Apoptosis signal-regulating kinase 1 in stress and immune response.
Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase of the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. ASK1 is preferentially activated by various cytotoxic stressors and plays pivotal roles in a wide variety of cellular response to them. Recent analyses of ASK1 orthologs in Caenorhabditis elegans and Drosophila melanogaster have revealed that ASK1 is an evolutionarily conserved signaling intermediate in stress responses and appears to constitute a primitive but efficient defense system against stimuli harmful to organisms. Consistent with this notion, ASK1 has been shown to be required for the innate immune response, which is essential for host defense against a wide range of pathogens. In this review, we focus on the molecular mechanisms by which ASK1 functions in stress and immune responses and discuss the possible involvement of ASK1 in human diseases.


Dual magnetobiochemical logic control of electrochemical processes based on local interfacial pH changes.
An electrode surface modified with a pH-sensitive polymeric brush was reversibly activated by local pH changes produced in situ by glucose oxidase associated with magnetic nanoparticles confined at the surface in the presence of an external magnet. The system mimics Boolean AND logic gate, with the magnetic and chemical input signals stimulating the electrochemical reactions at the switchable interface. Biomedical applications of the "smart" interface controlled by enzymatic reactions through local pH changes are anticipated in various implantable biomedical devices.


[Pediatric impact of COVID-19].
Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.


MorphoNet: an interactive online morphological browser to explore complex multi-scale data.
Powerful novel imaging and image-processing methods are revolutionizing many fields of biology, at scales ranging from the molecule to the functional organ. To support this big-data revolution, we develop a concept of generic web-based morphodynamic browser to interactively visualize complex image datasets, with applications in research and education. MorphoNet handles a broad range of natural or simulated morphological data, onto which quantitative geometric or genetic data can be projected.


Mouse models of infection for Neisseria meningitidis B,2b and Haemophilus influenzae type b diseases.
A disseminated and fatal infection was established in C57BL mice, injected intraperitoneally with either Neisseria meningitidis B,2b or Haemophilus influenzae type b bacteria plus enhancement factors. The effects of mucin, hemoglobin, and iron dextran as enhancement of bacterial infectivity in mice were evaluated individually and in combination. A mixture of mucin and hemoglobin was most effective in enhancing the virulence of the pathogens. Inbred mouse lines were more susceptible than outbred ones. Relative virulence of a number of bacterial strains was also compared in one selected mouse line. Neisseria meningitidis B,2b and Haemophilus influenzae type b strains were more virulent than non-B,2b and nontypable strains. Finally, the course of bacteremia for the two infections in mice was followed by quantitative blood cultures. The animals succumbed to the generalized condition within 72 h. In the case of Neisseria meningitidis B,2b, 10 organisms with 4% mucin and 1.6% hemoglobin were sufficient to kill 50% of the animals. For Haemophilus influenzae type b, 300 bacteria with 5% mucin and 2% hemoglobin were necessary to obtain similar effects.


Halogen bonding matters: visible light-induced photoredox catalyst-free aryl radical formation and its applications.
Photo-involving aryl halide activation plays a pivotal role in organic synthesis and materials science. Revealing the mechanism and understanding the photophysical and photochemical processes in the activation is of great importance. Here, we found that aryl halides could be directly activated to form aryl radicals via halogen bonding under visible light irradiation without using photocatalysts or high power light. The interaction between the aryl halide and Lewis base (Et3N), as well as the triplet state formation, play crucial roles. Halogen bonding between aryl halide and Et3N facilitates intersystem crossing (ISC) and leads to an abundance of the triplet aryl halide/Et3N complex, where the carbon-halogen bond is much lengthened and prone to fracture. Therefore, visible light-driven photoredox catalyst-free C-C coupling reaction and radical-initiated polymerization were achieved. Avoiding the use of a catalyst not only brings convenience for low-cost operation, but also facilitates further purification. Meanwhile, the wide scope of aryl halide tolerance provides opportunities for chemical synthesis and polymerization.


Childhood incident asthma and traffic-related air pollution at home and school.
Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma- and wheezing-free at study entry into the Southern California Children's Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO(2)), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25-1.82] and near schools (HR 1.45; 95% CI, 1.06-1.98). Ambient NO(2) measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18-4.01). In models with both NO(2) and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO(2) was attenuated (HR 1.37; 95% CI, 0.69-2.71). Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.


Seroepidemiologic study of Chlamydia pneumoniae and other chlamydial species in a hyperendemic area for trachoma in the Sudan.
Sera of inhabitants of Angola village in central Sudan were investigated for the prevalence of antibodies to Chlamydia trachomatis, C. pneumoniae, and C. psittaci by the microimmunofluorescence (MIF) test. Clinical examination of 616 persons showed that the village is hyperendemic for trachoma. Of the 448 children examined, 334 (75%) had signs of active trachoma. The corresponding prevalence in the 168 adults was 25%. Using MIF, antibodies to C. trachomatis were found in the sera of 27 (81%) children and of 37 (88%) adults with trachoma. Antibodies to C. pneumoniae occurred in 13% and 24% of the preschool and school trachomatous children, respectively, and in 64% of the adults, which reflects earlier exposure to C. pneumonia in the Sudan than generally reported from temperate zones. Antibodies to C. psittaci were found in 6% of the children less than 16 years old and in 17% of the adults. Of the patients with trachoma, 16% had antibodies to both C. trachomatis and C. pneumoniae. The prevalence of multiple antibodies to Chlamydia increased with age. Antibodies to all three species occurred in 3% of the patients. The study does not support the existence of protective immunity between C. pneumoniae, C. trachomatis, and C. psittaci, as shown by the high prevalence of chlamydial antibodies in the hyperendemic trachoma community studied.


Conventional real-time PCR-based detection of T790M using tumor tissue or blood in patients with EGFR TKI-resistant NSCLC.
Blood biopsy has many advantages over tissue biopsy for diagnosing acquired T790M mutation in patients with non-small-cell lung cancer, such as being less risky and painful. New techniques with high sensitivity (eg, droplet digital PCR) show promising results during blood biopsy, but the positive rates of identification are still quite unclear. Whether there are other factors, except technology, affecting the results of blood biopsy is unclear. In this study, we used conventional amplification refractory mutation system to detect tumor tissue or blood for T790M mutation in patients clinically resistant to tyrosine kinase inhibitors. A total of 45 patients treated at West China Hospital between 2014 and 2016 were analyzed. The positive rate of T790M mutation was 70.8% based on tissue biopsy and 37.5% based on blood biopsy. Of the 24 patients whose epidermal growth factor receptor gene was genotyped through tissue and blood biopsy, 10 (41.7%) were concordant for T790M mutation status (κ=0.006). Of the 17 patients positive for T790M by tissue biopsy, 7 (41.2%) were positive for T790M by blood biopsy, and 3 of these 7 were only weakly positive. Of the 7 patients negative for T790M by tissue biopsy, 2 (28.6%) were positive by blood biopsy. Our T790M detection rate is higher than that reported by other studies using digital droplet PCR. These results suggest that other factors (eg, clinical features), intrinsically connected with circulating tumor DNA level, also affect the results of blood biopsy, and thus cannot be controlled through technological optimization.


miR-1468-3p Promotes Aging-Related Cardiac Fibrosis.
Non-coding microRNAs (miRNAs) are powerful regulators of gene expression and critically involved in cardiovascular pathophysiology. The aim of the current study was to identify miRNAs regulating cardiac fibrosis. Cardiac samples of age-matched control subjects and sudden cardiac death (SCD) victims with primary myocardial fibrosis (PMF) were subjected to miRNA profiling. Old SCD victims with PMF and healthy aged human hearts showed increased expression of miR-1468-3p. In vitro studies in human cardiac fibroblasts showed that augmenting miR-1468-3p levels induces collagen deposition and cell metabolic activity and enhances collagen 1, connective tissue growth factor, and periostin expression. In addition, miR-1468-3p promotes cellular senescence with increased senescence-associated β-galactosidase activity and increased expression of p53 and p16. AntimiR-1468-3p antagonized transforming growth factor β1 (TGF-β1)-induced collagen deposition and metabolic activity. Mechanistically, mimic-1468-3p enhanced p38 phosphorylation, while antimiR-1468-3p decreased TGF-β1-induced p38 activation and abolished p38-induced collagen deposition. RNA sequencing analysis, a computational prediction model, and qPCR analysis identified dual-specificity phosphatases (DUSPs) as miR-1468-3p target genes, and regulation of DUSP1 by miR-1468-3p was confirmed with a dual-luciferase reporter assay. In conclusion, miR-1468-3p promotes cardiac fibrosis by enhancing TGF-β1-p38 signaling. Targeting miR-1468-3p in the older population may be of therapeutic interest to reduce cardiac fibrosis.


Putting zoo animal cancer into perspective.
As part of a comparative research agenda that promises insights that help extend the human lifespan and combat cancer, cancer prevalence in zoo animals has received recent attention. Here, we want to draw attention to a principle of cancer research that was introduced into the zoo world as early on as 1933, but that seems to have gone somewhat forgotten: Cancer is mainly a disease of old age, and therefore studies aiming at identifying taxa that are particularly susceptible or resistant to cancer must control for whether the respective zoo populations are 'old.' In a comparative context, 'old age' cannot be measured in absolute terms (e.g., years), but only in relation to a species' maximum lifespan: Species that achieve, across zoos, a higher mean lifespan as a percent of their maximum lifespan are 'older.' When applying this metric to former as well as more recently published data on cancer prevalence, it appears that those species that become relatively old in zoos-in particular, the carnivores-have a relatively high cancer prevalence. Any improvement in animal husbandry-which reduces premature deaths-should, by default, lead to more cancer. Cancer in zoo animals, like any other old-age condition, might therefore be embraced as a proxy for good husbandry. Rather than following a sensationalist approach that dramatizes disease and death per se, zoos should be clear about what their husbandry goals are, what relative longevities they want to achieve for which species, and what old-age diseases they should therefore expect: in the end, one has to die of something.


