[Drug exanthema in connection with trimethoprim and sulfamethoxazole treatment, triggered by leech therapy].
In a 58-year-old hospitalized woman with gonarthrosis a leech therapy was applied to both knee joints. In the evening of the following day she observed strong pruritus in the area of the leech bites; in addition a maculopapular exanthema appeared on the torso and her lower extremities. The allergic reaction lasted four days. Administration of antihistamines only led to a slight improvement of the symptoms. A full restitution could only be achieved after a systemic dose of glucocorticoids on the fourth day after leech therapy. Eight days before beginning of the leech therapy a five-day antibiotic therapy with trimethoprim and sulfamethoxazole (Cotrim forte) had been administered to treat an uncomplicated urinary infection. Allergic reactions are well-known complications of these antibiotics and of leech therapy. The four-day duration of the allergic reaction after leech therapy, however, was untypical. In order to explain these symptoms, a prick test and an epicutaneous test for the antibiotic components were executed five weeks after the leech therapy. Furthermore, a second leech therapy was administered and a lymphocyte transformation test (LTT) was carried out. The results of the LTT showed a sensitization for sulfamethoxazole and a possible sensitization for trimethoprim, the results of the epicutaneous test showed a positive reaction to sodium lauryl sulfate, a component of the antibiotic. In the area of the leech bites a clear local skin reaction was observed. These results suggest a drug exanthema, in all probability triggered by the leech therapy.


Lentivirus vectors using human and simian immunodeficiency virus elements.
Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34(+) cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans.


Single-nucleus sequencing of silkworm larval midgut reveals the immune escape strategy of BmNPV in the midgut during the late stage of infection.
The midgut is an important barrier against microorganism invasion and proliferation, yet is the first tissue encountered when a baculovirus naturally invades the host. However, only limited knowledge is available how different midgut cell types contribute to the immune response and the clearance or promotion of viral infection. Here, single-nucleus RNA sequencing (snRNA seq) was employed to analyze the responses of various cell subpopulations in the silkworm larval midgut to B. mori nucleopolyhedrovirus (BmNPV) infection. We identified 22 distinct clusters representing enteroendocrine cells (EEs), enterocytes (ECs), intestinal stem cells (ISCs), Goblet cell-like and muscle cell types in the BmNPV-infected and uninfected silkworm larvae midgut at 72 h post infection. Further, our results revealed that the strategies for immune escape of BmNPV in the midgut at the late stage of infection include (1) inhibiting the response of antiviral pathways; (2) inhibiting the expression of antiviral host factors; (3) stimulating expression levels of genes promoting BmNPV replication. These findings suggest that the midgut, as the first line of defense against the invasion of the baculovirus, has dual characteristics of "resistance" and "tolerance". Our single-cell dataset reveals the diversity of silkworm larval midgut cells, and the transcriptome analysis provides insights into the interaction between host and virus infection at the single-cell level.


Lynch Syndrome: Genomics Update and Imaging Review.
Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites. Over time, the accumulation of mutations in microsatellites and elsewhere in the genome can affect the production of important cellular proteins, spurring tumorigenesis. Universal testing of colorectal tumors for microsatellite instability (MSI) is now recommended to (a) prevent cases of Lynch syndrome being missed owing to the use of clinical criteria alone, (b) reduce morbidity and mortality among the relatives of affected individuals, and (c) guide management decisions. Organ-specific cancer risks and associated screening paradigms vary according to the sex of the affected individual and the type of germline DNA alteration causing the MSI. Furthermore, Lynch syndrome-associated cancers have different pathologic, radiologic, and clinical features compared with their sporadic counterparts. Most notably, Lynch syndrome-associated tumors tend to be more indolent than non-Lynch syndrome-associated neoplasms and thus may respond differently to traditional chemotherapy regimens. The high MSI in cases of colorectal cancer reflects a difference in the biologic features of the tumor, possibly with a unique susceptibility to immunotherapy. ©RSNA, 2018.


TAp63γ and ΔNp63β promote osteoblastic differentiation of human mesenchymal stem cells: regulation by vitamin D3 Metabolites.
The transcription factor p63 is required for skeletal formation, and is important for the regulation of 1α,25(OH)2D3 receptor (VDR) in human mesenchymal stem cells (hMSC). Herein we report that TAp63γ and ΔNp63β appear to be an integral part of the osteoblastic differentiation of hMSC and are differentially regulated by the vitamin D3 metabolites 1α,25(OH)2D3 and 24R,25(OH)2D3. We compared the endogenous expression of p63 isoforms (TA- and ΔNp63) and splice variants (p63α, -β, -γ), in naive hMSC and during osteoblastic differentiation of hMSC. TAp63α and -β were the predominant p63 variants in naive, proliferating hMSC. In contrast, under osteoblastic differentiation conditions, expression of p63 changed from the TAp63α and -β to the TAp63γ and ΔNp63β variants. Transient overexpression of the p63 variants demonstrated that TAp63β, ΔNp63β, and ΔNp63γ increased alkaline phosphatase activity and ΔNp63α and -γ increased the expression of mRNA for osteocalcin and osterix. Our results support the hypothesis that TAp63α and -β promote a naive state in hMSC. Moreover, TAp63γ is increased during and promotes early osteoblastic differentiation through the expression of pro-osteogenic genes; VDR, Osterix, Runx2 and Osteopontin. ΔNp63β also appears to support osteogenic maturation through increased alkaline phosphatase activity. Treatment with 1α,25(OH)2D3 increased the expression of mRNA for ΔNp63, while addition of 24R,25(OH)2D3 increased the expression of TA- and ΔNp63γ variants. These novel findings demonstrate for the first time that p63 variants are differentially expressed in naive hMSC (TAp63α,β), are important during the osteoblastic differentiation of hMSC (TAp63γ and ΔNp63β), and are differentially regulated by the vitamin D3 metabolites, 1α,25(OH)2D3 and 24R,25(OH)2D3. The molecular nuances and mechanisms of osteoblastic differentiation presented here will hopefully improve our understanding of bone development, complications in bone repair (mal- and non-union fractures), osteoporosis and possibly lead to new modalities of treatment.


Elevation of serum amylase levels after narcotic administration.
Hyperamylasemia after narcotic administration is found in some patients. To determine the source of the amylase, serum isoamylases were separated by column chromatography in a group of patients with response to a Prostigmin-morphine challenge. The increment of amylase activity was pancreatic amylase.


Confident body, confident child: Evaluation of a universal parenting resource promoting healthy body image and eating patterns in early childhood-6- and 12-month outcomes from a randomized controlled trial.
To evaluate Confident Body, Confident Child (CBCC), a universal parenting resource designed to promote positive body image and healthy eating patterns in children aged 2-6 years, at 6- and 12-months follow-up. A four-arm randomized controlled trial with 345 parents was conducted. Group (A) received the CBCC resource pack + workshop, (B) received the CBCC resource pack only, (C) received a nutrition booklet and (D) received no interventions until all questionnaires were completed (i.e., waitlist control). Measures of parenting variables relevant to child body image and eating patterns, and parent-report of child weight, were administered at baseline, 6-weeks post-intervention (results reported previously), and 6- and 12-months follow-up. Mixed effects modeling comparing group averages over time revealed that significant group differences on measures of knowledge, parenting intentions and the parental feeding practice of weight restriction were still present at 12-months follow-up, though the remaining measures showed no significant differences between groups over time. The two CBCC groups reported more positive and less negative outcomes than the nutrition booklet active control. The CBCC program achieved sustained improvements in some parenting variables at 12-months, suggesting its value as an effective parenting intervention. Changes to the intervention design, such as the addition of a follow-up parent workshop, however, would likely increase its efficacy.


Multivariate analysis of maize disease resistances suggests a pleiotropic genetic basis and implicates a GST gene.
Plants are attacked by pathogens representing diverse taxonomic groups, such that genes providing multiple disease resistance (MDR) are expected to be under positive selection pressure. To address the hypothesis that naturally occurring allelic variation conditions MDR, we extended the framework of structured association mapping to allow for the analysis of correlated complex traits and the identification of pleiotropic genes. The multivariate analytical approach used here is directly applicable to any species and set of traits exhibiting correlation. From our analysis of a diverse panel of maize inbred lines, we discovered high positive genetic correlations between resistances to three globally threatening fungal diseases. The maize panel studied exhibits rapidly decaying linkage disequilibrium that generally occurs within 1 or 2 kb, which is less than the average length of a maize gene. The positive correlations therefore suggested that functional allelic variation at specific genes for MDR exists in maize. Using a multivariate test statistic, a glutathione S-transferase (GST) gene was found to be associated with modest levels of resistance to all three diseases. Resequencing analysis pinpointed the association to a histidine (basic amino acid) for aspartic acid (acidic amino acid) substitution in the encoded protein domain that defines GST substrate specificity and biochemical activity. The known functions of GSTs suggested that variability in detoxification pathways underlie natural variation in maize MDR.


