Interstudy reproducibility of dark blood high-resolution MRI in evaluating basilar atherosclerotic plaque at 3 Tesla.
We aimed to evaluate the interscan, intraobserver, and interobserver reproducibility of basilar atherosclerotic plaque employing dark blood high-resolution magnetic resonance imaging (HR-MRI) at 3 Tesla. Sixteen patients (14 males and 2 females) with > 30% basilar stenosis as identified by conventional magnetic resonance angiography were prospectively recruited for scan and rescan examinations on a 3 Tesla MRI system using T2-weighted turbo spin-echo protocol. Two observers independently measured the areas of vessels and lumens. Wall area was derived by subtracting the lumen area from the vessel area. Areas of vessels, lumens and walls were compared for the evaluation of interscan variability of basilar plaque. To assess the intraobserver variability, one observer reevaluated all the images of the first scan after a 4-week interval. Fourteen patients were included in the final analysis. No clinically significant difference was observed for interscan, intraobserver, and interobserver measurements. The intraclass correlations for vessel, lumen, and wall areas were excellent and ranged from 0.973 to 0.981 for the interscan measurements, 0.997 to 0.998 for the intraobserver measurements and 0.979 to 0.985 for the interobserver measurements. The coefficients of variation for quantitative basilar morphology measurements were 4.31%-10.35% for the interscan measurements, 1.41%-4.62% for the intraobserver measurements and 3.79%-8.46% for the interobserver measurements. Compared with the interscan and interobserver measurements, narrow intervals of the scatterplots were observed for the intraobserver measurements by Bland-Altman plots. Basilar atherosclerotic plaque imaging demonstrates excellent reproducibility at 3 Tesla. The study proves that dark blood HR-MRI may serve as a reliable tool for clinical studies focused on the progression and treatment response of basilar atherosclerosis.


Tuberculosis Diagnosis Delaying Treatment of Cancer: Experience From a New Oncology Unit in Blantyre, Malawi.
Malawi is a low-income country in sub-Saharan Africa with limited health care infrastructure and high prevalance of HIV and tuberculosis. This study aims to determine the characteristics of patients presenting to Queen Elizabeth Central Hospital Oncology Unit, Blantyre, Malawi, who had been treated for tuberculosis before they were diagnosed with cancer. Clinical data on all patients presenting to the oncology unit at Queen Elizabeth Central Hospital from 2010 to 2014 after a prior diagnosis of tuberculosis were prospectively recorded, and a descriptive analysis was undertaken. Thirty-four patients who had been treated for tuberculosis before being diagnosed with cancer were identified between 2010 and 2014, which represents approximately 1% of new referrals to the oncology unit. Forty-one percent of patients were HIV positive. Mean duration of tuberculosis treatment before presentation to the oncology unit was 3.6 months. The most common clinical presentation was a neck mass or generalized lymphadenopathy. Lymphoma was the most common malignancy that was subsequently diagnosed in 23 patients. Misdiagnosis of cancer as tuberculosis is a significant clinical problem in Malawi. This study underlines the importance of closely monitoring the response to tuberculosis treatment, being aware of the possibility of a cancer diagnosis, and seeking a biopsy early if cancer is suspected.


Nutrient starvation promotes condensin loading to maintain rDNA stability.
Nutrient starvation or rapamycin treatment, through inhibition of target of rapamycin, causes condensation of ribosomal DNA (rDNA) array and nucleolar contraction in budding yeast. Here we report that under such conditions, condensin is rapidly relocated into the nucleolus and loaded to rDNA tandem repeats, which is required for rDNA condensation. Rpd3-dependent histone deacetylation is necessary and sufficient for condensin's relocalization and loading to rDNA array, suggesting that histone modification plays a regulatory role for condensin targeting. Rapamycin independently, yet coordinately, inhibits rDNA transcription and promotes condensin loading to rDNA array. Unexpectedly, we found that inhibition of rDNA transcription in the absence of condensin loading leads to rDNA instability. Our data suggest that enrichment of condensin prevents rDNA instability during nutrient starvation. Together, these observations unravel a novel role for condensin in the maintenance of regional genomic stability.


Iodide sensing via electrochemical etching of ultrathin gold films.
Iodide is an essential element for humans and animals and insufficient intake is still a major problem. Affordable and accurate methods are required to quantify iodide concentrations in biological and environmental fluids. A simple and low cost sensing device is presented which is based on iodide induced electrochemical etching of ultrathin gold films. The sensitivity of resistance measurements to film thickness changes is increased by using films with a thickness smaller than the electron mean free path. The underlying mechanism is demonstrated by simultaneous cyclic voltammetry experiments and resistance change measurements in a buffer solution. Iodide sensing is conducted in buffer solutions as well as in lake water with limits of detection in the range of 1 μM (127 μg L(-1)) and 2 μM (254 μg L(-1)), respectively. In addition, nanoholes embedded in the thin films are tested for suitability of optical iodide sensing based on localized surface plasmon resonance.


Ultrasonography of the shoulder: asymptomatic findings from working-age women in the general population.
[Purpose] The aim of this study was to estimate the prevalence of abnormal shoulder ultrasonographic findings in a sample of asymptomatic women. [Subjects and Methods] A secondary analysis of a cross-sectional study was performed. We recruited 305 women (aged 18-56 years). All the subjects had a structured interview screening for self-reported symptoms and underwent a shoulder ultrasonographic examination, in which both shoulders were examined. The radiologist was blinded to the clinical history of the participants. All detectable shoulder abnormalities were collected. [Results] Of the subjects, 228 (74.75%) were asymptomatic at both shoulders, and 456 asymptomatic shoulders were analyzed. Lack of uniformity (supraspinatus, infraspinatus, subscapularis, and biceps brachii long head) was found in 28 shoulders (6.14%), 19 (4.17%) on the dominant side and 9 (1.97%) on the non-dominant side. Tendinosis (supraspinatus, infraspinatus, subscapularis, and biceps brachii long head) was found in 19 shoulders (5.32%), 12 (2.63%) on the dominant side and 7 (1.53%) on the non-dominant side. Calcification and other abnormal findings were reported. [Conclusion] The most common abnormalities were calcifications within the rotator-cuff tendons and humeral head geodes; other degenerative findings were less common.


Hepatic macrophage iron aggravates experimental alcoholic steatohepatitis.
One prime feature of alcoholic liver disease (ALD) is iron accumulation in hepatic macrophages/Kupffer cells (KC) associated with enhanced NF-kappaB activation. Our recent work demonstrates a peroxynitrite-mediated transient rise in intracellular labile iron (ILI) as novel signaling for endotoxin-induced IKK and NF-kappaB activation in rodent KC. The present study investigated the mechanism of KC iron accumulation and its effects on ILI response in experimental ALD. We also tested ILI response in human blood monocytes. Chronic alcohol feeding in rats results in increased expression of transferrin (Tf) receptor-1 and hemochromatosis gene (HFE), enhanced iron uptake, an increase in nonheme iron content, and accentuated ILI response for NF-kappaB activation in KC. Ex vivo treatment of these KC with an iron chelator abrogates the increment of iron content, ILI response, and NF-kappaB activation. The ILI response is evident in macrophages derived from human blood monocytes by PMA treatment but not in vehicle-treated monocytes, and this differentiation-associated phenomenon is essential for maximal TNF-alpha release. PMA-induced macrophages load iron dextran and enhance ILI response and TNF-alpha release. These effects are reproduced in KC selectively loaded in vivo with iron dextran in mice and more importantly aggravate experimental ALD. Our results suggest enhanced iron uptake as a mechanism of KC iron loading in ALD and demonstrate the ILI response as a function acquired by differentiated macrophages in humans and as a priming mechanism for ALD.


[Experimental vaginitis in rats].
The authors present an experimental model of vaginal inflammation in female rats, through local instillation of different substances causing inflammation of varying degrees. The inflammatory reaction was studied macroscopically, histologically and biochemically. Using polysiloxane as a protective substance of vaginal mucosa was found to be of therapeutic interest.


The ability of comorbidity indices to predict mortality in an orthopedic setting: a systematic review.
Several comorbidity indices have been created to estimate and adjust for the burden of comorbidity. The objective of this systematic review was to evaluate and compare the ability of different comorbidity indices to predict mortality in an orthopedic setting. A systematic search was conducted in Embase, MEDLINE, and Cochrane Library. The search were constructed around two primary focal points: a comorbidity index and orthopedics. The last search were performed on 13 June 2019. Eligibility criteria were participants with orthopedic conditions or who underwent an orthopedic procedure, a comparison between comorbidity indices that used administrative data, and reported mortality as outcome. Two independent reviewers screened the studies using Covidence. The area under the curve (AUC) was chosen as the primary effect estimate. Of the 5338 studies identified, 16 met the eligibility criteria. The predictive ability of the different comorbidity indices ranged from poor (AUC < 0.70) to excellent (AUC ≥ 0.90). The majority of the included studies compared the Elixhauser Comorbidity Index (ECI) and the Charlson Comorbidity Index (CCI). In-hospital mortality was reported in eight studies reporting AUC values ranging from 0.70 to 0.92 for ECI and 0.68 to 0.89 for CCI. AUC values were generally lower for all other time points ranging from 0.67 to 0.78. For 1-year mortality the overall effect size ranging from 0.67 to 0.77 for ECI and 0.69 to 0.77 for CCI. The results of this review indicate that the ECI and CCI can equally be used to adjust for comorbidities when analyzing mortality in an orthopedic setting. The protocol for this systematic review was registered on PROSPERO, the International Prospective Register of Systematic Reviews on 13 June 2019 and can be accessed through record ID 133,871.


In Vivo Crystallization of Three-Domain Cry Toxins.
Bacillus thuringiensis (Bt) is the most successful, environmentally-friendly, and intensively studied microbial insecticide. The major characteristic of Bt is the production of proteinaceous crystals containing toxins with specific activity against many pests including dipteran, lepidopteran, and coleopteran insects, as well as nematodes, protozoa, flukes, and mites. These crystals allow large quantities of the protein toxins to remain stable in the environment until ingested by a susceptible host. It has been previously established that 135 kDa Cry proteins have a crystallization domain at their C-terminal end. In the absence of this domain, Cry proteins often need helper proteins or other factors for crystallization. In this review, we classify the Cry proteins based on their requirements for crystallization.


