Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.
The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions.


Calcium-Containing Crystals and Osteoarthritis: an Unhealthy Alliance.
Osteoarthritis (OA) is the most common form of joint disease globally and is associated with significant morbidity and disability. Increasing evidence points to an important inflammatory component in the development and progression of OA. The precise pathways involved in OA inflammatory processes remain to be clarified. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals can induce inflammation and arthritis and recent studies point to a potential pathogenic role in OA. In the light of this evidence, we explore the relationship and potential mechanistic pathways linking calcium-containing crystals and OA. CPP crystals induce inflammation through the NLRP3 inflammasome while BCP crystals mediate both NLRP3 dependent and independent effects. BCP crystals have been demonstrated to induce key mitogenic and inflammatory pathways and contribute to cartilage degradation. Calcium-containing crystals induce key inflammatory pathways and may represent an attractive novel target in OA, a condition devoid of effective treatments.


Nanomechanical Properties and Phase Behavior of Phenylalanine Amyloid Ribbon Assemblies and Amorphous Self-Healing Hydrogels.
Phenylalanine was the minimalistic and first of numerous nonproteinaceous building blocks to be demonstrated to form amyloid-like fibrils. This unexpected organization of such a simple building block into canonical architecture, which was previously observed only with proteins and peptides, has numerous implications for medicine and supramolecular chemistry. However, the morphology of phenylalanine fibrils and their mechanical properties was never characterized in solutions. Here, using electron and atomic force microscopy, we analyze the morphological and mechanical properties of phenylalanine fibrils in both air and fluids. The fibrils demonstrate an exceptionally high Young's modulus (up to 30 GPa) and are found to be composed of intertwined protofilaments in a helical or twisted ribbon morphology. In addition, X-ray scattering experiments provide convincing evidence of an amyloidal cross-β-like secondary structure within the nanoassemblies. Furthermore, increasing the phenylalanine concentration results in the formation of highly homogenous, noncrystalline, self-healing hydrogels that display storage and loss moduli significantly higher than similar noncovalently cross-linked biomolecular nanofibrillar scaffolds. These remarkably stiff nanofibrillar hydrogels can be harnessed for various technological and biomedical applications, such as self-healing, printable, structural, load-bearing 3D scaffolds. The properties of this simple but quite remarkable hydrogel open a possibility to utilize it in the biomaterial industry.


Yerba Mate Extract in Microfibrillated Cellulose and Corn Starch Films as a Potential Wound Healing Bandage.
Microfibrillated cellulose films have been gathering considerable attention due to their high mechanical properties and cheap cost. Additionally, it is possible to include compounds within the fibrillated structure in order to confer desirable properties. Ilex paraguariensis A. St.-Hil, yerba mate leaf extract has been reported to possess a high quantity of caffeoylquinic acids that may be beneficial for other applications instead of its conventional use as a hot beverage. Therefore, we investigate the effect of blending yerba mate extract during and after defibrillation of Eucalyptus sp. bleached kraft paper by ultrafine grinding. Blending the extract during defibrillation increased the mechanical and thermal properties, besides being able to use the whole extract. Afterwards, this material was also investigated with high content loadings of starch and glycerine. The results present that yerba mate extract increases film resistance, and the defibrillated cellulose is able to protect the bioactive compounds from the extract. Additionally, the films present antibacterial activity against two known pathogens S. aureus and E. coli, with high antioxidant activity and increased cell proliferation. This was attributed to the bioactive compounds that presented faster in vitro wound healing, suggesting that microfibrillated cellulose (MFC) films containing extract of yerba mate can be a potential alternative as wound healing bandages.


Deletion of the fyn-kinase gene alters behavioral sensitivity to ethanol.
An earlier study showed that deletion of the fyn-kinase gene enhanced sensitivity to ethanol's sedative hypnotic effects and suggested that this was associated with diminished fyn-kinase phosphorylation of NMDA receptors. The authors of that study speculated that this resulted in an inability of the null mutants to develop acute tolerance to ethanol, leading to the longer ethanol-induced sleep times. However, in vivo acute tolerance to ethanol was not examined directly. To address the role of fyn-kinase in mediating acute tolerance, as well as sensitivity to several other behavioral effects of ethanol, we studied an independently generated population of fyn null mutant and wild-type mice. Homozygous mutants exhibited longer ethanol sleep times that could not be attributed to differences in initial sensitivity, and impaired acute tolerance to the motor incoordinating effects of ethanol as measured by using the stationary dowel, but not the rotarod. Fyn-kinase null mutants were more sensitive to the anxiolytic effects of ethanol when tested using the elevated plus maze, and males displayed a lower preference for ethanol in a two-bottle choice paradigm. Finally, mutant and wild-type mice did not differ in sensitivity to the hypothermic effects of ethanol. The genotypes also did not differ in blood-ethanol clearance, eliminating a metabolic explanation for these behavioral differences. These results show that fyn-kinase modulates acute tolerance to ethanol and suggest a role for fyn in mediating ethanol's anxiolytic and reinforcing properties.