Analysis of exon 1 mutations in the androgen receptor gene.
Eleven mutations in exon 1 of the androgen receptor gene (AR) have been identified in 15 individuals with Androgen Insensitivity syndrome (AIS). Nine of the mutations yield a stop codon directly, or due to a frameshift, in individuals with complete AIS (CAIS). One individual with CAIS had three different mutations in exon 1: one is nominally silent (Glu 211; GAG 995 GAA); two are missense (Pro 390 Arg and Glu 443 Arg). Five unrelated individuals with either CAIS, partial AIS (PAIS) or mild AIS (MAIS) had GAG 995 GAA as their only alteration. This report almost doubles the number of exon 1 mutations stored in the AR Mutation Database, reinforces their highly predominant nonsense character, and identifies Pro 390 and/or Gln 443 as residues that are probably necessary for one or more specific functions of the AR's N-terminal transactivation domain.


Nature-inspired hierarchical materials for sensing and energy storage applications.
Nature-inspired hierarchical architectures have recently drawn enormous interest in the materials science community, being considered as promising materials for the development of high-performance wearable electronic devices. Their highly dynamic interfacial interactions have opened new horizons towards the fabrication of sustainable sensing and energy storage materials with multifunctional properties. Nature-inspired assemblies can exhibit impressive properties including ultrahigh sensitivity, excellent energy density and coulombic efficiency behaviors as well as ultralong cycling stability and durability, which can be finely tuned and enhanced by controlling synergistic interfacial interactions between their individual components. This tutorial review article aims to address recent breakthroughs in the development of advanced Nature-inspired sensing and energy storage materials, with special emphasis on the influence of interfacial interactions over their improved properties.


Treatment of myelitis in Behçet's disease with rituximab.
Behçet's disease (BD) is a chronic inflammatory disorder that involves the parenchymal central nervous system (neuro-BD, NBD) approximately in 5-49% of patients, causing lesions rarely located in the spinal cord (SC). We report the first case of NBD-myelitis treated with intravenous rituximab. A 41-year-old man affected by BD presented with mild paraparesis with a miliary involvement and a 'net-like' gadolinium enhancement (Gde) of the SC. After a therapeutic attempt with pulsed cyclophosphamide and intravenous methylprednisolone, the clinical and neuroradiological course worsened. A progressive improvement was observed after rituximab administration associated with low doses of oral prednisone. No disease activity was detected and the patient reported no adverse event. After six rituximab cycles, cervical MRI was normal while thoracic MRI showed a slight T2-weighted hyperintensity of D4-D10 spinal tract without Gde. A combined use of rituximab and oral steroids resulted in a long-term suppression of NBD activity without any safety concern.


Does gender influence the likelihood or types of complications following cardiac surgery?
Over 410,000 cardiac surgeries are performed in American women each year. Women having coronary artery bypass graft (CABG) and valve surgery do so at an older age and with more cardiovascular risk factors than men. Women's smaller body size may also increase risk by increasing the technical difficulty of surgical procedures. Female CABG patients appear to have higher perioperative mortality and cardiac morbidity, although studies of neurologic outcomes in female CABG patients have produced equivocal findings. Women undergoing CABG tend to consume more hospital resources than men do in terms of blood transfusion, mechanical ventilation, and length of intensive care unit and overall hospital stay. With regard to valve surgery, women appear to have worse outcomes than men if the surgery is combined with a CABG operation. Women and men undergoing isolated aortic valve surgery have similar mortality, but little is known about gender differences in mitral and tricuspid valve surgery outcomes. Women who require heart transplantation tend to have idiopathic cardiomyopathy rather than the ischemic cardiomyopathy that is more common in male heart transplant candidates. Although female heart transplant recipients seem to have a stronger immunologic response after transplantation, which manifests in more frequent acute rejection episodes, it is not clear whether this increases women's mortality risk. Men appear to have a greater incidence of posttransplant vasculopathy than women. Further research is needed to identify risk factors for perioperative morbidity and mortality in women undergoing cardiac surgery and to develop medical interventions to mitigate these risks.


[Magnetic load in pneumonia patients].
The change of bronchial permeability under magnetic load has been investigated in 122 patients with pneumonia 18 to 60 years of age. Two variants of bronchial reaction and a correlation between the time to onset, severity of the reaction and bronchial inflammation have been found. Magnetic load proved able to reveal high magnetic sensitivity of the organism. Peculiarities of pneumonia clinical course and outcome in patients with high magnetic sensitivity show the necessity of additional medical and prophylactic measures.


Stochastic variations in sensory awareness are driven by noisy neuronal adaptation: evidence from serial correlations in perceptual bistability.
When the sensory system is subjected to ambiguous input, perception alternates between interpretations in a seemingly random fashion. Although neuronal noise obviously plays a role, the neural mechanism for the generation of randomness at the slow time scale of the percept durations (multiple seconds) is unresolved. Here significant nonzero serial correlations are reported in series of visual percept durations (to the author's knowledge for the first time accounting for duration impurities caused by reaction time, drift, and incomplete percepts). Serial correlations for perceptual rivalry using structure-from-motion ambiguity were smaller than for binocular rivalry using orthogonal gratings. A spectrum of computational models is considered, and it is concluded that noise in adaptation of percept-related neurons causes the serial correlations. This work bridges, in a physiologically plausible way, widely appreciated deterministic modeling and randomness in experimental observations of visual rivalry.


Immunogenetical penetrance in patients with primary biliary cirrhosis.
Two family cases of primary biliary cirrhosis (PBC) followed by the existence of autoantibodies such as anti-mitochondrial antibody, anti-nuclear antibody and anti-thyroid antibody are reported. Case O M has typical PBC, however, case H E is complicated by asymptomatic polymyositis. Common haplotypes of human leukocyte antigen (HLA) were observed as A24-Bw61 in the family members of case O M who had autoantibodies. Only the mother of case H E had identical HLA haplotypes such as A2, Aw31, Bw46, Bw61, DRw8, DRw52 and DQw1. From these results, it can be suggested that immunogenetic penetrance might be associated with the occurrence of familial PBC.


The Impact of COVID-19 on Missed Ophthalmology Clinic Visits.
To measure the COVID-19 pandemic impact on missed ophthalmology clinic visits and the influence of patient and eye disease characteristics on likelihood of missing clinic visits before and during the pandemic. A retrospective observational study analyzing eye clinic patients at a large tertiary care academic institution. We identified patients scheduled for eye care during pre-COVID-19 (January 1-February 29, 2020) and early COVID-19 (March 16-May 31, 2020) time periods. Missed appointment frequency and characteristics were evaluated during each time period. Multivariable logistic regression models were developed to examine adjusted odds of having at least one missed appointment during a given time period. Covariates included age, sex, race/ethnicity, marital status, preferred language (non-English vs English), insurance, distance from clinic, and diagnosis. Overall, 82.0% (n = 11,998) of pre-COVID-19 patients completed all scheduled visits, compared to only 59.3% (n = 9020) during COVID-19. Missed visits increased dramatically in late March 2020, then improved week by week through the end of May 2020. General ophthalmology/cataract and strabismus clinics had the highest rates of missed clinic visits during the COVID-19 period; neuro-ophthalmology, retina, cornea, oculoplastics and glaucoma had the lowest. Females, Blacks, Hispanics, Asians, ages 50+, and married patients had higher adjusted odds of missing clinic visits, both pre-COVID-19 and during COVID-19. Asian, elderly, and cataract patients had the highest adjusted odds of missing clinic visits during COVID-19 and had significant increases in odds compared to pre-COVID-19. Non-married, diabetic macular edema, and wet age-related macular degeneration patients had the lowest adjusted odds of missed visits during COVID-19. Missed clinic visits increased dramatically during the COVID-19 pandemic, particularly among elderly and nonwhite patients. These findings reflect differences in eye care delivery during the pandemic, and they indicate opportunities to target barriers to care, even during non-pandemic eras.


Test procedures for measuring the (sub)chronic effects of chemicals on the freshwater cyclopoid Eucyclops serrulatus.
The purpose of this study has been to describe test procedures for measuring the (sub)chronic effects of chemicals on the freshwater cyclopoid Eucyclops serrulatus. To this end we have adapted the setting of the standard full life-cycle protocol of the marine harpacticoid A. tenuiremis to E. serrulatus. We have tested the effects of 4 different diets, two temperatures and two rearing volumes on the survival, development, reproduction and population growth rates of this species. Our results have highlighted that full life-cycle tests can be run using 2 mL-glass vials, a diet consisting of a mixture of living cells of Chlorella sorokiniana and Scenedesmus quadricauda, at either 25 °C (test duration: 42 days) or 18 °C (test duration: 51 days). However, the best performance in terms of survival, development, reproducibility and population growth rates with this species was obtained at 18 °C, albeit with significantly longer test duration. Subchronic tests in 2 mL-glass vials with the mixture microalgal diet at both temperatures are available options if considered appropriate for the objectives of a given study. In particular, developmental tests from nauplius to copepodid may profitably be performed in about 11 days at 18 °C and in 6 days at 25 °C. Under the same test conditions, subchronic tests from copepodid to adult may be run in 19 days at 18 °C and in 16 days at 25 °C.


Implementing Social Determinant of Health Screening in a Family Medicine Clinic: A Pilot Study.
While unmet social needs can perpetuate barriers to health equity, health care staff may feel unprepared to address these needs. This article describes a pilot study on implementing a screening process for social determinants of health in a family medicine clinic where there was no prior standard of care. A quality improvement approach was used to frame the implementation and evolution of screening and follow-up strategies for social needs. Social determinant of health screening was successfully implemented during this pilot of 400 encounters, revealing a 26.3% prevalence. Options for addressing social needs grew during the study, although no statistically significant impact was observed on measured short-term health outcomes. Physicians can use quality improvement to counter clinical inertia toward addressing social determinants of health and also to concurrently screen and develop appropriate patient-oriented solutions in their clinics.


