Separation of arteries and veins using flow-induced phase effects in contrast-enhanced MRA of the lower extremities.
In 3-D contrast-enhanced magnetic resonance (MR) angiography of the lower extremities the goal is most often to enhance arterial structures while keeping veins and surrounding tissue unenhanced. Imaging during steady-state concentration of a blood pool agent or during poor timing of an extra-cellular contrast medium may result in simultaneous venous enhancement, making interpretation of the angiogram difficult. The aim of this study was to develop a post-processing method to separate the arteries from the veins in standard contrast-enhanced MR angiograms. The method was based on the different accumulation of flow-induced phase in the arteries and veins of the lower extremities. The method was tested in both phantom experiments and volunteers undergoing 3-D contrast-enhanced MR angiography using both an extra-cellular contrast medium and a blood pool agent. In the phantom studies, opposite directional flow was successfully separated at mean flow velocities as low as 9 cm/s. In the volunteer studies, the larger veins were successfully extinguished while the larger arteries were left unaffected. In smaller vessels with low flow velocities the separation was less successful. This was most apparent in vessels not oriented superior-inferior. The method developed here is promising for separating arteries from veins in contrast-enhanced MR angiography although the results could be further improved by either a different pulse sequence design or combining this method with other segmentation methods.


Clinical and radiological profile of posterior cortical atrophy and comparison with a group of typical Alzheimer disease and amnestic mild cognitive impairment.
Posterior cortical atrophy (PCA) is a rare dementia affecting higher visual processing and other posterior cortical functions with atrophy and hypometabolism in occipito-parieto-temporal areas, more on right side. The objective of the study was to explore the clinical, neuropsychological, and radiological features of PCA patients and to compare them with typical multi-domain amnestic Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients. Four out of 9 patients of PCA fulfilling the criteria of Tang-Wai et al. (2004), 10 patients each of AD and aMCI fulfilling NIA-AA criteria were chosen. Patients were assessed clinically by experienced neurologists. Neuropsychological assessment was performed with standardized validated tests. Each patient underwent an MRI. FDG-PET was done for all PCA and six AD patients. PCA patients were younger, cognitively more impaired with rapid progression showing predominant visuospatial deficits consistent with the damage to the upstream of visual processing. AD patients presented predominantly with amnestic symptoms, with visuospatial dysfunction in some and aMCI had mild memory loss. Marked atrophy and hypometabolism in occipital, parietal and temporal areas in PCA, atrophy and hypometabolism in medial temporal areas in AD and minimal non-localized atrophy in MRI in aMCI were seen. Two PCA patients showed hypometabolism extending to the medial temporal and one to the frontal cortex. The clinical and imaging features of PCA are consistent with the damage predominantly to the upstream of visual processing. The difference between PCA and typical AD suggests involvement of AD pathology at different sites within a common disease-relevant network of brain regions.


Production of perfluoroalkyl acids (PFAAs) from precursors in contaminated agricultural soils: Batch and leaching experiments.
Contamination of soils with per- and polyfluoroalkyl substances (PFAS) (e.g., aqueous film forming foams (AFFFs) or PFAS containing biosolids applied to agricultural soils) can lead to large scale groundwater pollution. For site management, knowledge about the extent and time scales of PFAS contamination is crucial. At such sites, often persistent perfluoroalkyl acids (PFAAs) and so-called precursors, which can be transformed into PFAAs, co-occur. In this study, the release of PFAAs from 14 soil samples from an agricultural site in southwest Germany contaminated via compost/paper sludge was investigated. Rapid leaching of C4-C8 perfluoroalkyl carboxylic acids (PFCA) was observed in saturated column tests, while slowing down with increasing chain-length (≥ C9 PFCAs). Two selected samples were further incubated in batch-tests after removal of existing C4-C8 PFCAs in extensive column leaching tests until a liquid-solid ratio of 10 l/kg. During 60 days of incubation, aqueous concentrations of C4-C8 PFCAs increased linearly by a factor of 29-222, indicating continuous production by transformation of precursors. The potential PFAA-precursor reservoir was estimated by the direct total oxidizable precursor (dTOP) assay. PFCA concentrations after the dTOP increased up to two orders of magnitude. Production rates determined in batch-tests combined with the results of dTOP assay were used to estimate time scales for the duration of C4-C8 PFCAs emission from the contaminated agricultural soils which likely will last for several decades.


Whole-Genome Sequence of Aneurinibacillus sp. Ricciae_BoGa-3, Isolated from Riccia fluitans.
Here, we present the Nanopore-only genome sequence of Aneurinibacillus sp. Ricciae_BoGa-3. It was isolated from Riccia fluitans ecotype BoGa-3 and its source was Botanical Garden Osnabrück (Germany). The complete circular genome is 4,981,254 bp with a GC content of 44.8%.


LncRNA LOXL1-AS1/miR-28-5p/SEMA7A axis facilitates pancreatic cancer progression.
Pancreatic cancer (PC), one of the most aggressive and lethal human malignancies, is associated with a deplorable prognosis despite progressive therapeutic strategies. Emerging evidence manifests that miR-28-5p is involved in several cancers, and its descending expression is associated with poor prognosis. Nevertheless, the function of miR-28-5p in PC remains unclear. Thus, the underlying regulatory mechanism of miR-28-5p in PC is urgent to be clarified. In the present study, we first recognized miR-28-5p was downregulated in PC, and miR-28-5p overexpression inhibited cell proliferation and migration in PC. Then miR-28-5p was verified to act as a molecular sponge of LOXL1-AS1. Therefore, the function of LOXL1-AS1 was further explored in PC, presenting that LOXL1-AS1 suppression inhibited cell proliferation and migration. What is more, SEMA7A was found to be a target gene for miR-28-5p and was upregulated in PC. In addition, LOXL1-AS1 could positively regulate SEMA7A expression while miR-28-5p could negatively regulate SEMA7A expression. According to rescue experiments, SEMA7A overexpression partially neutralized LOXL1-AS1 silence-mediated inhibitory function on progression in PC. Taken together, all the data demonstrated that LOXL1-AS1/miR-28-5p/SEMA7A axis facilitated pancreatic cancer progression, which may be regarded as an innovative therapeutic target for PC treatment. SIGNIFICANCE OF THE STUDY: Our findings constitute the first report to delineate that lncRNA LOXL1-AS1/miR-28-5p/SEMA7A axis facilitates PC progression. According to our experimental results, we found the expression of miR-28-5p was downregulated in PC cells and miR-28-5p overexpression inhibited cell proliferation and migration in PC. LOXL1-AS1 could sponge miR-28-5p and then upregulate the expression of SEMA7A. Thus, LOXL1-AS1/miR-28-5p/SEMA7A axis facilitated PC progression. This initially proposed point might provide a novel molecular target for PC treatment.


SHANK3 Mutations Associated with Autism and Schizophrenia Lead to Shared and Distinct Changes in Dendritic Spine Dynamics in the Developing Mouse Brain.
Autism Spectrum Disorders (ASD) and schizophrenia are distinct neurodevelopmental disorders that share certain symptoms and genetic components. Both disorders show abnormalities in dendritic spines, which are the main sites of excitatory synaptic inputs. Recent studies have identified the synaptic scaffolding protein Shank3 as a leading candidate gene for both disorders. Mutations in the SHANK3 gene have been linked to both ASD and schizophrenia; however, how patient-derived mutations affect the structural plasticity of dendritic spines during brain development is unknown. Here we use live two photon in vivo imaging to examine dendritic spine structural plasticity in mice with SHANK3 mutations associated with ASD and schizophrenia. We identified shared and distinct phenotypes in dendritic spine morphogenesis and plasticity in the ASD-associated InsG3680 mutant mice and the schizophrenia-associated R1117X mutant mice. No significant changes in dendritic arborization were observed in either mutant, raising the possibility that synaptic dysregulation may be a key contributor to the behavioral defects previously reported in these mice. These findings shed light on how patient-linked mutations in SHANK3 affect dendritic spine dynamics in the developing brain, which provides insight into the synaptic basis for the distinct phenotypes observed in ASD and schizophrenia.


Nutrient improvement for simultaneous production of exopolysaccharide and mycelial biomass by submerged cultivation of Schizophyllum commune AGMJ-1 using statistical optimization.
Exopolysaccharides (EPS) of fungal origin have attracted special attention from researchers due to their multifarious applications in the food and pharmaceutical industries. In the present study, optimization of the process parameters for the production of exopolysaccharide by Schizophyllum commune AGMJ-1 was studied using one factor at a time (OFAT) method, Plackett-Burman design (PBD) and response surface methodology (RSM). OFAT method revealed xylose and yeast extract to be the most effective carbon and nitrogen sources and pH 5.3 as an optimum for maximum EPS production. Xylose, yeast extract and KCl were screened as statistically significant variables for EPS production using PBD. RSM based on the central composite design estimated that maximum EPS (4.26 g L-1), mycelial biomass (14 g L-1) and specific yield (0.45 g g-1) were obtained when concentration of xylose, yeast extract and KCl were set at 2.5 g % (w/v), 0.83 g % (w/v) and 6.53 mg % (w/v), respectively, in the production medium.


Anti-proliferative effects of green tea polyphenol EGCG on Ha-Ras-induced transformation of intestinal epithelial cells.
Oncogenic Ras mutations are frequently observed in colorectal cancer and participate in neoplastic transformation of intestinal epithelial cells. Accumulating evidence demonstrates the chemopreventive properties of green tea on colon carcinogenesis. Here we investigated the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), to inhibit proliferation of intestinal epithelial cells (RIE-1) transfected with an inducible Ha-Ras(Val12) cDNA. EGCG inhibited cell proliferation induced by oncogenic Ras and blocked cell cycle transition at G1 phase via inhibition of cyclin D1 expression. The EGCG IC(50) was 42microM in transformed cells and 81microM in non-transformed cells. EGCG also promoted E-cadherin expression, which is downregulated by Ras transformation. This study demonstrates the potential of the natural compound EGCG as an effective adjuvant therapy for colon tumors bearing Ras mutations.