[Diagnostic value of (18)F-FDG PET/CT imaging plus serum tumor marker assays for pulmonary lesions and clinical significance of SUVmax].
To evaluate the diagnostic value of (18)F-FDG positron emission tomography/computed tomography (PET/CT) plus serum tumor marker assay in lung cancer and explore the correlation between standard uptake value (SUVmax) with clinicopathologic factors in lung cancer. A total of 177 cases of lung cancer diagnosed by radiography or computed tomography (CT) were recruited.(18)F-FDG PET/CT imaging and detection of three lung cancer related serum markers (carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed within one week in all cases. The sensitivity, specificity and accuracy of those approaches were calculated through comparing the results with pathologic examinations. Also the associations between SUVmax and clinicopathologic features were analyzed. Among them, 145 patients were detected to have lung cancer by pathologic diagnosis while the other 32 patients had benign lung diseases. The sensitivity, specificity, accuracy of (18)F-FDG PET/CT imaging, serum tumor markers and their combination in assessing lung cancers were 89.7%, 78.1%, 87.6%; 89.7%, 78.1%, 87.6% and 96.6%, 56.3%, 89.3% respectively. The combination of (18)F-FDG PET/CT and serum tumor markers in lung lesions showed significantly higher sensitivity than serum tumor markers and (18)F-FDG PET/CT alone (P = 0.000, P = 0.002). Its accuracy was also significantly higher than those of tumor markers (P < 0.05). Compared with (18)F-FDG PET/CT alone, the accuracy was higher in combination group. But the difference showed no statistical significance (P > 0.05). SUVmax was significantly associated with tumor staging, tumor size and pathologic type. The combination of (18)F-FDG PET/CT and tumor markers may improve the positive diagnostic rate of lung cancer. And SUVmax can help to evaluate tumor staging and determine pathological types.


Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure.
Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF). We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No-HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long-chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no-HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance. We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.


Zirconia Use in Dentistry - Manufacturing and Properties.
Several types of metal-free ceramics have been developed to meet the patients demand for natural looking appearance restorations. Owing to their biocompatibility and good mechanical properties zirconia has been successfully used in recent years as a dental biomaterial. Due to its high opacity zirconia cores are generally covered with ceramic veneers that provide a more natural appearance but have frequent incidence of chipping. As an alternative to veneered zirconia full-contour zirconia restorations become more widely used nowadays. The paper reviews the current knowledge and scientific data of the zirconia use in dentistry in order to compare the zirconia based dental restorations with the metal-ceramic ones and also the two types of dental restoration based on zirconia, veneered or monolithic zirconia.


DeepAntigen: a novel method for neoantigen prioritization via 3D genome and deep sparse learning.
The mutations of cancers can encode the seeds of their own destruction, in the form of T-cell recognizable immunogenic peptides, also known as neoantigens. It is computationally challenging, however, to accurately prioritize the potential neoantigen candidates according to their ability of activating the T-cell immunoresponse, especially when the somatic mutations are abundant. Although a few neoantigen prioritization methods have been proposed to address this issue, advanced machine learning model that is specifically designed to tackle this problem is still lacking. Moreover, none of the existing methods considers the original DNA loci of the neoantigens in the perspective of 3D genome which may provide key information for inferring neoantigens' immunogenicity. In this study, we discovered that DNA loci of the immunopositive and immunonegative MHC-I neoantigens have distinct spatial distribution patterns across the genome. We therefore used the 3D genome information along with an ensemble pMHC-I coding strategy, and developed a group feature selection-based deep sparse neural network model (DNN-GFS) that is optimized for neoantigen prioritization. DNN-GFS demonstrated increased neoantigen prioritization power comparing to existing sequence-based approaches. We also developed a webserver named deepAntigen (http://yishi.sjtu.edu.cn/deepAntigen) that implements the DNN-GFS as well as other machine learning methods. We believe that this work provides a new perspective toward more accurate neoantigen prediction which eventually contribute to personalized cancer immunotherapy. Data and implementation are available on webserver: http://yishi.sjtu.edu.cn/deepAntigen. Supplementary data are available at Bioinformatics online.


Elastin turnover in malignant solid tumors.
Desmosine, a crosslinking amino acid unique to elastin, was investigated as a possible biomarker for cancer. Twenty-eight normal controls, median age 67 years, had a median value for urine desmosine of 43.5 picomoles desmosine/mg creatinine. The median for 19 untreated cancer subjects of similar age was significantly higher (175 picomoles desmosine/mg creatinine, p < 0.001). Urine desmosine levels in 55 subjects currently receiving chemotherapy, as well as 67 individuals who had survived cancer and were currently clinically disease free, were not significantly different from controls. Our findings indicate that elastin is being turned over in malignant solid tumors, releasing significantly elevated levels of desmosine in the urine.


International study of physician's opinion on physician-patient sex concordance when treating athletes.
The effect of physician-patient sex concordance in medicine has been reported in many studies. Whether physicians believe that the sex concordance between physician and athlete influences treatment has not been investigated. Whether physicians believe that the sex concordance between physician and athlete influences treatment. Cross-sectional study. Online survey PARTICIPANTS: 1193 Sports medicine physicians in 51 countries. Participants were sports medicine physicians trained in orthopedics (n = 443 [37.1%]) and nonorthopedics (n = 750 [62.9%]) INTERVENTIONS: n/a MAIN OUTCOME MEASURES: Participants were asked to decide whether sex of the physician made them better suited to care for athletes of concordant or different sexes along with their personal background. Orthopedic sports medicine physicians agreed less than nonorthopedic sports medicine physicians regarding the statement "MALE sports medicine physicians are better suited than their female counterparts to care for MALE athletes" (Odds ratio 0.56, 95 % CI 0.35-0.91, p = 0.02), and compared to sports medicine physicians based in Europe, those based in Asia agreed more to this statement (OR 7.91, 95 % CI 5.63-14.79, p = 0.02). In addition, regarding the statement "FEMALE sports medicine physicians are better suited than their male counterparts to care for FEMALE athletes", compared to sports medicine physicians based in Europe, those based in Asia (OR 9.12, 95 % CI 5.63-14.79, p = 0.02 ) and North America (OR 2.18, 95 % CI 1.46-3.25, p < 0.01 ) agreed more and Orthopedic sports medicine physicians agreed less than nonorthopedic sports medicine physicians (OR 0.61, 95 % CI 0.39-0.93, p = 0.02) to this statement. Sports medicine physicians trained in orthopedics agreed less to the importance of sex concordance but those based in Asia agreed to this compared to sports medicine physicians practicing in other regions when the dependents factors were adjusted. This article is protected by copyright. All rights reserved.


Anterior instability of the shoulder due to capsular laxity.
Thirty cases of anterior instability of the shoulder are reported where the only or pre-eminent pathological condition observed at operation was an abnormal laxity of the joint capsule. Four clinical pictures emerged - recurrent distortion, recurrent subluxation, recurrent dislocation, dislocation followed by recurrent subluxation - presumably due to increasing degrees of instability. In 13 cases, surgery consisted of stabilisation of the anterior joint capsule at the neck of the glenoid with a staple, and in 17 cases, capsulo-muscular plastic surgery with the aim of reducing the excessive width of the joint capsule and shortening the subscapularis. Satisfactory results were obtained in 90% of the cases. Although the quality of the results was not conditioned by the type of surgery used, capsulo-muscular plastic surgery appears to be the best method for the correction of the pathological condition responsible for the instability.


Nanoparticles exposing neurotensin tumor-specific drivers.
Nanoparticles have attracted much attention for their potential application as in vivo carriers of drugs. Labeling of nanoparticles with bioactive markers that are able to direct them toward specific biological target receptors has led to a new generation of drug delivery systems. In particular, low molecular weight peptides that remain stable in vivo could be promising tools to selectively drive nanoparticles loaded with active components to tumor cells. We reported, recently, that tetrabranched neurotensin peptides (NT4) may be used to selectively target tumor cells with liposomes. Liposomes functionalized with tetrabranched neurotensin peptide, NT4, and loaded with doxorubicin showed clear advantages in cell binding, anthracyclin internalization, and cytotoxicity in respect of not functionalized liposomes. In this study, we compare branched (NT4) versus linear (NT) peptides in the ability to drive liposomes to target cells and deliver their toxic cargo. We showed here that the more densely decorated liposomes had a better activity profile in terms of drug delivery. Presentation of peptides to the cell membranes in the grouped shape provided by branched structure facilitates liposome cell binding and fusion.


Success and Recurrence Rate after Radial Extracorporeal Shock Wave Therapy for Plantar Fasciopathy: A Retrospective Study.
Background and Aims. The exploration of an individualised protocol of radial extracorporeal shock wave therapy (rESWT) for plantar fasciopathy, assessing success rates and the recurrence rate over a 1-year period after treatment, is not yet identified in literature. Methods and Results. Between 2006 and 2013, 68 patients (78 heels) were assessed for plantar fasciopathy. An individualised rESWT treatment protocol was applied and retrospectively analysed. Heels were analysed for mean number of shock wave impulses, mean pressure, and mean frequency applied. Significant mean pain reductions were assessed through Visual Analogue Scale (VAS) after 1-month, 3-month, and 1-year follow-up. Success rates were estimated as the percentage of patients having more than 60% VAS pain decrease at each follow-up. 1-year recurrence rate was estimated. The mean VAS score before treatment at 6.9 reduced to 3.6, 1 month after the last session, and to 2.2 and 0.9, after 3 months and 1 year, respectively. Success rates were estimated at 19% (1 month), 70% (3 months), and 98% (1 year). The 1-year recurrence rate was 8%. Moderate positive Spearman's rho correlation (r = 0.462, p < 0.001) was found between pretreatment pain duration and the total number of rESWT sessions applied. Conclusions. Individualised rESWT protocol constitutes a suitable treatment for patients undergoing rESWT for plantar fasciitis.


Ultrasound control of progressive hydrocephalus in infancy.
The authors conducted multidimensional echotomography on 119 infants to determine hydrocephalus and other disorders. The process proved quite reliable in showing changes in ventricle size. They raise the idea of conducting broad scale preventive screening among infants in danger groups to achieve early diagnosis.