What constitutes a good hand offs in the emergency department: a patient's perspective.
The aim is to determine, from the patient's perspective, what constitutes a good hand-off procedure in the emergency department (ED). The secondary purpose is to evaluate what impact a formalized hand-off had on patient knowledge, throughput and customer service This study used a randomized controlled clinical trial involving two unique hand-off approaches and a convenience sample. The study alternated between the current hand-off process that documented the process but not specific elements (referred to as the informal process) to one using the IPASS the BATON process (considered the formal process). Consenting patients completed a 12-question validated questionnaire on how the process was perceived by patients and about their understanding why they waited in the ED. Statistical analysis using SPSS calculated descriptive frequencies and t-tests. In total 107 patients were enrolled: 50 in the informal and 57 in the formal group. Most patients had positive answers to the customer survey. There were significant differences between formal and informal groups: recalling the oncoming and outgoing physician coming to the patient's bed (p = 0.000), with more formal group recalling that than informal group patients; the oncoming physician introducing him/herself (p = 0.01), with more from the formal group answering yes and the physician discussing tests and implications with formal group patients (p = 0.02). This study was done at an urban inner city ED, a fact that may have skewed its results. A comparison of suburban and rural EDs would make the results stronger. It also reflected a very high level of customer satisfaction within the ED. This lack of variance may have meant that the correlation between customer service and handoffs was missed or underrepresented. There was no codified observation of either those using the IPASS the BATON script or those using informal procedures, so no comparison of level and types of information given between the two groups was done. There could have been a bias of those attending who had internalized the IPASS the BATON procedures and used them even when they were assigned to the informal group. A hand off from one physician to the next in the emergency department is best done using a formalized process. IPASS the BATON is a useful tool for hand off in the ED in part because it involved the patient in the process. The formal hand off increased communication between patient and doctor as its use increased the patient's opportunity to ask and respond to questions. The researchers evaluated an ED physician specific hand-off process and illustrate the value and impact of involving patients in the hand-off process.


IL-17A (-197G/A) and IL-17F (7488T/C) gene polymorphisms and cancer risk in Asian population: a meta-analysis.
Interleukin (IL)-17 has been shown to play an important role in the pathogenesis of inflammation and cancer. The IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms have been extensively investigated with cancer risk, but individually published results have been inconclusive. The aim of this study was to clarify the effects of the IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms on cancer risk in Asian populations. Relevant studies were identified by searching databases extensively. The association between the IL-17A (-197G/A) and IL-17F (7488T/C) polymorphisms and cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 12 articles with adequate information satisfied our inclusion criteria; these included 12 studies, with 4,540 cases and 5,875 controls, of IL-17A (-197G/A) polymorphism and seven studies, with 1,960 cases and 3,226 controls, of IL-17F (7488T/C) polymorphism. In the overall analysis, the IL-17A (-197G/A) polymorphism was significantly associated with increased cancer risk (P<0.05), for all genetic models. However, there was no statistically significant association between IL-17F (7488T/C) and cancer risk (P>0.05), for any genetic models. Furthermore, stratification by cancer type revealed a significant correlation between the IL-17A (-197G/A) polymorphism and cancer risk for all cancer types. When stratified by source of controls, a significant correlation was observed between the IL-17A (-197G/A) polymorphism and cancer risk in the population-based control subgroup but not in hospital-based control subgroup. In conclusion, our meta-analysis provides evidence that the IL-17A (-197G/A) polymorphism might be associated with cancer risk, while no evidence suggested a significant association between IL-17F (7488T/C) polymorphism and cancer risk.


Processing of copper converter slag for metal reclamation. Part I: Extraction and recovery of copper and cobalt.
Clean processing of copper converter slag to reclaim cobalt and copper could be a challenge. An innovative and environmentally sound approach for recovering valuable metals from such a slag has been developed in the present study. Curing the slag with strong sulphuric acid, without re-smelting or roasting as practiced currently in the industry, render it accessible to leaching, and more than 95% of cobalt and up to 90% of copper was extracted together with iron by water leaching, leaving silica behind in a residue. The copper in the leach liquor was recovered by cementation with iron and the dissolved iron crystallized as ferrous sulphate monohydrate. The cobalt in the mother-liquor rich in iron was recovered by either cementation or sulphide precipitation. Operation variables in the new process were also investigated and optimized.


Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo.
PGC1 alpha is a co-activator involved in adaptive thermogenesis, fatty-acid oxidation and gluconeogenesis. We describe the identification of several isoforms of a new human PGC1 alpha homologue, cloned independently and named PGC1 beta. The human PGC1 beta gene is localized to chromosome 5, has 13 exons and spans more than 78 kb. Two different 5' and 3' ends due to differential splicing were identified by rapid amplification of cDNA ends PCR and screening of human cDNA libraries. We show that PGC1 beta variants in humans, mice and rats are expressed predominantly in heart, brown adipose tissue, brain and skeletal muscle. PGC1 beta expression, unlike PGC1 alpha, is not up-regulated in brown adipose tissue in response to cold or obesity. Fasting experiments showed that PGC1 alpha, but not PGC1 beta, is induced in liver and this suggests that only PGC1 alpha is involved in the hepatic gluconeogenesis. No changes in PGC1 beta gene expression were observed associated with exercise. Human PGC1 beta-1a and -2a isoforms localized to the cell nucleus and, specifically, the isoform PGC1 beta-1a co-activated peroxisome-proliferator-activated receptor-gamma, -alpha and the thyroid hormone receptor beta1. Finally, we show that ectopic expression PGC1 beta leads to increased mitochondrial number and basal oxygen consumption. These results suggest that PGC1 beta may play a role in constitutive adrenergic-independent mitochondrial biogenesis.


Image-guided Irreversible Electroporation of Localized Prostate Cancer: Functional and Oncologic Outcomes.
Background Irreversible electroporation (IRE) is a nonthermal ablative method based on the formation of nanoscale defects in cell membranes leading to cell death. Clinical experience with the technique for treatment of prostate cancer remains limited. Purpose To evaluate urogenital toxicity and oncologic outcome of MRI-transrectal US fusion-guided IRE of localized prostate cancer. Materials and Methods In this prospective study, men with biopsy-proven, treatment-naive, low- to intermediate-risk prostate cancer (prostate-specific antigen [PSA], ≤15 ng/mL; Gleason score, ≤3 + 4; clinical stage, ≤T2c; lesion size at multiparametric MRI, ≤20 mm) underwent focal MRI/transrectal US fusion-guided IRE between July 2014 and July 2017. Primary end point was the urogenital toxicity profile of focal IRE by using participant-reported questionnaires. Secondary end points were biochemical, histologic, and imaging measures of oncologic control. Analyses were performed by using nonparametric and χ2 test statistics. Results Thirty men were included (median age, 65.5 years); mean PSA level was 8.65 ng/mL and mean tumor size was 13.5 mm. One grade III adverse event (urethral stricture) was recorded. The proportion of men with erection sufficient for penetration was 83.3% (25 of 30) at baseline and 79.3% (23 of 29; P > .99) at 12 months. Leak-free and pad-free continence rate was 90% (27 of 30) at baseline and 86.2% (25 of 29; P > .99) at 12 months. Urogenital function remained stable at 12 months according to changes in the modified International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms, or ICIQ-MLUTS, and the International Index of Erectile Function, or IIEF-5, questionnaires (P = .58 and P = .07, respectively). PSA level decreased from a baseline median value of 8.65 ng/mL (interquartile range, 5-11.4 ng/mL) to 2.35 ng/mL (interquartile range, 1-3.4 ng/mL) at 12 months (P < .001). At 6 months, 28 of 30 participants underwent posttreatment biopsy. The rate of in-field treatment failure was 17.9% (five of 28) as determined with multiparametric prostate MRI and targeted biopsies at 6 months. Conclusion After a median follow-up of 20 months, focal irreversible electroporation of localized prostate cancer was associated with low urogenital toxicity and promising oncologic outcomes. © RSNA, 2019 Online supplemental material is available for this article.


Comparison of data-fitting models for schistosomiasis: a case study in Xingzi, China.
When modelling prevalence data, epidemiological studies usually employ either Gaussian, binomial or Poisson models. However, reasons are seldom given in the literature why the chosen model was felt to be the most appropriate. In this study, we compared all three models for fitting schistosomiasis risk in Xingzi county, Jiangxi province, People's Republic of China. Parasitological data from conventional surveys were available for 36,208 individuals aged between 6 and 65 years from 42 sampled villages and used in combination with environmental data to map the spatial patterns of schistosomiasis risk. The results show that the Poisson model fitted the data best and this model identified the role of environmental risk factors in explaining the geographical variation of schistosomiasis risk. These factors were further used to develop a predictive map, which has important implications for the control and eventual elimination of schistosomiasis in the People's Republic of China.


