found in the prespecified sites, yielding an AEF rate of 0% (P < 0.0001). Adoption of active esophageal cooling during RF ablation of the left atrium for the treatment of atrial fibrillation was associated with a significant reduction in AEF rate.


Religion, Sexual Orientation, and Suicide Attempts Among a Sample of Suicidal Adolescents.
Despite condemnation of same-sex attraction by certain religious groups, few studies have explored the relationship between religion, same-sex attraction, and suicidality. This study examined the moderating effect of same-sex attraction on the relationship between parent/adolescent religiosity and suicide ideation/attempts in a suicidal adolescent sample (N = 129). Linear and negative binomial regressions tested the effects of a two-way dichotomous (same-sex attraction, yes/no) by continuous (religiosity) interaction on ideation and attempts, respectively. The interaction was not significant for ideation. However, high religiosity was associated with more attempts in youth reporting same-sex attraction but fewer attempts in those reporting opposite-sex attraction only.


Clinical information systems in the academic medical center.
Introducing new clinical information systems at an academic medical center presents unique challenges related to: Academic infrastructure. Diversity. Communication. The purpose of this article is to describe these special challenges and strategies used at the University of Michigan Medical Center (UMMC) in response. After numerous discussions with colleagues at other academic institutions, we believe that these challenges are remarkably similar at many if not most academic medical centers across the country.


Biocompatible, hyperbranched nanocarriers for the transport and release of copper ions.
Core-shell and core-multishell nanocarriers were designed to transport copper ions into cells. Herein, we present their synthesis and physicochemical characterization and demonstrate the high influence of their architectures on the loading and release of copper. Their low toxicity may open a new way to balance the Cu-homeostasis in neurodegenerative diseases.


Stepwise Dosing Protocol for Increased Throughput in Label-Free Impedance-Based GPCR Assays.
Label-free impedance-based assays are increasingly used to non-invasively study ligand-induced GPCR activation in cell culture experiments. The approach provides real-time cell monitoring with a device-dependent time resolution down to several tens of milliseconds and it is highly automated. However, when sample numbers get high (e.g., dose-response studies for various different ligands), the cost for the disposable electrode arrays as well as the available time resolution for sequential well-by-well recordings may become limiting. Therefore, we here present a serial agonist addition protocol which has the potential to significantly increase the output of label-free GPCR assays. Using the serial agonist addition protocol, a GPCR agonist is added sequentially in increasing concentrations to a single cell layer while continuously monitoring the sample's impedance (agonist mode). With this serial approach, it is now possible to establish a full dose-response curve for a GPCR agonist from just one single cell layer. The serial agonist addition protocol is applicable to different GPCR coupling types, Gq Gi/0 or Gs and it is compatible with recombinant and endogenous expression levels of the receptor under study. Receptor blocking by GPCR antagonists is assessable as well (antagonist mode).


Chromatin accessibility profiling by ATAC-seq.
The assay for transposase-accessible chromatin using sequencing (ATAC-seq) provides a simple and scalable way to detect the unique chromatin landscape associated with a cell type and how it may be altered by perturbation or disease. ATAC-seq requires a relatively small number of input cells and does not require a priori knowledge of the epigenetic marks or transcription factors governing the dynamics of the system. Here we describe an updated and optimized protocol for ATAC-seq, called Omni-ATAC, that is applicable across a broad range of cell and tissue types. The ATAC-seq workflow has five main steps: sample preparation, transposition, library preparation, sequencing and data analysis. This protocol details the steps to generate and sequence ATAC-seq libraries, with recommendations for sample preparation and downstream bioinformatic analysis. ATAC-seq libraries for roughly 12 samples can be generated in 10 h by someone familiar with basic molecular biology, and downstream sequencing analysis can be implemented using benchmarked pipelines by someone with basic bioinformatics skills and with access to a high-performance computing environment.


Socioeconomic position and inflammatory and immune biomarkers of cardiovascular disease: applications to the Panel Study of Income Dynamics.
Biomarkers are an important aspect of research linking psychosocial stress and health. This article aims to characterize the biological pathways that may mediate the relationship between socioeconomic position (SEP) and cardiovascular disease (CVD) and address opportunities for further research within the Panel Study of Income Dynamics (PSID), with a focus on psychosocial stressors related to SEP. We review the literature on CVD biomarkers, including adhesion and proinflammatory molecules (interleukin-6, other cytokines, C-reactive proteins, fibrinogen, etc.) and microbial pathogens. The impact of socioeconomic determinants and related psychosocial stressors on CVD biomarkers mediated by behavioral and central nervous system pathways are described. We also address measurement and feasibility issues, including specimen collection methods, processing and storage procedures, laboratory error, and within-person variability. In conclusion, we suggest that PSID consider adding important assessments of specific CVD biomarkers and mediating behavioral measures, health, and medications that will ultimately address many of the gaps in the literature regarding the relationship between SEP and cardiovascular health.


Effect of ouabain on exogenous substrate oxidation by isolated cardiac myocytes.
Ouabain (10(-4) M) stimulated glucose oxidation and inhibited octanoate oxidation by isolated cardiac myocytes. Omission of potassium or calcium from the buffer abolished the ouabain stimulation of glucose oxidation. The inhibition of octanoate oxidation by ouabain persisted in the calcium deficient media.


Sourcing thermotolerant poly(ethylene terephthalate) hydrolase scaffolds from natural diversity.
Enzymatic deconstruction of poly(ethylene terephthalate) (PET) is under intense investigation, given the ability of hydrolase enzymes to depolymerize PET to its constituent monomers near the polymer glass transition temperature. To date, reported PET hydrolases have been sourced from a relatively narrow sequence space. Here, we identify additional PET-active biocatalysts from natural diversity by using bioinformatics and machine learning to mine 74 putative thermotolerant PET hydrolases. We successfully express, purify, and assay 51 enzymes from seven distinct phylogenetic groups; observing PET hydrolysis activity on amorphous PET film from 37 enzymes in reactions spanning pH from 4.5-9.0 and temperatures from 30-70 °C. We conduct PET hydrolysis time-course reactions with the best-performing enzymes, where we observe differences in substrate selectivity as function of PET morphology. We employed X-ray crystallography and AlphaFold to examine the enzyme architectures of all 74 candidates, revealing protein folds and accessory domains not previously associated with PET deconstruction. Overall, this study expands the number and diversity of thermotolerant scaffolds for enzymatic PET deconstruction.


Family pathology and father-daughter incest: restricted psychopathy.
Father-daughter incest can be found in dysfunctional families of many types. The concept of restricted psychopathy is discussed and examples of this concept in relation ot incest behavior are given. Three cases of father-daughter incest are presented. Ramifications of the concept of restricted psychopathy as it applies to father-daughter incest are discussed.


Estimating Insulin Sensitivity and Beta-Cell Function from the Oral Glucose Tolerance Test: Validation of a new Insulin Sensitivity and Secretion (ISS) Model.
Efficient and accurate methods to estimate insulin sensitivity (SI) and beta-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes. Many methods exist, ranging in input data and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic models (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new ISS (Insulin Secretion and Sensitivity) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. The model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. The model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including post-challenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts including individuals at high risk of prediabetes (adult women with a wide range of BMI and adolescents with obesity). The new model had strong correlation with gold-standard estimates from intravenous glucose tolerance tests and hyperinsulinemic-euglycemic clamp. The ISS model has broad clinical applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.


Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes.
Mild traumatic brain injury (mTBI) and postconcussion syndrome (PCS) are common among military combatants. Hyperbaric oxygen (HBO2 ) is a proposed treatment for these conditions, but it has not been rigorously studied. The objective of this study was to determine the effects of HBO2 by 3 months post compression at 2 commonly employed dosing levels to treat PCS; whether specific subgroups may have benefited; and if no overall effect was found, whether benefit is masked by other conditions. This randomized, double-blind, sham-controlled study was conducted at the Naval Air Station in Pensacola, Florida on 61 male Marines with a history of mTBI and PCS. Intervention consisted of 40 once daily 60-minute hyperbaric chamber compressions at 2.0 atmospheres absolute (ATA) at 1 of 3 randomly preassigned oxygen fractions, resulting in respective blinded groups with an oxygen-breathing exposure equivalent to (1) surface air (sham), (2) 100% oxygen at 1.5ATA, or (3) 100% oxygen at 2.0ATA. The main outcome measure was the Rivermead Post-Concussion Questionnaire-16 (RPQ-16) collected before compressions and at 2 later points. The interaction of time by intervention group was not significant for improvement on the RPQ-16. Nor was there evidence of efficacy on the RPQ-16 for any subgroup. No significant time by intervention interaction was found for any functional, cognitive, or psychomotor secondary outcome measure at an unadjusted 0.05 significance level. Using a randomized control trial design and analysis including a sham, results showed no evidence of efficacy by 3 months post-compression to treat the symptomatic, cognitive, or behavioral sequelae of PCS after combat-related mTBI.


Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer.
The short arm of chromosome 3 is thought to harbor a novel oncogenic locus that is important in the genesis of lung cancer. The region at 3p21 is believed to contain a distinct locus that is sensitive to loss from the action of tobacco smoke carcinogens and has been reported to be specifically targeted for deletion in lung cancer. To investigate whether 3p21 alteration in lung cancer is associated with carcinogen exposure, PCR-based analysis was performed to detect loss of heterozygosity (LOH) on chromosome 3 at 3p21 in non-small cell lung carcinoma (NSCLC). We also measured instability at the BAT-26 locus, because the mismatch DNA repair gene, hMLH1, is found at 3p21. LOH at 3p21 was analyzed for association with the clinical features of NSCLC, p53 mutation status, polynuclear aromatic hydrocarbon-DNA adduct levels (measured using 32P-postlabeling) and carcinogen exposure information including cigarette smoking and asbestos exposure. Of 219 lung cancers, 150 cases (68.5%) were informative at the D3S1478 locus, and 44.2% of squamous cell carcinoma cases and 30.2% of adenocarcinoma cases showed 3p21 LOH. None of the cancers showed BAT-26 instability. The prevalence of 3p21 LOH was higher in both current and former smokers compared with never smokers and was higher in p53 mutated cases. Among squamous cell carcinoma cases, there was a strong association of increased 3p21 LOH with increasing polynuclear aromatic hydrocarbon-DNA adducts levels (P = 0.03), as well as an increased prevalence LOH with earlier age of smoking initiation (P = 0.02). Our results confirm that 3p21 LOH is strongly associated with measures of biologically effective dose of exposure to tobacco carcinogens. Our results also suggest that alterations of hMLH1 are not related to any of the reported associations, because there was no evidence of microsatellite instability. Finally, LOH in 3p21 may be an early molecular event in NSCLC, because it is significantly associated with a tendency to start smoking at a young age.


Hemoglobin potentiates the production of reactive oxygen species by alveolar macrophages.
The objectives of this investigation were (1) to determine the effects of hemoglobin on the production of reactive oxygen species by activated rat alveolar macrophages, (2) to determine a possible mechanism for these effects, and (3) to determine which part of the hemoglobin molecule is responsible for these effects. Production of reactive oxygen species by phorbol myristate acetate (PMA)-stimulated cells was assessed by measuring luminol-enhanced chemiluminescence (CL). Hemoglobin enhances PMA-stimulated CL in a dose-dependent manner. The effect is maximal at 0.5-1.0 microM hemoglobin where PMA-induced CL is increased by approximately 20-fold. Superoxide anion release from PMA-stimulated cells is not affected by hemoglobin. However, the hemoglobin-induced enhancement of PMA-stimulated CL is inhibited by superoxide dismutase, catalase, dimethylthiourea, or deferoxamine. These results suggest that hydroxyl radical may be formed from hydrogen peroxide which is derived from superoxide anion. Measurements of electron spin resonance spectra following spin trapping of radicals verify that hydroxyl radicals are produced by the cells in the presence of PMA and hemoglobin. The hemoglobin effects appear to require iron in a protoporphyrin complex, because hemin stimulates PMA-induced CL, whereas neither ferrous nor ferric iron has any effect. These findings taken together suggest that hemoglobin can act as a biological Fenton reagent to enhance the production of reactive oxygen species from alveolar macrophages and potentially contribute to lung damage during leakage of blood into the alveolar spaces.


Mammalian nicotinic receptors with alpha7 subunits that slowly desensitize and rapidly recover from alpha-bungarotoxin blockade.
One of the most abundant nicotinic receptors in the nervous system is a species that contains the alpha7 gene product, rapidly desensitizes, and binds alpha-bungarotoxin with great affinity. The receptor has a high relative permeability to calcium and performs a variety of functions including presynaptic modulation of transmitter release and postsynaptic generation of synaptic currents. Fast excitatory transmission in mammalian intracardiac ganglia is mediated primarily by nicotinic receptors, and although intracardiac ganglion neurons express the alpha7 gene, no toxin-sensitive response has been detected previously in them. We report here that whole-cell patch-clamp recordings from freshly dissociated intracardiac ganglion neurons reveal a nicotinic response that desensitizes slowly and is blocked by alpha-bungarotoxin in a rapidly reversible manner. The only rat gene previously thought capable of forming such receptors was alpha9, but no evidence suggests that the alpha9 gene is expressed in neurons. We find that reverse transcription (RT)-PCR detects alpha7 but not alpha9 mRNA in the ganglia. In addition, the pharmacology of the nicotinic response is typical of alpha7-containing receptors but differs in several respects from that expected for alpha9. Binding experiments with immunotethered receptors identifies a ganglionic species that contains the alpha7 gene product. Moreover, intracellular perfusion of the cells with an anti-alpha7 monoclonal antibody specifically reduces the amplitude of the toxin-sensitive response. The results indicate that alpha7-containing receptors are responsible for the slowly desensitizing, toxin-reversible response and suggest that the receptors are modified in cell-specific ways to influence their functional properties.


Work-up and management of lone atrial fibrillation: results of the European Heart Rhythm Association Survey.
The purpose of this European Heart Rhythm Association (EHRA) survey was to explore the work-up and management of lone atrial fibrillation (AF) among the European centres. Thirty-two European centres, all members of the EHRA electrophysiology (EP) research network, responded to this survey and completed the list of questions. The prevalence of lone AF has been reported to be ≤10% by 19 (60%) of the participating centres. The presence of isolated left atrial enlargement and left ventricular diastolic dysfunction represent heart disease according to 50 and 84% of the centres, respectively, and exclude the diagnosis of lone AF. Fifty-nine per cent of responders do not routinely consider genetic testing in lone AF patients. The initial therapeutic approach in symptomatic paroxysmal lone AF is antiarrhythmic drug therapy as reported by 31 (97%) of the centres. Pulmonary vein isolation only is the first ablation strategy for patients with symptomatic persistent lone AF at 27 (84%) of the responding centres. Assessment for sleep apnoea, obesity, and intensive sports activity in lone AF is performed at 27 (84%) centres. In conclusion, this EP Wire survey confirms that the term 'lone AF' is still used in daily practice. The work-up typically includes screening for known risk factors but not genetic testing. The preferred management of paroxysmal lone AF is rhythm control with antiarrhythmic drugs, whereas pulmonary vein isolation is the first ablation strategy for the majority of patients with symptomatic persistent lone AF.