Spatial and temporal trends of mercury concentrations in young-of-the-year spottail shiners (Notropis hudsonius) in the St. Lawrence River at Cornwall, ON.
The St. Lawrence River at Cornwall, Ontario is an "Area of Concern" because of mercury (Hg) biomagnification from bottom sediments. To assess the spatial and temporal distribution of Hg in the food web, young-of-the-year (YOY) spottail shiners (Notropis hudsonius) were collected in August 2005 from five sites along the Cornwall waterfront within a Hg-contaminated zone and two reference zones. The results were compared to analyses made between 1979 and 2000 by the Ontario Ministry of the Environment. Total Hg concentrations in spottail shiners from the contaminated zone were significantly higher than in reference zones, confirming previous observations. Within the contaminated zone, there were significant differences in Hg concentrations among three sites spaced about 500 m apart, consistent with a high degree of site fidelity of YOY fish and suggesting a possible internal source of Hg. Hg concentrations in spottail shiners are decreasing regionally, although year-to-year variability was high, particularly in the contaminated zone. Stable isotope analyses of spottail shiners did not reveal any differences in nitrogen isotope composition among zones that would indicate differences in food-web structure and Hg biomagnification. However, carbon sources at an upstream reference zone were not the same as within the Area of Concern. Differences in carbon isotope composition at two sites within the contaminated zone corresponded to differences in Hg concentrations, consistent with a unique internal source of Hg. The variation in Hg contamination of YOY spottail shiners over fine spatial and temporal scales provide important insights about the potential release of Hg from contaminated sediments and the role of climate in regional trends. Sessile YOY fish provide a precise indicator for demonstrating these differences and for assessing their cause.


Herlyn-Werner-Wunderlich syndrome: a rare presentation with pyocolpos.
Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome with only a few hundred reported cases described since 1922. Only a handful of these cases have been associated with pyocolpos. Mullerian duct anomalies have an incidence of 2-3%. While OHVIRA constitutes 0.16-10% of these Mullerian duct anomalies. Symptoms usually present shortly after menarche when hematocolpos develops during menstruation resulting in dysmenorrhea and a pelvic mass. The pelvic mass is the collection of blood products within the obstructed hemivagina. The first study in the diagnostic work-up is usually ultrasonography, which typically demonstrates a pelvic fluid collection which can simulate other disease processes thus confounding the diagnosis. MRI findings of the pelvis reveal a didelphic uterus. Imaging of the abdomen reveals agenesis of the ipsilateral kidney. MRI is beneficial in characterizing the didelphic uterus and vaginal septum for pre-operative planning. Understanding the imaging findings, in conjunction with the clinical presentation, is critical for early diagnosis in attempting to prevent complications such as endometriosis or adhesions from chronic infections with subsequent infertility.


Low albumin levels increase endothelial NO production and decrease vascular NO sensitivity.
Hypoalbuminaemia is associated with increased risk of cardiovascular disease. It is unclear whether endothelial dysfunction is a direct result of low albumin or whether it is caused by factors like chronic inflammation or dyslipidaemia. In this study, the effect of low albumin concentrations on endothelial nitric oxide synthase (eNOS)-dependent NO production was determined in vitro and ex vivo. eNOS activity, assessed by arginine-citrulline conversion, and NO production, determined by 4,5-diaminofluorescein diacetate, electron paramagnetic resonance and Griess colorimetry, were measured in cultured endothelial cells expressing high levels of eNOS (bEnd.3) after exposure to albumin concentrations ranging from 0.5 mmol/l (33 g/l) to 0 mmol/l. Analbuminaemic and control rat plasma NO metabolites and aortic eNOS protein mass were determined, and aortic endothelium-independent and endothelium-dependent vasodilator tone were measured ex vivo under albumin-free conditions. In vitro, eNOS activity was significantly increased in the absence of albumin (75 +/- 2 vs 26 +/- 6 pmol/min/mg protein; P < 0.01). Low albumin levels consistently increased NO production in endothelial cells. Plasma NO metabolites were increased (18.2 +/- 1.9 vs 12.5 +/- 0.8 micromol/l; P < 0.05) and endothelium-independent relaxation was markedly blunted in analbuminaemic rats, resulting in a considerably higher ED50 (80 +/- 2 vs 1.1 +/- 0.2 nmol/l, P < 0.01), while endothelium-dependent dilatation was slightly, but significantly, increased. Aortic eNOS protein mass was not affected. This implies that in vivo hypoalbuminaemia reduces vascular NO sensitivity. We show that low albumin as such seems to enhance, rather than diminish, eNOS-mediated endothelial NO production.


A Novel PBPK Modeling Approach to Assess Cytochrome P450 Mediated Drug-Drug Interaction Potential of the Cytotoxic Prodrug Evofosfamide.
Evofosfamide is a cytotoxic small-molecule prodrug preferentially activated under hypoxic conditions. The cytotoxicity of evofosfamide impacted the generation of in vitro drug-drug interaction (DDI) data, especially in vitro induction results. Therefore, a novel physiologically based pharmacokinetic (PBPK) approach was used, which involved available in vitro and clinical data of evofosfamide and combined it with induction data from the prototypical cytochrome P450 (CYP)3A inducer rifampicin. The area under the concentration-time curve (AUC) ratios of midazolam were above 0.80, indicating that induction of CYP3A by evofosfamide administered weekly is unlikely to occur in humans. Moreover, static and PBPK modeling showed no clinically relevant inhibition via CYP2B6, CYP2D6, and CYP3A4. In conclusion, PBPK models were used to supplement in vitro information of a cytotoxic compound. This approach may set a precedent for future studies of cytotoxic drugs, potentially reducing the need for clinical DDI studies and providing more confidence in the clinical use of approved cytotoxic compounds for which DDI information is sparse.


Asystole in young athletic women during breast augmentation: a report of three cases.
Reported herein are three cases of spontaneous bradycardia progressing to asystole during routine breast augmentation in healthy, adult female patients with a history of endurance training and resting bradycardia (heart rate <60 beats per minute). The incidence of this phenomenon is minimally reported and virtually unexplained in literature. Our goal is to alert the plastic surgery community of the possibility of these events occurring without warning in athletic patients, attempt to explain these findings, and provide a plan of action to minimize morbidity and mortality in these patients. The most severe case was that of a 38-year-old female who became severely bradycardic progressing to asystole during routine breast augmentation. She had no history of any medical problems, but did have a resting heart rate of <60. Glycopyrrolate, an antimuscarinic agent, was given and chest compressions started. After 10-20 s of chest compressions the patient's normal sinus rhythm resumed. Two other cases are also reported, although these patients responded to antimuscarinic agents without requiring chest compressions. Both were endurance athletes with a resting heart rate of <60. Bradycardia caused by a vagal response during surgery is not uncommon and routinely treated successfully with administration of atropine-like agents. Bradycardia progressing to frank asystole is rare and has not been reported in young, otherwise healthy, aesthetic surgery patients. This report should serve to alert the plastic surgeon to the possibility of this situation occurring and how to treat it successfully, especially in the outpatient or office-based surgery setting. Level of Evidence V This journal requires that authors assign a level of evidence to each article.


A New Epizoanthus Species (Cnidaria: Anthozoa: Epizoanthidae) Associated with the Gastropod Mollusk Guildfordia triumphans from Southern Japan.
From previous research, it is known that hermit crabs predominantly dwell in vacated gastropod shells. Several epibiotic taxa are known to live on gastropod shells inhabited by hermit crabs, including some species of the zoantharian genus Epizoanthus. Although many previous taxonomic studies have focused on hermit-crab-associated Epizoanthus species, and have resulted in the description of several species, gastropod-associated species have received comparatively much less attention. At least five Epizoanthus species associated with gastropods have been formally described, but some species have not been found or examined since their original description. In Japan, specimens on the gastropod mollusk Guildfordia triumphans have been found and examined in previous studies, but no formal taxonomic conclusions were made. In this study, we formally describe Epizoanthus rinbou sp. n. from southern Japan based on molecular phylogenetic analyses combined with morphological observations. Epizoanthus rinbou sp. n. is located within an Epizoanthus clade consisting of species associated with gastropods, hermit crabs, sea urchins, and barnacles, as well as non-associated Epizoanthus species. The present study highlights the utility of molecular phylogeny for understanding the diversity and relationships of gastropod-associated Epizoanthus species.


Agaricus bisporus (edible mushroom lectin) inhibits ocular fibroblast proliferation and collagen lattice contraction.
The edible mushroom lectin from Agaricus bisporus (ABL) has antiproliferative effects on a range of cell types. This investigation was undertaken to test whether it might have inhibitory activity on Tenon's capsule fibroblasts in in vitro models of wound healing and therefore have a use in the modification of scar formation after glaucoma surgery.Human ocular fibroblasts in monolayers and in three-dimensional collagen lattices were exposed to ABL (0-100 microg ml(-1)). Proliferation was studied by the MTS assay and by counting haematoxylin-stained cells; contraction was measured as a change in the diameter of three-dimensional collagen lattices. Toxicity was investigated using a fluorescent viability assay. FITC-labelled lectin was used to study cell binding and internalization of ABL.ABL caused a dose-dependent inhibition of proliferation and lattice contraction without significant toxicity. Proliferation was inhibited by 5-40% in the dose range 20-100 microg ml(-1) Significant inhibition of lattice contraction was achieved with 40 microg ml(-1) ABL, and at 100 microg ml(-1) contraction was completely prevented. FITC-ABL binds to the cell surface and accumulates around the nuclear envelope when internalized. These experiments have shown that ABL possesses key features required of an agent that might control scarring processes and suggest that ABL might be especially useful where subtle modification of healing is needed. Further evaluation is warranted.