Relationship of metabolic syndrome and fibrinolytic dysfunction to cardiovascular disease.
The clustering of impaired glucose metabolism, elevated triglycerides, low HDL cholesterol, and abdominal obesity is known as the metabolic syndrome. Individuals with this syndrome suffer an excess of cardiovascular disease (CVD) for reasons that are unclear. We randomly sampled 1276 adults of South Asian, Chinese, European, and Native Indian ancestry from 4 communities in Canada. Participants provided fasting blood samples for glucose, lipids, and fibrinolytic measurements; had an oral glucose tolerance test; and underwent a B-mode carotid ultrasound examination. CVD was determined by history and ECG. The prevalence of the metabolic syndrome was 25.8% (95% CI, 23.5 to 28.2) and varied substantially by ethnic group: 41.6% among Native Indians, 25.9% among South Asians, and 22.0% among Europeans, compared with 11.0% among the Chinese (overall, P=0.0001). People with the metabolic syndrome had more atherosclerosis (maximum intimal medial thickness, 0.78+/-0.18 versus 0.74+/-0.18 mm; P=0.0005), CVD (17.2% versus 7.0%; P=0.0001), and elevated plasminogen activator inhibitor-1 (24.2 versus 14.6 U/mL; P=0.001) compared with levels among people without the metabolic syndrome. For the same amount of atherosclerosis, people with the metabolic syndrome had a greater prevalence of CVD, even among nondiabetic individuals. This difference in CVD prevalence among the groups was attenuated after adjustment for plasminogen activator inhibitor-1 levels, suggesting that fibrinolytic dysfunction mediates the increased risk of CVD in individuals with the metabolic syndrome. CVD among people with the metabolic syndrome is explained by their excess of atherosclerosis and impaired fibrinolysis. Interventions to prevent atherosclerosis progression and improve fibrinolytic function require evaluation in this high-risk group.


KDOQI US commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD.
The 2012 KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for Anemia in Chronic Kidney Disease provides clinicians with comprehensive evidence-based recommendations to improve patient care. In this commentary, we review these recommendations and the underlying evidence. Most recommendations are well reasoned. For some, the evidence is unclear and recommendations require some qualification. While the KDIGO guideline stresses the potential risks of intravenous iron therapy, withholding iron might have its own risks. The recommendation to avoid hemoglobin levels falling below 9 g/dL sets a lower bound of "acceptability" that may increase blood transfusion. Given the lack of research supporting the optimal transfusion strategy for end-stage renal disease patients, it is difficult to weigh the risks and benefits of red blood cell transfusion. We find a paucity of evidence that hemoglobin concentration targeted between 11 and 11.5 g/dL is associated with a safety risk. Although the evidence that erythropoiesis-stimulating agent use improves patient quality of life is poor, it is possible that the instruments used to measure quality of life may not be well attuned to the needs of chronic kidney disease or dialysis patients. Our last section focuses specifically on the recommendations to treat anemia in children.


The Interplay between the Cellular Response to DNA Double-Strand Breaks and Estrogen.
Cancer development is often connected to impaired DNA repair and DNA damage signaling pathways. The presence of DNA damage in cells activates DNA damage response, which is a complex cellular signaling network that includes DNA repair, activation of the cell cycle checkpoints, cellular senescence, and apoptosis. DNA double-strand breaks (DSBs) are toxic lesions that are mainly repaired by the non-homologous end joining and homologous recombination repair (HRR) pathways. Estrogen-dependent cancers, like breast and ovarian cancers, are frequently associated with mutations in genes that play a role in HRR. The female sex hormone estrogen binds and activates the estrogen receptors (ERs), ERα, ERβ and G-protein-coupled ER 1 (GPER1). ERα drives proliferation, while ERβ inhibits cell growth. Estrogen regulates the transcription, stability and activity of numerus DDR factors and DDR factors in turn modulate ERα expression, stability and transcriptional activity. Additionally, estrogen stimulates DSB formation in cells as part of its metabolism and proliferative effect. In this review, we will present an overview on the crosstalk between estrogen and the cellular response to DSBs. We will discuss how estrogen regulates DSB signaling and repair, and how DDR factors modulate the expression, stability and activity of estrogen. We will also discuss how the regulation of HRR genes by estrogen promotes the development of estrogen-dependent cancers.


Early development of the central and peripheral nervous systems is coordinated by Wnt and BMP signals.
The formation of functional neural circuits that process sensory information requires coordinated development of the central and peripheral nervous systems derived from neural plate and neural plate border cells, respectively. Neural plate, neural crest and rostral placodal cells are all specified at the late gastrula stage. How the early development of the central and peripheral nervous systems are coordinated remains, however, poorly understood. Previous results have provided evidence that at the late gastrula stage, graded Wnt signals impose rostrocaudal character on neural plate cells, and Bone Morphogenetic Protein (BMP) signals specify olfactory and lens placodal cells at rostral forebrain levels. By using in vitro assays of neural crest and placodal cell differentiation, we now provide evidence that Wnt signals impose caudal character on neural plate border cells at the late gastrula stage, and that under these conditions, BMP signals induce neural crest instead of rostral placodal cells. We also provide evidence that both caudal neural and caudal neural plate border cells become independent of further exposure to Wnt signals at the head fold stage. Thus, the status of Wnt signaling in ectodermal cells at the late gastrula stage regulates the rostrocaudal patterning of both neural plate and neural plate border, providing a coordinated spatial and temporal control of the early development of the central and peripheral nervous systems.


Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.
Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population.


From co-design to co-production: Approaches, enablers, and constraints in developing a public health, capacity-building solution.
Investigating how co-designed knowledge can be translated to co-produce a public health capacity-building solution for difficult-to-engage population groups drawing on the co-production experience of a prevention-focused, capacity-building mental health solution targeting primary producers. A qualitative study undertaken in rural and regional Victoria involving members of the design working group including project team (7px), digital design team (5px), marketing team (3px), and funding partner representatives. The study design involved reflective practice to collect data to identify the phases of co-production and assess the design working group members' experiences. The analysis involved inductive coding using Braun and Clarke's thematic analysis. Identifying major points of divergence and/or convergence; enablers and/or constraints; and ways to better navigate and strengthen the co-production process. Given members of the design working group, diverse skills sets divergence was experienced in all co-production phases. Divergence was also experienced between the project team and the funding partner given the uniqueness of working conditions and requirements of workers in the primary production industry. The project team applied an iterative development process to project management; encouraging iterative cycles to create/test/revise among the teams, and with the funding partner, until each was satisfied with the end result (convergence). When developing a co-created public health prevention campaign it is critical that the project team focuses on relationship building among the members of the design working group and ensures adequate resourcing, development of shared understanding of project goals and target audience, ongoing communication, and a commitment to working iteratively.


Cardiovascular responses to family visits in coronary care unit patients.
Changes in four cardiovascular indicators: systolic blood pressure, diastolic blood pressure, heart rate, and premature ventricular contractions, were studied as responses to family visits and a 10-minute interview with the investigator in 24 patients in a coronary care unit. By use of a repeated-measures design, data were compared by multivariate analysis of variance. No significant differences were found between the group mean systolic and diastolic blood pressure, heart rate, and rate of premature ventricular contractions during family visits and interviews. The lowest systolic and diastolic blood pressure values were significantly lower during the visit than during the interview, suggesting that the visit had a calming effect on patients. Although the highest heart rate was significantly higher during the visit than during the interview, the difference was clinically inconsequential. The wide variance in premature ventricular contraction values suggests individual variation in responses, but no significant differences were found between visits and interviews. Although family visits were no more physiologically stressful than a comparative social interaction, select subsamples of patients with cardiac disease should be studied for more specific reaction patterns.


Stretch-tuneable dielectric mirrors and optical microcavities.
We demonstrate how tuneable Distributed Bragg Reflectors (DBRs) and resonant micro-cavities can be built by a scalable layer assembly of the transparent utility rubbers polydimethylsiloxane and polystyrene-polyisoprene. Stretching the devices by more than 60% leads to an affine contraction of the layer thicknesses thereby tuning both DBR and cavity modes across the entire visible spectrum. Such rapidly- and reversibly- stretch-tuneable cavities can be used in tuneable micro-lasers and for quantitative optical strain sensing applications.


LC-MS-based metabolomics reveals the mechanism of anti-gouty arthritis effect of Wuwei Shexiang pill.
Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.


Influence of Resveratrol on the Immune Response.
Resveratrol is the most well-known polyphenolic stilbenoid, present in grapes, mulberries, peanuts, rhubarb, and in several other plants. Resveratrol can play a beneficial role in the prevention and in the progression of chronic diseases related to inflammation such as diabetes, obesity, cardiovascular diseases, neurodegeneration, and cancers among other conditions. Moreover, resveratrol regulates immunity by interfering with immune cell regulation, proinflammatory cytokines' synthesis, and gene expression. At the molecular level, it targets sirtuin, adenosine monophosphate kinase, nuclear factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis. Resveratrol can suppress the toll-like receptor (TLR) and pro-inflammatory genes' expression. The antioxidant activity of resveratrol and the ability to inhibit enzymes involved in the production of eicosanoids contribute to its anti-inflammation properties. The effects of this biologically active compound on the immune system are associated with widespread health benefits for different autoimmune and chronic inflammatory diseases. This review offers a systematic understanding of how resveratrol targets multiple inflammatory components and exerts immune-regulatory effects on immune cells.