Atrazine and its degradation products in drinking water source and supply: Risk assessment for environmental and human health in Campinas, Brazil.
Atrazine is a broad-spectrum herbicide widely used worldwide to control grassy and broadleaf weeds. Atrazine's popularity is attributable to its cost-effectiveness and reliable performance. Relatedly, it is also an important micropollutant with a potential negative impact on biodiversity and human health. Atrazine has long been regularly detected in several environmental compartments, and its widespread use has resulted in ubiquitous and unpreventable contamination. Among pesticides sold in Brazil, atrazine has remained among the top-ranked active ingredients for the last several years. Thus, this study aimed to evaluate the occurrence of atrazine and three degradation products (hydroxyatrazine, desisopropylatrazine, and desethylatrazine) in surface water (Capivari and Atibaia rivers) and treated water, monthly sampling from two drinking water treatment plants in Campinas (São Paulo, Brazil). An analytical method using solid-phase extraction (SPE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to determine target compounds simultaneously. The method presented instrument quantification limits from 0.5 to 4.0 ng mL-1 and recovery values from 80 to 112%, with a maximum relative standard deviation of 6%. All analytes had a detection frequency of 100% from 2 to 2744 ng L-1. Statistical analysis showed no analyte removal after conventional water treatment. Also, the Capivari River showed greater analyte concentration than the Atibaia River. Performed risk assessments according to current Brazilian standards showed no human and environmental health risks. However, other risk assessment approaches may indicate potential risks, advocating for further research and ongoing surveillance.


Performance characteristics of recycled concrete aggregate as an unbound pavement material.
Use of recycled concrete aggregates (RCA) as a pavement material is one of the most sustainable engineering applications for the pavement industry. Investigation on the performance characteristics of RCA, such as elastic and plastic deformations of RCA is therefore, needed to assess RCA's application as an unbound pavement material. In this study, repeated load tri-axial (RLT) tests were conducted to investigate the response of RCA to elastic and plastic deformations under dynamic loads. The elastic and plastic properties were analysed through the 'resilient modulus' and the accumulation of plastic strain, respectively, at different confining stresses and moisture contents of the RCA specimens. The results from the tests revealed a steady gain of stiffness of the RCA specimens with an increase of load cycles at low moisture contents, high confining pressures and high vertical axial pressure.


Aromatase inhibitors and cyclooxygenase-2 (COX-2) inhibitors in endometriosis: new questions--old answers?
The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies for endometriosis-associated pain or recurrent disease are primarily aimed at downregulating ovarian function or antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is providing important results for the development of new, specific treatment modalities. Aromatase overexpression has recently been detected in endometriotic tissue. Aromatase (p450arom) is responsible for converting C19 androgens into estrogen in several types of human tissue. Aromatase activity causes local estrogen biosynthesis, which, in turn, stimulates prostaglandin E2 production by upregulating cyclooxygenase-2 (COX-2). Thus, a positive feedback cycle develops between the two systems. Another abnormality in endometriosis, the deficient 17beta-hydroxysteroiddehydrogenase type II (17beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations increase the amount of local estradiol and prostaglandin E2 in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance and even invasiveness. Consequently, aromatase and COX-2 are thought to be promising new therapeutic targets. Thus, specific aromatase inhibitors (e.g. Letrozol/Femara, Anastrozol/Arimidex or Exemestan/Aromasin) or selective COX-2 inhibitors (e.g. Celecoxib/Celebrex, Rofecoxib/Vioxx, Valdecoxib/Bextra) are of great interest and should be studied in clinical trials in premenopausal woman with endometriosis to expand the spectrum of currently available treatment options.


Evolutionary Deep Attention Convolutional Neural Networks for 2D and 3D Medical Image Segmentation.
Developing a convolutional neural network (CNN) for medical image segmentation is a complex task, especially when dealing with the limited number of available labelled medical images and computational resources. This task can be even more difficult if the aim is to develop a deep network and using a complicated structure like attention blocks. Because of various types of noises, artefacts and diversity in medical images, using complicated network structures like attention mechanism to improve the accuracy of segmentation is inevitable. Therefore, it is necessary to develop techniques to address the above difficulties. Neuroevolution is the combination of evolutionary computation and neural networks to establish a network automatically. However, Neuroevolution is computationally expensive, specifically to create 3D networks. In this paper, an automatic, efficient, accurate, and robust technique is introduced to develop deep attention convolutional neural networks utilising Neuroevolution for both 2D and 3D medical image segmentation. The proposed evolutionary technique can find a very good combination of six attention modules to recover spatial information from downsampling section and transfer them to the upsampling section of a U-Net-based network-six different CT and MRI datasets are employed to evaluate the proposed model for both 2D and 3D image segmentation. The obtained results are compared to state-of-the-art manual and automatic models, while our proposed model outperformed all of them.


Assessment of colistimethate sodium (COLOBREATHE) risk minimization measures implemented in the European Union: A cross-sectional study.
To assess the effectiveness of additional risk minimization measures (aRMMs) implemented in Europe for colistimethate sodium (CMS) among healthcare professionals (HCPs) and patients/caregivers following safety concerns regarding incorrect use of CMS delivered via Turbospin inhaler. A cross-sectional study was conducted among HCPs and patients/caregivers in Austria, Denmark, France, Germany, The Netherlands, and the United Kingdom between September 2016 and March 2018. Knowledge of the educational materials was assessed regarding common side effects, correct use of CMS and Turbospin inhaler, and capsule breakage. Awareness, receipt, and utilization of the aRMMs were also evaluated. Among 124 HCPs surveyed, the majority acknowledged awareness (86.2%), receipt (91.0%), and utilization (81.6%) of the CMS educational materials and were knowledgeable about the common CMS side effects (93.2%). Most HCPs correctly answered most questions regarding the proper use of CMS (>90%), yet only half knew how to correctly use the Turbospin inhaler (53.2%). Knowledge about capsule breakage was moderate (67.5%). Of the 29 patients/caregivers surveyed, almost half were aware of the educational materials (48.1%); of these, 69.2% received and used the materials. Most patients/caregivers were knowledgeable about the common CMS side effects (81.5%) and proper CMS use (>85%); however, knowledge about correct Turbospin inhaler use and potential for capsule breakage was moderate to low (48.1% and 37.9%, respectively). HCPs and patients/caregivers have good knowledge about the common side effects associated with CMS. However, knowledge of correct use of the Turbospin inhaler and capsule breakage was moderate to low.


Central mediation of hormonal influences on instrumental avoidance conditioning.
Two behaviorally active hormones of the pituitary-adrenal system are adrenocorticotropic hormones (ACTH) and corticosterone, and their behavioral effects are facilitation and inhibition of performance of previously learned avoidance responses, respectively. Their uptake, distribution and effects on central nervous system are reviewed. Hypothalamic neurotransmitter control of corticotropin releasing hormone (CRH) is described together with hypothalamic and extra-hypothalamic (hippocampal) regulation of pituitary-adrenal activity. Extra-hypothalamic mediation of the behavioral effects of ACTH is evaluated. Recent isotopic mappings of the efferents of the hippocampal formation have identified pathways from hippocampal subiculum to hypothalamus and posterior lateral and anterior thalamic nuclei. The evidence reviewed suggests a complex circuit involving hippocampal subiculum, thalamus and hypothalamus may be involved both in regulating pituitary-adrenal responses to stress and in mediating the effects of ACTH on avoidance behavior.


Noggin improves bone healing elicited by muscle stem cells expressing inducible BMP4.
The aim of this study was to test the hypothesis that a specific antagonist may enhance the efficacy of its corresponding growth factor in a regulated tissue engineering strategy. Our prior research has led to the development of a retroviral vector that enables optimal regulated bone morphogenetic protein 4 (BMP4) expression in vitro and regulated bone formation in vivo with transduced muscle stem cells. However, when implanted in critical-sized calvarial defects, these cells led to residual bone formation without induction or bone overgrowth with induction, even at reduced cell doses. We thus co-implanted the aforementioned cells with stem cells engineered to express Noggin, a specific BMP antagonist. This approach, while preserving our ability to regulate bone regeneration closely, prevented both the basal level bone regeneration and the bone overgrowth and, more importantly, led to the regeneration of bone that more closely resembled normal bone. We believe that this regulatable tissue engineering strategy, enhanced by utilizing a specific antagonist, constitutes a new paradigm for tissue engineering and regenerative medicine.


Implementation of an Internet Weight Loss Program in a Worksite Setting.
Worksite wellness programs typically produce modest weight losses. We examined whether an efficacious Internet behavioral weight loss program could be successfully implemented in a worksite setting. Participants were 75 overweight or obese employees/dependents of a large healthcare system who were given access to a 12-week Internet-based, multicomponent behavioral weight loss program. Assessments occurred at baseline, Month 3 (end of intervention), and Month 6 (follow-up). Retention was excellent (93% at Month 3 and 89% at Month 6). Intent-to-treat analyses demonstrated that participants lost an average (±SE) of -5.8 ± .60 kg from baseline to Month 3 and regained 1.1 ± .31 kg from Month 3 to Month 6; overall, weight loss from baseline to Month 6 was -4.7 ± .71 kg, p < .001. Men lost more weight than women, p = .022, and individuals who had a college degree or higher lost more weight than those with less education, p = .005. Adherence to viewing lessons (8 of 12) and self-monitoring (83% of days) was excellent and significantly associated with weight loss, ps < .05. An Internet-based behavioral weight management intervention can be successfully implemented in a worksite setting and can lead to clinically significant weight losses. Given the low costs of offering this program, it could easily be widely disseminated.


Guillain-Barré syndrome associated with inappropriate secretion of antidiuretic hormone following SARS-CoV-2 infection: A case-report.
In a system already preconditioned by previous damage, as results of the cytokine release syndrome complicating the COVID-19 disease, a small trigger may be sufficient to develop a SIADH complicating a GBS, even without a poor outcome.