Cranial nerve ischaemic arterial syndromes. A review.
Topographical vascular disorders involving combinations of cranial nerves are reviewed in this study. These are indicated by the correspondence between groupings of clinical manifestations and anatomical vascular distributions. Confirmatory evidence is provided by mishaps, following diagnostic or therapeutic angiography. Three systems play a role in the vascularization of cranial nerves: the inferolateral trunk (ILT), most often arising from the internal carotid artery, the middle meningeal system (MMS), and the ascending pharyngeal system (APS); the latter two are both derived from the external carotid artery. Conclusions concerning the ILT are least definite because of variations in vascular territory and the lack of confirmation from embolic events in a vascular region that is rarely the site of embolization. The specific ILT territory includes cranial nerve III and also nerves IV, VI and V1. Knowledge of the vascularization of nerve III may furnish explanations as to its different modes of involvement in diabetes mellitus. For the MMS, the cranial nerves concerned are V2, V3 and VII. Two vascular territories for the intrapetrous portion of nerve VII are defined: the first (stylomastoid artery) is limited to nerve VII; the second (MMS) supplies VII and V. Two examples of involvement of VII and V following selective MMS embolization are presented. A study of Bell's palsy associated with nerve V impairment is summarized. The APS supplies nerves IX, X, XI and XII; XI has a dual vascularization which explains why it can either be spared (as was the case in an angiographic accident) or involved (as in a case of herpes zoster). A vascular mechanism should be considered when cranial nerve lesions occur in the syndromes described here.


HLA-DQA1 and PLA2R1 polymorphisms and risk of idiopathic membranous nephropathy.
Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ α-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease. A Spanish cohort of 89 IMN patients and 286 matched controls without nephropathy was recruited between October of 2009 and July of 2012. Case-control studies for SNPs within HLA-DQA1 (rs2187668) and PLA2R1 (rs4664308) genes and CNVs for FCGR3A and FCGR3B genes were performed. The contribution of these polymorphisms to predict clinical outcome and renal function decline was analyzed. This study validated the association of these HLA-DQA1 and PLA2R1 SNPs with IMN in a Spanish cohort and its increased risk when combining both risk genotypes. No significant association was found between FCGR3 CNVs and IMN. These results revealed that HLA-DQA1 and PLA2R1 genotype combination adjusted for baseline proteinuria strongly predicted response to immunosuppressive therapy. HLA-DQA1 genotype adjusted for proteinuria was also linked with renal function decline. This study confirms that HLA-DQA1 and PLA2R1 genotypes are risk factors for IMN, whereas no association was identified for FCGR3 CNVs. This study provides, for the first time, evidence of the contribution of these HLA-DQA1 and PLA2R1 polymorphisms in predicting IMN response to immunosuppressors and disease progression. Future studies are needed to validate and identify prognostic markers.


T-type voltage gated calcium channels are involved in endothelium-dependent relaxation of mice pulmonary artery.
In pulmonary arterial endothelial cells, Ca2+ channels and intracellular Ca2+ concentration ([Ca2+]i) control the release of vasorelaxant factors such as nitric oxide and are involved in the regulation of pulmonary arterial blood pressure. The present study was undertaken to investigate the implication of T-type voltage-gated Ca2+ channels (T-VGCCs, Cav3.1 channel) in the endothelium-dependent relaxation of intrapulmonary arteries. Relaxation was quantified by means of a myograph in wild type and Cav3.1-/- mice. Endothelial [Ca2+]i and NO production were measured, on whole vessels, with the fluo-4 and DAF-fm probes. Acetylcholine (ACh) induced a nitric oxide- and endothelium-dependent relaxation that was significantly reduced in pulmonary arteries from Cav3.1-/- compared to wild type mice as well as in the presence of T-VGCC inhibitors (NNC 55-0396 or mibefradil). ACh also increased endothelial [Ca2+]i and NO production that were both reduced in Cav3.1-/- compared to wild type mice or in the presence of T-VGCC inhibitors. Immunofluorescence labeling revealed the presence of Cav3.1 channels in endothelial cells that co-localized with endothelial nitric oxide synthase in arteries from wild type mice. TRPV4-, beta2 adrenergic- and nitric oxide donors (SNP)-mediated relaxation were not altered in Cav3.1-/- compared to wild type mice. Finally, in chronically hypoxic mice, a model of pulmonary hypertension, ACh relaxation was reduced but still depended on Cav3.1 channels activity. The present study thus demonstrates that T-VGCCs, mainly Cav3.1 channel, contribute to intrapulmonary vascular reactivity in mice by controlling endothelial [Ca2+]i and ACh-mediated relaxation.