Glycosides from the leaves of Fraxinus Hubeiensis.
Fraxinus hubeiensis is a plant endemic to China and widely used as folk medicine to treat various diseases. However, its chemical constituents have never been reported sufficiently. Thus, the primary objective of this study was to investigate the phytochemical constituents and biological activities of F. hubeiensis leaves. Hence, combined column chromatographic and spectroscopic techniques were used to identify and characterize the secondary metabolites such as a pair of 3-keto-glycoside epimers (1) and (2), along with five known compounds (3 ~ 7). The results of α-glucosidase inhibitory activity exhibited that 1 and 2 had moderate activity with IC50 values of 359.50 and 468.43 µM, respectively, compared to a positive control acarbose with the IC50 value of 164.08 µM. However, Compounds 1-6 were shown to be inactive against the tested microbes.


New multidimensional functional diversity indices for a multifaceted framework in functional ecology.
Functional diversity is increasingly identified as an important driver of ecosystem functioning. Various indices have been proposed to measure the functional diversity of a community, but there is still no consensus on which are most suitable. Indeed, none of the existing indices meets all the criteria required for general use. The main criteria are that they must be designed to deal with several traits, take into account abundances, and measure all the facets of functional diversity. Here we propose three indices to quantify each facet of functional diversity for a community with species distributed in a multidimensional functional space: functional richness (volume of the functional space occupied by the community), functional evenness (regularity of the distribution of abundance in this volume), and functional divergence (divergence in the distribution of abundance in this volume). Functional richness is estimated using the existing convex hull volume index. The new functional evenness index is based on the minimum spanning tree which links all the species in the multidimensional functional space. Then this new index quantifies the regularity with which species abundances are distributed along the spanning tree. Functional divergence is measured using a novel index which quantifies how species diverge in their distances (weighted by their abundance) from the center of gravity in the functional space. We show that none of the indices meets all the criteria required for a functional diversity index, but instead we show that the set of three complementary indices meets these criteria. Through simulations of artificial data sets, we demonstrate that functional divergence and functional evenness are independent of species richness and that the three functional diversity indices are independent of each other. Overall, our study suggests that decomposition of functional diversity into its three primary components provides a meaningful framework for its quantification and for the classification of existing functional diversity indices. This decomposition has the potential to shed light on the role of biodiversity on ecosystem functioning and on the influence of biotic and abiotic filters on the structure of species communities. Finally, we propose a general framework for applying these three functional diversity indices.


Shear stress as a driver of degradation for protein-based therapeutics: More accomplice than culprit.
Protein degradation is a major concern for protein-based therapeutics. It may alter the biological activity of the product and raise the potential for undesirable effects on the patients. Among the numerous drivers of protein degradation, shear stress has been the focus around which much work has revolved since the 1970s. In the pharmaceutical realm, the product is often processed through several unit operations, which include mixing, pumping, filtration, filling, and atomization. Nonetheless, the drug might be exposed to significant shear stresses, which might cooperatively contribute to product degradation, together with interfacial stress. This review presents fundamentals of shear stress about protein structure, followed by an overview of the drivers of product degradation. The impact of shear stress on protein stability in different unit operations is then presented, and recommendations for limiting the adverse effects on the biopharmaceutical formulations are outlined. Finally, several devices used to explore the effects of shear stress are discussed.


Tasting arterial blood: what do the carotid chemoreceptors sense?
The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose, and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO)-regulated hydrogen sulfide (H2S), stemming from hypoxia, depolarizes type I cells by inhibiting certain K(+) channels, facilitates voltage-gated Ca(2+) influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signaling is an area of ongoing study.


Xenopus laevis actin-depolymerizing factor/cofilin: a phosphorylation-regulated protein essential for development.
Two cDNAs, isolated from a Xenopus laevis embryonic library, encode proteins of 168 amino acids, both of which are 77% identical to chick cofilin and 66% identical to chick actin-depolymerizing factor (ADF), two structurally and functionally related proteins. These Xenopus ADF/cofilins (XADs) differ from each other in 12 residues spread throughout the sequence but do not differ in charge. Purified GST-fusion proteins have pH-dependent actin-depolymerizing and F-actin-binding activities similar to chick ADF and cofilin. Similarities in the developmental and tissue specific expression, embryonic localization, and in the cDNA sequence of the noncoding regions, suggest that the two XACs arise from allelic variants of the pseudotetraploid X. laevis. Immunofluorescence localization of XAC in oocyte sections with an XAC-specific monoclonal antibody shows it to be diffuse in the cortical cytoplasm. After fertilization, increased immunostaining is observed in two regions: along the membrane, particularly that of the vegetal hemisphere, and at the interface between the cortical and animal hemisphere cytoplasm. The cleavage furrow and the mid-body structure are stained at the end of first cleavage. Neuroectoderm derived tissues, notochord, somites, and epidermis stain heavily either continuously or transiently from stages 18-34. A phosphorylated form of XAC (pXAC) was identified by 2D Western blotting, and it is the only species found in oocytes. Dephosphorylation of >60% of the pXAC occurs within 30 min after fertilization. Injection of one blastomere at the 2 cell stage, either with constitutively active XAC or with an XAC inhibitory antibody, blocked cleavage of only the injected blastomere in a concentration-dependent manner without inhibiting nuclear division. The cleavage furrow of eggs injected with constitutively active XAC completely regressed. Blastomeres injected with neutralized antibody developed normally. These results suggest that XAC is necessary for cytokinesis and that its activity must be properly regulated for cleavage to occur.


Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages.
Altered macrophage kinetics is a pivotal mechanism of visceral obesity-induced inflammation and cardiometabolic risk. Because monocytes can differentiate into either proatherogenic M1 macrophages or anti-inflammatory M2 macrophages, approaches that limit M1 while promoting M2 differentiation represent a unique therapeutic strategy. We hypothesized that adiponectin may prime human monocytes toward the M2 phenotype. Adiponectin promoted the alternative activation of human monocytes into anti-inflammatory M2 macrophages as opposed to the classically activated M1 phenotype. Adiponectin-treated cells displayed increased M2 markers, including the mannose receptor (MR) and alternative macrophage activation-associated CC chemokine-1. Incubation of M1 macrophages with adiponectin-treated M2-derived culture supernatant resulted in a pronounced inhibition of tumor necrosis factor-alpha and monocyte chemotactic protein-1 secretion. Activation of human monocytes into M2 macrophages by adiponectin was mediated, in addition to AMP-activated protein kinase and peroxisome proliferator-activated receptor (PPAR)-gamma, via PPAR-alpha. Furthermore, macrophages isolated from adiponectin knockout mice demonstrated diminished levels of M2 markers such as MR, which were restored with adiponectin treatment. We report a novel immunoregulatory mechanism through which adiponectin primes human monocyte differentiation into anti-inflammatory M2 macrophages. Conditions associated with low adiponectin levels, such as visceral obesity and insulin resistance, may promote atherosclerosis, in part through aberrant macrophage kinetics.


Leukocyte filtration lesion impairs functional coagulation in banked whole blood.
Whole blood (WB) transfusion is a promising alternative to component therapy in hemostatic resuscitation. Use of banked WB requires filtration of white blood cells (leukoreduction) and an established shelf life during which WB retains coagulant capacities. The goal of this study was to define the time course of coagulation stability in leukoreduced compared to unfiltered WB under standard refrigeration conditions. Twelve WB units were donated by healthy volunteers after routine screening. Five units underwent standard leukocyte filtration and five did not. Two units were aliquoted into filtered and unfiltered samples, with platelets added to each sample on day 14. Units were stored at 4°C and sampled on days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, and 35 for immediate thromboelastography (TEG) analysis, and centrifuged and stored at -80°C for later calibrated automated thrombogram and coagulation factor assays. K-dependent factors and fibrinogen were low normal, decreased slightly over 35 days and were similar between unfiltered and filtered units. Labile factors were better preserved in filtered units, although unfiltered units did not show impaired coagulation over 35 days. Filtered blood had delayed clot initiation on days 0, 1, and 2 as measured by TEG R (p < 0.021); slower clot progression (TEG α-angle) on days 0, 1, 2, 3, 4, 5, and 6 (p < 0.023); weaker final clot (TEG MA) on all days (p < 0.0001). Thrombin generation was delayed on day 28 (p = 0.046) and decreased on days 10, 21, 28, and 35 (p < 0.034). Addition of platelets to filtered WB rescued TEG MA. Filtered WB had decreased functional clotting capacity and thrombin generation and may not be suitable for hemostatic resuscitation as the sole blood product. Therapeutic, level IV.


Diagnostic endoscopic retrograde cholangiopancreatography.
Endoscopic retrograde cholangiopancreatography (ERCP) is still a gold standard in the diagnostic work-up of the pancreaticobiliary system. However, the problem of post-ERCP pancreatitis has not yet been solved. Since the appearance of magnetic resonance cholangiopancreatography (MRCP), there has been a trend for it to replace ERCP as an imaging tool. At present, MRCP equipment is not available at every institution. In addition, MRCP images are not satisfactorily comparable to those provided by ERCP, although technological advances will fill this gap in the near future. If this is achieved, diagnostic ERCP may be reduced to the specific tasks of obtaining histological and cytological materials, and for functional studies.