Rapid and Visual Differentiation of Mycobacterium tuberculosis From the Mycobacterium tuberculosis Complex Using Multiplex Loop-Mediated Isothermal Amplification Coupled With a Nanoparticle-Based Lateral Flow Biosensor.
Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis (MTB), but other members of the Mycobacterium tuberculosis complex (MTBC), especially Mycobacterium bovis (pyrazinamide-resistant organisms), may also be involved. Thus, the ability to rapidly detect and identify MTB from other MTBC members (e.g., M. bovis, Mycobacterium microti, Mycobacterium africanum) is essential for the prevention and treatment of TB. A novel diagnostic method for the rapid detection and differentiation of MTB, which employs multiplex loop-mediated isothermal amplification (mLAMP) combined with a nanoparticle-based lateral flow biosensor (LFB), was established (mLAMP-LFB). Two sets of specific primers that target the IS6110 and mtp40 genes were designed according to the principle of LAMP. Various pathogens were used to optimize and evaluate the mLAMP-LFB assay. The optimal conditions for mLAMP-LFB were determined to be 66°C and 40 min, and the amplicons were directly verified by observing the test lines on the biosensor. The LAMP assay limit of detection (LoD) was 125 fg per vessel for the pure genomic DNA of MTB and 4.8 × 103 CFU/ml for the sputum samples, and the analytical specificity was 100%. In addition, the whole process, including the clinical specimen processing (35 min), isothermal amplification (40 min), and result confirmation (1-2 min), could be completed in approximately 80 min. Thus, mLAMP-LFB is a rapid, reliable, and sensitive method that is able to detect representative members of MTBC and simultaneously differentiate MTB from other MTBC members, and it can be used as a potential screening tool for TB in clinical, field, and basic laboratory settings.


Pulmonary preconditioning, injury, and inflammation modulate expression of the candidate tumor suppressor gene ECRG4 in lung.
The human c2orf40 gene encodes a candidate tumor suppressor called Esophageal Cancer-Related Gene-4 (ECRG4) that is a cytokine-like epigenetically-regulated protein that is characteristically downregulated in cancer, injury, inflammation, and infection. Here, we asked whether ECRG4 gene expression is detectable in lung epithelial cells and if its expression changes with inflammation, infection, and/or protective preconditioning. We used immunoblotting, PCR, and quantitative PCR to measure ECRG4 and either inhalation anesthesia preconditioning, lipopolysaccharide injection, or laparotomy to modulate lung inflammation. Immunoblotting establishes the presence of the full-length 14 kDa ECRG4 peptide in mouse lung. Immunohistochemistry localizes ECRG4 to type l alveolar epithelial cells. Basal ECRG4 mRNA is greater than TNF-α, IL-1β, and IL-6 but following inflammatory lung injury, TNF-α, IL-1β, IL-6, and IL-10 are upregulated while ECRG4 gene expression is decreased. Similar findings are observed after an intravenous administration of lipopolysaccharide. In contrast, lung preconditioning with isoflurane anesthesia increases lung ECRG4 gene expression. Over-expression of ECRG4 in human lung epithelial cells in vitro decreases cell proliferation implying that a loss of ECRG4 in vivo would be permissive to cell growth. This study supports the hypothesis that ECRG4 acts as a sentinel growth inhibitor in lung alveolar epithelial cells. Its downregulation by injury, infection, and inflammation and upregulation by preconditioning supports a role for ECRG4 in regulating the alveolar epithelium response to injury and inflammation. By extension, the findings support a functional consequence to its inhibition by promoter hypermethylation (i.e. lung cancer) and suggest potential benefits to its upregulation.


The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones.
The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms.


Effects of nutritional intervention strategies in the primary prevention of overweight and obesity in school settings: systematic review and network meta-analysis.
To examine the effects of different nutritional intervention strategies in the school setting on anthropometric and quality of diet outcomes by comparing and ranking outcomes in a network meta-analysis. Systematic review and network meta-analysis. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Education Resources Information Centre (ERIC), PsycInfo, CAB Abstracts, Campbell Library, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) BiblioMap, Australian Education Index, Joanna Briggs Institute Evidence-Based Practice (JBI EBP) database, Practice-based Evidence in Nutrition (PEN) database, ClinicalTrials.gov, Current Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. A systematic literature search was performed from inception to 2 May 2022. Cluster randomised controlled trials meeting these study criteria were included: generally healthy school students aged 4-18 years; intervention with ≥1 nutritional components in a school setting; and studies that assessed anthropometric measures (eg, body mass index, body fat) or measures related to the quality of diet (eg, intake of fruit and vegetables), or both. Random effects pairwise meta-analyses and network meta-analyses were performed with a frequentist approach. P scores, a frequentist analogue to surface under the cumulative ranking curve, ranging from 0 to 1 (indicating worst and best ranked interventions, respectively) were calculated. Risk of bias was assessed with Cochrane's RoB 2 tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was used to rate the certainty of evidence. 51 cluster randomised controlled trials involving 75 954 participants and seven intervention nodes were included. Inconsistency could not be assessed (except for intake of fruit and vegetables) because the network meta-analyses were based mainly on star shaped networks with no direct evidence for specific pairs of nutritional interventions. Overall, little or no evidence was found to support a difference in body mass index, body weight, body fat, or waist circumference and moderate improvements in intake of fruit and vegetables with nutritional interventions in a school setting. Low to moderate certainty of evidence further suggested that multicomponent nutritional interventions likely reduced the prevalence (odds ratio 0.66, 95% confidence interval 0.55 to 0.80) and incidence (0.67, 0.47 to 0.96) of overweight compared with a control group. Based on low certainty of evidence, nutrition education and multicomponent interventions may be more effective than a control group (ie, usual practice) for increasing intake of fruit and vegetables. Multicomponent nutritional interventions were ranked the most effective for reducing body mass index (P score 0.76) and intake of fat (0.82). Nutrition education was ranked as best for body mass index z score (0.99), intake of fruit and vegetables (0.82), intake of fruit (0.92), and intake of vegetables (0.88). The findings suggest that nutritional interventions in school settings may improve anthropometric and quality of diet measures, potentially contributing to the prevention of overweight and obesity in childhood and adolescence. The findings should be interpreted with caution because the certainty of evidence was often rated as low. The results of the network meta-analysis could be used by policy makers in developing and implementing effective, evidence based nutritional intervention strategies in the school setting. PROSPERO CRD42020220451.


Evolocumab, a PCSK9 inhibitor, protects human endothelial cells against H2O2-induced oxidative stress.
Recent surveys have shown an association between proprotein convertase subtilisin/kexin type 9 (PCSK9) and oxidative stress. In this investigation, the effect of evolocumab an anti-PCSK9 antibody was assessed against oxidative damage caused by hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVEC). Viability of HUVEC was measured by MTT assay. Hydroperoxides and malondialdehyde (MDA) levels, and ferric reducing antioxidant power (FRAP) were detected in HUVEC that pre-treated with evolocumab and, then exposed to H2O2. Evolocumab significantly prevented the cytotoxicity induced by H2O2 at the concentrations of 5-100 µg/ml. Pre-treatment of HUVEC with evolocumab reduced hydroperoxides and MDA levels and also increased FRAP value in intra- and extra-cellular mediums compared with H2O2 stimulated cells at different concentration ranges. This study displayed anti-oxidative and cytoprotective activities of evolocumab against oxidative damage caused by H2O2 in endothelial cells.


A constructive hybrid structure optimization methodology for radial basis probabilistic neural networks.
In this paper, a novel heuristic structure optimization methodology for radial basis probabilistic neural networks (RBPNNs) is proposed. First, a minimum volume covering hyperspheres (MVCH) algorithm is proposed to select the initial hidden-layer centers of the RBPNN, and then the recursive orthogonal least square algorithm (ROLSA) combined with the particle swarm optimization (PSO) algorithm is adopted to further optimize the initial structure of the RBPNN. The proposed algorithms are evaluated through eight benchmark classification problems and two real-world application problems, a plant species identification task involving 50 plant species and a palmprint recognition task. Experimental results show that our proposed algorithm is feasible and efficient for the structure optimization of the RBPNN. The RBPNN achieves higher recognition rates and better classification efficiency than multilayer perceptron networks (MLPNs) and radial basis function neural networks (RBFNNs) in both tasks. Moreover, the experimental results illustrated that the generalization performance of the optimized RBPNN in the plant species identification task was markedly better than that of the optimized RBFNN.


Promising hydrogen storage properties and potential applications of Mg-Al-Pd trilayer films under mild conditions.
We prepared a series of nano-sized Mg-Al-Pd trilayer films and investigated their hydrogen storage properties under mild conditions. Results showed that Al 1 nm sample had the best absorption kinetics and excellent optical properties at room temperature, making it a promising candidate for hydrogen sensors and smart windows.


Endostatin induces endothelial cell apoptosis.
Endostatin, a carboxyl-terminal fragment of collagen XVIII, has been shown to regress tumors in mice. In this study, we have analyzed the mechanism of endostatin action on endothelial cells and nonendothelial cells. Endostatin treatment of cow pulmonary artery endothelial cells caused apoptosis, as demonstrated by three methods, annexin V-fluorescein isothiocyanate staining, caspase 3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay. Moreover, addition of endostatin led to a marked reduction of the Bcl-2 and Bcl-XL anti-apoptotic protein, whereas Bax protein levels were unaffected. These effects were not seen in several nonendothelial cells. Collectively, these findings provide important mechanistic insight into endostatin action.