Retrospective Analysis of Efficacy and Toxicity of Hypo-fractionated Radiotherapy in Breast Carcinoma.
The conventional dose fractionation of adjuvant radiotherapy (RT) to whole breast is 45-50 Gy in 25 fractions as 1.8-2.0-Gy per fraction. Lumpectomy cavity with a 1.5-2-cm margin receieves additional 10- 16 Gy doseas boost. Alternative dose fraction schedules used in various randomised trials have established the role of hypofractionated radiotherapy (HRT) in early breast cancer. HRT allows time and cost saving thus better patient compliance. However the efficacy and toxicity of HRT in locally advanced breast cancer is still under evaluation. To study the toxicity and efficacy of Hypofractionated Radiotherapy (HRT) as compared to Conventional Radiotherapy (CRT) in breast cancer at our centre. A retrospective analysis of breast cancer patients treated between October 2012- September 2014 with adjuvant radiation therapy as CRT or HRT. The data of these patients was retrieved and analysed regarding demographic profile, stage at presentation, pathological type, extent of surgery, chemotherapy, efficacy and toxicity of HRT. The toxicity assessment was done as per RTOG toxicity criteria. The data were analysed using SPSS software version 20.0. A total of 100 patients with carcinoma breast who received radiotherapy over two years were analysed. Age ranged from 18-90 years, mean 49.15 ± 12.7 years. Fifty-five patients were post-menopausal, predominant clinical feature was painless lump in the breast (98%). Early stage (Stage I and II) constituted 41%, locally advanced disease in 59%. Modified radical mastectomy was done in 75%, breast conserving surgery in 25%. A 56 patients received HRT and 44 were treated with CRT. The most common acute toxicity was skin grade I. An 18% patients in HRT arm and 30% patients in conventional arm developed grade II skin toxicity (p=0.23). Dysphagia grade I was seen in 10% cases in CRT arm and 12% in HRT arm. The median follow-up period was 11.3 months with 2 loco-regional failures in each arm. HRT seems to be equally efficacious and no more toxic than CRT in carcinoma breast even in unselected sub-group of patients.


Course of psychotic symptoms, depression and global functioning in persons at clinical high risk of psychosis: Results of a longitudinal observation study over three years focusing on both converters and non-converters.
The aim of this study was to test the validity of the CHR state by focusing on the course of psychosis spectrum symptoms, depression and global functioning in converters and non-converters. A total of 188 CHR-positive subjects (60.2% men) aged between 13 and 35years (mean=20.5) at study outset were assessed five times (t0-t4) over a total observation period of 36months. Conversion to manifest psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). Measures of positive and negative symptoms were assessed with the Structured Interview for Prodromal Syndromes (SIPS), depression with the Calgary Depression Scale (CDS), and global functioning with the Global Assessment of Functioning Scale (GAF). Converters scored higher over time on all SIPS scales apart from grandiosity (Cohen's d: 0.5-0.7; all p<0.001), higher on the CDS (d=0.43, p=0.001) and lower on the GAF (d=0.69, p<0.001) than did non-converters. Positive and negative symptoms as well as depression were most severe at study outset (t0) and then declined sharply following a linear function over the three-year observation period (t1-t4) across groups (all linear contrasts p<0.001). In conclusion, converters showed significantly more psychopathological symptoms and poorer functioning before crossing the diagnostic threshold for manifest psychosis. CHR-subjects who convert to manifest psychosis during follow-up appear to be recovering from illness rather than becoming ill. Major issues involve the poor discrimination of CHR state and psychosis as well as the dichotomous definition of both at-risk and disease states. Further examination in other CHR-samples is warranted.


Experimental investigation of anti-colliding pulse mode-locked semiconductor lasers.
We experimentally demonstrate anti-colliding pulse mode-locking (ACPML) in an integrated semiconductor laser. The device geometry consists of a gain section and a saturable absorber (SA) section located immediately next to one of the cavity facets. After depositing a low-reflection coating on the SA facet and a high-reflection coating on the gain section facet, the threshold is unchanged, while the modulation of the SA is increased. The data presented here confirm that the ACPML configuration improves the peak output power of the pulses, reduces the amplitude fluctuation and timing jitter, and expands the biasing parameter range over which the stable mode-locking operation occurs.


Public policy: effective treatment for tobacco disease.
Public policy initiatives offer greater promise than other strategies for reducing the major public health problem of death and disease due to smoking. Three of the most critical public policy areas today are smoke-free environments, youth access, and advertising. While earlier laws separated smokers and nonsmokers into separate sections, the focus now is on smoke-free environments. Various places, however, most notably restaurants, often remain polluted with tobacco smoke and put women at heightened risk of disease and death. Restricting youth access to tobacco products has also gained momentum in the 1990s. The recently proposed Food and Drug Administration regulations designed to reduce smoking by minors by 50% over seven years are the most significant national public policy initiatives ever to address the problem of children smoking. Measures to counter the tobacco industry's massive advertising and promotion campaigns have also increased. The federal government has begun enforcing the prohibition on cigarette advertising on television, and local jurisdictions have restricted tobacco billboards and point-of-sale advertising.


Gastric antral vascular ectasia and solitary rectal ulcer syndrome - two rare diagnoses as the cause of anemia in a single patient: case report.
Gastric antral vascular ectasia (GAVE) and solitary rectal ulcer syndrome (SRUS) are both mentioned in the literature as rare causes of iron deficiency anemia and gastrointestinal (GI) bleeding. GAVE accounts for up to 4 % of upper non-variceal GI bleeding; SRUS is a rare benign disorder that presents with rectal bleeding. We present the case of a 75-year-old patient who was admitted to our facility with anemia. In the same patient, we encountered chronic bleeding from GAVE and SRUS. Both diagnoses were treated endoscopically: GAVE by argon plasma coagulation and a subsequent treatment with proton pump inhibitors and SRUS by adrenaline injection and clipping, consecutively treated with mesalazine enemas. The patient was successfully cured, resulting in a stable level of hemoglobin and no recurrent GI bleeding. We report a unique case of chronic GI bleeding caused by two uncommon diagnoses. The co-occurrence of GAVE and SRUS has not been previously described or published.Key words: anemia - endoscopy - gastric antral vascular ectasia (GAVE) - gastrointestinal bleeding - solitary rectal ulcer syndrome (SRUS).


Endplate channel block by guanidine derivatives.
The effects of the n-alkyl derivatives of guanidine on the frog neuromuscular junction were studied using the two-microelectrode voltage clamp and other electrophysiological techniques. Methyl-, ethyl-, and propylguanidine stimulated the nerve-evoked release of transmitter. However, amyl-and octylguanidine had no apparent presynaptic action. All of the derivatives blocked the postsynaptic response to acetylcholine, the potency sequence being octyl-greater than amyl-greater than propyl-, methyl-greater than ethylguanidine. Methyl- and octylguanidine did not protect the receptor from alpha-bungarotoxin block, suggesting that these compounds do not bind to the receptor but probably block the ionic channel. Methyl-, ethyl-, and propylguanidine shortened inward endplate currents but prolonged outward currents. Amylguanidine prolonged both inward and outward endplate currents, and the currents became biphasic at negative membrane potentials. Octylguanidine increased the rate of decay of endplate currents at all potentials. All of the derivatives blocked inward endplate currents more markedly than outward currents, resulting in a highly nonlinear current-voltage relation. Methyl-, ethyl-, and propylguanidine reversed the voltage dependence of endplate current decay, while amyl-and octylguanidine reduced the voltage dependence of endplate current decay. Octylguanidine appears to block the ionic channel in both the open and the closed state. The block of the open channel follows pseudo-first-order kinetics with a forward rate constant of 4-6 X 10(7) M-1 s-1.