Identifying disease genes using machine learning and gene functional similarities, assessed through Gene Ontology.
Identifying disease genes from a vast amount of genetic data is one of the most challenging tasks in the post-genomic era. Also, complex diseases present highly heterogeneous genotype, which difficult biological marker identification. Machine learning methods are widely used to identify these markers, but their performance is highly dependent upon the size and quality of available data. In this study, we demonstrated that machine learning classifiers trained on gene functional similarities, using Gene Ontology (GO), can improve the identification of genes involved in complex diseases. For this purpose, we developed a supervised machine learning methodology to predict complex disease genes. The proposed pipeline was assessed using Autism Spectrum Disorder (ASD) candidate genes. A quantitative measure of gene functional similarities was obtained by employing different semantic similarity measures. To infer the hidden functional similarities between ASD genes, various types of machine learning classifiers were built on quantitative semantic similarity matrices of ASD and non-ASD genes. The classifiers trained and tested on ASD and non-ASD gene functional similarities outperformed previously reported ASD classifiers. For example, a Random Forest (RF) classifier achieved an AUC of 0. 80 for predicting new ASD genes, which was higher than the reported classifier (0.73). Additionally, this classifier was able to predict 73 novel ASD candidate genes that were enriched for core ASD phenotypes, such as autism and obsessive-compulsive behavior. In addition, predicted genes were also enriched for ASD co-occurring conditions, including Attention Deficit Hyperactivity Disorder (ADHD). We also developed a KNIME workflow with the proposed methodology which allows users to configure and execute it without requiring machine learning and programming skills. Machine learning is an effective and reliable technique to decipher ASD mechanism by identifying novel disease genes, but this study further demonstrated that their performance can be improved by incorporating a quantitative measure of gene functional similarities. Source code and the workflow of the proposed methodology are available at https://github.com/Muh-Asif/ASD-genes-prediction.


The pR UV+ plasmid, transfected into mammalian cells, enhances their UV survival.
It has been recently reported that the pR plasmid enhances the UV survival in E.coli c600. In order to test whether this function may be expressed also in mammalian cells, LTA (tk- aprt-) mouse cells were cotransformed with pR plasmid DNA and ptk1 plasmid as selectable marker. Tk+ transformants were analyzed for their UV survival and for the presence of pR DNA sequences by blot-hybridization. The results show a correlation between the enhanced UV survival and presence of pR DNA sequences in cotransformed LTA mouse cells.


Vascular cell adhesion molecule-1 expression and hematopoietic supportive capacity of immortalized murine stromal cell lines derived from fetal liver and adult bone marrow.
Ontogeny-specific differences in hematopoietic behavior may be influenced by unique adhesive interactions between hematopoietic cells and the microenvironment, such as that mediated by vascular cell adhesion molecule-1 (VCAM-1, CD 106). Although VCAM-1 is variably expressed during vertebrate development, we hypothesized that VCAM-1 expression might be linked to the enhanced capacity of the fetal liver microenvironment to support hematopoiesis. To test this we used immortalized murine stromal cell lines derived from midgestation fetal liver and adult bone marrow to compare the functional expression of VCAM-1. Molecular analysis of VCAM-1 expression was performed on stromal cell lines using Northern blot analysis, immunoprecipitation studies, and solid-phase enzyme-linked immunosorbent assay. Hematopoietic studies were performed by coculturing fetal liver cells with stromal cell lines, and the functional readout was determined by high-proliferative potential colony-forming cell (HPP-CFC) adherence assays. In contrast to our initial hypothesis, we observed greater expression of VCAM-1 messenger ribonucleic acid and protein on an adult marrow stromal cell line. In functional studies, anti-VCAM-1 antibody inhibited the binding of nearly half of the HPP-CFCs to adult marrow stroma but had a minimal effect on their binding to fetal liver stroma, despite the greater adherence of HPP-CFCs to fetal stroma. We conclude that VCAM-1 influences the hematopoietic supportive capacity of immortalized murine stroma derived from adult bone marrow. Our studies suggest that cellular interactions other than those mediated by VCAM-1 are involved in the increased adhesive capacity of immortalized murine stroma derived from fetal liver.