Composition and spectra of copper-carotenoid sediments from a pyrite mine stream in Spain.
Mine drainages of La Poderosa (El Campillo, Huelva, Spain), located in the Rio Tinto Basin (Iberian Pyrite Belt) generate carotenoid complexes mixed with copper sulfates presenting good natural models for the production of carotenoids from microorganisms. The environmental conditions of Rio Tinto Basin include important environmental stresses to force the microorganisms to accumulate carotenoids. Here we show as carotenoid compounds in sediments can be analyzed directly in the solid state by Raman and Luminescence spectroscopy techniques to identify solid carotenoid, avoiding dissolution and pre-concentration treatments, since the hydrous copper-salted paragenesis do not mask the Raman emission of carotenoids. Raman spectra recorded from one of these specimens' exhibit major features at approximately 1006, 1154, and 1520 cm(-1). The bands at 1520 cm(-1) and 1154 cm(-1) can be assigned to in-phase C=C (γ(-1)) and C-C stretching (γ(-2)) vibrations of the polyene chain in carotenoids. The in-plane rocking deformations of CH3 groups linked to this chain coupled with C-C bonds are observed in the 1006 cm(-1) region. X-irradiation pretreatments enhance the cathodoluminescence spectra emission of carotenoids enough to distinguish organic compounds including hydroxyl and carboxyl groups. Carotenoids in copper-sulfates could be used as biomarkers and useful proxies for understanding remote mineral formations as well as for terrestrial environmental investigations related to mine drainage contamination including biological activity and photo-oxidation processes.


Pathophysiology of GvHD and Other HSCT-Related Major Complications.
For over 60 years, hematopoietic stem cell transplantation has been the major curative therapy for several hematological and genetic disorders, but its efficacy is limited by the secondary disease called graft versus host disease (GvHD). Huge advances have been made in successful transplantation in order to improve patient quality of life, and yet, complete success is hard to achieve. This review assimilates recent updates on pathophysiology of GvHD, prophylaxis and treatment of GvHD-related complications, and advances in the potential treatment of GvHD.


Direct proof that the primary site of action of cytochalasin on cell motility processes is actin.
We have previously described the isolation of a mutant KB cell (Cyt 1 mutant) resistant to the cytotoxic effect of cytochalasin B (CB). The Cyt 1 mutant carries an altered form of beta-actin (beta'-actin) and lacks normal beta-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). Increased resistance of the Cyt 1 mutant to CB in vivo is reflected in altered properties of beta'-actin in vitro (Toyama, S., and S. Toyama. 1988. J. Cell Biol. 107:1499-1504). Here, we show that the mutation in beta-actin is solely responsible for the cytochalasin-resistant phenotype of the Cyt mutant. We have isolated a cDNA clone encoding beta'-actin from Cyt 1 cells. Sequence analysis reveals two mutations in the coding region that substitute two amino acid residues (Val139----Met and Ala295----Asp). Expression of the beta'-actin cDNA confers cytochalasin resistance upon transformed cytochalasin-sensitive KB cells. Levels of resistance to CB in the transformed cell clones correlate well with amounts of beta'-actin polypeptide. Both of the two mutations in beta'-actin are necessary for the high level expression of cytochalasin resistance. Overall, we conclude that the primary site of action of cytochalasin on cell motility processes in vivo is actin.


FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy.
The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.


O6-alkylguanine-DNA alkyltransferase has opposing effects in modulating the genotoxicity of dibromomethane and bromomethyl acetate.
O(6)-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that removes O(6)-alkylguanine adducts. The interaction of dibromomethane (CH(2)Br(2)) and bromomethyl acetate (BrCH(2)OAc) with AGT was studied in vitro, and the effect of AGT on their toxicity and mutagenicity was investigated using Escherichia coli strain TRG8 (lacking endogenous AGT) that expressed human AGT or its inactive C145A mutant. Both CH(2)Br(2) and BrCH(2)OAc reacted with AGT at its cysteine acceptor site, abolishing its DNA repair activity with the latter agent being much more potent. The formation of AGT-Cys(145)S-CH(2)OAc by BrCH(2)OAc was confirmed by mass spectral analysis, but the presumed AGT-Cys(145)S-CH(2)Br adduct from CH(2)Br(2) was too unstable for such characterization. In the presence of CH(2)Br(2), AGT was covalently cross-linked to an oligodeoxyribonucleotide, 5'-d(AG)(8)-3', but no cross-link was formed by BrCH(2)OAc. Survival of cells exposed to CH(2)Br(2) was reduced, and the number of mutants was greatly increased when wild-type AGT was present. The cytotoxicity of CH(2)Br(2) was similar to that of BrCH(2)CH(2)Br(2), but the mutagenicity was about four times less. Virtually all of the AGT-mediated mutants induced by CH(2)Br(2) in the rpoB gene were at G:C sites with equal numbers of transitions to A:T and transversions to T:A. In contrast, BrCH(2)OAc was more than 10-fold less genotoxic than CH(2)Br(2) and the survival of cells exposed to BrCH(2)OAc was not affected by AGT. The number of mutations (almost all G:C to A:T transitions) induced by BrCH(2)OAc was slightly reduced by the presence of wild-type AGT and substantially increased by the inactive C145A mutant. These results with CH(2)Br(2) are consistent with a mechanism in which reaction at the active site Cys145 residue followed by attack of AGT-Cys(145)S-CH(2)Br at guanine in DNA forms a covalent adduct, which leads to cytotoxicity and to mutagenicity. The results with BrCH(2)OAc suggest that it reacts directly with DNA to form O(6)-(CH(2)OAc)guanine, which, if unrepaired, causes G:C to A:T transitions. Our experiments reveal two novel pathways (direct inactivation of AGT and formation of AGT-Cys(145)S-CH(2)-DNA adducts) by which CH(2)Br(2) may cause damage to the genome in addition to the well-recognized pathway involving activation by GSTs.


Efficacy of multiplex PCR procedure for Iranian Streptococcus pneumoniae isolates.
Identifying regional types and evaluating the frequency of pneumococcal strains has become increasingly important especially in vaccination. The purpose of this study was the identification and frequency determination of our regional serotype and evaluation of the performance of recent type specific multiplex PCR for the diagnosis of streptococcus pneumonia serotypes. All isolated S. pneumonia from suspected patients in Tehran and Isfahan Hospitals from June to December of 2012 were evaluated. All specimens and their serotypes were identified through a conventional method and specific antisera. Serotype specific multiplex PCR was applied and ran in seven reactions consisting of 34 S. pneumonia primer pairs plus a primer pair as an internal control for this purpose. Overall, 14 genotype specific serotypes (including two subtypes for 19 and 23) were detected and had identical results with stereotyping method except for serotype 28 and one of the identified serotype 23. The serotypes 19, 6 and 23 were dominant with the frequency of 51.8%. A cross reactivity was also observed between genotypes 1 and 9A/9V. Applied multiplex PCR format can be suitable and cost effective tool for identification of S. pneumonia serotypes.


Reliability of seizure classification using a semistructured interview.
Methods for standardized classification of epileptic seizures are important for both clinical practice and epidemiologic research. In this study, we developed a strategy for standardized classification using a semistructured telephone interview and operational diagnostic criteria. We interviewed 1,957 adults with epilepsy ascertained from voluntary organizations. To confirm and expand the seizure history, we also interviewed a first-degree relative for 67% of subjects and obtained medical records for 59%. Three lay reviewers used all available information to classify seizures. To assess reliability, each reviewer classified a sample of subjects assigned to the others. In addition, an expert physician classified a sample of subjects assigned to two of the reviewers. Agreement was "moderate-substantial" for generalized-onset seizures, both for the comparisons between pairs of lay reviewers and for the neurologist versus lay reviewers. Agreement was "substantial-almost perfect" for partial-onset seizures, both for pairs of lay reviewers and for the neurologist versus lay reviewers. These results suggest that seizures can be reliably classified by lay reviewers, using operational criteria applied to symptoms ascertained in a semistructured telephone interview.


Comparison of Enrichment Broths for Supporting Growth of Shiga Toxin-Producing Escherichia coli.
Detection of Shiga toxin-producing Escherichia coli (STEC) in complex sample matrices remains challenging. In an attempt to improve detection, nonselective and selective enrichment broths were compared as follows: (1) trypticase soy broth (TSB) was compared with TSB plus novobiocin, vancomycin, rifampicin, bile salts, and potassium tellurite (TSB-NVRBT) for supporting growth of STEC in pure culture; (2) E. coli broth (EC), TSB, and TSB plus bile salts (mTSB) were compared for enrichment of STEC O26, O45, O103, O104, O111, O121, O145, and O157 (STEC-8) in inoculated cattle fecal samples; (3) EC, TSB, and mTSB were compared for the detection of STEC-8 in inoculated cattle fecal samples. Fecal samples were inoculated with wild-type STEC-8 or nalidixic acid- or rifampicin-resistant derivatives of the same strains at 100, 1000, or 10,000 colony-forming units per gram (CFU/g) of feces. In pure culture, the mean STEC CFU/mL following enrichment in TSB was 1.17 log10 greater than that in TSB-NVRBT (P < 0.05). In inoculated fecal samples, EC enrichment yielded growth of STEC-8 (6.42 log10 CFU/g) that was significantly greater than in TSB (6.23 log10 CFU/g; P < 0.05), and numerically but not significantly greater than in mTSB (6.37 log10 CFU/g; P = 0.60). Wild-type STEC strains were detected in 43.8 % (21/48) of the samples enriched in EC and mTSB compared to 27.1 % (13/48) of the samples enriched in TSB (P = 0.15). Overall, STEC grew significantly better when enriched in EC compared to TSB. Modification of TSB by the addition of bile salts improved the growth and detection of STEC compared to TSB alone.