3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration.
Corneal regeneration has always been a challenge due to its sophisticated structure and undesirable keratocyte-fibroblast transformation. Herein, we propose 3D printing of a biomimetic epithelium/stroma bilayer implant for corneal regeneration. Gelatin methacrylate (GelMA) and long-chain poly(ethylene glycol) diacrylate (PEGDA) are blended to form a two-component ink, which can be printed to different mechanically robust programmed PEGDA-GelMA objects by Digital Light Processing (DLP) printing technology, due to the toughening effect of crystalline crosslinks from long-chain PEGDA on GelMA hydrogel after photo-initiated copolymerization. The printed PEGDA-GelMA hydrogels support cell adhesion, proliferation, migration, meanwhile demonstrating a high light transmittance, and an appropriate swelling degree, nutrient permeation and degradation rate. A bi-layer dome-shaped corneal scaffold consisting of rabbit corneal epithelial cells (rCECs)-laden epithelia layer and rabbit adipose-derived mesenchymal stem cells (rASCs)-laden orthogonally aligned fibrous stroma layer can be printed out with a high fidelity and robustly surgical handling ability. This bi-layer cells-laden corneal scaffold is applied in a rabbit keratoplasty model. The post-operative outcome reveals efficient sealing of corneal defects, re-epithelialization and stromal regeneration. The concerted effects of microstructure of 3D printed corneal scaffold and precisely located cells in epithelia and stroma layer provide an optimal topographical and biological microenvironment for corneal regeneration.


Inhibition of the reductive activation of a valyl-tRNA synthetase from yeast by unsaturated fatty acids and associated observations on newly found lipophilic substances from yeast.
The reductive activation of a valyl-tRNA synthetase from yeast is strongly inhibited by 1-30 microM unsaturated fatty acids, and the inhibition is antagonized by 10-100 microM saturated fatty acids. Diethylstilbestrol also inhibits the activation. The possibility that unesterified palmitoleic and oleic acids are bona fide regulatory effectors is supported by a dramatic inverse relation between their cellular content and the growth rate of commercial bakers' yeast. An increase in the ratio of unsaturated to saturated acids with slowing growth in a laboratory strain, S288C, also supports the regulatory hypothesis. The free fatty acids are extracted into slightly acidified 50% alcohol together with traces of numerous novel lipophilic substances. One of these is suggested to function as a cofactor in conjunction with a heat-stable polypeptide that activates valyl-tRNA synthetase.


Whole genome sequencing of clinical specimens reveals the genomic diversity of porcine reproductive and respiratory syndrome viruses emerging in China.
The Porcine reproductive and respiratory syndrome virus (PRRSV), a single (+) RNA virus, is characterized by high genome variability and constant evolution. Owing to increasingly complex mutations, there is a growing difficulty in accessing the whole genome. Additionally, there is limited knowledge on PRRSV intra-host nucleotide variants, which may reflect the complex viral-host dynamics. Here, we performed next-generation sequencing on four clinical lung tissues to reveal the genomic diversity and highlight virus-host interactions. The complete genomes of the HN0713 and GDYJ1224 strains shared 90.7% and 91.3% homology with the lineage 1 strain NADC30, respectively, while the GDGZ0408 and GDHY0425 strains shared 92.0% and 91.6% homology with the JXA1 strain, respectively. Recombination analysis showed that the ORF5-7 genes of the GDGZ0408 and GDHY0425 strains, whose complete genomes belong to lineage 8.7 based on the phylogenetic tree, are both recombined with lineage 3 strains. Furthermore, nsp3, nsp10-12, ORF2 genes and a part of the 3'-UTR of the GDHY0425 strain were provided by the lineage 5.1 strain. Two lineage 1 strains (GDYJ1224 and HN0713) were produced by a recombination of lineages 8.7 and 1. Additionally, the lineage 3 strain was associated with the recombinant HN0713 strain. We determined the intra-host single nucleotide variant frequencies and found more than 200 sites at a frequency of >1% in all samples. GDGZ0408 with parts of the nsp9 and nsp10 genes of HP-PRRSV lineage 8.7 presented more genetically diverse populations than others, indicating that lineage 8.7 might drive robust intra-host single nucleotide variants (iSNVs). Moreover, in the iSNV pools, nsp2 and ORF2a presented the highest mutation dynamic. Overall, this study provided evidence for the alarmingly increasing recombination and ever-changing evolutionary dynamics of PRRSV, and revealed the potential causes of vaccine escape, providing a novel insight into the nucleotide variant population in clinical samples.


Development of an analytical method based on solid-phase extraction and LC-MS/MS for the monitoring of current-use pesticides and their metabolites in human urine.
Pyrethroids, organophosphorus pesticides and fipronil have been listed as priority chemicals in human biomonitoring studies because of their wide use and potential health effects in humans. The determination of 13 pesticides, including pyrethroids (deltamethrin, cypermethrin, permethrin, cyfluthrin, bifenthrin), organophosphorus (chlorpyrifos, chlorpyrifos-methyl, and malathion), fipronil, neonicotinoids (imidacloprid, acetamiprid and thiacloprid) and triazole (prothioconazole), together with 13 corresponding metabolites in human urine samples was achieved by solid-phase extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. All targeted compounds, except malathion dicarboxylic acid, were measured with a mean within-accuracy (n = 5) of 71%-114% (RSD: 1%-14%) and between-run (n = 15) accuracy of 80%-118% (RSD: 2%-14%). Limits of quantitation of the targeted analytes ranged from 0.1 to 16 pg/mL. The detection result of urine samples from 25 volunteers indicated that the detection frequencies of 3,5,6-trichloro-2-pyridinol (median: 448 pg/mL), 6-chloropyridine-3-carboxylic acid (median: 193 pg/mL), 2-methyl-3-phenylbenzoic acid (median: 181 pg/mL), 3-phenoxybenzoic acid (median: 99 pg/mL), 2-isopropyl-6-methyl-4-pyrimidinol (median: 77 pg/mL), cyfluthrin (median: 59 pg/mL), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (cis-DCCA, median: 53 pg/mL), trans-DCCA (median: 25 pg/mL), prothioconazole (median: 21 pg/mL), imidacloprid (median: 7 pg/mL), and prothioconazole-desthio (median: 1 pg/mL) were > 50%. The obtained results show that the validated method is suitable for the human biomonitoring of these current-use pesticides and their metabolites.


Bovine serum albumin-sodium alkyl sulfates bioconjugates as drug delivery systems.
Precipitation of bovine serum albumin (BSA) by anionic surfactants with alkyl chains of increasing lengths (octyl, decyl, dodecyl sulfates) was studied at room temperature, at pH 3.0, in isotonic sodium chloride solution. The particle size of albumin, the zeta potential, the surface charge and fluorescent properties of BSA-surfactant composites were investigated concerning addition of increasing amount of surfactant. The thermal stability of the systems was monitored by calorimetric analysis (DSC). The formation of the well-ordered structure in the self-assembly process in liquid phase was studied by XRD measurement. The structure of the precipitated BSA-surfactant nanocomposites was characterized by small-angle X-ray scattering (SAXS). Finally, ibuprofen (IBU) molecules were enclosed in BSA-surfactant bioconjugate systems and the release properties of the drug were investigated. It has been found out that, as a consequence to the increasing number of carbon atoms in the alkyl chains of the surfactant, the structure and the fluorescent properties of the aggregates formed can be controlled due to the increase in the hydrophobicity of BSA-surfactant composites. The bioconjugates are well applicable as carrier to realize controlled release of drug molecules.


Editorial Commentary: Osteochondral Allograft of the Humeral Head.
Despite reports of significant improvement in some patients, osteochondral allograft of the humeral head could be considered a procedure of last resort.


Neurotrophins and Their Receptors, Novel Therapeutic Targets for Pelvic Pain in Endometriosis, Are Coordinately Regulated by IL-1β via the JNK Signaling Pathway.
Pelvic pain in women with endometriosis is attributed to neuroinflammation and afferent nociceptor nerves in ectopic and eutopic endometrium. The hypothesis that uterine nociception is activated by IL-1β, a prominent cytokine in endometriosis, was tested herein. Immunofluorescence histochemistry confirmed the presence of neurons in human endometrial tissue. Expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors in endometrial tissue and cells was validated by immunohistochemistry and Western blotting. Isolated endometrial stromal cells (ESCs) were subjected to dose-response and time-course experiments with IL-1β and kinase inhibitors to characterize in vitro biomarkers. Neural biomarkers were co-localized in endometrial nerve fibers. NGF, BDNF, and their receptors tropomyosin receptor kinase (Trk) A, TrkB, and p75 neurotrophin receptor were all expressed in primary ESCs. IL-1β stimulated higher TrkA/B expression in ESCs derived from endometriosis cases (2.8- ± 0.2-fold) than cells from controls (1.5- ± 0.3-fold, t-test, P < 0.01), effects that were mediated via the c-Jun N-terminal kinase (JNK) pathway. BDNF concentrations trended higher in peritoneal fluid of endometriosis cases but were not statistically different from controls (P = 0.16). The results support the hypothesis that NGF and BDNF and their corresponding receptors orchestrate innervation of the endometrium, which is augmented by IL-1β. We postulate that JNK inhibitors, such as SP600125, have the potential to reduce neuroinflammation in women with endometriosis.


Uncoupling psychological from physiological markers of heat acclimatization in a military context.
Heat acclimatization may help personnel who travel to areas with a hot climate (WBGT > 27 °C), making them operationally more efficient and performant through improvements in physiological and psychological parameters. Their work-related physical activities may aid active heat acclimatization. However, it is unknown whether adding physical training to improve adaptation is effective, particularly if there is sufficient time for full acclimatization, classically reached after 15 days. Thirty French soldiers (Training group, T) performed a progressive and moderate (from three to five 8-min running sets at 50-60% of their speed at VO2max with 4-min periods of active recovery in between) aerobic training program upon arriving at their base in United Arab Emirates (~40 °C and 20% RH). A control group (30 soldiers; No Training, NT) continued to perform only their usual outdoor military activities (~5 h d-1). A field heat stress test (HST: three 8-min running sets at 50% of the speed at VO2max) was performed before (D0), during (D10), and after (D15) the heat acclimatization period to assess physiological and psychological changes. An 8-km trial in battledress was then performed at D17. Although physiological modifications were mostly similar (p < 0.001 for all) for both groups (rectal temperature at the end of the HST: -0.58 ± 0.51 vs -0.53 ± 0.40 °C, HR at the end of the HST: -21 ± 12 vs -19 ± 9 bpm, and sweat osmolality: -47 ± 30 vs -26 ± 32 mOsmol.l-1 between D15 and D0 for T and NT groups, respectively), thermal discomfort (-31 ± 4 vs -11 ± 5 mm between D15 and D0, p = 0.001) and rates of perceived exertion (-3.0 ± 0.4 vs -1.4 ± 0.3 D15 and D0, p = 0.001) were much lower in the T than NT group during the HST. HST-induced modifications in facial temperature only decreased in the T group (-1.08 ± 0.28 between D15 and D0, p < 0.001). Moreover, there was a difference in perceived thermal discomfort during the 8-km trial (40 ± 20 vs 55 ± 22 mm for the T and NT groups, respectively, p = 0.010). Thus, a 15-day, low-volume training regimen during a mission in a hot and dry environment has a modest impact on physiological adaptation but strongly decreases the perceived strain of exertion and climate potentially via greater reductions in facial temperature, even during a classical operational physical task in a military context.