The injurious effect of neutrophils on pneumocytes in vitro.
Neutrophils have been implicated in the pathogenesis of pulmonary injury in many clinical entities, but in vitro studies of neutrophil-mediated pneumocyte damage are limited. To study the role of neutrophils in mediating pulmonary injury, we cocultured these cells with monolayers of human A549 pneumocytes and rat type II alveolar cells. As indexes of injury, we measured cell detachment from monolayers, frank cytolysis, and the effect on pneumocyte protein and DNA synthesis. Unstimulated neutrophils effected minimal lysis or detachment of both pneumocyte targets, but neutrophils stimulated with phorbal myristate acetate and other secretogogues produced marked target cell detachment without lysis, which was time- and dose-dependent. Supernatants of activated neutrophils were similarly effective, suggesting that the mediator was a stable, soluble substance. Catalase and superoxide dismutase were minimally inhibitory to neutrophil-mediated detachment, and neutrophils from patients with chronic granulomatous disease produced detachment comparable to that produced by normal neutrophils. Furthermore, target cells were quite resistant to reagent H2O2 and non-neutrophil-derived toxic oxygen species, further suggesting that oxidative injury was not a major factor in causing detachment. Target cells were susceptible to detachment by the neutral proteases, elastase and collagenase, whereas neutrophil-mediated detachment was markedly inhibited by neutral protease and elastase inhibitors. Human and bovine serum were also inhibitory, but not albumin or pepstatin A, an acid protease inhibitor. Furthermore, we found that activated neutrophils inhibited protein and DNA synthesis of pneumocyte targets, providing additional evidence that neutrophils cause nonlytic injury to pneumocytes. These studies indicate that stimulated neutrophils cause nonlethal injury to pneumocytes, as measured by detachment from monolayers, and inhibition of vital intracellular synthetic functions. The mechanism of detachment is through the action of granule neutral proteases, rather than toxic oxygen metabolites, and is probably due to degradation of the extracellular matrix of the pneumocytes. In vivo, detachment could lead to desquamation of alveolar cells and increased permeability of the epithelial barrier of the lung. Similarly, inhibition of protein and DNA synthesis could have profound effects on the normal function and replication of alveolar epithelium.


Carbamoyl phosphate compartmentation in Neurospora: histochemical localization of aspartate and ornithine transcarbamoylases.
Carbamoyl phosphate is required for arginine and pyrimidine synthesis. In the arginine pathway, it is used in the ornithine transcarbamoylase (EC 220.127.116.11) reaction; in the pyrimidine pathway, it is used in the aspartate transcarbamoylase (EC 126.96.36.199) reaction. In Neurospora crassa, two pathway-specific enzymes catalyze the synthesis of carbamoyl phosphate, and two path-specific pools of carbamoyl phosphate are maintained. Histochemical studies show that ornithine transcarbamoylase is located in mitochondria, and, with less certainty, that aspartate transcarbamoylase is confined largely to nuclei. The enzymes that form carbamoyl phosphate are associated with the respective transcarbamoylases in the cell. Therefore, the segregation of carbamoyl phosphate pools could be accounted for by one or both organellar membranes, which demarcate two separate sites of carbamoyl phosphate metabolism in Neurospora. The alternative possibility that the enzyme complex that produces and consumes carbamoyl phosphate in the pyrimidine pathway could explain the channelling of carbamoyl phosphate, wholly or in part, is discussed.


[Mineral metabolism and COVID-19: is there a connection?]
Due to global spread of COVID-19, the search for new factors that could influence its clinical course becomes highly important. This review summarize the relevant publications on the association between immune system and the main regulators of mineral homeostasis including. In addition, we have highlighted the various aspects of phosphorus-calcium metabolism related to the acute respiratory diseases and in particular to COVID-19. The data about the calcium-phosphorus metabolism in SARS-CoV-2 infection is required to understand the possible clinical implications and to develop new therapeutic and preventive interventions.


Catalysis-Induced Phase Separation and Autoregulation of Enzymatic Activity.
We present a thermodynamically consistent model describing the dynamics of a multicomponent mixture where one enzyme component catalyzes a reaction between other components. We find that the catalytic activity alone can induce phase separation for sufficiently active systems and large enzymes, without any equilibrium interactions between components. In the limit of fast reaction rates, binodal lines can be calculated using a mapping to an effective free energy. We also explain how this catalysis-induced phase separation can act to autoregulate the enzymatic activity, which points at the biological relevance of this phenomenon.


Helicobacter pylori infection: How does age influence the inflammatory pattern?
The inflammatory pattern during Helicobacter pylori (H. pylori) infection is changeable and complex. During childhood, it is possible to observe a predominantly regulatory response, evidenced by high concentrations of key cytokines for the maintenance of Treg responses such as TGF-β1 and IL-10, in addition to high expression of the transcription factor FOXP3. On the other hand, there is a predominance of cytokines associated with the Th1 and Th17 responses among H. pylori-positive adults. In the last few years, the participation of the Th17 response in the gastric inflammation against H. pylori infection has been highlighted due to the high levels of TGF-β1 and IL-17 found in this infectious scenario, and growing evidence has supported a close relationship between this immune response profile and unfavorable outcomes related to the infection. Moreover, this cytokine profile might play a pivotal role in the effectiveness of anti-H. pylori vaccines. It is evident that age is one of the main factors influencing the gastric inflammatory pattern during the infection with H. pylori, and understanding the immune response against the bacterium can assist in the development of alternative prophylactic and therapeutic strategies against the infection as well as in the comprehension of the pathogenesis of the outcomes related to that microorganism.


Pathogenesis of systemic air embolism during bronchoscopic Nd:YAG laser operations.
The occurrence of systemic air embolism during bronchoscopic neodymium:yttrium-aluminum garnet laser operations has been suspected. Here we describe its mechanism. Two patients with embolic cardiac and neurologic complications after bronchoscopic neodymium: yttrium-aluminum garnet laser tumor ablation are described. A subsequent third patient was monitored for intracardiac and aortic air by transesophageal echocardiography. A review of the literature and safety recommendations are discussed. The appearance of systemic air emboli was related to the use of the laser fiber air coolant at high flow and resolved by decreasing the air flow. The presence of intracardiac and aortic air was associated with hypotension and inferior ischemic electrocardiographic changes. Systemic air embolism during bronchoscopic laser operations is a potentially catastrophic complication and is related to the use of gas-cooled laser fibers and contact probes. We recommend using the noncontact mode whenever possible and maintaining the coaxial coolant air flow at the minimum level or using a fluid coolant if contact is necessary.


European Code against Cancer 4th Edition: Process of reviewing the scientific evidence and revising the recommendations.
The European Code Against Cancer is a set of recommendations to give advice on cancer prevention. Its 4th edition is an update of the 3rd edition, from 2003. Working Groups of independent experts from different fields of cancer prevention were appointed to review the recommendations, supported by a Literature Group to provide scientific and technical support in the assessment of the scientific evidence, through systematic reviews of the literature. Common procedures were developed to guide the experts in identifying, retrieving, assessing, interpreting and summarizing the scientific evidence in order to revise the recommendations. The Code strictly followed the concept of providing advice to European Union citizens based on the current best available science. The advice, if followed, would be expected to reduce cancer risk, referring both to avoiding or reducing exposure to carcinogenic agents or changing behaviour related to cancer risk and to participating in medical interventions able to avert specific cancers or their consequences. The information sources and procedures for the review of the scientific evidence are described here in detail. The 12 recommendations of the 4th edition of the European Code Against Cancer were ultimately approved by a Scientific Committee of leading European cancer and public health experts.


[Studies on the effects of low-dose selenium and high-dose cadmium on myocardial injury].
The effects of low-dose selenium and high-dose cadmium on myocardial injury were studied in weanling S.D. rats fed with feed containing controlled levels of selenium and cadmium. Results indicated low-dose selenium and high-dose cadmium could injure heart and myocardial cell membrane system to a certain extent, and cause focal necrosis and reduction in activities of glutathione peroxidase and cytochrome oxidase of heart muscle in rats. It suggested there were certain factors in the grain produced in the areas where Keshan disease was prevalent, which injured heart muscle in rats. So, selenium supplement could prevent from myocardial injury caused by the grain grown in those areas.


Differential Effects of Cod Proteins and Tuna Proteins on Serum and Liver Lipid Profiles in Rats Fed Non-Cholesterol- and Cholesterol-Containing Diets.
Fish muscles are classified into white and red muscles, and the chemical composition of the two fish muscles have many differences. Few reports have assessed the health-promoting functions of white fish muscle proteins (WFP) and red fish muscle proteins (RFP). We therefore evaluated the mechanisms underlying the alteration of lipid profiles and cholesterol metabolism following the intake of WFP prepared from cod and RFP prepared from light muscles of tuna. Male Wistar rats were divided into six dietary groups: casein (23%), WFP (23%), and RFP (23%), with or without 0.5% cholesterol and 0.1% sodium cholate. Compared to the WFP-containing diet, the RFP-containing diet supplemented with cholesterol and sodium cholate significantly increased serum and liver cholesterol contents. However, in the RFP groups, an alteration in cholesterol metabolism including an increased tendency to excrete fecal sterols and hepatic cholesterol 7α-hydroxylase was related to the reduction of hepatic cholesterol contents. This phenomenon might be related to the tendency of an increased food intake in RFP-containing diets. These results highlight the differential effects of WFP and RFP on serum and liver lipid profiles of Wistar rats fed non-cholesterol- or cholesterol-containing diets under no fasting condition.


Preliminary measurements of optical properties in human abscess cavities prior to methylene blue photodynamic therapy.
As part of our ongoing Phase 1 clinical trial to establish the safety and feasibility of methylene blue photodynamic therapy (MB-PDT) for human deep tissue abscess cavities, we have shown that determination of abscess wall optical properties is vital for the design of personalized treatment plans aiming to optimize light dose. To that end, we have developed and validated an optical spectroscopy system for the assessment of optical properties at the cavity wall, including a compact fiber-optic probe that can be inserted through the catheter used for the standard of care abscess drainage. Here we report preliminary findings from the first three human subjects to receive these optical spectroscopy measurements. We observed wide variability in concentrations of oxy- and deoxy-hemoglobin prior to MB administration, ranging from 7.3-213 μM and 0.1-47.2 μM, respectively. Reduced scattering coefficients also showed inter-patient variability, but recovered values were more similar between subjects (5.5-10.9 cm-1 at 665 nm). Further, methylene blue uptake was found to vary between subjects, and was associated with a reduction in oxygen saturation. These measured optical properties, along with pre-procedure computed tomography (CT) images, will be used with our previously developed Monte Carlo simulation framework to generate personalized treatment plans for individual patients, which could significantly improve the efficacy of MB-PDT while ensuring safety.