In Situ Fabrication of SnS2/SnO2 Heterostructures for Boosting Formaldehyde-Sensing Properties at Room Temperature.
Formaldehyde, as a harmful gas produced by materials used for decorative purposes, has a serious impact on human health, and is also the focus and difficulty of indoor environmental polution prevention; hence, designing and developing gas sensors for the selective measurement of formaldehyde at room temperature is an urgent task. Herein, a series of SnS2/SnO2 composites with hollow spherical structures were prepared by a facile hydrothermal approach for the purpose of formaldehyde sensing at room temperature. These novel hierarchical structured SnS2/SnO2 composites-based gas sensors demonstrate remarkable selectivity towards formaldehyde within the concentration range of sub-ppm (0.1 ppm) to ppm (10 ppm) at room temperature. Notably, the SnS2/SnO2-2 sensor exhibits an exceptional formaldehyde-sensing performance, featuring an ultra-high response (1.93, 0.1 ppm and 17.51, 10 ppm), as well as good repeatability, long-term stability, and an outstanding theoretical detection limit. The superior sensing capabilities of the SnS2/SnO2 composites can be attributed to multiple factors, including enhanced formaldehyde adsorption, larger specific surface area and porosity of the hollow structure, as well as the synergistic interfacial incorporation of the SnS2/SnO2 heterojunction. Overall, the excellent gas sensing performance of SnS2/SnO2 hollow spheres has opened up a new way for their detection of trace formaldehyde at room temperature.


Biomechanical asymmetries differ between autograft types during unplanned change of direction after ACL reconstruction.
Nine months after anterior cruciate ligament (ACL) reconstruction, athletes who undergo surgery using a bone-patellar-tendon-bone (BPTB) autograft demonstrate higher loading asymmetries during vertical jumping than those with a hamstring tendon (HT) autograft. These asymmetries may transfer into sporting movements with a greater ACL injury risk. The aim of this study was to compare between-limb asymmetries in knee mechanics and task performance during an unplanned 90° change-of-direction (CoD) task in male field sport athletes reconstructed with BPTB or HT autografts. Seventy-eight male multidirectional field sport athletes with either a BPTB (n = 39) or HT (n = 39) autograft completed maximal unplanned CoD trials in a three-dimensional motion capture laboratory at approximately 9 months post-surgery. A mixed-model 2x2 ANOVA (autograft type x limb) was used to compare variables related to ACL injury risk (e.g., internal knee moments) and performance (e.g., completion time) between autografts and limbs. Statistical parametric mapping was used for a waveform comparison throughout stance, supplemented with a discrete point analyses of peak knee moments and performance variables. Interaction effects were found at the knee joint, with BPTB demonstrating greater asymmetries than HT in knee extension moment (p < 0.001); resultant ground reaction force (p < 0.001); peak knee external rotation moment (p = 0.04); and knee adduction (p = 0.05), medial rotation (p < 0.001), and flexion (p < 0.001) angles. No differences were found between autografts for any performance variable. BPTB demonstrated greater lower-limb biomechanical asymmetries than HT during CoD, which may influence knee loading and longer-term outcomes and should thus be targeted during rehabilitation prior to return to play.


Patterns of Opioid Prescriptions in the Veterans Health Administration for Patients with Chronic Low-Back Pain after the Onset of the COVID-19 Pandemic: A Retrospective Cohort Analysis.
The COVID-19 pandemic led to severe disruptions in healthcare and a relaxation of rules surrounding opioid prescribing-changes which led to concerns about increased reliance on opioids for chronic pain and a resurgence of opioid-related harms. Although some studies found that opioid prescriptions increased in the first six months of the pandemic, we know little about longer term effects of the pandemic on opioid prescriptions. Further, despite the prevalence of pain in veterans, we know little about patterns of opioid prescriptions in the Veterans Health Administration (VA) associated with the pandemic. Using a retrospective cohort of VA patients with chronic low back pain, we examined the proportion of patients with an opioid prescription and mean morphine-milligram equivalents (MME) over a three-year period-one year prior to and two years after the pandemic's onset. Analyses revealed that both measures fell during the entire observation period. The largest decrease in odds of filling an opioid prescription occurred in the first quarter of the pandemic, but this downward trend continued throughout the observation period, albeit at a slower pace. Clinically meaningful differences in opioid prescriptions and dose over time did not emerge based on patient race or rurality; however, differences emerged between female and male veterans, with decreases in opioid prescriptions slowing more markedly for women after pandemic onset. These findings suggest that the pandemic was not associated with short- or long-term increases in opioid prescriptions or dose in the VA. PERSPECTIVE: This article examines opioid prescribing over a three-year period-one year prior to and two years after the onset of the COVID-19 pandemic-for VA patients with chronic low-back pain. Results indicate that, despite disruptions to healthcare, opioid prescriptions and dose decreased over the entire observation period.