Problem gambling and concurrent emotional/behavioral problems among Greek adolescents.
Problem gambling in adolescents constitutes a major health problem. Very few studies have investigated the relationship of adolescent gambling with emotional/behavioral problems. The aim of this study was to examine the association between adolescent problem gambling and emotional/behavioral problems using data from a school survey in the greater Athens area. The total sample consisted of 2159 high school students (45.4% males and 54.6% females) from a random and representative sample of public and private schools in the greater Athens area. Data were collected in the form of self-reported questionnaires during one school hour. To access problem gambling the Diagnostic and Statistical Manual of Mental Disorders-IV Multiple Response Adapted for Juveniles questionnaire was administered to the study population. The presence of emotional/behavioral problems was assessed via the Strengths and Difficulties Questionnaire. Full data from 2141 participants were analyzed. Eighteen questionnaire with incomplete data were excluded. Problem gambling in adolescence is in line with the presence of emotional/behavioral problems. All Strengths and Difficulties Questionnaire subscales were significantly associated with problem gambling. Specifically, emotional symptoms, conduct problems, attention/hyperactivity, and social dysfunction were all significantly and independently associated with adolescent pathologic gambling. The prosocial scale had lower scores in problem gamblers. This article aims to highlight and discuss the coexistence of adolescent problem gambling with other symptoms. The significant association of emotional/behavioral problems among adolescents with problem gambling indicates a need to screen for these symptoms and for their subsequent treatment among adolescents with problem gambling.


Metabolic studies of pyruvate- and lactate-perfused guinea pig hearts by 13C NMR. Determination of substrate preference by glutamate isotopomer distribution.
Guinea pig hearts perfused in vitro with 99% enriched [3-13C]pyruvate and [3-13C]lactate have been examined by 13C NMR spectroscopy at 75.45 MHz. Resonances from the intracellular metabolites, glutamate, aspartate, alanine, citrate, malate, lactate, and acetylcarnitine are detected in the [3-13C]pyruvate-perfused hearts while glutamate is the only metabolite observed in the [3-13C]lactate-perfused hearts. Extracts obtained from individual freeze-clamped hearts run under high resolution conditions show similar distributions of metabolites indicating that the intracellular concentrations of these metabolites are indeed quite dependent upon the substrate being utilized. The excellent signal to noise in the spectra of lactate-perfused hearts allows observation of spin-spin coupling between 13C-enriched nuclei in the various glutamate isotopomers within the intact heart. It is shown that the steady-state distribution of glutamate isotopomers is determined by the amount of 12C- versus 13C-enriched acetyl-CoA entering the citric acid cycle and this provides the basis for a direct determination of substrate utilization by the heart in the presence of competing substrates. Similar information may be derived from the 13C spectrum of an extract prepared from a single [3-13C]pyruvate-perfused heart. Our results indicate that lactate is preferred over glucose by the guinea pig heart even in the presence of insulin.


Attachment insecurity predicts responses to an interdisciplinary chronic pain rehabilitation program.
The aim of this study was to examine the hypothesis that attachment insecurity is associated with poorer responses to interdisciplinary treatment for chronic pain. Patients (n = 235) admitted to a 4-week interdisciplinary rehabilitation program were recruited. At pre-treatment, participants completed a battery of questionnaires assessing adult attachment styles and dimensions, as well as pain intensity, disability, self-efficacy, pain catastrophizing, and depressive symptoms. The latter measures were completed again at post-treatment. Nearly two-thirds of participants (65.5 %) reported having an insecure attachment style. Attachment insecurity was unrelated to pre- and post-treatment reports of pain intensity and pain-related disability, but was significantly associated with most other clinical variables at both time points. Regression analyses controlling for pre-treatment functioning indicated that attachment insecurity was associated with less improvement in pain catastrophizing, pain self-efficacy, and depressive symptoms. Further research is warranted to investigate the processes by which attachment characteristics influence patients' responses to chronic pain rehabilitation.


Ultrastructure of sciatic nerve of armadillo infected with Mycobacterium leprae.
Ultrastructural observation of sciatic nerves from eight Armadillos were made. Six animals had intravenous inoculation of M. leprae, one had of foot pad, while one had natural leprosy. The available nerves were biopsied at various time sequence ranging from five weeks to twenty four months. Semithin sections did not reveal any neuropathy. Ultrastructurally perineurium was thick and endoneurial collagen was increased. Initially demyelination of non-myelinated fibres was seen in all nerves irrespective of mode of infection. This was followed by demyelination of small myelinated fibres. Active remyelination was predominantly after 17 months. Schwann cell activity was increased and various stages of division were seen. Bacilli were extracellular, intraxonal, in endothelium and in perineurium. Significant observations were on blood vessels. These observations are discussed.


Ant Abundance along a Productivity Gradient: Addressing Two Conflicting Hypotheses.
The number of individuals within a population or community and their body size can be associated with changes in resource supply. While these relationships may provide a key to better understand the role of abiotic vs. biotic constraints in animal communities, little is known about the way size and abundance of organisms change along resource gradients. Here, we studied this interplay in ants, addressing two hypotheses with opposite predictions regarding variation in population densities along resource gradients- the 'productivity hypothesis' and the 'productivity-based thinning hypothesis'. The hypotheses were tested in two functional groups of ground-dwelling ants that are directly primary consumers feeding on seeds: specialized seed-eaters and generalist species. We examined variations in colony density and foraging activity (a size measurement of the forager caste) in six ant assemblages along a steep productivity gradient in a semi-arid region, where precipitation and plant biomass vary 6-fold over a distance of 250km. An increase in the density or foraging activity of ant colonies along productivity gradients is also likely to affect competitive interactions among colonies, and consequently clinal changes in competition intensity were also examined. Ant foraging activity increased with productivity for both functional groups. However, colony density revealed opposing patterns: it increased with productivity for the specialized seed-eaters, but decreased for the generalist species. Competition intensity, evaluated by spatial partitioning of species at food baits and distribution of colonies, was uncorrelated with productivity in the specialized seed-eaters, but decreased with increasing productivity in the generalists. Our results provide support for two contrasting hypotheses regarding the effect of resource availability on the abundance of colonial organisms- the 'productivity hypothesis' for specialized seed-eaters and the 'productivity-based thinning hypothesis' for generalist species. These results also stress the importance of considering the role of functional groups in studies of community structure.


Role of squamous cell carcinoma antigen-1 on liver cells after partial hepatectomy in transgenic mice.
Squamous Cell Carcinoma Antigen-1 (SCCA1) overexpression has been observed in tumours of epithelial origin and in hepatocellular carcinoma. Previous data indicate that this serpin inhibits apoptosis, while its proliferative activity was only recently proposed. The aim of this study was to evaluate the effect of SCCA1 on liver cells in a transgenic mouse model after partial hepatectomy. Twenty-one C57BL/6J mice (11 transgenic for human SCCA1, 10 wild-type) underwent partial hepatectomy and were sacrified after one week. Apoptosis and proliferation markers were determined in the liver at sacrifice, while a cytokine panel was measured in serum. Transgenic mice showed a relative liver weight significantly higher than wild-type mice at sacrifice (mean +/- SD, 5.38+/-0.50% vs 4.84+/-0.29%, p=0.0221), while no difference (p=0.2403) was observed in two untreated control groups (6 transgenic, 6 wild-type mice). Active caspase-3 was significantly lower in transgenic mice than in wild-type mice (p=0.0047). The transgenic mouse group showed overall higher proliferative activity at sacrifice, compared to wild-type mice, with increased proliferation parameters. Cytokine analysis revealed a remarkable and opposite sex-dependent behaviour of interleukin (IL)-6 after hepatectomy. At variance with wild-type mice, a significant IL-6 increase was documented only in transgenic females (p=0.0313), even more relevant than that observed in wild-type males. In conclusion, transgenic mice expressing SCCA1 showed higher liver regenerative potential compared to wild-type mice, supporting the dual role of this serpin as an anti-apoptotic and pro-proliferative stimulus for liver cells in vivo.