Stimuli-Responsive Luminescent Copper Nanoclusters in Alginate and Their Sensing Ability for Glucose.
Visually observable pH-responsive luminescent materials are developed by integrating the properties of aggregation-induced emission enhancement of Cu nanoclusters (NCs) and the Ca2+-triggered gelatin of alginate. Sodium alginate, CaCO3 nanoparticles, and Cu NCs are dispersed in aqueous solution, which is in a transparent fluid state, showing weak photoluminescence (PL). The introduced H+ can react with the CaCO3 nanoparticles to produce free Ca2+, which can cross-link the alginate chains into gel networks. Meanwhile, a dramatic increase in the PL intensity of Cu NCs and a blue shift in the PL peak appeared, assigned to the Ca2+-induced enhancement and gelatin-induced enhancement, respectively. Their potential application as a sensor for glucose is also demonstrated based on the principle that glucose oxidase can recognize glucose and produce H+, which further triggers the above-mentioned two-stage enhancement. A linear relationship between the PL intensity and the concentration of glucose in the range of 0.1-2.0 mM is obtained, with the limit of detection calculated as 3.2 × 10-5 M.


Rising Inequality and Intergenerational Mobility: The Role of Public Investments in Human Capital.
One consequence of the rise in inequality witnessed over the past 40 years is its potentially negative impact on intergenerational mobility if parents at the bottom of the income distribution invest significantly less in their children's human capital. I consider whether public investments in children can potentially offset the inequality of private investments. Specifically, examining changes in public spending in 25 Organization for Economic Co-operation and Development countries over the period 2000-2009, I find that increases in spending on health are most strongly associated with reductions in the importance of family background and declines in inequality in the production of child human capital as measured by the Program for International Student Assessment test scores among 15-year-olds. Public spending on family support, housing, and education are also moderately related. In contrast, increased spending on the elderly is associated with increases in the importance of parental background and inequality of child test scores. These results suggest that public investments in child human capital have the potential to offset the potentially negative impact of increasing income inequality on intergenerational mobility and inequality of the next generation. Further research firmly establishing a causal relationship is needed.


The radiobiological effects of heavy ions on mammalian cells and bacteria.
The radiobiological effects of heavy ions have been studied in experiments with mouse corneal epithelium, liver cells of rats irradiated in vivo, and the bacterium Escherichia coli B. From exposure of E. coli B to radiations with different LET, the effectiveness of the modifying influence of anoxia and some other radioprotectors has been determined.


Fanconi's syndrome induced by a monoclonal Vkappa3 light chain in Waldenstrom's macroglobulinemia.
Fanconi's syndrome (FS) is a disorder of sodium-dependent proximal tubule reabsorption, which may complicate plasma cell disorders producing a free monoclonal light chain (LC). FS often occurs in the setting of smoldering myeloma and features cytoplasmic crystalline inclusions of monoclonal kappa LC in proximal tubular cells and malignant plasma cells. Although the clinical and pathological presentation may vary, including lack of crystal formation, monoclonal kappa LCs that underlie FS show a striking genetic and biochemical homogeneity: they almost always belong to the Vkappa1 subgroup of variability and originate from 2 germline genes, O2/O12 or O8/O18. Their variable domain sequences present unusual hydrophobic residues, responsible for the resistance to proteolysis, which leads to LC accumulation in the endocytic compartment of proximal tubule cells. We report a patient with slowly progressive Waldenstrom's macroglobulinemia and full-blown FS with accumulation of a monoclonal kappa LC within proximal tubules, but no detectable crystalline organization. This LC, which belonged to the unusual Vkappa3 subgroup and derived from the L2/L16 germline gene, showed no common substitution with previously described FS kappaI LC and was sensitive to trypsin digestion. These data show that molecular and biochemical characteristics of kappa LCs in patients with FS are more heterogeneous than initially suspected. Mechanisms other than resistance of LCs to endosomal proteolysis probably are involved in the pathogenesis of FS-associated plasma cell dyscrasias.


Anthelmintic 1-cinnamamido-2,4-imidazolidinediones.
A series of 1-(substituted cinnamamido)-2,4-imidazolidinediones has been prepared from the corresponding cinnamoyl chlorides and 1-amino-2,4-imidazolidinedione hydrochloride in pyridine. These compounds possess a significant degree of anthelmintic activity against the mouse pinworm Syphacia obvelata. The most active compounds are those substituted with halogen or cyano groups.


Leech immunocytes contain proopiomelanocortin: nitric oxide mediates hemolymph proopiomelanocortin processing.
This report establishes the presence of mammalian-like proopiomelanocotropic hormone (POMC), and six of its peptides, including adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH), in the immune tissues of the leech Theromyzon tessulatum. The 25.4-kDa protein was purified by high pressure gel permeation chromatography, anti-ACTH-affinity column, and reverse-phase HPLC. Its characterization was performed by Edman degradation, enzymatic treatments, and electrospray mass spectrometry. Leech POMC exhibits considerable amino acid sequence similarity to mammalian POMC. Of the six peptides, three showed high sequence similarity to their vertebrate counterparts met-enkephalin, alpha-MSH, and ACTH: 100, 84.6, and 70%, respectively; whereas gamma-MSH, beta-endorphin, and gamma-lipotropin hormone exhibited only 45, 20, and 10% sequence identity, respectively. No dibasic amino acid residues were found at the C terminus of the gamma- and beta-MSH peptides. In contrast, the leech alpha-MSH was flanked at its C-terminal by the Gly-Arg-Lys amidation signal. ACTH and corticotropin-like intermediary pituitary peptide were also C-terminally flanked by dibasic amino acid residues. The coding region of leech POMC was obtained by reverse transcription-PCR using degenerated oligonucleotide primers. Circulating levels of ACTH and MSH were 10 and 1 fmol/microl hemolymph, respectively. Morphine, in a dose-dependent manner, increased the levels of both peptides threefold; this effect was blocked by naloxone treatment. Similar results were found with the anandamide. Leech ACTH was processed to MSH by the enzymes neutral endopeptidase (24.11) and angiotensin-converting enzyme. Leech alpha-MSH had the same activity as authentic alpha-MSH in two bioasssay systems. Taken together, the study demonstrates that POMC is present in invertebrates and its immunoregulatory actions have been conserved during evolution.


[Instillation of a new anticancer preparation for the treatment of superficial bladder cancer: comparison of clinical efficacy between peplomycin emulsion in hydroxypropylcellulosum and peplomycin in saline solution on tumor reduction].
Clinical efficacy of a new preparation of peplomycin emulsion in hydroxypropylcellulosum (HPC-PEP) was studied in 26 patients to compared with that in 14 patients administered with 60 mg of PEP in 20 ml saline (S-PEP). The HPC-PEP was a mixture of 90 mg PEP suspended in 30 ml of 1% HPC. Both of preparations were retained in the bladder cavity over an hour after the instillation. Intravesical instillation was performed once for the patients with HPC-PEP, and 10 times repeatedly for the patients with S-PEP. A clinical evaluation was made on the basis of cytoscopic finding and cytology one week after the final instillation. According to the degree of tumor reduction, the results were classified into "disappearance", "greater than 50% reduction," and "no alteration or further growth" of primary tumor, which were referred respectively to "complete response (CR)", "partial response (PR)" and "not changed (NC)". The rates of CR and response were 27 and 73% respectively for the HPC-PEP administered patients, which were significantly higher than those of 8 and 43% respectively for the patients with S-PEP. In terms of configuration and number of tumor, intravesical HPC-PEP treatment was found to be superior to intravesical S-PEP treatment. In HPC-PEP treatment, a series of untoward symptoms such as bladder irritability and leukopenia was encountered at a frequency of 8%, which is much less than those seen in the S-PEP treatment. These clinical date suggest that HPC-PEP treatment against the superficial bladder tumors is superior to conventional S-PEP instillation in terms of administration frequency and potent doses available to tumor reduction.


Labdane-type diterpenoids from the fruits of Vitex trifolia.
Seven new labdane-type diterpenoids, vitextrifolins A-G (1-7), along with eight previously reported analogues, were isolated from the fruits of Vitex trifolia. The structures of 1-7 were elucidated by spectroscopic data interpretation. The isolates were evaluated for their cytotoxicity against four human cancer cell lines (A549, HCT116, HL-60, and ZR-75-30), but all were inactive (IC(50) < 5 μg/mL).


Impact of human immunodeficiency virus on 2-year revision rates following lumbar fusion for degenerative spinal conditions: a retrospective cohort study.
To our knowledge, no studies exist that evaluate the impact of human immunodeficiency virus (HIV) on long-term revision rates following lumbar fusion. This study aims to understand how HIV impacts 2-year revision rates and 90-day postoperative complication rates following primary lumbar fusion for degenerative spine conditions. Data collection was done using PearlDiver Patient Records Database, a national insurance database from 2010-2019. Patients who underwent primary lumbar fusion for degenerative diseases were divided into a cohort of patients that are HIV positive (HIV), have asymptomatic HIV (AHIV), acquired immune deficiency syndrome (AIDS), and HIV-negative at the time of their procedure. Univariate and multivariable regression analyses were performed to determine rates of revision surgery, surgical site infection (SSI), neurological complications, sensory deficits, bowel/bladder dysfunction and myelopathies within two years of surgery as well as 90-day postoperative complications. In total, 216,587 patients were included in this study. Of these, 631 patients (0.29%) had HIV including 502 patients (0.23%) with asymptomatic HIV and 129 patients (0.06%) with AIDS. Relative to the control cohort, patients with HIV had no difference in odds of two-year revision surgery, SSI, neurological complications, sensory deficits, bowel/bladder dysfunction and myelopathies. Patients with HIV did have increased odds of postoperative pneumonia (OR 1.592; 95% CI: 1.048-2.314; P=0.021). AIDS patients had greater odds of respiratory complications (OR 2.585; 95% CI: 1.075-5.264; P=0.017) and septic complications (OR 2.702; 95% CI: 1.122-5.514; P=0.013) 90-day postoperatively. Our study found that HIV positive status did not significantly affect two-year revision rates compared to the control group. However, there is a higher rate of pneumonia and respiratory complications among HIV positive patients. Before deciding to proceed with surgical intervention in HIV positive individuals, surgeons must carefully consider each patient's specific diagnosis, comorbidities, and risk factors.