Cefaclor Monohydrate-Loaded Colon-Targeted Nanoparticles for Use in COVID-19 Dependent Coinfections and Intestinal Symptoms: Formulation, Characterization, Release Kinetics, and Antimicrobial Activity.
Corona virus disease-2019 (COVID-19) emerged in Wuhan, China in December 2019 and was declared as a pandemic by the World Health Organization in March 2020. Although there is no complete treatment protocol for COVID-19, studies on this topic are ongoing, and it is known that broad-spectrum antibiotics such as cephalosporins are used for coinfections and symptoms in COVID-19 patients. Studies have shown that Staphylococcus aureus and Escherichia coli bacteria can cause symptoms such as diarrhea and coinfections accompanying COVID-19. Therefore, in this study, colon-targeted cefaclor monohydrate (CEF)-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit S100 nanoparticles (NPs) were prepared using a nanoprecipitation technique. The particle sizes of the CEF-loaded NPs were between 171.4 and 198.8 nm. The encapsulation efficiency was in the range of 58.4%-81.2%. With dissolution studies, it has been concluded that formulations prepared with Eudragit S100 (E-coded) and Eudragit S100+PLGA (EP-coded) are pH-sensitive formulations and they are targetable to the colon, whereas the formulation prepared only with PLGA (P-coded) can release a higher CEF rate in the colon owing to the slow release properties of PLGA. The release kinetics were fitted to the Korsmeyer-Peppas and Weibull models. The antibacterial activity of E-, EP-, and P-coded formulations was 16-fold, 16-fold, and 2-fold higher than CEF, respectively, for S. aureus and E. coli according to the microdilution results. As a result of the time killing experiment, all formulations prepared were found to be more effective than the antibiotic itself for long periods. Consequently, all formulations prepared in this study hope to guide researchers/clinicians in treating both gram-positive and gram-negative bacteria-induced infections, as well as COVID-19 associated coinfections and symptoms.


Pornography Addiction: An Exploration of the Association Between Use, Perceived Addiction, Erectile Dysfunction, Premature (Early) Ejaculation, and Sexual Satisfaction in Males Aged 18-44 Years.
The way men consume pornography changed over the last decade, with increased numbers of men presenting with self-perceived Internet pornography (IP) addiction and related sexual dysfunction. A lack of consensus and formal recognition in the DSM-5 lead to a variety of definitions of IP addiction. Currently, the majority of evidence linking IP addiction and sexual dysfunction was derived from consumers, case studies, and qualitative research. Where empirical measures were used, researchers found mixed outcomes in sexual response. Inconclusive data appeared to relate to the conflation of IP use and self-perceived IP addiction, and normal variations in sexual response with clinical diagnosis of sexual dysfunction. Thus, further empirical clarification is required to assess the impact of both IP use and self-perceived IP addiction, on men's sexual function. This study has 3 aims: First, to assess if there is an association between IP use alone and erectile dysfunction (ED), premature (early) ejaculation (EE) and sexual satisfaction (SS); Second, to assess whether there is an association between self-perceived IP addiction and ED, EE and SS. Third, to assess whether IP use or self-perceived IP addiction uniquely predicts ED, EE, SS in men. Correlation and regression analysis was conducted on a cross-sectional sample of 942 heterosexual men aged 18-44 years who participated in an online survey sourced from Reddit IP subgroups. Cyber-Pornography Use Inventory; International Index Erectile Dysfunction; The Checklist for Early Ejaculation Symptoms; New Sexual Satisfaction Scale; Depression Anxiety Stress Scale-21. There was no evidence for an association between IP use with ED, EE, or SS. However, there were small to moderate positive correlations between self-perceived IP addiction and ED, EE and sexual dissatisfaction. Further, self-perceived IP addiction uniquely predicted increased ED, EE and individual sexual dissatisfaction. Contrary to expectations, self-perceived IP addiction did not predict sexual dissatisfaction with one's sexual partner. These results suggest that IP use alone does not predict sexual dysfunction. Rather, self-perception of increased IP addiction was related to negative sexual outcomes. Thus, we concluded that subjective interpretation of ones IP use was a contributor to IP related sexual problems in our sample of males who share IP on social media sites. We recommend that clinicians consider self-perceived IP addiction as a possible contributing factor to sexual dysfunction. Whelan G, Brown J. Pornography Addiction: An Exploration of the Association Between Perceived Addiction, Erectile Dysfunction, Premature (Early) Ejaculation, and Sexual Satisfaction in Males Aged 18-44 Years. J Sex Med 2021;18:1582-1591.


Why Hearing Aids Fail and How to Solve This.
Hearing is one of the human's foremost sensors; being able to hear again after suffering from a hearing loss is a great achievement, under all circumstances. However, in the long run, users of present-day hearing aids and cochlear implants are generally only halfway satisfied with what the commercial side offers. We demonstrate here that this is due to the failure of a full integration of these devices into the human physiological circuitry. Important parts of the hearing network that remain unestablished are the efferent connections to the cochlea, which strongly affects the faculty of listening. The latter provides the base for coping with the so-called cocktail party problem, or for a full enjoyment of multi-instrumental musical plays. While nature clearly points at how this could be remedied, to achieve this technologically will require the use of advanced high-precision electrodes and high-precision surgery, as we outline here. Corresponding efforts must be pushed forward by coordinated efforts from the side of science, as the commercial players in the field of hearing aids cannot be expected to have a substantial interest in advancements into this direction.


COX-2-selective inhibitors (COXIBs): gastrointestinal safety.
COX-2 selective inhibitors (coxibs) have been developed with the primary aim to reduce/avoid gastrointestinal (GI) toxicity observed during conventional (non-selective) non-steroidal anti-inflammatory (NSAID) therapy. Coxibs have clearly and convincingly been shown to be superior to conventional NSAIDs with significantly less GI side effects. When hard endpoints such as perforation, obstruction, and serious bleeding considered, coxibs reduce the risk by approximately 50 percent. Although selective COX-2 inhibition seems not to be enough for complete elimination of GI toxicity, coxibs posses no more GI toxicity than placebo in prospective clinical studies and further increase in COX-2 selectivity does not reduce GI toxicity. For the initial aim developed, thus coxibs fulfilled their promise and will soon replace conventional NSAIDs.


Iodine Chemisorption, Interpenetration and Polycatenation: Cationic MOFs and CPs from Group 13 Metal Halides and Dipyridyl Linkers.
Invited for the cover of this issue are Klaus Müller-Buschbaum and co-workers at Giessen University. The image depicts an aluminium-based MOF as a novel material for the capture of iodine radioisotopes from a potential gas atmosphere exposure. Read the full text of the article at 10.1002/chem.202104171.


Dose-ranging study to assess the application of intranasal 2% mupirocin calcium ointment to eradicate Staphylococcus aureus nasal colonization.
Mupirocin nasal ointment may be prescribed for decolonization prior to surgical procedures, especially for carriers of methicillin-resistant Staphylococcus aureus (MRSA). The approved regimen for decolonization of S. aureus from the anterior nares is twice daily for 5 d (10 doses). We performed a two-center, randomized, open-label study to compare the utility of six and 10 doses for decolonization of S. aureus. Patients expecting to undergo surgery were screened for S. aureus nasal carriage approximately three weeks prior to the procedure. Those found to be positive were offered enrollment in the study. In the first arm (n=41), patients were randomized to receive 2, 3, or 5 d (six or 10 doses) of treatment prior to their operation. Their anterior nares were swabbed for culture and S. aureus polymerase chain reaction (PCR) during the decolonization therapy period as well as for four weeks after surgery. In the second arm (n=60), all patients were given 5 d (10 doses) of nasal mupirocin treatment, and the patient's anterior nares were swabbed for culture and S. aureus PCR for four weeks after surgery. Data from six of the patients were excluded from analysis because of failure to submit swabs after operation. All S. aureus isolates were tested for susceptibility to mupirocin and the presence of the mecA gene to detect MRSA. In Arm 1, 16 patients received 10 doses of mupirocin, 18 received six doses (twice daily for 3 d), and 7 received six doses (thrice daily for 2 d). In the second arm, all patients received 10 doses of mupirocin (twice a day for 5 d). Overall, 89.5% patients who received 10 doses of mupirocin remained decolonized for at least four weeks after surgery versus 68.0% of patients who received six doses (p=0.016). There was no difference between arms 1 and 2 for those given mupirocin twice daily for 5 d. The ten-dose regimen is superior to any six-dose regimen for de-colonizing S. aureus from the anterior nares of patients and for maintaining the decolonized state for at least four weeks after therapy.


In vitro evaluation of physical vapor deposition coated beta titanium orthodontic archwires.
To determine in vitro the frictional properties, surface morphology, and load deflection rate with looped designs of two newly developed titanium aluminum nitride (TiAlN) and tungsten carbide/carbon (WC/C) physical vapor deposition (PVD) coated beta titanium orthodontic archwires coated with PVD. Frictional properties with Tidy's protocol, surface evaluation before and after friction testing with the help of scanning electron microscopy (ESEM), and load deflection rate with different orthodontic loops on Instron universal testing machine were evaluated. The results clearly indicate reduced frictional properties for WC/C coated archwires when compared with uncoated and TiAlN coated archwires. There were no significant surface alterations upon ESEM evaluation of friction tested archwires. Low load deflection rate was exhibited by both coated archwires, the difference in load deflection rate between the coated and uncoated archwires was statistically significant. WC/C coated wires can be recommended for even sliding mechanics due to reduced frictional properties, better surface characteristics, and low load deflection rate compared with TiAlN coated and uncoated archwires.