Probing the Response of the Amphibious Plant Butomus umbellatus to Nutrient Enrichment and Shading by Integrating Eco-Physiological With Metabolomic Analyses.
Amphibious plants, living in land-water ecotones, have to cope with challenging and continuously changing growth conditions in their habitats with respect to nutrient and light availability. They have thus evolved a variety of mechanisms to tolerate and adapt to these changes. Therefore, the study of these plants is a major area of ecophysiology and environmental ecological research. However, our understanding of their capacity for physiological adaptation and tolerance remains limited and requires systemic approaches for comprehensive analyses. To this end, in this study, we have conducted a mesocosm experiment to analyze the response of Butomus umbellatus, a common amphibious species in Denmark, to nutrient enrichment and shading. Our study follows a systematic integration of morphological (including plant height, leaf number, and biomass accumulation), ecophysiological (photosynthesis-irradiance responses, leaf pigment content, and C and N content in plant organs), and leaf metabolomic measurements using gas chromatography-mass spectrometry (39 mainly primary metabolites), based on bioinformatic methods. No studies of this type have been previously reported for this plant species. We observed that B. umbellatus responds to nutrient enrichment and light reduction through different mechanisms and were able to identify its nutrient enrichment acclimation threshold within the applied nutrient gradient. Up to that threshold, the morpho-physiological response to nutrient enrichment was profound, indicating fast-growing trends (higher growth rates and biomass accumulation), but only few parameters changed significantly from light to shade [specific leaf area (SLA); quantum yield (φ)]. Metabolomic analysis supported the morpho-physiological results regarding nutrient overloading, indicating also subtle changes due to shading not directly apparent in the other measurements. The combined profile analysis revealed leaf metabolite and morpho-physiological parameter associations. In this context, leaf lactate, currently of uncertain role in higher plants, emerged as a shading acclimation biomarker, along with SLA and φ. The study enhances both the ecophysiology methodological toolbox and our knowledge of the adaptive capacity of amphibious species. It demonstrates that the educated combination of physiological with metabolomic measurements using bioinformatic approaches is a promising approach for ecophysiology research, enabling the elucidation of discriminatory metabolic shifts to be used for early diagnosis and even prognosis of natural ecosystem responses to climate change.


[Why woman postpartum resume smoking].
Following a successful period of nicotine abstinence during pregnancy approximately 50% of all women relapse to smoking during the 6 months after delivery. About 34% of all children are exposed to environmental tobacco smoke due to maternal smoking. The objectives of this study are: (a) which women postpartum intend to start smoking again, (b) how does the intention to resume smoking influence the smoking status after 6 months and (c) what are the individual reasons to start smoking again. Four weeks after giving birth (T0) sociodemographic variables, smoking behaviour before pregnancy and the intention to resume smoking were assessed in a sample of 301 women who stopped smoking before or during pregnancy. Six months after giving birth (T1) 285 women answered questions regarding their smoking behaviour and reasons for relapse. After giving birth 13% of the women intended to start smoking again. There was no statistical difference between women intending to start and women not intending to start smoking again with regard to sociodemography and smoking behaviour (p > 0.05). Six months later of these significantly more women smoked compared to the women without intention to resume smoking (68% vs. 27%, chi2 = 23.6; df = 1, p < 0.05, OR = 5.5). Individual reasons to resume smoking were reported by 50 % of the women, stress being the most frequent reason. At least one of ten women who were abstinent during the course of their pregnancy intends to start smoking again. They do not differ from women not intending to resume smoking. The intention to resume smoking has a predictive value for an early relapse, but also every fourth woman without intention resumes smoking. Just half of the women report a personal reason for relapsing. The results underline the need for proactive interventions for relapse prevention.


Goblet cell-specific expression mediated by the MUC2 mucin gene promoter in the intestine of transgenic mice.
The regulation of MUC2, a major goblet cell mucin gene, was examined by constructing transgenic mice containing bases -2864 to +17 of the human MUC2 5'-flanking region fused into the 5'-untranslated region of a human growth hormone (hGH) reporter gene. Four of eight transgenic lines expressed reporter. hGH message expression was highest in the distal small intestine, with only one line expressing comparable levels in the colon. This contrasts with endogenous MUC2 expression, which is expressed at its highest levels in the colon. Immunohistochemical analysis indicated that goblet cell-specific expression of reporter begins deep in the crypts, as does endogenous MUC2 gene expression. These results indicate that the MUC2 5'-flanking sequence contains elements sufficient for the appropriate expression of MUC2 in small intestinal goblet cells. Conversely, elements located outside this region appear necessary for efficient colonic expression, implying that the two tissues utilize different regulatory elements. Thus many, but not all, of the elements necessary for MUC2 gene regulation reside between bases -2864 and +17 of the 5'-flanking region.