Combined features of pemphigus and pemphigoid induced by penicillamine.
D-Penicillamine is able to induce a bullous eruption with the clinical, histological and immunological features of pemphigus. We present a case that had all the characteristics of pemphigus, but also in vivo bound IgG against the dermo-epidermal junction, i.e. the immunological features of bullous pemphigoid. Since no subepidermal blistering was observed, it is concluded that the penicillamine-induced auto-antibodies against the basement membrane zone were biologically inactive.


Thermodynamic study of Th(IV) sorption on attapulgite.
Sorption of Th(IV) on attapulgite was studied as a function of pH and temperature under ambient conditions using batch technique. The results indicated that sorption of Th(IV) on attapulgite was strongly affected by pH values and temperature. The kinetic sorption of Th(IV) can be described by pseudo-second-order rate very well. Sorption isotherms of Th(IV) at 293.15, 308.15 and 323.15K were modeled by Langmuir and Dubinin-Radushkevich models very well, and the parameters indicated that the sorption of Th(IV) on attapulgite was strongly dependent on temperature and the sorption of Th(IV) increased with increasing temperature of the system. Enthalpy (DeltaH(0)), entropy (DeltaS(0)) and Gibbs free energy (DeltaG(0)) were calculated from the temperature dependent sorption data, and the results indicated that the sorption of Th(IV) on attapulgite was a spontaneous process, and the sorption was endothermic.


Results of Magnetic Resonance Imaging (MRI) Screening in Patients at High Risk for Breast Cancer.
Screening MRI as an adjunct to mammography is recommended by the ACS for patients with a lifetime risk for breast cancer > 20%. While the benefits are clear, MRI screening is associated with an increase in false-positive results. The purpose of this study was to analyze our institutional database of high-risk patients and assess the uptake of screening MRI examinations and the results of those screenings. Our institutional review board-approved High-Risk Breast Cancer Database was queried for patients enrolled from January 2017 to January 2023 who were at high risk for breast cancer in a comparative analysis between those who were screened versus not screened with MRIs. Variables of interest included risk factor, background, MRI screening uptake, and frequency and results of image-guided breast biopsies. A total of 254 of 1106 high-risk patients (23%) had MRI screening. Forty-six of 852 (5.3%) patients in the non-MRI-screened cohort and nine of 254 (3.5%) patients in the MRI-screened cohort were diagnosed with a malignant lesion after image-guided biopsy (p = 0.6). There was no significant difference between MRI and non-MRI guided biopsies in detecting breast cancer. All malignant lesions were T1 or in situ disease. The 254 patients in the MRI-screened group underwent 185 biopsies. Fifty-seven percent of MRI-guided biopsies yielded benign results. Although the addition of MRI screening in our high-risk cohort did not produce a significant number of additional cancer diagnoses, patients monitored in our high-risk cohort who developed breast cancer were diagnosed at very early stages of disease, underscoring the benefit of participation in the program.


12-month results of the standardised combination therapy for diabetic macular oedema: intravitreal bevacizumab and navigated retinal photocoagulation.
To evaluate the efficacy of a standardised combination therapy for clinically significant diabetic macular oedema using bevacizumab injections followed by navigated laser photocoagulation to stabilise retinal thickness. In this pilot study we retrospectively reviewed charts and imaging of 23 eyes treated with the standardised combination regimen. Eyes initially received monthly bevacizumab injections, followed by navigated laser photocoagulation when central retinal thickness (CRT) was <440 µm. Patients were then followed monthly for 12 months. At the time of navigated laser after bevacizumab treatment mean vision gain was +10.4 Early Treatment Diabetic Retinopathy Study letters (p<0.01) and CRT reduction was 146 µm (p<0.001). At 12 months from baseline, the vision gain remained stable at +10.6 Early Treatment Diabetic Retinopathy Study letters (p<0.01), and CRT reduction was stable at 137 µm (p<0.001). At 12 months from laser, the vision gain was 7.8 letters from baseline (p<0.01), with no significant change compared with the gain at 12 months from baseline (p=0.108). At 12 months from laser, CRT reduction was 125 µm from baseline (p<0.001), with no significant change compared with CRT reduction at 12 months from baseline (p=0.601). Total injections needed were 4.4 from baseline to month 12, with 1.3 reinjection needed after laser. 57% of the eyes didn't require injections after laser, while 43% needed two additional injections. Standardised combination therapy using bevacizumab injections followed by navigated laser treatment for clinically significant diabetic macular oedema demonstrated significant visual gain and CRT reduction after bevacizumab treatment and stabilisation after navigated laser up to 12 months. The number of injections required in 12 months was lower than reported in previous combination studies.


Lamicel does not promote induction of labour. A randomized controlled study.
Lamicel is a synthetic tent, which, when inserted in the cervical canal, dilates the cervix by osmosis. Lamicel as an adjunct to induction of labour with intravenous oxytocin or vaginal prostaglandin E2 has been examined in a randomized controlled trial. Ninety-one pregnant women with an unripe cervix participated in the study. No improvement in efficacy was observed in the Lamicel groups compared to the control groups, neither when induction of labour was performed with oxytocin nor with vaginal prostaglandin.


[Hysteroplasty for septate uterus by cleavage and mobilisation of the septum (author's transl)].
A new technique of hysteroplasty is proposed for the septate uterus. The uterine incision is anterior medline, leaving the posterior wall of the uterus untouched. The septum is split into two hemi-septa which are increased in such a way as to obtain two pediculated flaps, covered by endometrium. Anterior and posterior distribution of the flaps makes it possible to recreate a spacious single cavity.


Prostate cancer incidence in light of the spatial distribution of another screening-detectable cancer.
Bias in spatial analyses that overlook compositional and contextual factors of communities can be substantial. We first examined spatial patterns among 11,728 prostate cancer cases across Connecticut, 1994-98. A spatial scan statistic (SatScan™) identified two locations where average annual incidence rates significantly exceeded the statewide level and two locations with significantly lower disease rates. Extending the analysis to adjust rates for age and race/ethnicity greatly minimized, but did not eliminate, geographic variation. Adjustment for age and poverty level of communities eliminated significant variability across locales. Similarly, analysis adjusted for age and covariation of colorectal cancer incidence rates across the state accounted for all significant variation previously observed. These results suggest that accounting for a "detection effect" due to clinical patterns of another screenable condition may be as useful as adjusting spatial data for variability of socio-economic conditions.


Worms taste bitter: ASH neurons, QUI-1, GPA-3 and ODR-3 mediate quinine avoidance in Caenorhabditis elegans.
An animal's ability to detect and avoid toxic compounds in the environment is crucial for survival. We show that the nematode Caenorhabditis elegans avoids many water-soluble substances that are toxic and that taste bitter to humans. We have used laser ablation and a genetic cell rescue strategy to identify sensory neurons involved in the avoidance of the bitter substance quinine, and found that ASH, a polymodal nociceptive neuron that senses many aversive stimuli, is the principal player in this response. Two G protein alpha subunits GPA-3 and ODR-3, expressed in ASH and in different, nonoverlapping sets of sensory neurons, are necessary for the response to quinine, although the effect of odr-3 can only be appreciated in the absence of gpa-3. We identified and cloned a new gene, qui-1, necessary for quinine and SDS avoidance. qui-1 codes for a novel protein with WD-40 domains and which is expressed in the avoidance sensory neurons ASH and ADL.


Genes, odours and the recognition of parasitized individuals by rodents.
Social recognition, whereby animals identify and recognize other individual conspecifics, is a crucial prerequisite for a wide range of social behaviours. There are relationships among social odours (chemical signals), parasite recognition and avoidance that are associated with hormonal, neural and genomic mechanisms in rodents. Rodents use social odours to: (i) distinguish between infected and uninfected individuals; (ii) recognize specific infected individuals; and (iii) avoid and display aversive responses to infected individuals. There are genomic correlates of this parasite recognition and avoidance in which genes expressing the neuropeptide oxytocin have roles. In this article, we provide a framework ("micronet") by which the genetic, hormonal and neural interactions associated with social behaviours and recognition and avoidance of parasitized individuals can be explored.


Multiple triggering in a girl with Ehlers-Danlos syndrome: case report.
We report a case of multiple triggering associated with Ehlers-Danlos syndrome. We postulate that the propensity for tendon degeneration in Ehlers-Danlos syndrome coupled with repetitive microtrauma might lead to fraying of the tendon fibers and, consequently, triggering. Indeed, in our case, debridement of the tendons rather than resection of A1 pulley resulted in a good long-term functional outcome 2 years after surgery.


Endoscopic scoring system utilization for inflammatory bowel disease activity assessment: A multicenter real-world study from Argentina.
The frequency and patterns of use of scores for the assessment of endoscopic activity in inflammatory bowel disease patients are not known. To describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. A multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn's disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between 2018 and 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist's specialty, years of experience as well as expertise in IBD were assessed. A total of 1556 patients were included for analysis (31.94% patients with Crohn's disease). Mean age was 45.94±15.46. Endoscopic score reporting was found in 58.41% of colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%) for ulcerative colitis and Crohn's disease, respectively. In addition, 79.11% of endoscopic reports failed to comply with all recommendations on endoscopic reporting for inflammatory bowel disease. A significant proportion of endoscopic reports of inflammatory bowel disease patients do not include the description of an endoscopic score to assess mucosal inflammatory activity in a real-world setting. This is also associated with a lack of compliance in recommended criteria for proper endoscopic reporting.