Toward consensus in the analysis of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine as a noninvasive biomarker of oxidative stress.
Of the DNA-derived biomarkers of oxidative stress, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most frequently measured. However, there is significant discrepancy between chromatographic and immunoassay approaches, and intratechnique agreement among all available chromatography-based assays and ELISAs is yet to be established. This is a significant obstacle to their use in large molecular epidemiological studies. To evaluate the accuracy of intra/intertechnique and interlaboratory measurements, samples of phosphate buffered saline and urine, spiked with different concentrations of 8-oxoG, together with a series of urine samples from healthy individuals were distributed to ESCULA members. All laboratories received identical samples, including 2 negative controls that contained no added 8-oxodG. Data were returned from 17 laboratories, representing 20 methods, broadly classified as mass spectrometric (MS), electrochemical detection (EC), or enzyme-linked immunosorbant assay (ELISA). Overall, there was good within-technique agreement, with the majority of laboratories' results lying within 1 sd of their consensus mean. However, ELISA showed more within-technique variation than did the chromatographic techniques and, for the urine samples, reported higher values. Bland-Altman plots revealed good agreement between MS and EC methods but concentration-dependent deviation for ELISA. All methods ranked urine samples according to concentration similarly. Creatinine levels are routinely used as a correction factor for urine concentration, and therefore we also conducted an interlaboratory comparison of methods for urinary creatinine determination, in which the vast majority of values lay within 1 sd of the consensus value, irrespective of the analysis procedure. This study reveals greater consensus than previously expected, although concern remains over ELISA.-ESCULA [European Standards Committee on Urinary (DNA) Lesion Analysis], Evans, M. D., Olinski, R., Loft, S., Cooke, M. S. Toward consensus in the analysis of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine as a noninvasive biomarker of oxidative stress.


Biocalcification by halophilic bacteria for remediation of concrete structures in marine environment.
Microbial carbonate precipitation has emerged as a promising technology for remediation and restoration of concrete structures. Deterioration of reinforced concrete structures in marine environments is a major concern due to chloride-induced corrosion. In the current study, halophilic bacteria Exiguobacterium mexicanum was isolated from sea water and tested for biomineralization potential under different salt stress conditions. The growth, urease and carbonic anhydrase production significantly increased under salt stress conditions. Maximum calcium carbonate precipitation was recorded at 5 % NaCl concentration. Application of E. mexicanum on concrete specimens significantly increased the compressive strength (23.5 %) and reduced water absorption about five times under 5 % salt stress conditions compared to control specimens. SEM and XRD analysis of bacterial-treated concrete specimens confirmed the precipitation of calcite. The present study results support the potential of this technology for improving the strength and durability properties of building structures in marine environments.


Common carotid artery end-diastolic velocity is independently associated with future cardiovascular events.
Carotid ultrasound is widely used to measure haemodynamic parameters, such as intima-media thickness and blood flow velocities (i.e. peak-systolic velocity [PSV], end-diastolic velocity [EDV], and resistive index [RI]). However, the association between blood flow velocities and cardiovascular events remains unclear. Baseline data, including quantitative ultrasonography, were obtained from 3146 adults as part of the Cardiovascular Diseases Risk Factor Two-Township Study. Occurrence of ischaemic heart disease (IHD) and stroke was determined from insurance claims and death certificates. The hazard ratio (HR) of CVD (IHD and stroke combined) was calculated for EDV and PSV of the common carotid artery using Cox models. Net reclassification index and integrated discrimination index were used to evaluate the capacity of EDV to predict IHD, stroke, and CVD. Median follow-up was 12.8 years. There were 220 cases of IHD and 247 cases of stroke. The HR (95% CI) for CVD from univariate analysis was 4.54 (3.51-5.85) for EDV <15 cm/s relative to EDV ≥ 20 cm/s (p < 0.0001), and 3.23 (2.51-4.15) for PSV < 65 cm/s relative to PSV ≥ 80 cm/s (p < 0.0001). The HR (95% CI) for CVD from multivariate analysis was 1.66 (1.22-2.26) for EDV < 15 cm/s relative to EDV ≥ 20 cm/s, and 1.39 (1.03-1.89) for PSV < 65 cm/s relative to PSV ≥ 80 cm/s. EDV slightly but significantly improved prediction of CVD (integrated discrimination index 0.56%, p = 0.016). Low common carotid EDV and PSV were independently associated with future CVD, and EDV improved the prediction of future CVD. More prospective studies are required in different ethnic groups to understand the significance and implication of these findings.


Beyond the classic thermoneutral zone: Including thermal comfort.
The thermoneutral zone is defined as the range of ambient temperatures where the body can maintain its core temperature solely through regulating dry heat loss, i.e., skin blood flow. A living body can only maintain its core temperature when heat production and heat loss are balanced. That means that heat transport from body core to skin must equal heat transport from skin to the environment. This study focuses on what combinations of core and skin temperature satisfy the biophysical requirements of being in the thermoneutral zone for humans. Moreover, consequences are considered of changes in insulation and adding restrictions such as thermal comfort (i.e. driver for thermal behavior). A biophysical model was developed that calculates heat transport within a body, taking into account metabolic heat production, tissue insulation, and heat distribution by blood flow and equates that to heat loss to the environment, considering skin temperature, ambient temperature and other physical parameters. The biophysical analysis shows that the steady-state ambient temperature range associated with the thermoneutral zone does not guarantee that the body is in thermal balance at basal metabolic rate per se. Instead, depending on the combination of core temperature, mean skin temperature and ambient temperature, the body may require significant increases in heat production or heat loss to maintain stable core temperature. Therefore, the definition of the thermoneutral zone might need to be reformulated. Furthermore, after adding restrictions on skin temperature for thermal comfort, the ambient temperature range associated with thermal comfort is smaller than the thermoneutral zone. This, assuming animals seek thermal comfort, suggests that thermal behavior may be initiated already before the boundaries of the thermoneutral zone are reached.


Role of the Tumor Microenvironment in Regulating Pancreatic Cancer Therapy Resistance.
Pancreatic cancer has a notoriously poor prognosis, exhibits persistent drug resistance, and lacks a cure. Unique features of the pancreatic tumor microenvironment exacerbate tumorigenesis, metastasis, and therapy resistance. Recent studies emphasize the importance of exploiting cells in the tumor microenvironment to thwart cancers. In this review, we summarize the hallmarks of the multifaceted pancreatic tumor microenvironment, notably pancreatic stellate cells, tumor-associated fibroblasts, macrophages, and neutrophils, in the regulation of chemo-, radio-, immuno-, and targeted therapy resistance in pancreatic cancer. The molecular insight will facilitate the development of novel therapeutics against pancreatic cancer.


Beyond surveillance: a role for respondent-driven sampling in implementation science.
We are now in the fourth decade of the human immunodeficiency virus (HIV) pandemic. Several novel prevention tools have been identified, and prevalence and incidence have declined in many settings. A remaining challenge is the delivery of preventive interventions to hard-to-reach populations, including men who have sex with men and injection drug users. Leaders in the field of HIV have called for a new focus on implementation science, which requires a shift in thinking from individual randomized controlled trials to cluster-randomized trials. Multiple challenges need to be addressed in the conduct of cluster-randomized trials, including: 1) generalizability of the study population to the target population, 2) potential contamination through overlap/exchange of members of control and intervention clusters, and 3) evaluation of effectiveness at multiple levels of influence. To address these key challenges, we propose a novel application of respondent-driven sampling-a chain-referral strategy commonly used for surveillance-in the recruitment of participants for the evaluation of a cluster-randomized trial of a community intervention. We illustrate this application with an empirical example of a cluster-randomized trial that is currently under way to assess the effectiveness of men's wellness centers in improving utilization of HIV counseling and testing among men who have sex with men in India.


Cerebral aspergillosis in children. Report of three cases.
Between March and December of 1997, 3 cases of infantile cerebral aspergillosis appeared in our hospital. All patients presented some kind of immunosuppression associated with clinical findings of intracranial hypertension. After surgery, all cases were histopathologically confirmed and had positive cultures of Aspergillus. The first case was a patient with a history of subtotal resection of supratentorial ependymoma which presented a new enhancing mass on a control CT scan. Brain tumor recidiva was suspected, although, an Aspergillus granuloma was encountered on the tumor bed. Both other cases were found in patients who underwent transplantation: one presented multiple cerebral lesions after a renal transplant, and the other, after a bone marrow transplant, developed a rhinocerebral aspergillosis. The discussion was focused on the clinical findings, images and treatment of this cerebral infectious disease.


Vibration therapy accelerates healing of Stage I pressure ulcers in older adult patients.
The present study investigated whether vibration therapy using a vibrator could facilitate the healing of Stage I pressure ulcers (PrUs) in older adults. The study had a nonrandomized, blinded, controlled design. The subjects were hospital patients in long-term-care facilities with Stage I PrUs. In the experimental group, a vibrator (RelaWave; Matsuda Micronics Corp, Chiba, Japan) was used to apply vibration (frequency: 47 Hz; time: 10 seconds; amplitude modulation cycle: 15 seconds) for 15 minutes 3 times a day for up to 7 days, until Stage I PrUs healed. Apart from the vibration therapy, the experimental and control groups received the same care, which was provided according to PrU care guidelines. The number of healed ulcers was compared between 2 groups. The experimental group consisted of 16 patients with 20 Stage I PrUs; the control group consisted of 15 patients with 21 Stage I PrUs. In the experimental group, 8 (40.0%) PrUs healed; in the control group, 2 (9.5%) PrUs healed. The number of healed ulcers was significantly higher in the experimental group than in the control group (P = .033). The healing rate during the study period was significantly higher in the experimental group than in the control group (P = .018, logrank test). The hazard ratio adjusted for baseline risk factors was 0.031 (95% confidence intervals: 0.002-0.594, P = .021). The mean relative changes per day in wound area and intensity of redness were significantly greater in the experimental group than in the control group (P = .007, and P = .023, respectively). Based on these results, the use of the vibrator may facilitate the healing of Stage I PrUs.