An ethnographic study of stigma and ageism in residential care or assisted living.
This study explored aspects of stigmatization for older adults who live in residential care or assisted living (RC-AL) communities and what these settings have done to address stigma. We used ethnography and other qualitative data-gathering and analytic techniques to gather data from 309 participants (residents, family and staff) from six RC-AL settings in Maryland. We entered the transcript data into Atlas.ti 5.0. We analyzed the data by using grounded theory techniques for emergent themes. Four themes emerged that relate to stigma in RC-AL: (a) ageism in long-term care; (b) stigma as related to disease and illness; (c) sociocultural aspects of stigma; and (d) RC-AL as a stigmatizing setting. Some strategies used in RC-AL settings to combat stigma include family member advocacy on behalf of stigmatized residents, assertion of resident autonomy, and administrator awareness of potential stigmatization. Findings suggest that changes could be made to the structure as well as the process of care delivery to minimize the occurrence of stigma in RC-AL settings. Structural changes include an examination of how best, given the resident case mix, to accommodate care for persons with dementia (e.g., separate units or integrated care); processes of care include staff recognition of resident preferences and strengths, rather than their limitations.


"It would have been impossible before:" reflections on current gay life in Estonia.
Estonian gays and lesbians currently enjoy more freedom than ever before. However, they still lack many basic legal protections as well an ongoing, organized political movement. The findings of this small, exploratory study along with the personal experiences of the first author, suggests how cultural factors like individualism, a strong preference for privacy, and distrust of the government not only impede political action and community organization but also obstruct empirical investigation.


Dietary nucleotides reverse malnutrition and starvation-induced immunosuppression.
The requirement of dietary nucleotide sources for maximal helper T-cell function has been demonstrated. The effect of dietary nucleotide restriction was tested during two forms of nutritional stress: starvation and protein malnutrition. In the starvation model, mice were fed chow diet, nucleotide free or nucleotide free supplemented with 0.25% yeast RNA, for at least 4 weeks. The animals were then starved for 5 days, at which time they were killed and mitogen assays were performed using spleen cells. Animals previously maintained on the nucleotide-free diet supplemented with RNA showed a significant increase in spontaneous concanavalin A and phytohemagglutinin-stimulated blastogenesis. Protein malnutrition was induced by feeding Balb/c mice a protein-free diet for 7 to 10 days. These mice then received either the protein-free diet, the nucleotide-free diet, or the nucleotide-free diet supplemented with 0.25% yeast RNA. Popliteal lymph node assays were then performed. The chow diet, nucleotide-free diet, and nucleotide-free diet supplemented with 0.25% yeast RNA led to a restoration of body weight, but only the chow and supplemented diets restored significant popliteal lymph node immune reactivity. These studies using starvation and protein-malnutrition models clearly indicate the nutritional role of nucleotides in the maintenance and restoration of the immune response.


Deficits in emotion-regulation skills predict alcohol use during and after cognitive-behavioral therapy for alcohol dependence.
As emotion regulation is widely considered to be a primary motive in the misuse of alcohol, our aim in the study was to investigate whether deficits in adaptive emotion-regulation skills maintain alcohol dependence (AD). A prospective study investigated whether emotion-regulation skills were associated with AD and whether these skills predicted alcohol use during and after treatment for AD. Participants were 116 individuals treated for AD with cognitive-behavioral therapy. Emotion regulation and severity of AD symptoms were assessed by self-report. Alcohol use during treatment was assessed by Breathalyzer and urine analysis for ethyl glucuronide; alcohol use during the 3-month follow-up interval was assessed by self-report. Pretreatment emotion-regulation skills predicted alcohol use during treatment, and posttreatment emotion-regulation skills predicted alcohol use at follow-up, even when controlling for other predictors potentially related to emotion regulation. Among a broad range of specific emotion-regulation skills, the ability to tolerate negative emotions was the only skill that negatively predicted subsequent alcohol consumption when controlling for the other skills. Individuals in the AD sample reported significantly larger deficits in emotion-regulation skills than did those in a nonclinical control sample but significantly less than did those in a sample of individuals exclusively meeting criteria for major depressive disorder. Enhancement of general emotion-regulation skills, especially the ability to tolerate negative emotions, appears to be an important target in the treatment of AD.


Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease.
In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.