Internal lateral nasal osteotomy: double-guarded osteotome and mucosa tearing.
For the internal lateral nasal osteotomy, a 4-mm double-guarded straight osteotome that separates the external periost and mucoperiosteum while the osteotomy is progressing is presented. Before the osteotomy, the external periost and the internal mucoperiosteum are infiltrated with local anesthesia and elevated by tunneling with an elevator. As the sharp part is behind the guards, it is not possible for the osteotome to slip away laterally or medially from the nasal bone. By tunneling just at the base of the nasal bones, arteries, veins, and lymphatics are preserved while the superior part of the external periosteum and the internal mucoperichondrium maintained the bones in a stable position with firm support to both sides. Forty consecutive rhinoplasties were studied with an endoscope. In 35 primary rhinoplasties the mucosa laceration rate was 1.5%, whereas in secondary rhinoplasties it was 80%. The approach to the piriform aperture was intranasal in the first 16 cases and intraoral in the last 24 cases. The intraoral mucosal elevation and osteotomy were easier to carry out than in the intranasal approach. In general, minor lower-lid edema and ecchymosis were observed, possibly related to the fact that the periosteum was elevated, thus preserving the supraperiosteal arteries, veins, and lymphatics. When the mucosa was elevated, the internal irrigation of the mucosa and the lymphatics was also preserved, thus avoiding intraoperative bleeding, intranasal packing, and postoperative bleeding.


Cone-Beam Computed Tomography Detection of Separated Endodontic Instruments.
This study compared the accuracy, sensitivity, and specificity of different imaging diagnostic protocols, cone-beam computed tomography (CBCT) and digital periapical radiography (DPR), in identifying separated endodontic instruments in filled root canals. One hundred eight root canals from 36 mandibular molars were prepared and obturated. Of these, 84 were filled without separated instruments, and 24 were filled with the presence of a separated instrument (stainless steel hand file or reciprocating instrument). Subsequently, different CBCT imaging protocols were acquired: i-CAT Classic (ICC) (0.25-mm isotropic voxel), i-CAT Next Generation (ICN) (0.125-mm isotropic voxel), and PreXion 3D (PXD) (0.09-mm isotropic voxel). Moreover, a DPR exam was obtained (08 mA, 70 kVp, and exposure time of 0.2 seconds). Two calibrated endodontists evaluated each image for the presence or absence of fractured files on a 5-point scale, ranging from definitely absent to definitely present. The accuracy, sensitivity, and specificity measures for each method were estimated. The data were evaluated by Fisher exact test and binomial test. Nine instruments were identified in DPR (37.5%) and none in the CBCT protocols (P > .05). The type of instrument (stainless steel hand file or reciprocating instrument) did not influence the identification of the separated instrument (P > .05). This study showed that DPR is the most accurate and sensitive imaging technique, with 83.3% and 37.5%, respectively. DPR is the better imaging diagnostic exam to evaluate the presence of separated endodontic instruments inside a root canal in comparison with the ICC, ICN, and PXD tomographic protocols. However, most of the separated instruments were not identified.


Hospital Physicians' Perspectives on Occupational Stress During COVID-19: a Qualitative Analysis from Two US Cities.
US physicians are at risk for high rates of occupational stress and burnout, which the COVID-19 pandemic has intensified. As approaches targeting physicians' individual resilience have fallen short, researchers are increasingly calling for studies that investigate organizational drivers of stress and burnout. To understand the multi-dimensional systems factors shaping hospital physicians' occupational stress during the pandemic. Qualitative, semi-structured interviews conducted in February-October 2021. Hospitals in New York City and New Orleans. A purposive snowball sample of attending physicians and fellows in hospital medicine, emergency medicine, pulmonary critical care, and palliative care who spent at least 4 weeks providing inpatient COVID-19 care beginning in March 2020 was selected. The sample included 40 physicians from 14 hospitals in New York City and 39 physicians from nine hospitals in New Orleans. Descriptive analysis of participants' self-reported perceptions of occupational stress. Participants identified multiple factors shaping their occupational stress including individual-level factors such as age, work experience, and life stage; institutional-level factors such as resource disparities, institutional type and size, and policies; professional-level factors such as informal rationing and medical uncertainty; and societal-level factors such as the federal response, COVID politics, and social inequalities. Stressors within and across these four levels worked in combination to shape physicians' perceptions of occupational stress at the individual level. This article contributes to an emergent literature on systems-based approaches to occupational stress and burnout among physicians by demonstrating the intersections among societal conditions, professional cultures, institutional work environments, and individual stress. Findings from semi-structured interviews suggest that interventions to reduce physician stress and burnout may be more effective if they target systems factors and stressors at multiple levels.


Control of erythrocyte membrane microviscosity by insulin.
The human erythrocyte membrane binds insulin through high-affinity, low-capacity binding sites (dissociation constant Kd1 2.45 X 10(-9)M; capacity n1 207 fmol/mg protein) and low-affinity, high-capacity binding sites (Kd2 0.63 X 10(-6) M; n2 37 pmol/mg protein). Treatment of the erythrocyte membrane or the intact cells with the physiological concentration of insulin, which is within the range of Kd value of the high-affinity sites, results in a significant reduction of the membrane microviscosity and the filtration time of the intact cells. Use of supraphysiological concentrations of the hormone reverses the effect of the lower concentration of insulin on the membrane microviscosity and the filtration time.


Brief report: errorless versus errorful learning as a memory rehabilitation approach in Alzheimer's Disease.
Previous studies concerned with the use of errorless learning (EL) in memory rehabilitation of patients with Alzheimer's disease (AD) combined EL with other techniques, such as expanded rehearsal, to facilitate learning. These studies focused on the re-learning of previously familiar information and did not investigate the learning of novel information. The aim of the present study was to investigate if EL provides a better training technique for AD patients than errorful learning (EF). For this purpose, learning of familiar material and learning of novel associations in four patients with probable AD was compared under EL and EF conditions. Combined data analysis demonstrated a significant advantage of EL over EF both for old and novel learning. However, patients also learned significantly in the EF condition and the EL effect was not large enough to reach significance on an individual level. It is suggested that EL may be most beneficial for patients with profound amnesia, and in situations that make effortful processing difficult, but that residual explicit memory capacities may override EL benefits.


Liquid-liquid immiscibility in model membranes activates secretory phospholipase A2.
Secretory phospholipase A2 (sPLA2) hydrolyzes phosphatidylcholines (PC) within lipid bilayers to produce lyso-PC and a fatty acid, which can act as signaling molecule in biological membranes. The activity of sPLA2 depends on the membrane structure. Bilayer defects, curvature, and gel-fluid micro-heterogeneity are known to activate sPLA2. Here, we investigate if liquid-liquid immiscibility within model membranes is sufficient for sPLA2 activation. The onset of the hydrolytic activity of cobra-venom sPLA2 towards mixed monolayers of dimyristoyl-PC (DMPC)/cholesterol 2:1 (mol/mol) has been determined using infrared reflection-absorption spectroscopy (IRRAS) and polarization-modulated (PM-) IRRAS. The lag phase of sPLA2 activity increases exponentially with rising surface pressures starting at 12 mN/m. This indicates that enzyme activation is hampered at higher surface pressures. Below 12 mN/m, no lag phase is observed, and sPLA2 is efficiently activated. The surface pressure that is critical for sPLA2 activation correlates with the critical miscibility pressure according to the phase diagram of DMPC and cholesterol. Thus, coexisting, liquid-phase domains provide sufficient boundaries to activate sPLA2. Moreover, liquid-liquid immiscibility is an activating mechanism for sPLA2 that also applies to biological membranes under physiological conditions because the corresponding bilayer structure is associated with that of membrane rafts.


Enhanced activity of sodium-lithium countertransport in patients with cardiac syndrome X: a potential link between cardiac and metabolic syndrome X.
This study was aimed at assessing both stimulated insulinemia and the sodium-lithium countertransport in a selected group of patients with cardiac syndrome X. Hyperinsulinemia, which is frequently present in patients with cardiac syndrome X, is often associated with an enhanced activity of the sodium-lithium countertransport, an in vitro marker of sodium-hydrogen exchange. Fifteen patients with syndrome X and 14 matched controls were studied. After pharmacological washout, sodium-lithium countertransport was assessed from lithium-loaded red blood cells. Postload insulin levels were evaluated by a double-antibody radioimmunoassay. Maximal velocity of sodium-lithium countertransport was higher in patients with syndrome X compared to controls (635+/-200 vs. 324+/-49 micromol/liter/h, p = 0.001). Fourteen of the 15 patients with syndrome X (93%) presented sodium-lithium countertransport values higher than the mean +2 SD of the control group. At 120 min, 12 patients with syndrome X (80%) had plasma levels of insulin >420 pmol/liter, which corresponds to the mean value +2 SD of controls (p = 0.006). Both enhanced activity of the sodium-lithium countertransport and stimulated hyperinsulinemia are present in the vast majority of patients with cardiac syndrome X. As enhanced activity of the sodium-lithium countertransport has the potential to cause both glucose intolerance and smooth muscle hyperreactivity, it might represent a common cause of the metabolic and vascular alterations frequently found in syndrome X.


The influence of a non-ionic surfactant on rectal absorption of virus particles.
A bacterial virus, suspended in three different vehicles, was introduced into the rectum of rabbits. The virus was detected in the circulating blood as early as 10 min after the administration. The quantity of virus found in blood and the duration of its presence, were enhanced when a non-ionic surfactant was used as vehicle of the virus.