[Has the obligation to inform patients changed our mode of practice?].
From January 2000, the Council of State has harmonised the jurisprudence with the Court of Appeal, changing the responsibility of medical practitioners by requiring them to provide proof that information was both given and understood by their patients. This obligation to inform patients raises several questions: who should give the information? to whom should the information be addressed? how can proof of this information be provided? what should the information be? The authors sent a questionnaire to practicing cardiologists by the internet site of the French Society of Cardiology from the 1st December 2002 to 15th January 2003. Three hundred and thirty-two replies were received of which 305 could be exploited. The activities of the cardiologists who replied were mainly in public hospitals (51.8%), private (18.2%) or mixed (30%). Patient information was mainly performed before invasive procedures, especially coronary angiography (90%) or cardiac pacing (77.3%). On the other hand, it was less commonly undertaken before exercise stress tests (63.2%) or transoesophageal echocardiography (61.4%), although these percentages are much higher than those recorded during previous enquiries in 2000 and 2001. The information given was, in the large majority of cases, that proposed by the French Society of Cardiology and it was usually the practitioner who ordered the investigation who informed the patient (45.4%). In 2002, the role of the nurse was much greater as the nurse informed the patient in 27.2% of cases. The patient was generally given the information the day before the procedure was carried out (74.1%) with complementary information (90.7%), and less than 1% of patients declined the investigation under these conditions. In order to provide proof of patient information, the practitioner usually required the patient's signature (58.3% of cases); less commonly, the referring physician was informed by letter (13.9% of cases) or a note was made in the patient's file (33.9% of cases). The new requirements for patient information have changed medical practice in nearly 53.5% of cases. Finally, although patient information is considered to be part of the normal patient-doctor relationship in most cases (42.7%), doctors thought that patients interpreted this procedure as a cover for the medical team in 18.2% of cases. The information bases most commonly used to determine the methods of informing patients and the nature of the information to be provided were medical reviews (38.9%) or the internet (30.5%). The authors conclude that patient information is carried out before complementary cardiological investigations. The new laws of the Code of Public Health are not well known. Finally, the proof of patient information is not easily provided and the majority of cardiologists request written patient consent, which is not a legal requirement.


Readers weigh in on opioid epidemic.
I would like to see someone conduct a nationwide survey of primary care physicians regarding their views on narcotics for pain so that I can better understand my colleagues' perspectives on this issue.


Association between the severity of new-onset depression and unmet healthcare needs of South Korean adults.
Identifying whether the demand for medical services is catered to is an important issue. Given that depression is a major contributor to the overall global burden of disease, it could affect the use of healthcare. This study aims to examine the association between the severity of new-onset depression and unmet healthcare needs among South Korean adults. Data from 15,588 participants, derived from the 2014, 2016, and 2018 Korean National Health and Nutrition Examination Survey, were examined. Only individuals who were not diagnosed with depression was included to exclude those who visited hospitals to treat depression or were experiencing unmet healthcare needs due to depression. Depression was measured using the Patient Health Questionnaire-9 and unmet healthcare needs acted as the dependent variable. A multiple/multinomial logistic regression analysis was built to analyze the association between the variables. Individuals with severe depression had a higher risk of having unmet healthcare needs compared to those without (men: adjusted OR = 2.05, 95% CI = 1.40-3.00; women: adjusted OR = 2.20, 95% CI = 1.72-2.82). White-collar men with severe depression also had a higher risk of having unmet healthcare needs (adjusted OR = 9.72, 95% CI = 4.73-20.00). Individuals with severe depression had a higher risk of having unmet healthcare needs due to economic hardship than those without depression (men: adjusted OR = 3.01, 95% CI = 1.76-5.14, women: adjusted OR = 2.93, 95% CI = 1.96-4.38). This study identified a significant relationship between the severity of new-onset depression and the risk of having unmet healthcare needs among South Korean adults. Our study suggests that having severe depression contributed to a higher risk of unmet healthcare needs. Proper care to manage depression can be promoted through future intervention programs that alleviate the risk of having unmet healthcare needs.


T cells in myasthenia gravis specific for embryonic acetylcholine receptor.
In myasthenia gravis (MG) there is an autoimmune response against muscle acetylcholine receptor (AChR). Embryonic and adult muscles express different AChRs; embryonic AChR contains a gamma subunit, instead of the homologous epsilon subunit that contributes to form adult AChR. We report propagation from the blood of MG patients of T helper (TH) cell lines specific for human embryonic AChR, by cycles of stimulation with a pool of synthetic peptides corresponding to the complete sequence of the gamma subunit (gamma pool). The TH lines strongly recognized AChR from embryonic mammalian muscle, and reacted less or not at all with adult muscle AChR. The existence of TH cells specific for embryonic AChR strongly suggests that the primary anti-AChR sensitization in MG occurs in a tissue other than the innervated skeletal muscle. This may be within the thymus, which expresses an AChR similar or identical to embryonic muscle AChR.


The Biological Role of Klotho Protein in the Development of Cardiovascular Diseases.
Klotho is a membrane-bound or soluble antiaging protein, whose protective activity is essential for a proper function of many organs. In 1997, an accidental insertion of a transgene led to creation of transgenic mice with several age-related disorders. In Klotho-deficient mice, the inherited phenotypes closely resemble human aging, while in an animal model of Klotho overexpression, the lifespan is extended. Klotho protein is detected mainly in the kidneys and brain. It is a coreceptor for fibroblast growth factor and hence is involved in maintaining endocrine system homeostasis. Furthermore, an inhibition of insulin/insulin-like growth factor-1 signaling pathway by Klotho regulates oxidative stress and reduces cell death. The association between serum Klotho and the classic risk factors, as well as the clinical history of cardiovascular disease, was also shown. There are a lot of evidences that Klotho deficiency correlates with the occurrence and development of coronary artery disease, atherosclerosis, myocardial infarction, and left ventricular hypertrophy. Therefore, an involvement of Klotho in the signaling pathways and in regulation of a proper cell metabolism could be a crucial factor in the cardiac and vascular protection. It is also well established that Klotho protein enhances the antioxidative response via augmented production of superoxide dismutase and reduced generation of reactive oxygen species. Recent studies have proven an expression of Klotho in cardiomyocytes and its increased expression in stress-related heart injury. Thus, the antioxidative and antiapoptotic activity of Klotho could be considered as the novel protective factor in cardiovascular disease and heart injury.


The influence of orchidectomy on collagen glycosylation of trabecular bone in rat.
This study evaluates the effect of male rat castration on the degree of collagen glycosylation of bone. Twenty 100-day-old male Sprague-Dawley rats were subjected to either orchidectomy (n = 10) or sham operation (n = 10). After surgery animals were divided at random into 2 groups: the first group (5 sham operated and 5 orchidectomized) was sacrificed under anesthetic at 130 days of age, while the second group (5 sham operated and 5 orchidectomized) was sacrificed at 250 days of age. Femurs and tibiae were separated into cortical and trabecular bone, demineralized, hydrolyzed and analyzed by HPLC for hydroxylysine glycosides and hydroxyproline content. Orchidectomy causes an increased collagen glycosylation only in trabecular bone, as already observed in ovariectomized rats. However, the effect was not seen in the group of 130 day old rats, i.e. 30 days after orchidectomy, but was evident in the 250 day old rats, i.e. at 150 days from castration. These data suggest that collagen glycosylation could also be controlled by testosterone.


Mechanism of eIF6 release from the nascent 60S ribosomal subunit.
SBDS protein (deficient in the inherited leukemia-predisposition disorder Shwachman-Diamond syndrome) and the GTPase EFL1 (an EF-G homolog) activate nascent 60S ribosomal subunits for translation by catalyzing eviction of the antiassociation factor eIF6 from nascent 60S ribosomal subunits. However, the mechanism is completely unknown. Here, we present cryo-EM structures of human SBDS and SBDS-EFL1 bound to Dictyostelium discoideum 60S ribosomal subunits with and without endogenous eIF6. SBDS assesses the integrity of the peptidyl (P) site, bridging uL16 (mutated in T-cell acute lymphoblastic leukemia) with uL11 at the P-stalk base and the sarcin-ricin loop. Upon EFL1 binding, SBDS is repositioned around helix 69, thus facilitating a conformational switch in EFL1 that displaces eIF6 by competing for an overlapping binding site on the 60S ribosomal subunit. Our data reveal the conserved mechanism of eIF6 release, which is corrupted in both inherited and sporadic leukemias.


[The Angelchik prosthesis--intermediate term evaluation and results].
The clinical effectivity of the Angelchik-antireflux-prosthesis seems to be comparable with fundoplication; the mode of action of both procedures can well be explained by the hypothesis of "neutralizing of the gastric opening pressure". To insert an Angelchik prosthesis is a minor procedure in comparison to the Nissen procedure with a markedly lower operative risk. The long-term results, however, are deteriorated by specific complications due to the use of allogenic material. Following to fundoplication the results remain to be comparably good as in short term period even after a follow up beyond of one decade. Accordingly, the insertion of an Angelchik device should be confined nowadays only on the cases when the risks of long-term complications can be neglected in favor of a technically simple procedure. As for further development of the basic idea, it seems to be consequent to introduce an artificial wrap made of resorbable material.


The effect of accidental pre-lighting of turkey hens on subsequent reproduction.
The length of the light day was accidentally increased from nine hours to continuous light on one group of thirty-week old hens for an unknown period of not more than eleven days. Egg production, after attaining a level of twenty-five percent, ceased five weeks later as the result of restricting the length of the light day to four hours and two series of feed and water deprivations. One month later hens from the pre-lighted and control groups were brought into egg production. Pre-lighting depressed later egg production more in medium-bodied hens than in large-bodied hens. The major effect of pre-lighting was to reduce the length of a laying period included 9 weeks later with no significant effects on intensity of lay, number of broody periods or average length of the broody period. It was concluded that the egg production would not be greatly reduced by pre-lighting under the above conditions if the length of the laying period were shortened from 180 days to a normal 140-day period.


SeqEnrich: A tool to predict transcription factor networks from co-expressed Arabidopsis and Brassica napus gene sets.
Transcription factors and their associated DNA binding sites are key regulatory elements of cellular differentiation, development, and environmental response. New tools that predict transcriptional regulation of biological processes are valuable to researchers studying both model and emerging-model plant systems. SeqEnrich predicts transcription factor networks from co-expressed Arabidopsis or Brassica napus gene sets. The networks produced by SeqEnrich are supported by existing literature and predicted transcription factor-DNA interactions that can be functionally validated at the laboratory bench. The program functions with gene sets of varying sizes and derived from diverse tissues and environmental treatments. SeqEnrich presents as a powerful predictive framework for the analysis of Arabidopsis and Brassica napus co-expression data, and is designed so that researchers at all levels can easily access and interpret predicted transcriptional circuits. The program outperformed its ancestral program ChipEnrich, and produced detailed transcription factor networks from Arabidopsis and Brassica napus gene expression data. The SeqEnrich program is ideal for generating new hypotheses and distilling biological information from large-scale expression data.