Recent Advances and Controversial Issues in the Optimal Management of Asymptomatic Carotid Stenosis.
The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of AsxCS patients. A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis", "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS) and "transcarotid artery revascularization" (TCAR). Areas covered included: i) improvements in best medical treatment (BMT) for AsxCS patients and declining stroke risk, ii) technological advances in surgical/endovascular skills/techniques and outcomes, iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and, iv) the association between cognitive dysfunction and AsxCS. BMT is essential for all AsxCS patients, regardless of whether they will eventually be offered CEA/CAS/TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These include patients with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound, silent infarcts on brain CTA/MRA scans, reduced cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration and intraplaque hemorrhage. Treatment of AsxCS patients should be individualized, taking into consideration individual patient preferences/needs, clinical/imaging characteristics, and cultural/ethnic/social factors. Solid evidence supporting/refuting an association between AsxCS and cognitive dysfunction is lacking. The optimal management of AsxCS patients should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA/CAS/TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs/preference, clinical/imaging characteristics, social/cultural factors and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression/reversal of cognitive dysfunction.


Acid-activated Sodium Bentonite and Kaolin Clay: Comparative Study by Physicochemical Properties.
This paper aims to reveal the useful industrial aspects of kandite and montmorillonite group of clays using as a catalyst after acid activation. A comparative study of modified characteristics of clay samples has been explored based on industrial requirements. In this study sodium bentonite and kaolin clay have been focused. The modified characteristics of clay samples are investigated by characterization methods of FT-IR, XRD, SEM/EDAX, TGA and DSC before and after treated with 4M of Hydrochloric acid. Clay samples were refluxed at 105ºC and calcined at 500ºC consecutively for 3 hours at room temperature. Maximum crystalline size 104.02 nm has been evaluated for acid-activated sodium bentonite. Alkyl halides compounds have a strong band position for all samples and have more extent on acid activation. The small numbers of manganese particles have been noticed in the acidactivated samples. 14% of decrement and 61.02% of increment of aluminates have been found respectively for acid-activated kaolin and acid-activated sodium bentonite. The novelty of this study is about sodium bentonite characterization and the results show the prominent behaviour with structural, elemental, morphological, and thermal analysis. Acid-activated kaolin sample has less effect in comparison with acid-activated sodium bentonite. As the removal of the hydroxyl group of compounds has been reported through FT-IR and XRD analysis also some other industries like ceramic and paper industries may have accepted these types of modified minerals for special production with a simple process.


Forecasting The Impact of the 2023 Current Procedural Terminology Coding Changes On Ventral Hernia Work Relative Value Units. A Cross-Sectional Study.
In January 2023, significant changes were implemented to ventral hernia repair Current Procedural Terminology codes, with new codes replacing previous codes. The new codes were assigned a 0-day global period. The impact of these changes on clinical productivity remains unclear. Our objective was to forecast the impact of Current Procedural Terminology changes on ventral hernia-related work relative value units using historical data. Ventral hernia repairs performed between March 2021 and December 2022 on adults by a single surgeon with available 90-day follow-up were retrospectively retrieved from the Abdominal Core Health Quality Collaborative. Demographic, hernia, and operative and postoperative data were collected. The ventral hernia repairs were coded twice using the previous and new Current Procedural Terminology codes, and work relative value units were calculated using both systems. The median work relative value units per case were compared using the Wilcoxon signed-rank test. A total of 143 ventral hernia repairs were included. The median age was 59 years, and 50% of patients were male. Median hernia width and length were 3.5 and 5.0 cm, respectively. The most common ventral hernia types were incisional 57% and umbilical 33%. Twenty percent of hernias were recurrent, and 99% were elective repairs. 49% of the procedures were open, 30% robotic, and 21% laparoscopic. Component separation was performed in 16%. The median length of stay was 0.0, and the median number of 90-day outpatient postoperative visits was 1.0. The new Current Procedural Terminology coding system was associated with a higher median 90-day work relative value units per case (14.1) than the previous system (13.8) (P = .002). Subset analysis identified statistically higher median 90-day work relative value units per case using the new versus previous Current Procedural Terminology codes for hernias with the largest defect dimension >10 cm (23.3 vs 18.8), umbilical/epigastric/Spigelian hernias (9.2 vs 7.1), recurrent hernias (20.1 vs 17.3) and open ventral hernia repairs (9.8 vs 7.1), all P < .05. Median 90-day work relative value units per case were statistically lower using the new versus previous codes for non-recurrent (11.6 vs 13.8) and incarcerated/strangulated (14.8 vs 14.9) hernias, all P < .05. In the new coding system, postoperative care within 90-days contributed to a median of 1.3 work relative value units per case (9% of total 90-day work relative value units). We forecast that in our practice, the 2023 ventral hernia repair Current Procedural Terminology changes will result in a modest impact on clinical productivity. The impact of these changes on a particular practice depends on surgical practice patterns and ventral hernia case mix.


Kaposi's sarcoma: clinico-pathological analysis of human immunodeficiency virus (HIV) and non-HIV associated cases.
Kaposi s sarcoma (KS) is a angioformative lesion that classically occurs in elderly Eastern European and Mediterranean males but is also common in immunosuppressed individuals particularly human immunodeficiency virus (HIV)-infected patients. This study investigates the clinical and histopathological features of 47 patients with Kaposi s sarcoma from a teaching hospital in Sydney, Australia, in which 44 cases had adequate clinical follow-up information over a 10-year period. Most of the lesions were of late stage (37/47 cases; 79%), consisting of 11 cases of plaque stage KS and 26 cases of nodular stage KS with only 10 cases of early or patch stage KS. The majority of the HIV-positive cases (23/33; 70%) and all of the HIV-negative (14/14; 100%) cases had late stage lesions (p=0.020; X 2 -test). The histopathological features that were more common in the KS lesions of HIV-negative patients were lesional cell mitosis (p=0.0002), single cell necrosis (p=0.001), apoptosis (p=0.0001) and single cell anaplasia (p=0.0001). The KS lesions in HIV-positive patients tended to have dissecting blood vessels (14/33 cases; 42%) unlike those seen in HIV-negative patients (0/14 cases; 0%) (p=0.004). Most HIV-positive cases (30/33; 90%) were males (p=0.0068); and all these patients (33/33 cases; 100%) were <60 years old, in contrast to HIV-negative patients (1/11 cases; 9%) (p=0.0001). HIV status does not affect the occurrence of multiplicity of KS lesions. However, extracutaneous or visceral KS lesions were more likely to occur in HIV-positive patients (p=0.027). The number of cases of histologically proven KS cases has decreased markedly over the recent 5 year period of 1995-1999 (n=14), which was less than half of the number of the preceding 5 year period, 1990-1994 (n=33). In summary, there are distinct differences in the clinical and histopathological features of Kaposi s sarcoma lesions in HIV-positive and HIV-negative patients. Despite the recent discovery of the HHV8 virus as the initiating and promoting factor of most of the KS lesions, these differences indicated that there might be different mechanisms that occur in HIV-positive and HIV-negative patients in the development of this lesion.