Reduced tyrosine kinase receptor C mRNA levels in the frontal cortex of patients with schizophrenia.
Using a quantitative RNA-PCR approach tyrosine kinase receptor (trk) C mRNA levels were determined in brain material from the frontal cortex (BA10), temporal cortex (BA20) and cerebellum of control specimen and patients with schizophrenia, bipolar disorder or non-psychotic depression (15 subjects each). In the frontal cortex of schizophrenics there was a 5.8-fold reduction of trk C mRNA levels, which reached statistical significance (P < 0.05). Trk C levels in the cerebellum were positively correlated with lifetime fluphenazine equivalents (r = 0.54), suggesting that neuroleptics influence TRK C gene activity in the cerebellum. Moreover, the distinct medication-independent reduction of trk C mRNA may point to a disturbed neurotrophic gene activity in the frontal cortex of schizophrenic patients.


Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition.
Tungstate counteracts diabetes and obesity in animal models, but its molecular mechanisms remain elusive. Our Saccharomyces cerevisiae-based approach has found that tungstate alleviated the growth defect induced by nutrient stress and enhanced the activation of the GCN pathway. Tungstate relieved the sensitivity to starvation of a gcn2-507 yeast hypomorphic mutant, indicating that tungstate modulated the GCN pathway downstream of Gcn2p. Interestingly, tungstate inhibited Glc7p and PP1 phosphatase activity, both negative regulators of the GCN pathway in yeast and humans, respectively. Accordingly, overexpression of a dominant-negative Glc7p mutant in yeast mimicked tungstate effects. Therefore tungstate alleviates nutrient stress in yeast by in vivo inhibition of Glc7p. These data uncover a potential role for tungstate in the treatment of PP1 and GCN related diseases.


The "hay-fork" sign in the ultrasonographic diagnosis of intussusception.
Ultrasonography was used to evaluate a palpable abdominal mass in a woman. The characteristic "hay-fork" image led to the correct diagnosis of colocolic intussusception, which had not been suspected. This sign appears to be highly specific for intussusception.


Fertility sparing treatment of vaginal clear cell adenocarcinoma in a DES-Naïve young woman.
Primary vaginal cancer is rare and comprises 1-2% of female genital tract cancers. Among the types of vaginal cancer, adenocarcinoma accounts for only 10% with the peak incidence in women less than 20 years old. Clear cell type vaginal adenocarcinoma is most associated with exposure to diethylstilbestrol (DES) in-utero. We present a case of an 18-year-old nulliparous woman, DES-exposure naive, who was diagnosed with stage I clear cell vaginal adenocarcinoma during a routine pelvic exam for abnormal vaginal bleeding. She underwent a fertility-preserving radical vaginectomy and pelvic lymphadenectomy with neovagina creation and uterovaginal cervical reconstruction. She has been without disease for 28 months. Although rare, vaginal cancer can be diagnosed on routine women's health exams. Early screening and diagnosis allow for innovative fertility-preserving surgical approaches without compromising oncologic outcomes. To our knowledge, this is the first case of a fertility-preserving radical vaginectomy, neovagina creation using a vertical rectus abdominis myocutaneous (VRAM) flap, and uterocervicovaginal reconstruction to successfully treat early stage clear cell vaginal adenocarcinoma with surgery alone, sparing the patient from adjuvant chemotherapy or radiation.


Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants.
In recent years, research on phytochemicals has underscored pleiotropic actions and medicinal and health-promoting properties which certainly deserve serious attention [...].


Canine parvovirus--a review of epidemiological and diagnostic aspects, with emphasis on type 2c.
Canine parvovirus type 2 (CPV-2) emerged in late 1970s causing severe epizootics in kennels and dog shelters worldwide. Soon after its emergence, CPV-2 underwent genetic evolution giving rise consecutively to two antigenic variants, CPV-2a and CPV-2b that replaced progressively the original type. In 2000, a new antigenic variant, CPV-2c, was detected in Italy and rapidly spread to several countries. In comparison to the original type CPV-2, the antigenic variants display increased pathogenicity in dogs and extended host range, being able to infect and cause disease in cats. Epidemiological survey indicate that the newest type CPV-2c is becoming prevalent in different geographic regions and is often associated to severe disease in adult dogs and also in dogs that have completed the vaccination protocols. However, the primary cause of failure of CPV vaccination is interference by maternally derived immunity. Diagnosis of CPV infection by traditional methods has been shown to be poorly sensitive, especially in the late stages of infections. New diagnostic approaches based on molecular methods have been developed for sensitive detection of CPV in clinical samples and rapid characterisation of the viral type. Continuous surveillance will help assess whether there is a real need to update currently available vaccines and diagnostic tests.


[Second twin delivery in cephalic presentation. Apropos of a series of 127 patients].
In 2009, the French National College of Obstetricians and Gynaecologists (CNGOF) clinical practice guidelines encouraged the active management of the second twin (T2) in high and mobile cephalic presentation (CP) by performing systematic internal maneuvers. In our department, this type of management is less frequent as whenever T2 is not delivered spontaneously after a short time interval, an instrumental extraction is realized. We analyzed our practice for 5 years upon 127 twin pregnancies with a trial of vaginal delivery for T2 in CP. We compared the results following different modes of delivery which are: spontaneous delivery, instrumental extraction, and total breech extraction after manual internal version. No significant difference was found among the 3 groups in terms of maternal, fetal and neonatal well-being. Moreover, instrumental delivery was feasible, with a mean time interval for delivery between the 2 twins<15 minutes, even when performed by an obstetrician on training. The aim of our study was to evaluate our practice on T2 in CP, because this event can be quite tricky, thus discouraging less experienced obstetricians towards this practice and resulting in an increase in caesarean sections for T2. Instrumental delivery should be considered a possible option for any T2 in CP so as to ensure the continued existence of vaginal births for twin pregnancies.


C4d deposition is correlated with the level of antivimentin antibody in rat kidneys undergoing chronic allograft nephropathy.
Antivimentin antibody is often produced as an autoantibody after transplantation. C4d deposition, a marker of humoral immunity during transplantation, is believed to reflect alloantibodies. This study investigated the relationship between C4d deposition and humoral immunity to vimentin among rat kidneys undergoing chronic allograft nephropathy (CAN). Fisher 344 rat renal grafts were orthotopically transplanted into Lewis rats following the procedure of Kamada with our modification. All recipients were administered cyclosporine (CsA) (10 mg/kg(-1).d(-1) x 10 d) before being divided into 3 groups of oral treatments: (1) vehicle, (2) CsA (6 mg/kg(-1).d(-1)), and (3) mycophenolate mofetil (MMF; 20 mg/kg(-1).d(-1)). At 4, 8 and 12 weeks after transplantation, the rats were killed, the renal allografts harvested, and the sera collected. Serum creatinine (SCr) was measured and pathologic changes assessed according to the Banff 97 criteria. The antivimentin antibody was quantified by enzyme-linked immunosorbent assay. The deposition of C4d detected by immunofluorescence was analyzed by integrated optical density (IOD). Antivimentin antibody was observed in sera of all transplanted rats. The level of antivimentin antibody (IgGDeltaOD) increased gradually during the development of CAN from 4 weeks. Simultaneously, C4d deposition in peritubular capillaries also progressively strengthened. There was a strong positive correlation between the content of antivimentin antibody and C4d deposition (r = 0.892; P = .000). MMF simultaneously decreased antivimentin antibody formation and C4d deposition. In contrast, CsA had no significant effect. We demonstrated the production of antivimentin antibodies and the deposition of C4d during the development of CAN. There was a positive correlation between them. Whether humoral immunity to vimentin contributes to C4d deposition is not clear and further studies are needed to elucidate this issue.


Direct in situ photolithography of perovskite quantum dots based on photocatalysis of lead bromide complexes.
Photolithography has shown great potential in patterning solution-processed nanomaterials for integration into advanced optoelectronic devices. However, photolithography of perovskite quantum dots (PQDs) has so far been hindered by the incompatibility of perovskite with traditional optical lithography processes where lots of solvents and high-energy ultraviolet (UV) light exposure are required. Herein, we report a direct in situ photolithography technique to pattern PQDs based on the photopolymerization catalyzed by lead bromide complexes. By combining direct photolithography with in situ fabrication of PQDs, this method allows to directly photolithograph perovskite precursors, avoiding the complicated lift-off processes and the destruction of PQDs by solvents or high-energy UV light, as PQDs are produced after lithography exposure. We further demonstrate that the thiol-ene free-radical photopolymerization is catalyzed by lead bromide complexes in the perovskite precursor solution, while no external initiators or catalysts are needed. Using direct in situ photolithography, PQD patterns with high resolution up to 2450 pixels per inch (PPI), excellent fluorescence uniformity, and good stability, are successfully demonstrated. This work opens an avenue for non-destructive direct photolithography of high-efficiency light-emitting PQDs, and potentially expands their application in various integrated optoelectronic devices.


Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial.
To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes. 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks. After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups. Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus.


40-Year Follow-Up After the Fontan Operation: Long-Term Outcomes of 1,052 Patients.
There are limited long-term, single-cohort, follow-up studies available about patients after the Fontan operation. This study sought to determine the long-term outcome of all patients who had a Fontan operation at the Mayo Clinic. Records of all patients who had a modified Fontan operation between 1973 and 2012 were reviewed. A follow-up questionnaire was mailed to all patients alive at the time of the study. Overall, 10-, 20-, and 30-year survival for 1,052 patients was 74%, 61%, and 43%, respectively. Factors associated with decreased overall or late survival in multivariate analysis included pre-operative diuretic use, longer cardiopulmonary bypass time, operation prior to 1991, atrioventricular valve (AVV) replacement at the time of Fontan operation, elevated post-bypass Fontan (>20 mm Hg) or left atrial (>13 mm Hg) pressures, prolonged chest tube drainage (>21 days), post-operative ventricular arrhythmias, renal insufficiency, and development of protein-losing enteropathy (PLE). Pre-operative and intraoperative sinus rhythm were associated with improved survival. Long-term survival was similar for patients regardless of ventricular morphology. The most common reoperations were pacemaker insertion/revision in 212 patients (20%), Fontan revision/conversion in 117 patients (11%), and AVV repair/replacement in 66 patients (5%). Clinically significant late atrial or ventricular arrhythmias occurred in 468 patients (44%). Ninety-five patients (9%) developed PLE, and 5-, 10-, and 20-year survival after diagnosis of PLE was 50%, 35%, and 19%, respectively. As the surgical techniques for the Fontan operation have changed over the last 40 years, survival has improved. However, development of PLE and arrhythmias and the need for reoperation during long-term follow-up pose significant management challenges.