Diagnostic Value of Non-Contrast CT in Cerebrospinal Fluid Leakage After Endoscopic Transnasal Surgery for Sellar and Suprasellar Tumors.
We aimed to study the relationship between pneumocephalus on non-contrast CT (NCCT) and post-operative cerebrospinal fluid leakage (p-CFL) after endoscopic transsphenoidal sellar and suprasellar tumor surgeries. Data from patients who underwent endoscopic treatment for sellar or suprasellar tumors from January 2018 to March 2020 were consecutively collected and reviewed. The NCCT pneumocephalus (NP) was measured the first day after operation and the first day after the expansive sponge was extracted. p-CFL was determined according to post-operative clinical symptoms, high resolution CT and glucose test, and expert consensus. Of the 253 patients enrolled in this study, 32 (12.6%) had p-CFL. Compared with patients without p-CFL, patients with p-CFL had a higher occurrence of intra-operative CFL, a longer operation time, a higher rate of pneumocephalus on first-day NCCT after operation (i.e., first-day NP), and a higher rate of NP volume change between two NCCT measurements (referred to as the NP change) (all p < 0.05). In multivariate regression analysis, first-day NP was independently associated with p-CFL occurrence [odds ratio (OR)=6.395, 95% confidence interval (CI)=2.236-18.290, p=0.001). After adding the NP change into the regression model, first-day NP was no longer independently associated with p-CFL, and NP change (OR = 19.457, 95% CI = 6.095-62.107, p<0.001) was independently associated with p-CFL. The receiver operating characteristic curve comparison analysis showed that NP change had a significantly better predicting value than first-day NP (area under the curve: 0.988 vs. 0.642, Z=6.451, p=0.001). NP is an effective imaging marker for predicting p-CFL after endoscopic sellar and suprasellar tumors operation, and the NP change has a better predicting value.


Clinical guideline for pharmacological management of cancer pain: the Japanese Society of Palliative Medicine recommendations.
Pain is the most frequent and distressing symptom in cancer patients. As part of a worldwide effort to improve the quality of pain control, several clinical guidelines for the management of cancer pain have been published and revised in the last decade. The Japanese Society of Palliative Medicine first published a Japanese clinical guideline for the management of cancer pain in 2000. Since then, many clinical studies concerning cancer pain management have been conducted, new drugs have become available in Japan and the methodology of developing a guideline has been refined. Therefore, we decided to develop a novel clinical guideline. This review paper summarizes the recommendations and the rationales of this new clinical guideline for the pharmacological management of cancer pain. In addition, a short summary of the clinical guideline development process is provided. This new Japanese Society of Palliative Medicine guideline highlights the importance of conducting well-designed studies to identify the best practices in cancer pain management.


A comparison of the pathology of primary and secondary progressive multiple sclerosis.
The dynamics of primary progressive multiple sclerosis differ from those of the more common secondary progressive form. The observation by MRI that the frequency of enhancement with gadolinium-DTPA, a marker for blood-brain barrier dysfunction, is significantly less in the primary progressive form, has led to the hypothesis that inflammation is less intense in this group. To test this, we have studied postmortem material from nine cases judged from a retrospective analysis of case notes to show clear clinical evidence of either primary progressive or secondary progressive disease. Five hundred and seventy-eight lesions were analysed. There was significantly more inflammation in secondary progressive multiple sclerosis (as judged by the frequency of perivascular cuffing and cellularity of the parenchyma) than in primary progressive disease. These observations have implications for therapeutic strategies in progressive multiple sclerosis.


DNA and chromosomal damage in response to intermittent extremely low-frequency magnetic fields.
Considerable controversy still exists as to whether electric and magnetic fields (MF) at extremely low frequencies are genotoxic to humans. The aim of this study was to test the ability of alternating magnetic fields to induce DNA and chromosomal damage in primary human fibroblasts. Single- and double-strand breaks were quantified using the alkaline comet assay and the gammaH2AX-foci assay, respectively. Chromosomal damage was assayed for unstable aberrations, sister chromatid exchange and micronuclei. Cells were exposed to switching fields - 5min on, 10min off - for 15h over the range 50-1000microT. Exposure to ionizing radiation was used as a positive-effect calibration. In this study two separate MF exposure systems were used. One was based on a custom-built solenoid coil system and the other on a commercial system almost identical to that used in previous studies by the EU REFLEX programme. With neither system could DNA damage or chromosomal damage be detected as a result of exposure of fibroblasts to switching MF. The sensitive gammaH2AX assay could also not detect significant DNA damage in the MF-exposed fibroblasts, although the minimum threshold for this assay was equivalent to an X-ray dose of 0.025Gy. Therefore, with comparable MF parameters employed, this study could not confirm previous studies reporting significant effects for both the alkaline and neutral comet assays and chromosomal aberration induction.


Characterization of the antitumor activity of a polyantigenic immunomodulator (PAI): I--Utilization of cimetidine and cyclosporine A.
Cimetidine (CMT), cyclosporine A (CsA), interleukin 2 (IL 2), were used to characterize the anticancerous effect of a polyantigenic immunodulator (PAI). PAI consists of a mixture of inactivated bacteria and influenza virus in a peanut oil-arlacel A-aluminum monoesterate emulsion. Antitumoral activity was tested on Ehrlich's ascites tumor (EAT) implanted into Swiss-Webster (allogeneic) or C57BL/6J (syngeneic) mice. PAI antitumor activity was enhanced by CMT acting synergistically by reducing substantially the tumor growth and increasing the percentage of surviving mice, while CsA suppressed this activity. PAI or its individual components were able to induce significant lymphocyte blastogenesis in mouse (C57BL/6J)-spleen lymphocytes and IL-2 enhanced considerably this lymphoproliferative response. The results suggest that PAI acts at the level of cellular immunity.


Curative use of forequarter amputation for recurrent breast cancer over an axillary area: a case report and literature review.
Axillary recurrence of breast cancer that involves the brachial neurovascular bundle is uncommon. However, for many patients with such recurrence, forequarter amputation can play a palliative role in relieving excruciating pain and paralysis of the upper limb. Further, for those patients who do not have distant metastasis or other local-regional recurrence, forequarter amputation provides a chance for a cure. Only a few case reports of curative amputations for recurrent breast cancer are present in the literature. Here, we report a case of forequarter amputation for curative treatment of axillary recurrent breast cancer, together with a literature review. To date, we have followed the patient for three years after amputation, during which there has been no evidence of recurrence or metastasis. Although radical resection is feasible, it can be accompanied by surgical wound complications and psychosocial stress. Therefore, an organized multidisciplinary approach is needed to ensure the success of radical resection.


Effect of Nectaroscordum koelzi Methanolic Extract on Acute and Chronic Inflammation in Male Mice.
The present study deals with the effect of Nectaroscordum koelzi fruit extract on acute and chronic inflammation. A total of 84 NMRI mice were used in this study. The effect of the extract on acute inflammation was analyzed by increasing vascular permeability via acetic acid and xylene induced ear edema among mice. The extract was evaluated in terms of effects on chronic inflammation by means of the cotton pellet test among mice. For the assessment of inflammation degree, the mice paw edema volume was measured by the plethysmometric test. The findings showed that the extract was effective on acute inflammation induced by acetic acid in mice. In the xylene ear edema, N. koelzi extract indicated a significant activity in mice. In the cotton pellet method, the methanol extract produced a significant reduction in comparison with the control and dexamethasone. Mice paw edema volume decreased with the extract. In general, the data from the experiments indicated that the methanol extract of N. koelzi has an anti-inflammatory effect on acute and chronic inflammation. However, the exact contributing mechanisms have not been investigated for the pharmacological effects.


A whole genome screen for linkage disequilibrium in multiple sclerosis confirms disease associations with regions previously linked to susceptibility.
Linkage analysis in multiplex families has provisionally identified several genomic regions where genes influencing susceptibility to multiple sclerosis are likely to be located. It is anticipated that association mapping will provide a higher degree of resolution, but this more powerful approach is limited by the substantial genotyping effort required. Here, we describe the first use of DNA pooling to screen the whole genome for association in multiple sclerosis based on a 0.5 cM map of microsatellite markers and using four DNA pools derived from cases (n = 216), controls (n = 219) and trio families (n = 745 affected individuals and their 1490 parents). The 10 markers showing the greatest evidence for association with multiple sclerosis that emerge from this analysis include three from the HLA region on chromosome 6p (D6S1615, D6S2444 and TNFa), providing a positive control for the method, four from regions previously identified by linkage analysis in UK multiplex families (two mapping to chromosome 17q GCT6E11 and D17S1535; one to chromosome 1p GGAA30B06; and one to 19q D19S585), and three from novel sites with respect to linkage analysis (D1S1590 at 1q; D2S2739 at 2p; and D4S416 at 4q). Our results thus provide further supporting evidence for the candidature of 6p, 17q, 19q and 1p as regions encoding susceptibililty genes for multiple sclerosis. The protocol used in this UK-based study is now being extended to 18 additional sites in Europe in order to search for susceptibility genes shared between populations of common ancestry, as well as those that exert ethnically more restricted effects.


Short-term clinical and immunologic effects of scaling and root planing with Er:YAG laser in chronic periodontitis.
Recently, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser has been used for periodontal therapy. This study compared Er:YAG laser irradiation (100 mJ/pulse, 10 Hz, 12.9 J/cm(2)) with or without conventional scaling and root planing (SRP) to SRP only for the treatment of periodontal pockets affected with chronic periodontitis. Twenty-one subjects with pockets from 5 to 9 mm in non-adjacent sites were studied. In a split-mouth design, each site was randomly allocated to a treatment group: SRP and laser (SRPL), laser only (L), SRP only (SRP), or no treatment (C). The plaque index (PI), gingival index (GI), bleeding on probing (BOP), and interleukin (IL)-1beta levels in crevicular fluid were evaluated at baseline and at 12 and 30 days postoperatively, whereas probing depth (PD), gingival recession (GR), and clinical attachment level (CAL) were evaluated at baseline and 30 days after treatment. A statistical analysis was conducted (P <0.05). Twelve days postoperatively, the PI decreased for SRPL and SRP groups (P <0.05); the GI increased for L, SRP, and C groups but decreased for the SRPL group (P <0.05); and BOP decreased for SRPL, L, and SRP groups (P <0.01). Thirty days postoperatively, BOP decreased for treated groups and was lower than the C group (P <0.05). PD decreased in treated groups (P <0.001), and differences were found between SRPL and C groups (P <0.05). CAL gain was significant only for the SRP group (P <0.01). GR increased for SRPL and L groups (P <0.05). No difference in IL-1beta was detected among groups and periods. Er:YAG laser irradiation may be used as an adjunctive aid for the treatment of periodontal pockets, although a significant CAL gain was observed with SRP alone and not with laser treatment.