Caregiver burden at 6 months following severe traumatic brain injury.
Sixty-nine primary caregivers of people with a severe traumatic brain injury (TBI) were assessed at 6 months post injury. Caregivers completed questionnaires on the physical, cognitive, emotional, behavioural, and social functioning of the persons with the TBI. Caregiver psychosocial functioning and levels of subjective and objective burden were also assessed. Clinically significant levels of anxiety, depression, and impairment in social adjustment were evident in over a third of the caregivers. The frequency with which various changes in the person with the TBI and types of objective burden were reported had little relationship to the degree of distress caused by these changes. The person with TBI's social isolation and negative emotional behaviours caused the greatest degree of stress for caregivers. Caregivers were also most distressed by the impact that caregiving had on their personal health and free time. The results from a multiple regression analysis suggest that it is the presence of behavioural problems in the person with the TBI that has the most severe and pervasive impact on all aspects of caregiver functioning. It is suggested that these findings be taken into account when providing rehabilitation services to people with TBI and their families.


Impact of COVID-19 pandemic on consumer behavioural intention to purchase green products.
This study examined the fear of COVID-19 pandemic and its impact on consumer behavioural intention to purchase green products. The data was collected from consumers of Malaysia in hypermarkets. A total of 491 respondents were analyzed using the partial least square technique. The results indicated that the fear of the COVID-19 epidemic has a significant impact on health concerns, social media information, intolerance of uncertainty, and personal relevance, which in turn affect consumers' behavioural intention to purchase green products. With a serial mediating effect the results identified that fear of COVID-19 epidemic is associated with behavioural intention to purchase the green product. The findings of this study are crucial for understanding the swings in the green product purchase behaviour due to the ongoing uncertainty of COVID-19 crisis.


Copper, iron, and zinc contents of mature human milk.
Daily, weekly, and within-day variations in copper, iron, and zinc contents of human milk were investigated in order to determine whether one sample from an individual is representative of these elements. Total solids, fat, and protein contents were also measured. Fifty women in their 6th to 12th week of lactation each provided seven milk samples consisting of five consecutive daily samples and two additional samples collected either within a single day or at weekly intervals. Fat varied the most of all constituents and total milk solids reflected this variability. Values ranged from 0.2 to 10.4 g/100 ml for fat and from 8.58 to 17.49 g/100 ml for total solids. Protein varied from 0.76 to 2.04 g/100 ml among individuals, with little variation within an individual. Copper content varied considerably among women and within the same woman. With a large proportion of low values, the range was 0.09 to 0.63 mug/ml. Iron content was also found to vary within women as well as among women. Values ranged from less than 0.1 to 1.6 mug/ml with a preponderance of low values. Zinc content was more evenly distributed over the range of 0.14 to 3.95 mug/ml,and within an individual it did not vary widely. A representative estimate of copper and iron contents would therefore require multiple samples, whereas only one sample may provide a representative estimate of zinc content. Comparison of morning, midday, and evening values showed that copper and zinc are higher in the morning and iron is lower at this time. Increased amounts of copper, iron, and zinc were found in multiparous women whether or not they had previously lactated. Milk from older women had lower iron and higher copper and zinc contents than that from younger women. No differences were found in milk of women receiving dietary mineral and vitamin supplements. Calculations indicated that fully breast fed infants under 3 months of age receive approximately 0.35 mg/kg per day of zinc and 0.05 mg/kg per day of both copper and iron.


Serum retinol-binding protein 4 levels in nonobese women with polycystic ovary syndrome.
To test whether there was a difference in serum retinol-binding protein 4 (RBP4) levels between subjects with polycystic ovary syndrome (PCOS) and those with a healthy regular menstrual cycle and, in addition, to correlate serum RBP4 levels with a variety of parameters. Clinical study. University hospital. A total of 74 nonobese women were evaluated. Thirty-seven had PCOS, whereas the remaining 37 served as control subjects. Serum RBP4 levels were analyzed using ELISA. Serum levels of FSH, LH, TSH, E(2), T, insulin, glucose, cholesterol, triglycerides, and RBP4. The women with PCOS had higher levels of serum RBP4, waist-to-hip ratio, LH, T, insulin, homeostatic model assessment of insulin resistance, cholesterol, and triglycerides. Logistic regression analyses revealed a significant association between odds ratio (OR) values of PCOS and both T (OR = 1.125; 95% confidence interval [CI] 1.050-1.205), and cholesterol levels (OR = 1.029; 95% CI 1.004-1.056). Age and triglycerides were significantly correlated to serum RBP4 levels by multiple linear regression analysis. Our study has shown that [1] elevated RBP4 levels might arise from triglyceride metabolism, and that RBP4 levels might not be influenced by PCOS itself. [2] RBP4 might not be a useful marker of insulin resistance in subjects with PCOS.


Microstructure Evolution and Mechanical Properties of Underwater Dry and Local Dry Cavity Welded Joints of 690 MPa Grade High Strength Steel.
Q690E high strength low alloy (HSLA) steel plays an important role in offshore structures. In addition, underwater local cavity welding (ULCW) technique was widely used to repair important offshore constructions. However, the high cooling rate of ULCW joints results in bad welding quality compared with underwater dry welding (UDW) joints. Q690E high strength low alloy steels were welded by multi-pass UDW and ULCW techniques, to study the microstructural evolution and mechanical properties of underwater welded joints. The microstructure and fracture morphology of welded joints were observed by scanning electron microscope and optical microscope. The elemental distribution in the microstructure was determined with an Electron Probe Microanalyzer. The results indicated that the microstructure of both two welded joints was similar. However, martensite and martensite-austenite components were significantly different with different underwater welding methods such that the micro-hardness of the HAZ and FZ in the ULCW specimen was higher than that of the corresponding regions in UDW joint. The yield strength and ultimate tensile strength of the ULCW specimen are 109 MPa lower and 77 MPa lower, respectively, than those of the UDW joint. The impact toughness of the UDW joint was superior to those of the ULCW joint.


Dispersing and functionalizing multiwalled carbon nanotubes in TiO2 sol.
We report that oxidized multiwalled carbon nanotubes (MWCNTs) can be synchronously dispersed and functionalized in TiO2 sol via an in situ sol-gel process. Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and atomic force microscopy (AFM) were used to characterize the functionalized MWCNTs. The results revealed that the hydrolysis and condensation originated from Ti(OC4H9)4 molecules favor the dispersion of MWCNTs in as-prepared TiO2 sol. Based on the strong interaction between the oxidized MWCNTs and TiO2 sol during the in situ sol-gel process, MWCNT (core)-TiOx (shell) tubular composites and TiO2 nanotubes can be obtained through filtrating, washing, and annealing of this kind of TiO2 sol containing functionalized MWCNTs, as revealed by TEM, XPS, Raman spectroscopy, and redispersion experiment. By casting the dilute dispersion of functionalized MWCNTs onto a hydrophilic Si surface, discrete and individual nanotubes can be observed by AFM.


Cytokine-dependent Blimp-1 expression in activated T cells inhibits IL-2 production.
After Ag activation of naive T cells in vitro, extensive growth and differentiation into effector cells depend upon IL-2. DNA microarray analysis was used to identify IL-2-dependent molecules regulating this process. In this study, we show that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is expressed by a cytokine-dependent pathway in activated T lymphocytes. IL-2 production by activated CD4(+) and CD8(+) T cells inversely correlated with Blimp-1 levels as higher IL-2 production was associated with lower Blimp-1 expression. Furthermore, ectopic expression of Blimp-1 by activated T cells inhibited IL-2 production but enhanced granzyme B and CD25 expression. Collectively, these findings indicate that there is a negative feedback regulatory loop in activated T cells such that IL-2 inhibits its own production through induction of Blimp-1 while promoting an effector cell phenotype.


Authentication of an Italian PDO hazelnut ("Nocciola Romana") by NIR spectroscopy.
Common hazelnuts are widely present in human diet all over the world, and their beneficial effects on the health have been extensively investigated and demonstrated. Different in-depth researches have highlighted that the harvesting area can define small variations in the chemical composition of the fruits, affecting their quality. As a consequence, it has become relevant to develop methodologies which would allow authenticating and tracing hazelnuts. In the light of this, the present work aims to develop a non-destructive method for the authentication of a specific high-quality Italian hazelnut, "Nocciola Romana," registered with a protected designation of origin (PDO). Thus, different samples of this fruit have been analyzed by near-infrared (NIR) spectroscopy and then classification models have been built, in order to distinguish between the PDO fruits and the hazelnuts not coming from the designated region. In particular, two different classification approaches have been tested, a discriminant one, partial least squares-discriminant analysis, and a class-modeling one, soft independent modeling of class analogies. Both methods led to very high prediction capability in external validation on a test set (classification accuracy in one case, and sensitivity and specificity in the other, all higher than 92%), suggesting that the proposed methodologies are suitable for a rapid and non-destructive authentication of the product.


Muscle metabolic responses during 16 hours of intermittent heavy exercise.
The alterations in muscle metabolism were investigated in response to repeated sessions of heavy intermittent exercise performed over 16 h. Tissue samples were extracted from the vastus lateralis muscle before (B) and after (A) 6 min of cycling at approximately 91% peak aerobic power at repetitions one (R1), two (R2), nine (R9), and sixteen (R16) in 13 untrained volunteers (peak aerobic power = 44.3 +/- 0.66 mL.kg-1.min-1, mean +/- SE). Metabolite content (mmol.(kg dry mass)-1) in homogenates at R1 indicated decreases (p < 0.05) in ATP (21.9 +/- 0.62 vs. 17.7 +/- 0.68) and phosphocreatine (80.3 +/- 2.0 vs. 8.56 +/- 1.5) and increases (p < 0.05) in inosine monophosphate (IMP, 0.077 +/- 0.12 vs. 3.63 +/- 0.85) and lactate (3.80 +/- 0.57 vs. 84.6 +/- 10.3). The content (micromol.(kg dry mass)-1) of calculated free ADP ([ADPf], 86.4 +/- 5.5 vs. 1014 +/- 237) and free AMP ([AMPf], 0.32 +/- 0.03 vs. 78.4 +/- 31) also increased (p < 0.05). No differences were observed between R1 and R2. By R9 and continuing to R16, pronounced reductions (p < 0.05) at A were observed in IMP (72.2%), [ADPf] (58.7%), [AMPf] (85.5%), and lactate (41.3%). The 16-hour protocol resulted in an 89.7% depletion (p < 0.05) of muscle glycogen. Repetition-dependent increases were also observed in oxygen consumption during exercise. It is concluded that repetitive heavy exercise results in less of a disturbance in phosphorylation potential, possibly as a result of increased mitochondrial respiration during the rest-to-work non-steady-state transition.