L-cone pigment genes expressed in normal colour vision.
To directly test the hypothesis that only two pigment genes are expressed from the X-chromosome array, we examined expressed M and L pigment gene sequences from > 100 male eye donors. In this sample, there were eight men who expressed high levels of more than one L pigment gene in addition to M pigment genes. The fact that these eyes expressed both L and M pigment genes at significant levels suggests they were from men with normal colour vision. We reject the hypothesis that only two pigment genes from one X-chromosome array can be expressed.


The role of the state in financing and regulating primary care in Europe: a taxonomy.
Traditional health systems typologies were based on health system financing type, such as the well-known OECD typology. However, the number of dimensions captured in classifications increased to reflect health systems complexity. This study aims to develop a taxonomy of primary care (PC) systems based on the actors involved (state, societal and private) and mechanisms used in governance, financing and regulation, which conceptually represents the degree of decentralisation of functions. We use nonlinear canonical correlations analysis and agglomerative hierarchical clustering on data obtained from the European Observatory on Health Systems and Policy and informants from 24 WHO European Region countries. We obtain four clusters: 1) Bosnia Herzegovina, Czech Republic, Germany, Slovakia and Switzerland: corporatist and/or fragmented PC system, with state involvement in PC supply regulation, without gatekeeping; 2) Greece, Ireland, Israel, Malta, Sweden, and Ukraine: public and (re)centralised PC financing and regulation with private involvement, without gatekeeping; 3) Finland, Norway, Spain and United Kingdom: public financing and devolved regulation and organisation of PC, with gatekeeping; and 4) Bulgaria, Croatia, France, North Macedonia, Poland, Romania, Serbia, Slovenia and Turkey: public and deconcentrated with professional involvement in supply regulation, and gatekeeping. This taxonomy can serve as a framework for performance comparisons and a means to analyse the effect that different actors and levels of devolution or fragmentation of PC delivery may have in health outcomes.


Angiotensin II-induced changes in cochlear blood flow and blood pressure in normotensive and spontaneously hypertensive rats.
Previous investigations in our laboratory have measured significant increases in the circulating levels of the potent vasoconstrictive hormone, angiotensin II (AII; 26 and 64 pg/100 microliters plasma, normal and noise exposed, respectively), during and following noise exposure in the alert rat (Wright et al., 1981). In the present study, these levels were approximated through intra-arterial infusion in the anesthetized spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. Laser Doppler flowmeter measurements of cochlear blood flow (CBF) indicated that despite equivalent AII-induced elevations in systemic blood pressure, CBF in the SHR did not increase to the levels measured in the WKY. Pretreatment with the specific angiotensin receptor antagonist sarile, (Sar1,Ile8-AII), reduced AII-induced elevations in systemic blood pressure in members of both strains, but did not change the overall pattern of CBF. These results indicate that SHRs may have a compromised cochlear circulation that is refractory to increases in systemic blood pressure.


r-and K-selection in soil ciliates: a field and experimental approach.
Previously published field studies have suggested that the concept of r/K selection may be applied to terrestrial ciliates. A census was taken of the dominant groups, the Colpodea and Polyhymenophora, to determine species composition and absolute abundances in climatically unpredictable alpine and predictable lowland sites. In addition, two typical representatives of each of the two taxa (Colpoda aspera and Grossglockneria acuta, and Blepharisma undulans and Gonostomum affine, respectively) were selected for examination under laboratory conditions. Variables investigated were: the C/P index (ratio of Colpodea to Polyhymenophora), fertility, tolerance of altered environmental conditions, incidence in predictable or unpredictable biotopes, opportunism, competitive ability, and body size. Our own observations were supplemented by reference to the literature.The field census produced a higher C/P index in the unpredictable sites than in the predictable ones. The experiments show that C. aspera and G. acuta are less sensitive to changes in temperature and exhibit a more rapid rise in individual density as well as a higher number of individuals than do B. undulans and G. affine, although the former species have longer generation times at low temperatures. The explosive increase in number of individuals can be ascribed to the special reproductive strategy of the Colpodea (quadripartition in cysts). These results imply that the Colpodea are more r-selected as compared with the Polyhymenophora. That might be an explanation for their wide distribution and high density in unfavourable terrestrial habitats.


Reduction of postoperative pelvic adhesions with intraperitoneal 32% dextran 70: a prospective, randomized clinical trial.
Infertile women of reproductive age requiring an operation for distal tubal disease, endometriosis, or pelvic adhesions were recruited from nine study centers. Prior to closing the peritoneal cavity, 250 ml of 32% dextran 70 (n = 55) or saline (n = 47) was instilled into the dependent portion of the pelvis; 8 to 12 weeks later, laparoscopy was performed on those patients not pregnant. Patients with severe adnexal adhesions at the initial laparotomy had a greater reduction in adhesions if they received 32% dextran 70. Further, patients with a marked reduction in adhesion formation following the initial laparotomy were found to occur more frequently in the 32% dextran 70-treated group (26 of 51 for 32% dextran 70 versus 12 of 40 for saline; P less than 0.05). During second-look laparoscopy, adhesions were found to occur more frequently in control patients than in 32% dextran 70-treated patients at the following anatomic sites: ovary (P less than 0.05); cul-de-sac (P = 0.017); pelvic side wall (P less than 0.001). Thus, in a prospective, randomized, blinded clinical trial, the intraperitoneal high-molecular-weight dextran was found to reduce postoperative adhesion formation effectively.


Atypical mycobacterial cutaneous infections in Hong Kong: 10-year retrospective study.
To review the epidemiology of atypical mycobacterial cutaneous infection in Hong Kong. Retrospective study. Social Hygiene Service (Dermatology Division), the largest dermatological referral centre in Hong Kong. Patients with a diagnosis of atypical mycobacterial cutaneous infection based on clinical features, histopathology, with or without a positive culture during the period 1993 to 2002. Epidemiological data, clinical features, histology, microbiological investigation, and treatment response. Of 345,394 dermatological cases presented over the 10-year period, 33 (0.0096%) cases (19 male, 14 female) of atypical mycobacterial cutaneous infection were diagnosed. The most common type of infection was caused by Mycobacterium marinum (n=17, 51.5%), followed by Mycobacterium avium-intracellulare (n=3, 9.1%) and Mycobacterium chelonae (n=2, 6.1%). The upper limb, especially the hands and fingers, was the most common (69.7%) site of involvement. Tissue culture was positive in 18 (54.5%) cases. All biopsies showed granulomatous histology. Thirty-two patients received treatment and 31 responded. Twenty-six were treated with oral tetracycline group of antibiotics (minocycline, doxycycline, tetracycline). The duration of treatment ranged from 8 to 54 weeks (mean, 24 weeks). Mild transient adverse effects to treatment were reported in six cases. Atypical mycobacterial infection is rare in Hong Kong. Because of the low sensitivity of traditional culture techniques, atypical mycobacterial infection may be underdiagnosed if only culture-confirmed cases are included. Polymerase chain reaction provides a rapid and sensitive method to improve diagnostic accuracy. Tissue culture is crucial to determine antimicrobial susceptibility. In our study, tetracycline group of antibiotics, especially minocycline, was an effective treatment, particularly in cases caused by Mycobacterium marinum.


Long-term investigation of kidney ultrasound in cases of hemolytic uremic syndrome in children.
The aim is to describe the changes in initial findings of kidney ultrasound examinations in cases of hemolytic uremic syndrome (HUS) in children and to evaluate the respective importance of three sonographical parameters: echogenicity, corticomedullary differentiation (CMD), and kidney size. The correlation with laboratory parameters and proteinuria is analysed. Reports containing ultrasound examinations and laboratory values from 1989 through 2012 of 39 children (13 cases of atypical HUS and 26 cases of typical HUS, first diagnosis at age 4 months to 10 2/12 years) suffering from HUS were analysed retrospectively. Ultrasound scans of the right kidney (n = 312) were evaluated with regard to the factors echogenicity, CMD, and kidney volume (ml, percentile). Laboratory parameters included serum creatinine, endogenous creatinine clearance in 24-h urine collection, eGFR according to Schwartz, and the protein content of the 24-h urine collection. All patients initially had increased echogenicity of the kidneys. All kidney volumes were ranged in the higher percentiles (the median percentile was the 85th). For assessment of long-term progression, the echogenicity proved to be of higher importance than the CMD due to a significant correlation between laboratory parameters of kidney function and the echogenicity. Ultrasound examination of the kidneys is an important method in follow-up examinations of patients with HUS. Renal morphology correlates with laboratory parameters of kidney function.


Effects of laser-induced hyperthermia treatment on ionic permeability of myelinated nerve.
The effect of laser-induced hyperthermia on the ionic permeability of nerve membranes was studied using the nodes of Ranvier in amphibian myelinated nerve as a model. To effect a photothermal modification of nerve membrane functions, controlled laser irradiation consisting of a 5-sec thermal pulse was applied to the nodal membrane, increasing the temperature to a maximum of 48-58 degrees C at the node. Major electrophysiological changes observed in the nodal membrane following laser-induced hyperthermia were a differential reduction of the sodium and potassium permeability, an increase in the leakage current, and a negative shift on the potential axis of the steady-state Na inactivation. There was no significant change in the kinetics of ion channel activation and inactivation for treatments below 56 degrees C. The results suggest that a primary photothermal damage mechanism at temperatures below 56 degrees C could be a reduction in the number of active Na channels in the node, rather than a change in individual channel kinetics, or in the properties of the lipid bilayer of intervening nerve membrane. A differential heat sensitivity between the noninactivated and the inactivated Na channels is also suggested. For the treatments of 56 degrees C and above, a significant increase of membrane leakage current suggests an irreversible thermal damage to the lipid bilayer.