Multimodal assessment of sensorimotor shoulder function in patients with untreated anterior shoulder instability and asymptomatic handball players.
Functional evaluation of sensorimotor function of the shoulder joint is important for guidance of sports-specific training, prevention and rehabilitation of shoulder instability. Such assessment should be multimodal and comprise all qualities of sensorimotor shoulder function. This study evaluates feasibility of such multimodal assessment of glenohumeral sensorimotor function in patients with shoulder instability and handball players. Nine patients with untreated anterior instability of their dominant shoulder and 15 asymptomatic recreational handball players performed proprioceptive joint position sense and dynamic stabilization evaluations on an isokinetic device, as well as a functional throwing performance task. Outcome measures were analysed individually and equally weighted in a Shoulder-Specific Sensorimotor Index (S-SMI). Finally, isokinetic strength evaluations were conducted. We observed comparable sensorimotor functions of unstable dominant shoulders compared to healthy, contralateral shoulders (e.g. P=0.59 for S-SMI). Handball players demonstrated superior sensorimotor function of their dominant shoulders exhibiting a significantly higher throwing performance and S-SMI (P<0.001 and P=0.002, respectively), but comparable internal rotator peak torques for both shoulders (P>0.22). The present study proves feasibility of multimodal assessment of shoulder sensorimotor function in overhead athletes and patients with symptomatic anterior shoulder instability. Untreated shoulder instability led to a loss of dominance-related sensorimotor superiority indicating functional internal rotation deficiency. Dominant shoulders of handball players showed a superior overall sensorimotor function but weakness of dominant internal rotation constituting a risk factor for occurrence of posterior superior impingement syndrome. The S-SMI could serve as a diagnostic tool for guidance of sports-specific training, prevention and rehabilitation of shoulder instability.


Isolation and Characterisation of the Bundooravirus Genus and Phylogenetic Investigation of the Salasmaviridae Bacteriophages.
Bacillus is a highly diverse genus containing over 200 species that can be problematic in both industrial and medical settings. This is mainly attributed to Bacillus sp. being intrinsically resistant to an array of antimicrobial compounds, hence alternative treatment options are needed. In this study, two bacteriophages, PumA1 and PumA2 were isolated and characterized. Genome nucleotide analysis identified the two phages as novel at the DNA sequence level but contained proteins similar to phi29 and other related phages. Whole genome phylogenetic investigation of 34 phi29-like phages resulted in the formation of seven clusters that aligned with recent ICTV classifications. PumA1 and PumA2 share high genetic mosaicism and form a genus with another phage named WhyPhy, more recently isolated from the United States of America. The three phages within this cluster are the only candidates to infect B. pumilus. Sequence analysis of B. pumilus phage resistant mutants revealed that PumA1 and PumA2 require polymerized and peptidoglycan bound wall teichoic acid (WTA) for their infection. Bacteriophage classification is continuously evolving with the increasing phages' sequences in public databases. Understanding phage evolution by utilizing a combination of phylogenetic approaches provides invaluable information as phages become legitimate alternatives in both human health and industrial processes.


Droplet breakup in subsurface oil releases--part 1: experimental study of droplet breakup and effectiveness of dispersant injection.
Size distribution of oil droplets formed in deep water oil and gas blowouts have strong impact on the fate of the oil in the environment. However, very limited data on droplet distributions from subsurface releases exist. The objective of this study has been to establish a laboratory facility to study droplet size versus release conditions (rates and nozzle diameters), oil properties and injection of dispersants (injection techniques and dispersant types). This paper presents this facility (6 m high, 3 m wide, containing 40 m(3) of sea water) and introductory data. Injection of dispersant lowers the interfacial tension between oil and water and cause a significant reduction in droplet size. Most of this data show a good fit to existing Weber scaling equations. Some interesting deviations due to dispersant treatment are further analyzed and used to develop modified algorithms for predicting droplet sizes in a second paper (Johansen et al., 2013).


The impact of different warm-up protocols on vertical jump performance in male collegiate athletes.
The purpose of this study was to compare the impact of different types of warm-up on countermovement vertical jump (VJ) performance. Sixty-four male Division I collegiate football players completed a pretest for VJ height. The participants were then randomly assigned to a warm-up only condition, a warm-up plus static stretching condition, a warm-up plus dynamic stretching condition, or a warm-up plus dynamic flexibility condition. VJ performance was tested immediately after the completion of the warm-up. The results showed that there was a significant difference (P < .05) in VJ performance between the warm-up groups. Posttest jump performance improved in all groups; however, the mean for the static stretching group was significantly lower than the means for the other 3 groups. The static stretching negated the benefits gained from a general warm-up when performed immediately before a VJ test.


Clinical applications for topical 5-fluorouracil in the treatment of dermatological disorders.
Topical 5-fluorouracil (5-FU) has been used for the treatment of dermatological conditions for nearly half a century. Although the indications for 5-FU approved by the US Food and Drug Administration include actinic keratosis and superficial basal cell carcinoma, studies also have demonstrated therapeutic efficacy for 5-FU in the treatment of many other dermatological conditions, including squamous cell carcinoma in situ, warts, psoriasis of the nail, keratoacanthoma, and vitiligo. This review discusses clinical data which support the use of 5-FU for these disease states.


Biodistribution of liposomes of terbutaline sulfate in guinea pigs.
A series of liposomes was prepared with various lipid (egg phosphatidyl choline [egg PC], phosphatidyl glycerol [PG], dipalmitoyl phosphatidyl choline [DPPC], distearoyl phosphatidyl choline [DSPC], dipalmitoyl phosphatidyl glycerol [DPPG], phosphatidyl ethanolamine [PE], cholesterol [CH], and stearylamine [SA]) compositions, such as egg PC:PG:CH (55:5:40), DPPC:PG:CH (55:5:40), DSPC:DSPG:CH (55:5:40) egg PC:SA:CH (55:5:40), DSPE:DSPG:CH (55:5:40) in molar ratio. Liposomal formulations were administered to guinea pigs intravenously; 3 hr after the treatment, serum samples and various organs (e.g., liver, spleen, lung) were removed and analyzed for drug concentration by a high-performance liquid chromatographic (HPLC) method. Based on the above study, a liposomal preparation with better lung specificity was selected, and the time profile of these liposomes was determined in guinea pigs. Three hours postadministration, a significant difference in blood levels was observed between free terbutaline sulfate and the various liposomal formulations. Localization of the drug in the lungs increased considerably when encapsulated drug was used, and the highest percentage localization was observed with DSPC:DSPG:CH (55:5:40) liposomes. The percentage recovery of the drug in the lungs with egg PC:CH:SA (55:40:5) liposomes did not change significantly when compared with egg PC:CH:PG (55:40:5) liposomes. To establish the time course of disposition of the liposomes, DSPC:DSPG:CH (55:5:40) liposomes were selected. Terminal half-life t1/2 of the drug in blood with free drug solution was about 12 hr, whereas with liposomes, a twofold increase in t1/2 was observed. The disposition data indicated that the clearance of the drug was delayed by 1.5 times when incorporated into liposomes.


Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition.
3-β-hydroxysteroid-Δ8, Δ7-isomerase, known as Emopamil-Binding Protein (EBP), is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis, autophagy, oligodendrocyte formation. The mutation on EBP can cause Conradi-Hunermann syndrome, an inborn error. Interestingly, EBP binds an abundance of structurally diverse pharmacologically active compounds, causing drug resistance. Here, we report two crystal structures of human EBP, one in complex with the anti-breast cancer drug tamoxifen and the other in complex with the cholesterol biosynthesis inhibitor U18666A. EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands. The compounds exploit their positively-charged amine group to mimic the carbocationic sterol intermediate. Mutagenesis studies on specific residues abolish the isomerase activity and decrease the multidrug binding capacity. This work reveals the catalytic mechanism of EBP-mediated isomerization in cholesterol biosynthesis and how this protein may act as a multi-drug binder.