Recent failures of new potential symptomatic treatments for Parkinson's disease: causes and solutions.
One major goal of current research in Parkinson's disease (PD) is the discovery of novel agents to improve symptomatic management. The object of these new treatments should be to provide effective symptom control throughout the course of the disease without the development of side effects such as motor and psychiatric complications. Results of several clinical trials of new treatment options reported in the past 2 years have shown negative or unsatisfactory results. Most of the drugs and surgical procedures used in these studies had been tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys as well as in the classic 6-hydroxydopamine-lesioned rat model. They raise several questions about the true reliability of animal studies, the adequacy of the working hypotheses and design of clinical trials, the validity of tools in current use to evaluate a specific effect, and the selectivity of the drugs used. All these factors may explain failure. This review focuses on pharmacological and surgical treatments tested to improve the management of patients with motor fluctuations and dyskinesias. Some of the recent trials and possible reasons for their lack of success are critically analysed. Finally, some suggestions to avoid further failures and improve results are proposed.


The Bidirectional Link Between Diabetes and Kidney Disease: Mechanisms and Management.
The complex and mutually influential connection between diabetes mellitus and chronic kidney disease (CKD) is a significant focal point in the current healthcare landscape. Diabetes, a medical condition characterized by elevated blood glucose levels resulting from impaired insulin action or secretion, has become a significant global epidemic. It poses considerable challenges to healthcare systems and affects millions of individuals worldwide. Concurrently, CKD, characterized by the gradual decline of kidney function, has become a persistent health challenge. This narrative review explores the complex relationship between these two conditions, shedding light on their significant implications for public health, clinical practice, and biomedical research. The correlation between diabetes and kidney disease is not merely coincidental. Diabetes is recognized as a significant risk factor for CKD, as individuals with diabetes are considerably more vulnerable to developing renal complications. Diabetic nephropathy, a distinct type of kidney disease closely associated with diabetes, is a significant factor in developing end-stage renal disease. It is imperative to implement efficient diabetes management strategies to regulate blood sugar levels and prevent potential kidney damage. On the other hand, kidney disease may contribute to the development of diabetes. The kidneys regulate glucose levels by filtering the blood and selectively reabsorbing glucose as necessary. In compromised kidney function, such as CKD, impaired glucose metabolism can give rise to insulin resistance and diabetes. As a result, the management of kidney disease plays a dual role in both preserving renal function and preventing diabetes in individuals who are at risk. The coexistence of diabetes and kidney disease in a patient presents complex clinical challenges. Achieving effective management requires a meticulous balance between glycemic control and preservation of renal function. Failing to maintain this delicate equilibrium can lead to cardiovascular complications and subsequent hospitalizations. This comprehensive narrative review aims to thoroughly examine the pathophysiological mechanisms that connect diabetes and kidney disease. It will provide insights into the clinical manifestations and diagnostic methods, explore various approaches to managing the condition, discuss the crucial role of nutrition, delve into pharmacological interventions, emphasize the importance of patient education and self-care, and shed light on emerging research areas. In addition to impacting individual health outcomes, this reciprocal relationship has significant implications for healthcare systems, socioeconomic landscapes, and public health policy. Comprehending this complex interaction is crucial for making well-informed clinical judgments, improving patient care, and developing a more efficient public health approach to address the interconnected issues of diabetes and kidney disease.


Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate.
We have investigated whether Ezrin-radixin-moesin (ERM)-binding phosphoprotein-50/Na(+)/H(+) exchanger regulatory factor (EBP50/NHERF), a PDZ domain-containing phosphoprotein, is associated with the human kappa opioid receptor (hkor) and whether it regulates the trafficking and signaling of the hkor. When expressed in CHO cells stably transfected with the FLAG-tagged hkor (FLAG-hkor), EBP50/NHERF co-immunoprecipitated with FLAG-hkor, and the PDZ domain I, but not the PDZ domain II, of EBP50/NHERF was involved in the interaction. Treatment with the agonist (-)-(trans)-3,4- dichloro-N-methyl-N-[2-(1-pyrrolidiny)cyclohexyl]benzeneacetamide (U50,488H) enhanced the association of EBP50/NHERF with FLAG-hkor. Expression of EBP50/NHERF, but not a truncated form lacking the ERM-binding domain, abolished U50,488H-induced down-regulation of FLAG-hkor, which was apparently due to an increase in the recycling rate of internalized receptors. However, expression of EBP50/NHERF did not affect U50,488H binding affinity and U50,488H-stimulated [(35)S]guanosine 5'-3-O-(thio)triphosphate binding and p42/p44 MAP kinase activation, nor did it affect U50,488H-induced desensitization and internalization of FLAG-hkor. To determine the motif of FLAG-hkor involved in EBP50/NHERF binding, we generated two mutants, FLAG-hkor-A and FLAG-hkor-EE, in which one Ala or two Glu residues were added to the C terminus, respectively. Neither FLAG-hkor-A nor FLAG-hkor-EE co-immunoprecipitated with EBP50/NHERF, and U50,488H-induced down-regulation of FLAG-hkor-A and FLAG-hkor-EE were not affected by expression of EBP50/NHERF. Thus, EBP50/NHERF binds to the C terminus of FLAG-hkor and blocks the down-regulation of FLAG-hkor. The C-terminal sequence of the hkor, NKPV, is distinctly different from the sequence D(S/T)XL, the optimal C-terminal motif in the beta(2)-adrenergic receptor for EBP50/NHERF binding. EBP50/NHERF may have a broader binding specificity and may interact with a subset of G protein-coupled receptors to serve as a recycling signal for these receptors.


On the biaxial mechanical properties of the layers of the aortic valve leaflet.
All existing constitutive models for heart valve leaflet tissues either assume a uniform transmural stress distribution or utilize a membrane tension formulation. Both approaches ignore layer specific mechanical contributions and the implicit nonuniformity of the transmural stress distribution. To begin to address these limitations, we conducted novel studies to quantify the biaxial mechanical behavior of the two structurally distinct, load bearing aortic valve (AV) leaflet layers: the fibrosa and ventricularis. Strip biaxial tests, with extremely sensitive force sensing capabilities, were further utilized to determine the mechanical behavior of the separated ventricularis layer at very low stress levels. Results indicated that both layers exhibited very different nonlinear, highly anisotropic mechanical behaviors. While the leaflet tissue mechanical response was dominated by the fibrosa layer, the ventricularis contributed double the amount of the fibrosa to the total radial tension and experienced four times the stress level. The strip biaxial test results further indicated that the ventricularis exhibited substantial anisotropic mechanical properties at very low stress levels. This result suggested that for all strain levels, the ventricularis layer is dominated by circumferentially oriented collagen fibers, and the initial loading phase of this layer cannot be modeled as an isotropic material. Histological-based thickness measurements indicated that the fibrosa and ventricularis constitute 41% and 29% of the total layer thickness, respectively. Moreover, the extensive network of interlayer connections and identical strains under biaxial loading in the intact state suggests that these layers are tightly bonded. In addition to advancing our knowledge of the subtle but important mechanical properties of the AV leaflet, this study provided a comprehensive database required for the development of a true 3D stress constitutive model for the native AV leaflet.


Preferential attachment in the protein network evolution.
The Saccharomyces cerevisiae protein-protein interaction map, as well as many natural and man-made networks, shares the scale-free topology. The preferential attachment model was suggested as a generic network evolution model that yields this universal topology. However, it is not clear that the model assumptions hold for the protein interaction network. Using a cross-genome comparison, we show that (a) the older a protein, the better connected it is, and (b) the number of interactions a protein gains during its evolution is proportional to its connectivity. Therefore, preferential attachment governs the protein network evolution. Evolutionary mechanisms leading to such preference and some implications are discussed.


[The role of blood plasma porphyrins in the effects of He-Ne-laser on human leukocytes].
The He-Ne-laser induced effects in human blood leukocytes in the presence of autologic plasma were investigated. Experiments were performed in two ways: (1) He-Ne-laser irradiation of cells in the presence of autologic plasma or (2) laser irradiation and subsequent addition of autologic plasma to the cell suspension. The concentration dependencies of plasma additions were evaluated. To obtain different concentrations of porphyrins in plasma samples, we either diluted the samples with PBS or selected patients with different porphyrin plasma content. The effects of He-Ne-laser irradiation were characterized by the maximum effect dose (Dmax) of irradiation and the degree of maximum cell activation (Amax, priming index). In the first series of experiments, we irradiated leukocytes in the presence of autologic plasma taken from patients with pneumonia and bronchial asthma. It was found that Dmax decreased with increasing porphyrin concentration in plasma. It was observed that, at low porphyrin concentrations, Amax increased severalfold with increasing photosensitizer concentration. At a porphyrin concentration of 0.46 pmol a decrease in Amax was detected as the porhyrin concentration increased. The same effects were revealed at high doses of laser irradiation. Very similar effects were found in experiments with the addition of irradiated plasma to cells. However, the Amax value was considerably less compared to that after irradiation in the presence of plasma (160% vs. 230 - 270% upon combined irradiation of cells and plasma). The Dmax value was higher in the series of experiments in which plasma was irradiated separately. The results suggest that laser-induced leukocyte activation can be mediated by blood plasma porphyrins and the products of lipid peroxidation formed as a result of porphyrin-photosensitized lipid oxidation.


Graphing trillions of triangles.
The increasing size of Big Data is often heralded but how data are transformed and represented is also profoundly important to knowledge discovery, and this is exemplified in Big Graph analytics. Much attention has been placed on the scale of the input graph but the product of a graph algorithm can be many times larger than the input. This is true for many graph problems, such as listing all triangles in a graph. Enabling scalable graph exploration for Big Graphs requires new approaches to algorithms, architectures, and visual analytics. A brief tutorial is given to aid the argument for thoughtful representation of data in the context of graph analysis. Then a new algebraic method to reduce the arithmetic operations in counting and listing triangles in graphs is introduced. Additionally, a scalable triangle listing algorithm in the MapReduce model will be presented followed by a description of the experiments with that algorithm that led to the current largest and fastest triangle listing benchmarks to date. Finally, a method for identifying triangles in new visual graph exploration technologies is proposed.