Vocabulary Acquisition as a By-Product of Meaning-Oriented Auditory Training for Children Who Are Deaf or Hard of Hearing.
Purpose A meaning-oriented auditory training program for children who are deaf or hard of hearing (d/hh) was assessed with regard to its efficacy in promoting novel word learning. Method While administering the auditory training program, one of the authors (Elizabeth Mauzé) observed that children were learning words they previously did not know. Therefore, we systematically assessed vocabulary gains among 16 children. Most completed pretest, posttest, and retention versions of a picture-naming task in which they attempted to verbally identify 199 color pictures of words that would appear during training. Posttest and retention versions included both pictures used and not used during training in order to test generalization of associations between words and their referents. Importantly, each training session involved meaning-oriented, albeit simple, activities/games on a computer. Results At posttest, the percentage of word gain was 27.3% (SD = 12.5; confidence interval [CI] of the mean: 24.2-30.4) using trained pictures as cues and 25.9% (CI of the mean: 22.9-29.0) using untrained pictures as cues. An analysis of retention scores (for 13 of the participants who completed it weeks later) indicated strikingly high levels of retention for the words that had been learned. Conclusions These findings favor auditory training that is meaning oriented when it comes to the acquisition of different linguistic subsystems, lexis in this case. We also expand the discussion to include other evidence-based recommendations regarding how vocabulary is presented (input-based effects) and what learners are asked to do (task-based effects) as part of an overall effort to help children who are d/hh increase their vocabulary knowledge.


Predicting breast cancer with AI for individual risk-adjusted MRI screening and early detection.
Women with an increased life-time risk of breast cancer undergo supplemental annual screening MRI. We propose to predict the risk of developing breast cancer within one year based on the current MRI, with the objective of reducing screening burden and facilitating early detection. An AI algorithm was developed on 53,858 breasts from 12,694 patients who underwent screening or diagnostic MRI and accrued over 12 years, with 2,331 confirmed cancers. A first U-Net was trained to segment lesions and identify regions of concern. A second convolutional network was trained to detect malignant cancer using features extracted by the U-Net. This network was then fine-tuned to estimate the risk of developing cancer within a year in cases that radiologists considered normal or likely benign. Risk predictions from this AI were evaluated with a retrospective analysis of 9,183 breasts from a high-risk screening cohort, which were not used for training. Statistical analysis focused on the tradeoff between number of omitted exams versus negative predictive value, and number of potential early detections versus positive predictive value. The AI algorithm identified regions of concern that coincided with future tumors in 52% of screen-detected cancers. Upon directed review, a radiologist found that 71.3% of cancers had a visible correlate on the MRI prior to diagnosis, 65% of these correlates were identified by the AI model. Reevaluating these regions in 10% of all cases with higher AI-predicted risk could have resulted in up to 33% early detections by a radiologist. Additionally, screening burden could have been reduced in 16% of lower-risk cases by recommending a later follow-up without compromising current interval cancer rate. With increasing datasets and improving image quality we expect this new AI-aided, adaptive screening to meaningfully reduce screening burden and improve early detection.


On the robustness of the adaptive lasso to model misspecification.
Penalization methods have been shown to yield both consistent variable selection and oracle parameter estimation under correct model specification. In this article, we study such methods under model misspecification, where the assumed form of the regression function is incorrect, including generalized linear models for uncensored outcomes and the proportional hazards model for censored responses. Estimation with the adaptive least absolute shrinkage and selection operator, lasso, penalty is proven to achieve sparse estimation of regression coefficients under misspecification. The resulting estimators are selection consistent, asymptotically normal and oracle, where the selection is based on the limiting values of the parameter estimators obtained using the misspecified model without penalization. We further derive conditions under which the penalized estimators from the misspecified model may yield selection consistency under the true model. The robustness is explored numerically via simulation and an application to the Wisconsin Epidemiological Study of Diabetic Retinopathy.


Interbrain phase synchronization during turn-taking verbal interaction-a hyperscanning study using simultaneous EEG/MEG.
Recently, neurophysiological findings about social interaction have been investigated widely, and hardware has been developed that can measure multiple subjects' brain activities simultaneously. These hyperscanning studies have enabled us to discover new and important evidences of interbrain interactions. Yet, very little is known about verbal interaction without any visual input. Therefore, we conducted a new hyperscanning study based on verbal, interbrain turn-taking interaction using simultaneous EEG/MEG, which measures rapidly changing brain activities. To establish turn-taking verbal interactions between a pair of subjects, we set up two EEG/MEG systems (19 and 146 channels of EEG and MEG, respectively) located ∼100 miles apart. Subjects engaged in verbal communication via condenser microphones and magnetic-compatible earphones, and a network time protocol synchronized the two systems. Ten subjects participated in this experiment and performed verbal interaction and noninteraction tasks separately. We found significant oscillations in EEG alpha and MEG alpha/gamma bands in several brain regions for all subjects. Furthermore, we estimated phase synchronization between two brains using the weighted phase lag index and found statistically significant synchronization in EEG and MEG data. Our novel paradigm and neurophysiological findings may foster a basic understanding of the functional mechanisms involved in human social interactions. Hum Brain Mapp 39:171-188, 2018. © 2017 Wiley Periodicals, Inc.