Hermite-cosine-Gaussian laser beam and its propagation characteristics in turbulent atmosphere.
Hermite-cosine-Gaussian (HcosG) laser beams are studied. The source plane intensity of the HcosG beam is introduced and its dependence on the source parameters is examined. By application of the Fresnel diffraction integral, the average receiver intensity of HcosG beam is formulated for the case of propagation in turbulent atmosphere. The average receiver intensity is seen to reduce appropriately to various special cases. When traveling in turbulence, the HcosG beam initially experiences the merging of neighboring beam lobes, and then a TEM-type cosh-Gaussian beam is formed, temporarily leading to a plain cosh-Gaussian beam. Eventually a pure Gaussian beam results. The numerical evaluation of the normalized beam size along the propagation axis at selected mode indices indicates that relative spreading of higher-order HcosG beam modes is less than that of the lower-order counterparts. Consequently, it is possible at some propagation distances to capture more power by using higher-mode-indexed HcosG beams.


The ras suppressor, RSU-1, enhances nerve growth factor-induced differentiation of PC12 cells and induces p21CIP expression.
The Rsu-1 Ras suppressor gene was isolated based on its ability to inhibit v-Ras transformation. Using Rsu-1 transfectants of the pheochromocytoma cell line PC12, we demonstrated previously that Rsu-1 expression inhibited Jun kinase activation but enhanced Erk2 activation in response to epidermal growth factor. In the present study, the Rsu-1 PC12 transfectants were used to investigate the role of Rsu-1 in nerve growth factor (NGF)- and v-Ki-ras-mediated neuronal differentiation. NGF-induced neurite extension was enhanced, not inhibited, by the expression of Rsu-1 in PC12 cells. The activation of Erk kinase activity in response to NGF was sustained longer in the Rsu-1 transfectants compared with the vector control cells. During NGF-mediated differentiation, an increase in the expression of specific mRNAs for the early response genes Fos, cJun, and NGF1a was detected in both the vector control and Rsu-1 transfectants. The expression of the differentiation-specific genes VGF8 and SCG10 was similar in Rsu-1 transfectants compared with the vector control cells. The induction of Rsu-1 expression in these cell lines did not inhibit v-Ki-ras-induced differentiation, as measured by neurite extension. These data suggest that although Rsu-1 blocked some Ras-dependent response(s), these responses were not required for differentiation. Moreover, the induction of Rsu-1 expression in the PC12 clones resulted in growth inhibition and p21(WAF/CIP) expression. Hence, Rsu-1 expression enhances NGF-induced differentiation while inhibiting the growth of cells.


Bayesian selection of nucleotide substitution models and their site assignments.
Probabilistic inference of a phylogenetic tree from molecular sequence data is predicated on a substitution model describing the relative rates of change between character states along the tree for each site in the multiple sequence alignment. Commonly, one assumes that the substitution model is homogeneous across sites within large partitions of the alignment, assigns these partitions a priori, and then fixes their underlying substitution model to the best-fitting model from a hierarchy of named models. Here, we introduce an automatic model selection and model averaging approach within a Bayesian framework that simultaneously estimates the number of partitions, the assignment of sites to partitions, the substitution model for each partition, and the uncertainty in these selections. This new approach is implemented as an add-on to the BEAST 2 software platform. We find that this approach dramatically improves the fit of the nucleotide substitution model compared with existing approaches, and we show, using a number of example data sets, that as many as nine partitions are required to explain the heterogeneity in nucleotide substitution process across sites in a single gene analysis. In some instances, this improved modeling of the substitution process can have a measurable effect on downstream inference, including the estimated phylogeny, relative divergence times, and effective population size histories.


An evaluation of nursing care in cancer patients.
The aim of the present study was to identify what hospitalized cancer patients expect from nurses in terms of the care they receive. The specific aims of this study were: (i) to identify those individuals to whom the patients felt closest in the hospital setting and (ii) to evaluate nurses' management of cancer patients during their stay in the hospital. The sample included patients hospitalized at Ege University Hospital and Suat Seren District Hospital, Izmir, Turkey. We found significant differences between the scores of satisfaction and dissatisfaction and gender age, education, occupation, type of cancer and the mode of treatment (p < 0.05). The majority of the cancer patients reported that nursing management was unsatisfactory. Some demographic factors such as cultural and social status affected patients' expectations.


Analysis of T-wave Amplitude Adaptation to Heart Rate Using RR-binning of Long-Term ECG Recordings.
The prognosis of patients with coronary artery disease at the early stage of the disease is a challenge of modern cardiology. There is an urgent need to risk stratify these patients. Holter technology is a cheap and cost effective tool to evaluate electrical abnormalities in the heart. We propose to investigate T-amplitude adaptation to heart rate (HR) using RR-binning. We used daytime recordings from healthy subjects and subjects with acute myocardial infarction (AMI) from the Telemetric and Holter ECG Warehouse. The AMI subjects were divided into two groups based on location of their infarction (group A: anterior or anterior lateral, group B: inferior or inferior lateral). Both AMI groups had acute and stable phase recordings. Population-based T-adaptation to HR was observed for healthy subjects (R2 = 0.92) but was less pronounced for AMI subjects: [Formula: see text].


Monitoring of human herpesviruses-6 and -7 DNA in saliva samples during the acute and convalescent phases of exanthem subitum.
The amounts of the DNAs of human herpesviruses-6 (HHV-6) and -7 (HHV-7) in saliva samples were monitored during the acute and convalescent phases of exanthem subitum (ES) to elucidate the kinetics of virus shedding after ES. A total of 247 saliva samples were collected from 17 children (5 males and 12 females: 8-31 months old at onset). The monitoring period ranged from 152 to 721 days after onset, and in 15 children it was longer than 1 year. Among the 17 cases, 16 were attributed to HHV-6B, while a single case was attributed to HHV-7. Detection rates and average amounts of HHV-6 DNA in saliva samples after ES attributed to HHV-6B were low in the acute phase, increased to the maximum in the convalescent phase at 3-7 months, and then decreased. In addition, to investigate the source of infection, saliva samples from the older siblings (age 3-9 years) and parents of ES patients and children with a history of ES were also examined. The detection rate of HHV-6 DNA in saliva samples from 3- to 9-year-old children was significantly higher than the rate in adult saliva samples. Taken together, these findings suggest that the saliva of children in the convalescent phase of ES might be a more likely source of HHV-6 infection than that of adults. J. Med. Virol. 89:696-702, 2017. © 2016 Wiley Periodicals, Inc.


Burden of common multiple-morbidity constellations on out-of-pocket medical expenditures among older adults.
On average, adults aged 60 years or older have 2.2 chronic diseases, contributing to the over 60 million Americans with multiple morbidities. We aimed to understand the financial implications of the most frequent multiple morbidities among older adults. We analyzed Health and Retirement Study data, determining out-of-pocket medical expenses from 1998 and 2002 separately and examining differences in the impact of multiple-morbidity constellations on these expenses. We paid particular attention to the most common disease constellations - hypertension, arthritis, and heart disease. An increasing prevalence of multiple morbidity (58% compared with 70% of adults had two or more chronic conditions in 1998 and 2002, respectively) was accompanied by escalating out-of-pocket expenditures (2,164 dollars in 1998, increasing by 104% to 3,748 dollars in 2002). Individuals with two, three, and four chronic conditions had health care expenditure increases of 41%, 85%, and 100%, respectively, over 4 years. Such patterns were particularly noticeable among the oldest old, those with higher educational attainment, and women, although having supplementary health insurance or Medicaid mitigated these expenses. Finally, there were significant differences in out-of-pocket expenditure levels among the multiple-morbidity combinations. Increasing rates of multiple morbidities in conjunction with escalating health care costs and stable or declining incomes among elders warrant creative attention from providers, researchers, and policy makers. Further understanding how specific multiple-morbidity constellations impact out-of-pocket spending moves us closer to effective interventions to support vulnerable elders.