Calibration of a Land Subsidence Model Using InSAR Data via the Ensemble Kalman Filter.
The application of interferometric synthetic aperture radar (InSAR) has been increasingly used to improve capabilities to model land subsidence in hydrogeologic studies. A number of investigations over the last decade show how spatially detailed time-lapse images of ground displacements could be utilized to advance our understanding for better predictions. In this work, we use simulated land subsidences as observed measurements, mimicking InSAR data to inversely infer inelastic specific storage in a stochastic framework. The inelastic specific storage is assumed as a random variable and modeled using a geostatistical method such that the detailed variations in space could be represented and also that the uncertainties of both characterization of specific storage and prediction of land subsidence can be assessed. The ensemble Kalman filter (EnKF), a real-time data assimilation algorithm, is used to inversely calibrate a land subsidence model by matching simulated subsidences with InSAR data. The performance of the EnKF is demonstrated in a synthetic example in which simulated surface deformations using a reference field are assumed as InSAR data for inverse modeling. The results indicate: (1) the EnKF can be used successfully to calibrate a land subsidence model with InSAR data; the estimation of inelastic specific storage is improved, and uncertainty of prediction is reduced, when all the data are accounted for; and (2) if the same ensemble is used to estimate Kalman gain, the analysis errors could cause filter divergence; thus, it is essential to include localization in the EnKF for InSAR data assimilation.


Significant lability of guaiacylglycerol beta-phenacyl ether under alkaline conditions.
It was observed that the beta-O-4 bond cleavage of a dimeric phenolic lignin model compound with an alpha-carbonyl group at the B-ring, 2-(2-ethoxy-4-formylphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol (I), is extremely fast in a mild anaerobic alkaline treatment (0.45 mol/L NaOH, 95 degrees C, 0.8 MPa of N2). This phenomenon significantly contrasts with the case of a common dimeric phenolic lignin model compound without any specific functional group, 1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol (II). The most plausible mechanism is the migration of the B-ring from the beta- to the alpha-position following the SNAr mechanism. Because this migration affords the alkaline labile phenolic alpha-O-4-type compound (XI), the formation of the quinone methide as well as the cleavage of the originally alkaline very stable alkyl-aryl ether bond is promoted. This promotion of the quinone methide formation explains why a relatively large amount of 4-hydroxy-3-methoxybenzaldehyde (IV) is produced from I in an oxygen-alkali treatment.


Allergic reaction caused by articaine.
We report the case of a 51-year-old woman who had an immediate skin reaction after subcutaneous administration of a local anesthetic (LA) composed of articaine and epinephrine before a dental procedure. The patient subsequently underwent further dental procedures without LA. Skin prick tests performed with commercial LAs (lidocaine, mepivacaine, bupivacaine and articaine) were negative with epinephrine and all LAs except articaine. In 10 healthy controls, skin prick tests with articaine were negative. Subcutaneous challenge test with mepivacaine (0.3 and 0.5 ml) was negative. Provocations with the remaining anesthetics of the amide group were not carried out due to the patient's refusal.


Global heterogeneity of glomerular volume distribution in early diabetic nephropathy.
Morphologic characteristics in early stage of nephropathy of noninsulin-dependent diabetes mellitus (NIDDM) have not been determined despite the fact thatdiagnosis in this stage of the disease is important for the prognosis. We hypothesized that heterogeneity in glomerular volume-distribution may be a sensitive index of early stage of diabetic nephropathy in NIDDM. In spontaneous diabetic rats [Otsuka Long-Evans Tokushima Fatty (OLETF) rat (N= 5)] of 27 to 28 weeks, an experimental model of early diabetic nephropathy in human NIDDDM and age-matched control rats [Long Evans Tokushima Lean (LETO) rat (N= 5)], we completely filled the kidney with contrast medium. Glomeruli were visualized as three-dimensional images using x-ray micro-computed tomography (micro-CT). Glomerular volumes (N= 400 in each kidney) were directly measured and evaluated as absolute volume and normalized values to kidney weight and body weight. Scattering of glomerular volume-distribution was evaluated as coefficient variation (CV) (SD/mean). The CV was significantly larger in OLETF rat (0.195) comparing to LETO rat (0.146, P < 0.01). This difference was even consistent under the normalization to kidney weight and body weight. Absolute glomerular volume was larger in OLETF rat compared to LETO rat (P < 0.005); however, when glomerular volume was normalized, this variable was comparable between two groups. We visualized three-dimensional glomerular images in the early stages of diabetic nephropathy using micro-CT and quantified the heterogeneity in glomerular volume distribution throughout the cortex by direct measurement of the individual. We propose that heterogeneity in glomerular volume distribution is a sensitive parameter to ascertain early diabetic nephropathy in NIDDM.


Numerical evaluation of cytologic data. XIII. Curve fitting and curvilinear regression.
A method of curve fitting is described by which curves can be fitted to data for which the independent variables are not spaced equidistantly. The method uses the calculation of regression coefficients for an appropriate polynomial. Testing of the plotted curve by computation of the residual sum of squares is shown also, as is use of a "coefficient of partial determination" to test the statistical significance of the degree of polynomial chosen.


Rhodium(i)-catalyzed cascade C(sp2)-H bond alkylation - amidation of anilines: phosphorus as traceless directing group.
We introduce a versatile Rh(i)-catalyzed cascade reaction, combining C(sp2)-H bond functionalization and amidation between N-arylphosphanamines and acrylates. This innovative approach enables the rapid synthesis of dihydroquinolinone scaffolds, a common heterocycle found in various pharmaceuticals. Notably, the presence of the phosphorus atom facilitates the aniline ortho-C(sp2)-H bond activation prior to N-P bond hydrolysis, streamlining one-pot intramolecular amidation. Moreover, we demonstrate the applicability of this reaction by synthesizing an antipsychotic drug. Detailed mechanistic investigations revealed the involvement of a Rh-H intermediate, with substrate inhibition through catalyst saturation.


The relationship between serum oestradiol concentration and energy balance in young women distance runners.
Reproductive dysfunction in women distance runners has been linked to an imbalance between energy intake (EI) and energy expenditure (EE) which leads to an energy deficit. To determine whether ovarian suppression is associated with an energy deficit, the relationships between serum oestradiol (E2) concentration and indices of energy balance (EB) were explored in a group of women runners with a variety of menstrual patterns and a range of activity levels. Subjects comprised 33 women distance runners of mean (SD) age 27.2 (1.8) years. Sixteen of these women were defined as eumenorrhoeic (11-13 menstrual bleeds per year during the past 2 years), 8 as oligomenorrhoeic (< or = 3 menstrual bleeds per year for 2 years) and 9 as amenorrhoeic (absence of menses for > 1 year). Their volume of running training ranged from 36 to 97 km x wk(-1) [mean (SD): 68.6 (21.4) km x wk(-1). The body mass index (BMI) and percent body fat (BF) of each subject was measured. Their mean daily energy balance (EB) was calculated by subtracting their dietary EI from their estimated EE recorded over 7 days. Serum concentrations of E2, total T3 and IGF-1 were measured from a fasting blood sample (taken in early follicular phase for Eu women). Relationships between serum E2, T3 and IGF-1, EB, BMI and BF were explored using bivariate correlation and regression analysis. The results showed that the most powerful predictors of serum E2 concentration were estimated EB (r = 0.88, P<0.001), serum T3 (r=0.94, P<0.001) and IGF-1 (r=0.84; P<0.001). Weaker correlations were observed between serum E2 and BMI (r=0.42; P=0.008) and serum E2 and BF (r=0.48; P=0.004). These relationships add support to the hypothesis that reproductive dysfunction in women distance runners is associated with an energy deficit.


Integrin-β5, a miR-185-targeted gene, promotes hepatocellular carcinoma tumorigenesis by regulating β-catenin stability.
The tumour microenvironment is essential for cancer progress and metastasis. Integrin-β5 (ITGB5), a member of the integrin family, has been implicated to mediate the interactions of cells with the extracellular matrix (ECM) and promote tumorigenesis in several malignancies. However, the role of ITGB5 in hepatocellular carcinoma (HCC) is still unknown. The biological function of ITGB5 in HCC was investigated using migration, colony formation assays. The potential molecular mechanism of ITGB5 in regulating HCC tumorigenesis and β-catenin stabilization was investigated by western blotting, co-immunoprecipitation and ubiquitination assays. The expression level of ITGB5 mediated by miR-185 was confirmed by bioinformatic analysis, luciferase assay. The clinical significance of ITGB5 was based on human tissue microarray (TMA) analysis. Here, we found that the expression of ITGB5 is increased in HCC tissues. Elevated ITGB5 markedly facilitates HCC cell migration and tumorigenesis in vitro and in vivo. Further mechanistic studies revealed that ITGB5, as a partner of β-catenin, directly interacts with β-catenin and inhibits its degradation, thus leading to WNT/β-catenin activity. Subsequently, we also found that ITGB5 is a direct targeted gene of miR-185. The downregulation of miR-185 in HCC cells promotes an increase in ITGB5. An additional increase of ITGB5 is associated with β-catenin upregulation and a miR-185 decrease in HCC tissues. Our data reveal that the miR-185-ITGB5-β-catenin pathway plays an important role in HCC tumorigenesis, and ITGB5 may be a promising specific target for HCC therapy.