Altered, but not diminished specific T cell response in chronic mucocutaneous candidiasis patients.
Patients suffering from chronic mucocutaneous infections with the yeast Candida albicans (CMC) are discussed to have an underlying primary cellular immunodeficiency. In order to characterise cellular immunity in CMC patients, we analysed chemotaxis and myeloperoxidase (MPO) releases of neutrophils and T cell proliferation and cytokine production to Candida albicans. Patients with chronic mucocutaneous candidiasis (n = 4) and healthy volunteers of same sex and similar age (n = 14) were enrolled into the study. Neutrophil chemotaxis was assessed by transwell migration assay, and MPO release by ELISA. T cell proliferation capacity was investigated by thymidine incorporation and cytokine secretion in supernatants by ELISA. Neither neutrophil migration nor MPO release differed between CMC patients and healthy controls. The relative lymphocyte stimulation index (SI Candida/SI PHA) was heterogenous, but overall it was higher in CMC patients compared to controls. However, Candida-specific IFN-gamma production was significantly reduced in CMC patients. Notably, Candida-specific T cell IL-10 production was markedly higher in CMC patients. The inability to clear the yeast Candida albicans in our CMC patients does not seem to be due to an impaired neutrophil function or reduced antigen specific proliferation of lymphocytes. In fact, our patients tended to proliferate stronger to Candida antigen relative to PHA than healthy controls. However, the impaired Th1 cytokine production with an enhanced IL-10 production could play an important role in the pathogenesis of chronic mucocutaneous Candida infections.


The effectiveness of three sets of school-based instructional materials and community training on the acquisition and generalization of community laundry skills by students with severe handicaps.
This study examined the effectiveness of three sets of school-based instructional materials and community training on acquisition and generalization of a community laundry skill by nine students with severe handicaps. School-based instruction involved artificial materials (pictures), simulated materials (cardboard replica of a community washing machine), and natural materials (modified home model washing machine). Generalization assessments were conducted at two different community laundromats, on two machines represented fully by the school-based instructional materials and two machines not represented fully by these materials. After three phases of school-based instruction, the students were provided ten community training trials in one laundromat setting and a final assessment was conducted in both the trained and untrained community settings. A multiple probe design across students was used to evaluate the effectiveness of the three types of school instruction and community training. After systematic training, most of the students increased their laundry performance with all three sets of school-based materials; however, generalization of these acquired skills was limited in the two community settings. Direct training in one of the community settings resulted in more efficient acquisition of the laundry skills and enhanced generalization to the untrained laundromat setting for most of the students. Results of this study are discussed in regard to the issue of school versus community-based instruction and recommendations are made for future research in this area.


The fibrinolytic system attenuates vascular tone: effects of tissue plasminogen activator (tPA) and aminocaproic acid on renal microcirculation.
1. The renal medulla is a major source of plasminogen activators (PA), recently shown to induce vasodilation in vitro. Treatment with PA inhibitors has been associated with renal dysfunction, suggesting compromised renal microvasculature. We investigated the impact of the PA inhibitor epsilon amino-caproic acid (EACA) upon vascular tone in vitro, and studied the effect of both tPA and EACA upon intrarenal hemodynamics in vivo. 2. In vitro experiments were carried out in isolated aortic rings and with cultured vascular smooth muscle cells. Studies of renal microcirculation and morphology were conducted in anesthetized Sprague-Dawley rats. 3. In isolated aortic rings, EACA (but not the other inhibitors of the fibrinolytic system PAI-1 or alpha-2 antiplasmin) reduced the half-maximal effective concentration of phenylephrine (PE) required to induce contraction (from 32 nm in control solution to 2 and 0.1 nm at EACA concentrations of 1 and 10 microm, respectively). Using reteplase (retavase) in the same model, we also provide evidence that the vasoactivity of tPA is in part kringle-dependent. In cultured vascular smooth muscle cells, Ca(2+) internalization following PE was enhanced by EACA, and retarded by tPA. 4. In anesthetized rats, EACA (150 mg x kg(-1)) did not affect systemic blood pressure, total renal or cortical blood flow. However, the outer medullary blood flow declined 12+/-2% below the baseline (P<0.03). By contrast, tPA (2 mg x kg(-1)), transiently increased outer medullary blood flow by 8+/-5% (P<0.02). Fibrin microthrombi were not found within the renal microvasculature in EACA-treated animals. 5. In conclusion, both fibrinolytic and antifibrinolytic agents modulate medullary renal blood flow with reciprocal effects of vasodilation (PA) and vasoconstriction (EACA). In vitro studies suggest that these hemodynamic responses are related to direct modulation of the vascular tone.


The role of drug timing and histoincompatibility barrier in prolongation of cardiac graft survival in mice treated with donor-specific blood and cyclophosphamide.
In the H-2-compatible donor-recipient combination (BALB/c----DBA/2), pretransplant donor-specific blood transfusion (DST) significantly prolonged graft survival. Concomitant use of immunosuppression by cyclophosphamide (CY) brought about potentiation of DST effect, resulting in long-term graft survival. In contrast, in the 'strong' H-2-incompatible combination (BALB/c----CBA/H) pretreatment of the recipients with donor-specific blood resulted in hyperacute graft rejection or in impairment of drug-induced immunosuppression when DST was used with a single dose of CY. In this model however, combination of DST with both pre- and posttransplant CY immunosuppression interacted beneficially to produce significant donor-specific prolongation of graft survival.


Mitigation of heat strain by wearing a long-sleeve fan-attached jacket in a hot or humid environment.
This study examined whether a fan-attached jacket (FAJ) may mitigate the heat strain in hot or humid environment. Nine healthy men engaged in 60-min sessions on a bicycle ergometer (4 metabolic equivalents [METs] workload) in hot-dry (40°C and 30% relative humidity) and warm-humid (30°C and 85% relative humidity) environments. Both are equivalent to an approximately 29°C wet-bulb globe temperature. The experiment was repeated-once wearing an ordinal jacket (control condition) and once wearing a long-sleeve FAJ that transfers ambient air at a flow rate of 12 L/s (FAJ condition)-in both environments. Increases in core temperatures in hot-dry environment were not statistically different between control and FAJ; however, that in the warm-humid environment were significantly different between control and FAJ (0.96 ± 0.10°C and 0.71 ± 0.11°C in rectal temperature, P < .0001; and 0.94 ± 0.09°C and 0.61 ± 0.09°C in esophageal temperature, P < .0001). Changes in heart rate were different between control and FAJ in both environments (62 ± 3 bpm and 47 ± 7 bpm, P < .0001 in hot-dry environment; and 61 ± 3 bpm and 46 ± 5 bpm, P < .0001 in the warm-humid environment) and decrease of %weight change was different in hot-dry environment (1.59 ± 0.12% and 1.25 ± 0.05%, P = .0039), but not in the warm-humid environment. Wearing a FAJ may mitigate heat strain both in hot or humid environments.


Clinical and economic outcomes associated with amlodipine/renin-angiotensin system blocker combinations.
Since treatment regimen type can influence adherence and other outcomes, this study examined adherence, cardiovascular events, and economic outcomes in patients with hypertension treated with fixed-dose combination (FDC) amlodipine/olmesartan (AML/OM), FDC AML/benazepril (AML/BEN), and loose-dose combination AML plus angiotensin II receptor blockers (LDC AML/ARBs). Commercial health plan enrollees aged at least 18 years with index claim(s) for AML/OM, AML/BEN, or LDC AML/ARB were identified. Absence of study drug 6 months pre index, and continuous enrollment for at least 12 months post index were required. Descriptive analyses were executed to make comparisons between treatments, as well as multivariate models adjusting for baseline demographic and clinical characteristics, including propensity for assignment to study drug. Descriptive results suggested mean follow-up adherence was higher in the AML/OM cohort [proportion of days covered (PDC) = 0.63] compared with the AML/BEN (PDC = 0.55; p < 0.001) and LDC AML/ARB cohorts (PDC = 0.34; p < 0.001). The proportion of individuals with an incident follow-up cardiovascular event composite was lower in the AML/OM cohort versus the AML/BEN and LDC AML/ARB cohorts (5.94% versus 7.85% and 16.89% respectively). Adjusted Cox models suggested that patients initiated on LDC AML/ARB (hazard ratio 1.35; p < 0.001), but not on AML/BEN, were at greater risk of a follow-up cardiovascular event (composite) compared with AML/OM. Adjusted generalized linear models suggested that mean follow-up per-member-per-month overall costs were higher in the AML/BEN (cost ratio = 1.169; p < 0.001; unadjusted mean cost US$780) and LDC AML/ARB cohorts (cost ratio = 1.286; p < 0.001; unadjusted mean cost US $1394) compared with the AML/OM cohort (unadjusted mean cost US $740). The results suggested that treatment with FDC AML/OM was associated with greater likelihood of adherence and lower overall costs than with FDC AML/BEN and LDC AML/ARB, and lower risk of cardiovascular event composite versus LDC AML/ARB.


Increased Insulin Resistance and Glucagon Levels in Mild/Inactive Systemic Lupus Erythematosus Patients Despite Normal Glucose Tolerance.
To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT). In this cross-sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age- and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake. SLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT-4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size [ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin-to-glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole-body insulin sensitivity (P = 0.06; ES -0.5) when compared with the CTRL group. Fasting proinsulin-to-insulin ratio and proinsulin-to-insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9). We have identified that SLE patients had a bi-hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT-4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone.


Fractionally charged skyrmions in fractional quantum Hall effect.
The fractional quantum Hall effect has inspired searches for exotic emergent topological particles, such as fractionally charged excitations, composite fermions, abelian and nonabelian anyons and Majorana fermions. Fractionally charged skyrmions, which support both topological charge and topological vortex-like spin structure, have also been predicted to occur in the vicinity of 1/3 filling of the lowest Landau level. The fractional skyrmions, however, are anticipated to be exceedingly fragile, suppressed by very small Zeeman energies. Here we show that, slightly away from 1/3 filling, the smallest manifestations of the fractional skyrmion exist in the excitation spectrum for a broad range of Zeeman energies, and appear in resonant inelastic light scattering experiments as well-defined resonances slightly below the long wavelength spin wave mode. The spectroscopy of these exotic bound states serves as a sensitive tool for investigating the residual interaction between composite fermions, responsible for delicate new fractional quantum Hall states in this filling factor region.