Speed-up of DNA melting algorithm with complete nearest neighbor properties.
We describe an optimized algorithm, which is faster and more accurate compared to previously described algorithms, for computing the statistical mechanics of denaturation of nucleic acid sequences according to the classical Poland-Scheraga type of model. Nearest neighbor thermodynamics has been included in a complete and general way, by rigorously treating nearest neighbor interactions, helix end interactions, and isolated base-pairs. This avoids the simplifications of previous approaches and achieves full generality and controllability with respect to thermodynamic modeling. The algorithm computes subchain partition functions by recursion, from which various quantitative aspects of the melting process are easily derived, for example the base-pairing probability profiles. The algorithm represents an optimization with respect to algorithmic complexity of the partition function algorithm of Yeramian et al. (Biopolymers 1990, 30, 481-497): we reduce the computation time for a base-pairing probability profile from O(N2) to O(N), where N is the sequence length. This speed-up comes in addition to the speed-up due to a multiexponential approximation of the loop entropy factor as introduced by Fixman and Freire22 and applied by Yeramian et al. The speed-up, however, is independent of the multiexponential approximation and reduces time from O(N3) to O(N2) in the exact case. A method for representing very large numbers is described, which avoids numerical overflow in the partition functions for genomic length sequences. In addition to calculating the standard base-pairing probability profiles, we propose to use the algorithm to calculate various other probabilities (loops, helices, tails) for a more direct view of the melting regions and their positions and sizes. This can provide a better understanding of the physics of denaturation and the biology of genomes.


The recovery of three-dimensional structure from image curves.
A class of inferences is described which allows the recovery of three-dimensional structures from the two-dimensional curves in an image. Unlike most previous methods, these inferences do not require restrictive assumptions or prior knowledge regarding the scene. They are based on the assumption that the camera viewpoint and the positions of the illumination sources are independent of the objects in the scene. From these independence assumptions, it can be shown that many potential interpretations of image curves are highly improbable. By eliminating these improbable interpretations it is possible to segment the image into sets of related image features and derive many three-space relations.


Galpha12 and Galpha13 regulate extracellular signal-regulated kinase and c-Jun kinase pathways by different mechanisms in COS-7 cells.
Many growth factors and agonists for G protein-coupled receptors activate mitogen-activated protein (MAP) kinase pathways, including the extracellular signal-regulated kinase (ERK) pathway and the c-Jun kinase (JNK) pathway. Transient transfection of dominant negative and constitutively active pathway components in COS-7 cells shows that two G protein subunits, Galpha12 and Galpha13, inhibit the ERK pathway and stimulate the JNK pathway. Constitutively active (GTPase-deficient) Galpha12 and Galpha13 both inhibit ERK pathway activation by epidermal growth factor. A Galpha13/alphaz chimera, which responds to stimulation by Gi-coupled receptors, mediates inhibition of ERK via such a receptor, the dopamine-2 receptor. In addition, expression of a dominant negative mutant of the GTPase, Cdc42, blocks activation of the JNK pathway by Galpha12 and Galpha13 but does not alter inhibition of ERK activation by the same Galpha proteins; conversely, mutationally activated Cdc42 stimulates the JNK pathway but has no effect on the ERK pathway. Our results show that different mechanisms mediate two effects of Galpha12 and Galpha13: the ERK pathway inhibition is mediated at the level of MAP kinase kinase in a Ras- and Raf-independent fashion, whereas the JNK pathway stimulation is mediated by Cdc42.


A pixel-resolution video switcher for eye-contingent display changes.
Moving-mask and moving-window paradigms are used to study the spatial and temporal aspects of visual information processing. Due to technical limitations, these paradigms have frequently been applied to reading, but only rarely to scene perception. Existing moving-mask or moving-window techniques for graphical stimuli usually blank the display inside or outside a square window, respectively. A new moving-window technique is presented here that uses a purpose-designed video switcher and three synchronized video boards. The first video board contains the stimulus presented inside the window. The second video board contains the stimulus to be presented outside the window. The third video board contains a black-and-white image of the window that is used as a key signal for the video switcher. The video switcher selects between the video signals of the first and the second video board on a pixel-by-pixel basis, controlled by the key signal generated by the third video board. By panning the image of the third video board, the window can be moved very rapidly. Here we use oval windows, centered on the fixation spot as measured by an eye-tracker. The normal stimulus is visible inside the window, whereas manipulated information is presented outside the window, or vice versa.


Sarcoids in two captive tapirs (Tapirus bairdii): clinical, pathological and molecular study.
This case report describes for the first time sarcoids in tapirs (Tapirus bairdii), namely, a 2-year-old male and a 3.6-year-old female born and housed at the same facility. The male presented with a 3-cm nodular, red, pedunculated, hairless, ulcerated mass on the inner surface of the left pinna. No recurrence or additional growths were present during the 3 years following surgical excision of the mass. The female presented with a similar 2-cm mass on the inner surface of the right pinna, which recurred 2 months following surgical excision, but was subsequently successfully treated locally with liquid nitrogen with no further recurrence during a 2-year follow-up period. Histologically, these two masses closely resembled equine sarcoids. Similarly, an association with bovine papillomavirus 1 was demonstrated using polymerase chain reaction and in situ hybridization.


The development of the MIBBO: A measure of resident preferences for physical activity in long term care settings.
Offering physical activities matching with the preferences of residents in long-term care facilities could increase compliance and contribute to client-centered care. A measure to investigate meaningful activities by using a photo-interview has been developed ("MIBBO"). In two pilot studies including 133 residents living on different wards in long-term care facilities, feasibility, most chosen activities, and consistency of preferences were investigated. It was possible to conduct the MIBBO on average in 30 min with the majority (86.4%) of residents. The most frequently chosen activities were: gymnastics and orchestra (each 28%), preparing a meal (31%), walking (outside, 33%), watering plants (38%), and feeding pets (40%). In a retest one week after the initial interview 69.4% agreement of chosen activities was seen. The MIBBO seems a promising measure to help health care professionals in identifying residents' preferred activities. Future research should focus on the implementation of the tailored activity plan, incorporating it into the daily routine.


Phototherapy in skeletal muscle performance and recovery after exercise: effect of combination of super-pulsed laser and light-emitting diodes.
Recent studies with phototherapy have shown positive results in enhancement of performance and improvement of recovery when applied before exercise. However, several factors still remain unknown such as therapeutic windows, optimal treatment parameters, and effects of combination of different light sources (laser and LEDs). The aim of this study was to evaluate the effects of phototherapy with the combination of different light sources on skeletal muscle performance and post-exercise recovery, and to establish the optimal energy dose. A randomized, double-blinded, placebo-controlled trial with participation of 40 male healthy untrained volunteers was performed. A single phototherapy intervention was performed immediately after pre-exercise (baseline) maximum voluntary contraction (MVC) with a cluster of 12 diodes (4 of 905 nm lasers-0.3125 mW each, 4 of 875 nm LEDs-17.5 mW each, and 4 of 670 nm LEDs-15 mW each- manufactured by Multi Radiance Medical™) and dose of 10, 30, and 50 J or placebo in six sites of quadriceps. MVC, delayed onset muscle soreness (DOMS), and creatine kinase (CK) activity were analyzed. Assessments were performed before, 1 min, 1, 24, 48, 72, and 96 h after eccentric exercise protocol employed to induce fatigue. Phototherapy increased (p < 0.05) MVC was compared to placebo from immediately after to 96 h after exercise with 10 or 30 J doses (better results with 30 J dose). DOMS was significantly decreased compared to placebo (p < 0.05) with 30 J dose from 24 to 96 h after exercise, and with 50 J dose from immediately after to 96 h after exercise. CK activity was significantly decreased (p < 0.05) compared to placebo with all phototherapy doses from 1 to 96 h after exercise (except for 50 J dose at 96 h). Pre-exercise phototherapy with combination of low-level laser and LEDs, mainly with 30 J dose, significantly increases performance, decreases DOMS, and improves biochemical marker related to skeletal muscle damage.