Depth Stratification Leads to Distinct Zones of Manganese and Arsenic Contaminated Groundwater.
Providing access to safe drinking water is a global challenge, for which groundwater is increasingly being used throughout the world. However, geogenic contaminants limit the suitability of groundwater for domestic purposes over large geographic areas across most continents. Geogenic contaminants in groundwater are often evaluated individually, but here we demonstrate the need to evaluate multiple contaminants to ensure that groundwater is safe for human consumption and agricultural usage. We compiled groundwater chemical data from three aquifer regions across the world that have been reported to have widespread As and Mn contamination including the Glacial Aquifer in the U.S., the Ganges-Brahmaputra-Mehta Basin within Bangladesh, and the Mekong Delta in Cambodia, along with newly sampled wells in the Yangtze River Basin of China. The proportion of contaminated wells increase by up to 40% in some cases when both As and Mn contaminants are considered. Wilcoxon rank-sum analysis indicates that Mn contamination consistently occurs at significantly shallower depths than As contaminated wells in all regions. Arsenic concentrations in groundwater are well predicted by redox indicators (Eh and dissolved oxygen) whereas Mn shows no significant relationship with either parameter. These findings illustrate that the number of safe wells may be drastically overestimated in some regions when Mn contamination is not taken into account and that depth may be used as a distinguishing variable in efforts to predict the presence of groundwater contaminants regionally.


Proposed frustrated-total-reflection acoustic sensing method.
Modulation of electromagnetic energy transmission through a frustrated-total-reflection device by pressure-induced changes in the index of refraction is proposed for use as an acoustic detector. Maximum sensitivity occurs for angles of incidence near the critical angle. The minimum detectable pressure in air is limited by Brownian noise. Acoustic propagation losses and diffraction of the optical beam by the acoustic signal limit the minimum acoustic wavelength to lengths of the order of the spatial extent of the optical beam. The response time of the method is fast enough to follow individual acoustic waves.


Posterior versus anterior circulation infarction: how different are the neurological deficits?
Distinguishing between symptoms of posterior circulation infarction (PCI) and anterior circulation infarction (ACI) can be challenging. This study evaluated the frequency of symptoms/signs in the 2 vascular territories to determine the diagnostic value of particular symptoms/signs for PCI. Neurological deficits were reviewed and compared from 1174 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. The diagnostic value of specific symptoms/signs for PCI was determined by measuring their sensitivity, specificity, positive predictive value (PPV), and the OR. Homolateral hemiplegia (PCI, 53.6% versus ACI, 74.9%; P<0.001), central facial/lingual palsy (PCI, 40.7% versus ACI, 62.2%; P<0.001), and hemisensory deficits (PCI, 36.4% versus ACI, 34.2%; P=0.479) were the 3 most common symptoms/signs in PCI and ACI. The signs with the highest predictive values favoring a diagnosis of PCI were Horner's syndrome (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), crossed sensory deficits (3.0% versus 0%; P<0.001; PPV=100.0%; OR=3.98), quadrantanopia (1.3% versus 0%; P<0.001; PPV=100.0%; OR=3.93), oculomotor nerve palsy (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), and crossed motor deficits (4.0% versus 0.1%; P<0.001; PPV=92.3%; OR=36.04); however, all had a very low sensitivity, ranging from 1.3% to 4.0%. This study indicates that the symptoms/signs considered typical of PCI occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate PCI from ACI. Neuroimaging is vital to ensure accurate localization of cerebral infarction.


Incidence of canine heartworm (Dirofilaria immitis) in Malaysia.
A total of 764 adult dogs were examined for microfilariae and adult worms of D immitis and 197 (25-8 per cent) were found to be infected. Direct blood examinations revealed only 47-2 per cent of the infected dogs whereas the blood serum examination detected 57-8 per cent of them. These results showed that the absence of circulating microfilariae could not be relied upon to be an accurate indication of the absence of patent heartworm infection. The average number of heartworms per dog was 5-5 with a range of one to 50.


Airway compromise during central venous cannulation in an undiagnosed tubercular retropharyngeal abscess: a case report.
Central venous cannulation is often associated with complications during insertion even by expert's hand and with the aid of ultrasound. We encountered a patient for central line insertion through the right internal jugular vein having a retropharyngeal abscess of tubercular origin. We accidentally punctured the abscess cavity leading to increased respiratory distress and subsequent need of intubation to the patient. This kind of complication during central line insertion has never been reported before. We intend to report such a case to alert everyone about the grave complications it can lead to and the methods to minimize them in the times ahead.


Crocetin Attenuates Sepsis-Induced Cardiac Dysfunction via Regulation of Inflammatory Response and Mitochondrial Function.
Sepsis-induced systemic inflammation can induce cardiac dysfunction, which can result in heart failure and death. Recently, natural drugs/compounds have received increased attention as therapeutic agents to prevent sepsis-induced cardiac dysfunction. Crocetin (CRO) is a natural compound that has been shown to reduce inflammation and cytotoxicity in cardiac ischemia/reperfusion injury. However, the effects of CRO on sepsis-induced cardiac dysfunction have not been evaluated. In this study, we used lipopolysaccharide (LPS)-induced H9c2 cells as an in vitro model to mimic cardiac sepsis. Crocetin significantly alleviated LPS-induced cytotoxicity, cellular apoptosis, and oxidative stress through increased Bcl-2 activity and PI3K-Akt signaling and suppression of caspase 3 and caspase 9 activities. Furthermore, CRO dramatically decreased the mRNA levels of TNF-α, IL-1, IL-6, and IL-8 via suppression of p65/Keap1 signaling and activation of Nrf2/HO-1/NQO1 signaling. In addition, CRO protected mitochondrial respiration, free fatty acid β-oxidation, and mitochondrial morphology in LPS-induced H9c2 cells. This study showed that CRO attenuated LPS-induced cardiac dysfunction via regulation of the inflammatory response and mitochondrial function and potentially had an effect on sepsis-induced cardiac dysfunction.


Mapping the neuroethological signatures of pain, analgesia, and recovery in mice.
Ongoing pain is driven by the activation and modulation of pain-sensing neurons, affecting physiology, motor function, and motivation to engage in certain behaviors. The complexity of the pain state has evaded a comprehensive definition, especially in non-verbal animals. Here, in mice, we used site-specific electrophysiology to define key time points corresponding to peripheral sensitivity in acute paw inflammation and chronic knee pain models. Using supervised and unsupervised machine learning tools, we uncovered sensory-evoked coping postures unique to each model. Through 3D pose analytics, we identified movement sequences that robustly represent different pain states and found that commonly used analgesics do not return an animal's behavior to a pre-injury state. Instead, these analgesics induce a novel set of spontaneous behaviors that are maintained even after resolution of evoked pain behaviors. Together, these findings reveal previously unidentified neuroethological signatures of pain and analgesia at heightened pain states and during recovery.


N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia.
Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ERβ, but only the aqueous fraction increased androgen receptors and ERα. In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ERβ without affecting androgen receptors and ERα. This effect was not observed with aqueous fraction of methanolic extract of red maca.


Intrarenal angiotensin III is the predominant agonist for proximal tubule angiotensin type 2 receptors.
In angiotensin type 1 receptor-blocked rats, renal interstitial (RI) administration of des-aspartyl(1)-angiotensin II (Ang III) but not angiotensin II induces natriuresis via activation of angiotensin type 2 receptors. In the present study, renal function was documented during systemic angiotensin type 1 receptor blockade with candesartan in Sprague-Dawley rats receiving unilateral RI infusion of Ang III. Ang III increased urine sodium excretion, fractional sodium, and lithium excretion. RI coinfusion of specific angiotensin type 2 receptor antagonist PD-123319 abolished Ang III-induced natriuresis. The natriuretic response observed with RI Ang III was not reproducible with RI angiotensin (1-7) alone or together with angiotensin-converting enzyme inhibition. Similarly, neither RI angiotensin II alone or in the presence of aminopeptidase A inhibitor increased urine sodium excretion. In the absence of systemic angiotensin type 1 receptor blockade, Ang III alone did not increase urine sodium excretion, but natriuresis was enabled by the coinfusion of aminopeptidase N inhibitor and subsequently blocked by PD-123319. In angiotensin type 1 receptor-blocked rats, RI administration of aminopeptidase N inhibitor alone also induced natriuresis that was abolished by PD-123319. Ang III-induced natriuresis was accompanied by increased RI cGMP levels and was abolished by inhibition of soluble guanylyl cyclase. RI and renal tissue Ang III levels increased in response to Ang III infusion and were augmented by aminopeptidase N inhibition. These data demonstrate that endogenous intrarenal Ang III but not angiotensin II or angiotensin (1-7) induces natriuresis via activation of angiotensin type 2 receptors in the proximal tubule via a cGMP-dependent mechanism and suggest aminopeptidase N inhibition as a potential therapeutic target in hypertension.


Outcomes following staged bilateral total hip replacement: does first-side surgery predict the second?
Patient-reported outcome measures (PROMs) for bilateral staged total hip replacements (THRs) were reviewed to determine whether first-side surgery can predict second-side outcomes. A retrospective review was undertaken of a consecutive cohort of staged bilateral THRs using the same approach, implant and technique, from August 2009 to February 2020. Minimal important change (MIC) in PROMs was set at ≥5. A total of 296 consecutive staged bilateral THRs were performed in 148 patients. Mean time interval between sides was 25 months (range 2-102). Mean age was 63.2 years for the first side and 65.3 years for the second; 62.8% of patients were female. Mean body mass index was 31.08 for the first side, increasing to 31.57 for the second side (p = 0.248). One-year follow-up PROMs were available for 96.6% and 92.5% of the first and second side, respectively. Mean PROMs improvement at 1 year was 26.4 for the first side and 25.1 for the second side (p = 0.207). Some 97.9% of patients achieved MIC for the first side and 96.3% for the second side (p = 0.092). Eight patients failed to reach an MIC on one side, all were female (p < 0.001); however, MIC was achieved for the contralateral side. Seven of eight patients (87.5%) achieved MIC by 2 years. This study identified no significant difference between first- and second-side PROMs improvements following staged bilateral THRs at 1-year follow-up. Failure to reach MIC on one side does not preclude success on the other. Female patients were more prone to not reach MIC at 1 year, but improvement was still subsequently achieved in the majority of cases. The informed consent process is able to reflect this expectation.