Clinical heterogeneity of SAPHO syndrome: challenging diagnose and treatment.
Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare disease which is often misdiagnosed and under-recognized, because of its peculiar and heterogeneous clinical presentation. Its main features consist of cutaneous and osteoarticular manifestations, the latter affecting more often the anterior chest wall and having typical radiologic findings. There are no validated diagnostic criteria for SAPHO and no guidelines for treatment, due mainly to its rarity; as a consequence, therapy is empirical and aimed to control pain and modifying inflammatory process. To date, the use of anti-TNF agents has been proved to be a valid alternative for patients unresponsive to conventional treatments, such as NSAIDs, corticosteroids, DMARDs and biphosphonates. The clinical heterogeneity of the disease, possibly due to differences in pathogenic mechanism of different manifestations, is challenging for both diagnosis and treatment, which should aim to control both skin and bone involvement in different clinical subsets. Here, we summarize the current status of knowledge about the SAPHO syndrome and present two cases of patients with very different disease manifestations, suggesting the need for personalized treatment.


Rh-Pt bimetallic catalysts: synthesis, characterization, and catalysis of core-shell, alloy, and monometallic nanoparticles.
Rh@Pt core-shell, RhPt (1:1) alloy, and Rh + Pt monometallic nanoparticles (NPs) were prepared using standard polyol reduction chemistry in ethylene glycol (EG) with standard inorganic salts and polyvinylpyrrolidine (PVP(55000)) stabilizers. PVP-free colloids were also prepared but less stable than the PVP-protected NPs. Rh@Pt core-shell particles were prepared from 2.7, 3.3, and 3.9 nm Rh cores with varying shell thicknesses (approximately 1 and approximately 2 ML). The particles were characterized by a combination of TEM, single-particle EDS, EDS line scans, XRD analysis, Debye Function simulations, FT-IR, and micro-Raman CO-probe experiments. The three different architectures were evaluated for preferential oxidation of CO in hydrogen (PROX) using 1.0 wt % Pt loadings in Al(2)O(3) supports. For hydrogen feeds with 0.2% CO and 0.5% O(2) the Rh@Pt NP catalyst has the best activity with complete CO oxidation at 70 degrees C and very high PROX selectivity at 40 degrees C with 50% CO conversion.


Kangaroo Mother Care in Colombia: A Subaltern Health Innovation against For-profit Biomedicine.
This ethnographic study presents the origins, growth, and collapse of the first Kangaroo Mother Care (KMC) program, a well-established practice for neonatal care created in 1978 in Colombia. The WHO and UNICEF praised this zero-cost revolutionary technique for its promotion of skin-to-skin contact between premature and low-birth-weight newborns and family members. KMC facilitates early hospital discharge, brings many clinical and psychological benefits, and constitutes an excellent alternative to placing babies in incubators. However, these benefits and political potential against biomedical interventions were undermined after being relabeled as a "reverse innovation," a business concept that encourages corporate investments in low-income countries to develop technologies that can both solve global health problems and boost multinational corporations profits. In response, I propose "subaltern health innovations" as a label for KMC that accounts for the power dynamics in global health between health care initiatives that originate in the Global South and neoliberal configurations of for-profit biomedicine.


Partial liver transplantation-living donor liver transplantation and split liver transplantation.
In the last two decades, liver transplantation (LTx) has become the treatment of choice for several liver diseases including hepatocellular carcinoma in selected cases. Improvements in surgical and anesthesiological procedures have increased patient survival after LTx, resulting in excellent 1-year survival rates. The rate-limiting factor to further increase the number of LTx is the extreme shortage of suitable organs with the consequence that pediatric and adult patients are dying on the waiting list. At present, mortality reported for pediatric and adult patients on the waiting list is 10 to 20%. Living-donor liver transplantation and split liver transplantation are measurements to reduce the severe lack of cadaveric grafts by expanding the donor pool. Major centers around the world now routinely perform partial LTx in infants and adults with survival success equivalent to that after full-size liver transplantation.


Altered basement membrane synthesis in the testis after tissue injury.
The basement membrane plays an important role in maintaining the structural and functional integrity of tissues. Altered basement membrane structure has been associated with severe functional impairment of the testis in several conditions, including vasectomy, autoimmune orchitis, cryptorchidism, and following x-irradiation. We have used efferent duct ligation as a model to examine seminiferous tubular basement membrane morphology, synthesis, and gene expression to determine whether altered basement membrane synthesis is responsible for the aberrant structures noted after tissue injury. On days 2 and 3 after ligation, both the seminiferous epithelium and the basement membrane appeared normal, but 7 days after ligation, the seminiferous epithelium began to degenerate. The basement membrane appeared detached from the epithelium, and redundant patches of basement membrane were observed adjacent to the Sertoli cells at 14 and 21 days postligation. Immunoprecipitation indicated an increase in laminin protein synthesis in the ligated tubules at the same time. Northern blot analysis showed increases in transcript levels for laminin as well as collagen IV and heparan sulfate proteoglycan. These data show that new protein synthesis is responsible, at least in part, for the duplication of the basement membrane coincident with the tissue damage caused by efferent duct ligation.


Novel Configurations of Ultrahigh Frequency (≤600 MHz) Analog Frontend for High Resolution Ultrasound Measurement.
In this article, an approach to designing and developing an ultrahigh frequency (≤600 MHz) ultrasound analog frontend with Golay coded excitation sequence for high resolution imaging applications is presented. For the purpose of visualizing specific structures or measuring functional responses of micron-sized biological samples, a higher frequency ultrasound is needed to obtain a decent spatial resolution while it lowers the signal-to-noise ratio, the difference in decibels between the signal level and the background noise level, due to the higher attenuation coefficient. In order to enhance the signal-to-noise ratio, conventional approach was to increase the transmit voltage level. However, it may cause damaging the extremely thin piezoelectric material in the ultrahigh frequency range. In this paper, we present a novel design of ultrahigh frequency (≤600 MHz) frontend system capable of performing pseudo Golay coded excitation by configuring four independently operating pulse generators in parallel and the consecutive delayed transmission from each channel. Compared with the conventional monocycle pulse approach, the signal-to-noise ratio of the proposed approach was improved by 7⁻9 dB without compromising the spatial resolution. The measured axial and lateral resolutions of wire targets were 16.4 µm and 10.6 µm by using 156 MHz 4 bit pseudo Golay coded excitation, respectively and 4.5 µm and 7.7 µm by using 312 MHz 4 bit pseudo Golay coded excitation, respectively.


"A case of ocular ischemic syndrome in spontaneous acute internal carotid dissection: The importance of multidisciplinary management".
To emphasize that ocular ischemic syndrome (OIS) is a rare but threatening condition. It is a consequence of occlusion or dissection of internal carotid artery (ICA). A 66-year-old caucasian male presented in the emergency room with painful vision loss in his right eye and mild neurological symptoms. He was diagnosed ocular ischemic syndrome (OIS) in ICA and ophthalmic artery occlusion due to right ICA dissection. It is very important to know and be able to recognise OIS as it may often be misdiagnosed or treated as a different entity. Patients with ICA occlusion and OIS must be treated as soon as possible by a stroke unit team to resolve ICA occlusion/dissection and by the ophthalmologist to prevent further ocular related complications.


Tau-positive fine granules in the cerebral white matter: a novel finding among the tauopathies exclusive to parkinsonism-dementia complex of Guam.
We examined the autopsied brains of cases of 6 types of tauopathy: parkinsonism-dementia complex of Guam (PDC), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Pick disease, Alzheimer disease (AD), and myotonic dystrophy together with Guamanian controls. Light microscopy sections of these brains were examined using anti-tau antibodies. Tau-positive fine granules (TFGs) were globe-shaped, and 3 to 6 mum in diameter, were observed predominantly in the frontal white matter in 30 of the 35 patients with PDC. However, no TFGs were found in association with PSP, myotonic dystrophy, Pick disease, AD, or CBD. Western blot analysis of frozen brain tissue taken from the PDC cases revealed that the frontal cortex was hyperphosphorylated and contained 6 tau isoforms (3R+4R tau). However, in the present study, it was revealed that the novel TFGs in the white matter of patients with PDC was composed of 4R tau. Western blot analysis of sarkosyl-insoluble tau from the white matter of the PDC cases showed 2 major bands of 60 and 64 kDa and one minor band of 67 kDa. After dephosphorylation, these bands resolved into one major band of 4-repeat (4R) tau isoform and 3 minor bands of 3-repeat (3R) and 4R tau isoforms. Moreover, the TFGs observed in cases in which the number of neurofibrillary tangles (NFTs) was higher than the threshold level were not correlated with the presence of cortical NFTs. In conclusion, these novel TFGs were found almost exclusively in PDC brains and could therefore be considered as a characteristic neuropathologic marker of this particular tauopathy. The TFGs were hyperphosphorylated tau-positive structures that may be formed by a different mechanism from that used to produce cortical NFTs.


Becoming independent: political participation and youth transitions in the Scottish referendum.
Sociological debates on youth engagement with electoral politics play out against a backdrop of supposed 'decline' in civic participation (e.g. Putnam , Norris, ), in turn contextualized by theories of individualization in 'late' or 'reflexive' modernity (Beck, Giddens). However, the enfranchisement of 16 and 17 year olds in the 2014 Scottish Independence Referendum catalysed remarkably high levels of voter turnout among this youngest group, and was accompanied by apparently ongoing political engagement. We explored this engagement among a strategic sample of young 'Yes' voters, in the immediate aftermath of this exceptional political event. Analysis of qualitative interview data generated an unanticipated finding; that interviewees narrated their political engagement biographically, articulated their referendum participation reflexively, and located their new political ideas, allegiances and actions in the context of their own transitions to 'independent' adulthood. This inspired us to rethink young people's political engagement in relation to youth transitions. Doing so enables a synthesis of divergent strands in the sociology of youth, and offers new insights into the combinations of 'personal' agentic and 'political' structural factors involved in young people's politicization.