Relaxation versus exercise for improved quality of life in lymphoma survivors-a randomised controlled trial.
Lymphoma survivors experience persisting needs as a consequence of disease and treatment, which have an impact on quality of life (QoL). There is evidence supporting the use of relaxation and exercise to improve QoL, but there is no agreement on which is more beneficial. This study aims to compare a relaxation intervention versus an exercise intervention to determine which has a greater impact on QoL post-chemotherapy. Eligible participants (n = 46) were randomised to a relaxation or exercise intervention for 12 weeks. QoL was assessed at baseline, 6 weeks and post-intervention using the European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) questionnaire, which is a valid and reliable tool. The summary score and all EORTC domains were assessed. There was a significant difference in QoL post-intervention between groups (p = 0.029) while adjusting for baseline QoL, with the exercise group demonstrating a larger improvement. Within-group QoL significantly improved pre- to post-intervention in both the relaxation (p = 0.036) and exercise (p = 0.004) groups. A self-management intervention of either exercise or relaxation can help significantly improve QoL in lymphoma survivors following chemotherapy. While exercise is preferred, a relaxation intervention would also have a beneficial impact on QoL. Lymphoma survivors should be routinely screened and those with decreased QoL referred for an exercise programme, or relaxation for survivors who are unable to exercise or choose not to. A home-based programme can have a significant positive impact on QoL and is a feasible and effective method in the current climate. Clinical Trials ID NCT02272751.


Danggui Sini decoction for treating diabetic peripheral neuropathy: A protocol of systematic review and meta-analysis of randomized controlled trials.
Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetic patients, which seriously affects the quality of life of patients. At present, mainstream drugs have problems such as poor efficacy and side effects. Traditional Chinese medicine (TCM) has extensive clinical experience in the prevention and treatment of diabetes and chronic complications, and it also shows clear advantages in the treatment of DPN. Clinical studies have confirmed that Danggui Sini decoction (DSD), a TCM decoction, can improve the clinical symptoms and signs of DPN patients. Therefore, we will conduct a systematic review to clarify the effectiveness and safety of DSD for DPN. We will search every database from the built-in to October 2020. Chinese literature comes from CNKI, Wanfang, VIP, and CBM databases. English literature mainly searches Cochrane Library, PubMed, Web of Science, and EMBASE. At the same time, we will also search for clinical registration tests and gray literatures. This study only screened clinical randomized controlled trials (RCT) for DSD for DPN. The two researchers independently conducted literature selection, data extraction and quality assessment. Dichotomous data is represented by relative risk (RR), continuous data is represented by mean difference (MD) or standard mean deviation (SMD), and the final data is fixed effect model (FEM) or random effect model (REM), depending on whether it exists Heterogeneity. The main result is clinical efficacy and nerve conduction velocity. Fasting blood glucose, 2 hours postprandial blood glucose, blood lipid, hemorheology, and adverse events are secondary results. Finally, a meta-analysis was conducted through Review Manager software version 5.3. This study will conduct a comprehensive analysis based on the currently released DSD data for the treatment of DPN and provide high-quality evidence of clinical efficacy and safety. This systematic review aims to provide new options for DSD treatment of DPN in terms of its efficacy and safety. The review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines, or peer-reviewed journals. INPLASY202040157.


Characterizing and optimizing adsorption for olive mill wastewater processing in Loukkos, Morocco.
The present research consists of studying the characterization and treatment of the olive mill wastewater (OMWW) resulting from the olive industries of the region of Loukkos, Morocco. According to the national plan for green Morocco, the annual volumes of OMWW discharges increase with the expansion of the areas of olive plantations compared to agricultural activities. The study of the organic, mineral, and microbiological composition of the obtained OMWW showed that they are rich in microbiological (FMAT, Let M., and B.L.), mineral (total Kjeldhal nitrogen, orthophosphate, total phosphorus, sodium, potassium, calcium, copper, iron, zinc, manganese, and lead ions), and organic (COD, BOD5, and polyphenols) micropollutants with very high percentages that are higher than the standards in force. The treatment used in this study is the combined process of aerated lagooning/adsorption using powdered activated carbon after optimization of the experimental parameters (mass concentration of activated carbon (AC) and agitation rapidity (Ar)) by experiment design method. The obtained physicochemical parameters, such as pH, total suspended solids (TSS), chemical oxygen demand (COD), rate of discoloration, and polyphenol content of raw OMWW, were 4.87, 0.63, 80.3, 0.8, and 1.45 g/l, respectively. The results of these parameters for the treated OMWW were obtained in the order of 6.10, 0.22, 28, 0.28, and 0.44 g/l for pH, TSS, COD, discoloration rate, and polyphenol content, respectively. These results show that the proposed treatment significantly reduced acidity, TSS, COD, discoloration rate, and polyphenol contents, with a performance of about 25.26, 65, 65.13, 65, and 69.65%, respectively. This indicates that there is significant performance in the processing of exploited OMWW.


[Local anesthesia failure problems in conservative dental therapy clinic].
There were evaluated the prevalence of local anesthetic injection failure in therapeutic dentistry. 121 practitioners were interrogated using a special questionnaire. In the second stage of our study 447 teeth in caries and pulpitis patients were treated using articaine based local anesthesia. Results showed that anesthesia failure problem is still important. Prevalence of anesthesia failure differs depending on dental diagnosis and number of tooth. It is more for pulpitis in comparison with caries. The most difficult for achieving adequate anesthesia teeth are lower molars.


Miniature ultrasonic probes for diagnosis and treatment of digestive tract diseases.
To investigate the clinical value of miniature ultrasonic probes (MUPs) for the diagnosis and treatment of digestive tract diseases. Endoscopic ultrasonography (EUS) was performed for patients with its indications with 7.5-20 MHz MUPs and double-cavity electronic endoscope. According to the diagnosis of MUPs, patients who had indications of treatment received endoscopic resection or surgical excision. Postoperative histological results were compared with the preoperative diagnosis of MUPs. A few patients without endoscopic resection or surgical excision were periodically followed up with MUPs. A total of 537 patients were examined by MUPs, of them, 256 were diagnosed with gastrointestinal submucosal lesions, 146 with pseudo-submucosal lesions, 50 with digestive tract cancers, 17 with peptic ulcer, 11 with cholecystolithiasis, 8 with chronic pancreatitis, and 2 with achalasia and 47 were diagnosed as normal. After MUPs examinations, 220 patients received endoscopic resection or surgical excision, and the postoperative histological results of 211 patients were completely consistent with the preoperative diagnosis of MUPs. The diagnostic accuracy of MUPs was 95.9%. The result of follow-up with MUPs indicated that gastrointestinal leiomyoma, lipoma, phlebangioma and cyst were unchanged within 1-2 years. The patients who received endoscopic resection or centesis did not have any complications. MUPs are of value in diagnosing gastrointestinal submucosal lesions, staging of digestive tract cancers and biliary-pancreatic diseases. They play a very important role in making therapeutic plans.


High-resolution 3-T MRI of the fingers: review of anatomy and common tendon and ligament injuries.
OBJECTIVE. With high-resolution 3-T MRI, the complex anatomy of the fingers can be imaged in exquisite detail to provide an accurate diagnosis of clinically important ligament and tendon injuries. CONCLUSION. We present our 3-T MRI protocol using a dedicated hand-and-wrist coil and review normal MRI anatomy of the fingers. We emphasize a systematic approach to the interpretation of finger MRI examinations and illustrate this approach with examples of tendon and ligament abnormalities.