A Widefield Light Microscopy-Based Approach Provides Further Insights into the Colonization of the Flea Proventriculus by Yersinia pestis.
Yersinia pestis (the agent of flea-borne plague) must obstruct the flea's proventriculus to maintain transmission to a mammalian host. To this end, Y. pestis must consolidate a mass that entrapped Y. pestis within the proventriculus very early after its ingestion. We developed a semiautomated fluorescent image analysis method and used it to monitor and compare colonization of the flea proventriculus by a fully competent flea-blocking Y. pestis strain, a partially competent strain, and a noncompetent strain. Our data suggested that flea blockage results primarily from the replication of Y. pestis trapped in the anterior half of the proventriculus. However, consolidation of the bacteria-entrapping mass and colonization of the entire proventricular lumen increased the likelihood of flea blockage. The data also showed that consolidation of the bacterial mass is not a prerequisite for colonization of the proventriculus but allowed Y. pestis to maintain itself in a large flea population for an extended period of time. Taken as the whole, the data suggest that a strategy targeting bacterial mass consolidation could significantly reduce the likelihood of Y. pestis being transmitted by fleas (due to gut blockage), but also the possibility of using fleas as a long-term reservoir. IMPORTANCE Yersinia pestis (the causative agent of plague) is one of the deadliest bacterial pathogens. It circulates primarily among rodent populations and their fleas. Better knowledge of the mechanisms leading to the flea-borne transmission of Y. pestis is likely to generate strategies for controlling or even eradicating this bacillus. It is known that Y. pestis obstructs the flea's foregut so that the insect starves, frantically bites its mammalian host, and regurgitates Y. pestis at the bite site. Here, we developed a semiautomated fluorescent image analysis method and used it to document and compare foregut colonization and disease progression in fleas infected with a fully competent flea-blocking Y. pestis strain, a partially competent strain, and a noncompetent strain. Overall, our data provided new insights into Y. pestis' obstruction of the proventriculus for transmission but also the ecology of plague.


Transient posterior localization of a kinesin fusion protein reflects anteroposterior polarity of the Drosophila oocyte.
During oogenesis in Drosophila, determinants that will dictate abdomen and germline formation are localized to the 'polar plasm' in the posterior of the oocyte. Assembly of the polar plasm involves the sequential localization of several messenger RNAs and proteins to the posterior of the oocyte, beginning with the localization of oskar mRNA and Staufen protein during stages 8 and 9 of oogenesis. The mechanism by which these two early components accumulate at the posterior is not known. We have investigated whether directed transport along microtubules could be used to accomplish this localization. We have made a fusion protein composed of the bacterial beta-galactosidase enzyme as a reporter, joined to part of the plus-end-directed microtubule motor, kinesin, and have found that the fusion protein transiently localizes to the posterior of the oocyte during stages 8 and 9 of oogenesis. Treatment with the microtubule-depolymerizing agent colchicine prevents both the localization of the fusion protein and the posterior transport of oskar mRNA and Staufen protein. Furthermore, the fusion protein localizes normally in oocytes mutant for either oskar and staufen, but not in other mutants in which oskar mRNA and Staufen protein are mislocalized. Association with a plus-end-directed microtubule motor can promote posterior localization of a reporter protein during oogenesis. The genetic requirements for this localization and its sensitivity to colchicine, both of which are shared with the posterior transport of oskar mRNA and Staufen protein, suggest that similar mechanism may function in both processes.


Hormesis, ethics, and public policy: an overview.
This article synthesizes the major points made in the preceding essays on the topic of "Hormesis and Ethics." The questions and concerns raised in these essays are organized into three general categories: (1) scientific issues, (2) practical concerns, and (3) "explicitly ethical" considerations. The present article concludes with several suggestions. First, researchers would do well to address scientific concerns about the generalizability of hormesis. Second, it would be helpful to gather further information about the frequency that hormetic effects are beneficial for organisms over the long term. Third, more information is needed about the toxic exposures that the public is already receiving and about the potential synergistic effects of those exposures. Fourth, further reflection is warranted about whether regulations should, on one hand, maximize the ratio of benefits to risks for the population as a whole or, on the other hand, protect individuals from health risks to which they do not consent and for which they cannot easily be compensated.


Influence of level of dietary protein or energy on effects of ractopamine in finishing swine.
The effect of ractopamine, a beta-adrenergic agonist, on growth, nutrient utilization, and carcass composition was studied in pigs fed either 18% CP, 12% CP, or 18% CP restricted (RES = 67% of ad libitum) diets. The 18 and 12% CP diets provided 3.52 and 3.68 Mcal of DE/kg, respectively. All pigs were fed a low-protein (12% CP) diet during pretreatment growth from 15 to 60 kg. Ractopamine at 20 or 30 ppm (30 ppm for RES pigs) in the diet was fed from 60 kg live BW until slaughter at 105 kg (9 pigs/treatment). No ractopamine treatment effect (P greater than .05) was observed for either daily gain or gain/feed, although gain/feed was improved by 8% in both of the ad libitum groups. Ractopamine treatment resulted (P less than .01) in an overall reduction of carcass lipid by 8%, an increase of carcass protein by 5%, and a 21% improvement in the efficiency of protein utilization; the greatest changes occurred in the pigs fed the 12% CP diet (-17%, +11%, and +32%, respectively). The ad libitum daily feed intake was 15% less for pigs fed the 12% CP diet than for those fed the 18% CP diet (P less than .01), and there was a 10% reduction in intake of both diets with the addition of ractopamine (P less than .05). Both carcass lipid and protein deposition seemed to be closely related to energy intake (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)


MiR-96-5p alleviates inflammatory responses by targeting NAMPT and regulating the NF-κB pathway in neonatal sepsis.
Neonatal septicemia is a serious infectious disease in the neonatal period. MicroRNAs (miRNAs) have been reported to participate in the inflammatory responses in neonatal sepsis. The aim of the present study was to explore the effects and molecular mechanism of miR-96-5p on regulating the inflammatory responses in neonatal sepsis. MiR-96-5p was low expressed while nicotinamide phosphoribosyltransferase (NAMPT) was high expressed in the serum of neonatal septicemia patients. The expression of miR-96-5p was decreased in LPS-induced inflammatory responses. Besides, miR-95-5p relieved LPS-induced inflammatory responses in RAW264.7 cells. NAMPT was demonstrated as a potential target of miR-96-5p, and knockdown of NAMPT reduced inflammatory in RAW264.7 cells stimulated with LPS. Moreover, overexpression of NAMPT reversed the effects of miR-96-5p on LPS-induced inflammatory responses. In addition, miR-96-5p inhibited nuclear factor (NF)-κB signaling pathway in RAW264.7 cells stimulated with LPS. MiR-96-5p alleviated inflammatory responses via targeting NAMPT and inhibiting NF-κB pathway in neonatal sepsis.


Reference to psychiatric consultation in the discharge letter of general hospital inpatients.
The consultation-liaison psychiatrist is frequently confronted with the consultees' lack of adherence to the consultants' recommendations. The aim of this study was to investigate the question if and how the C-L psychiatrist's diagnoses and recommendations are mentioned in the consultee's final medical report and thus communicated to the physician responsible for the aftercare. Psychiatric consult reports of a consecutive sample of 144 patients of the departments of neurology, internal medicine, and gynecology and obstetrics at the University Hospital of Zurich were compared to the content of the respective discharge letters. Some kind of information about the psychiatric consultation was found in 84 percent of the discharge letters (consultation as such: 71.5%; psychiatric diagnosis: 66.7%; recommendations: 76.2%. Length of stay, timing of the consultation, length of the consult report and type of recommendation correlated significantly with the mention of psychiatric aspects in the final medical report. Psychotropic medication and psychiatric hospitalization were the recommendations most reliably mentioned. Psychiatric consultation seems to be taken seriously by attending physicians and is communicated in a high percentage to the physicians responsible for the aftercare. Nevertheless, in patients where active post-discharge management is needed the C-L psychiatrist should actively manage referral to outpatient settings and/or instruct primary care providers.


Renal cells transformed with SV40 contain a high-conductance calcium-insensitive potassium channel.
The inside-out variant of the patch-clamp technique was used to investigate the properties of a K+ channel occurring in 20% of patches from two renal cell lines transformed with the wild-type simian virus 40 (SV40) (Vandewalle et al. J. Cell. Physiol. 141: 203-221, 1989). This channel was practically absent from the primary cultures of renal cortical cells from which the cell lines were originally derived. With identical K(+)-rich solutions on both sides of the membrane patch, the channel showed an inwardly rectifying current-voltage relationship with unit conductances of 151.8 +/- 4.8 pS at negative and 86.4 +/- 5.9 pS at positive voltages (n = 18). When K+ in the bath was replaced by Na+, a mean reversal potential of 57.0 +/- 5.2 mV (n = 6) was observed from which a K(+)-to-Na+ permeability ratio of 13 was calculated. The channel was insensitive to internal Ca2+ and was blocked by internal Ba2+. No clear dependence on voltage was apparent. This channel bears no resemblance to any epithelial K+ channel and may be a novel type of K+ channel. Its occurrence in two transformed cell lines with quite distinct phenotypes, one of proximal cells (RC.SV1) and the other of thick ascending limb cells (RC.SV2), suggests that transformation by SV40 might be responsible for its appearance.


Endovenous radiofrequency ablation and combined foam sclerotherapy treatment of multiple refluxing perforator veins in a Klippel-Trenaunay syndrome patient.
We describe an unusual pattern of venous abnormality and the use of endovenous radiofrequency ablation, using the TRans-Luminal Occlusion of Perforator technique to treat multiple refluxing perforators in a 29-year-old patient with Klippel-Trenaunay syndrome. Klippel-Trenaunay syndrome is a rare congenital anomaly characterised by a triad of features including unilateral limb overgrowth, venous varicosities and capillary malformations of the affected limb. Ultrasound findings demonstrated 22 incompetent perforator veins in the lateral aspect of the patients left leg, communicating with a complex network of large calibre varicosities causing unilateral leg oedema and pain. Staged radiofrequency ablation procedures using the Olympus Celon RFITT (radiofrequency-induced thermotherapy; please see Technical Note) device under local anaesthetic were performed. These procedures were followed with two sessions of foam sclerotherapy. This case report describes the efficacy of this treatment regime and this patient's significantly improved morbidity 18 months after initial treatment.