Perceptions of outcomes of implant therapy in patients with ectodermal dysplasia syndromes.
The purpose of this study was to evaluate patient-specific outcomes and satisfaction using dental implants in a population affected with ectodermal dysplasia. Patient-based data were collected using a self-reported survey instrument sent to patients belonging to a private patient foundation and/or treated previously at a government clinic. A standardized survey instrument was developed to evaluate patient satisfaction, outcomes, and potential complications using dental implants. The survey instrument was mailed to 253 affected individuals self-reported to have various forms of ectodermal dysplasia and who were voluntarily participants in the National Foundation for Ectodermal Dysplasias and/or were participants in the US National Institute for Dental Craniofacial Research Intramural Ectodermal Dysplasia clinical research program. A total of 109 responses were obtained (43% response rate). The duration following completion of implant therapy ranged from to 1 to 23 years. Of the 109 participants, 50% reported either an implant or prosthetic complication with implant treatment, and 24% reported some form of failure with implant therapy. However, 91% of participants reported being either satisfied or very satisfied with dental implants, and 95% reported that the treatment was worth the time and cost. Affected individuals receiving tooth replacement therapy with dental implants reported satisfaction with the outcome. A higher level of complications, including infection, mechanical problems, and implant loss, relative to the unaffected population was reported.


[Electrophysiologic manifestations of the effect of monoaminergic systems on the cerebral cortex].
Various forms of electropgraphic display of monoaminergic neurotransmitter system effect upon the cerebral cortex are discussed. Comparison of theoretical and experimental results suggests a modulating role of serotoninergic and noradrenergic systems.


Effects of asbestos-related pleural disease on pulmonary function.
The relationship between loss of pulmonary function and the presence of asbestos-related pleural disease was evaluated for 913 Minnesota asbestos workers. Asbestos-related pleural disease was categorized as circumscribed plaques or diffuse thickening. Compared with workers with normal pleura, workers with plaques had a decreased mean percentage for predicted forced vital capacity (FVC) and predicted forced expiratory volume in 1 s (FEV1.0). Diffuse thickening was associated with more profound decreases in FVC and FEV1.0. No relationship was seen between FEV % [(100 x FEV1.0)/FVC)] and either type of pleural disease. Dyspnea was associated with diffuse thickening more so than plaques. These results remained after control for pack-years of smoking, extent of parenchymal disease, and the presence of pulmonary disease history. Pleural plaques and diffuse pleural thickening were considered independent risk factors for the loss of lung function.


Antimicrobial peptide delivery strategies: use of recombinant antimicrobial peptides in paratransgenic control systems.
Antimicrobial peptides (AMP's) are small peptides that have evolved as part of an innate cell defense mechanism in many organisms. We are currently developing methodologies to use these molecules to control the transmission of vector borne diseases utilizing a paratransgenic strategy. In this approach, symbiotic or commensal microbes of host insects are transformed to express gene products that interfere with pathogen transmission. These genetically altered microbes are re-introduced back to the insect where expression of the engineered molecules decreases the host's ability to transmit the pathogen. In previous work, we demonstrated that the paratransgenic expression of the AMP, cecropin A, by transformed microbes residing in the midgut of the reduviid bug, reduced carriage of the parasite, T. cruzi, substantially. In more recent work, we reported a dramatic increase in parasite killing efficiency when AMP's are used in combination. Further, the AMP concentrations required for parasite killing are decreased by at least 10-fold. In this review, we discuss the feasibility of utilizing other AMP's, individually or in combination, as effector molecules to control the transmission of leishmania parasites by sand flies and to control Vibriosis, a highly devastating disease in shrimp mariculture.


Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.
Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.


Pachyonychia congenita: a case report.
A 21-year-old man presented with hypertrophic nail dystrophy and subungual debris of all 20 nails, hyperkeratotic plaques on the heels of both feet, and oral leukokeratosis. He had an extensive family history of similar clinical findings. The patient's clinical presentation and history were consistent with pachyonychia congenita (PC), an autosomal dominant genodermatosis caused by mutations in the genes for keratin 6, K6a and K6b; keratin 16, K16; and keratin 17, K17.


Odontogenic keratocysts in Nevoid basal cell carcinoma syndrome: a case report.
Nevoid basal cell carcinoma syndrome, a rare autosomal dominant disorder, comprises a number of abnormalities such as multiple nevoid basal cell carcinomas, skeletal abnormalities and multiple odontogenic keratocysts. Considering the rarity of this syndrome, we present a 12-year-old boy affected by this syndrome. He had multiple okcs, calcification of falx cerebri, bifid ribs, frontal bossing and hypertelorism. Characteristic cutaneous manifestation (nevoid basal cell carcinoma) was not present in this patient. The jaw cysts were treated with marsupialization then enucleation. The dental clinician may be the first to encounter and identify this syndrome, when the multiple cystlike radiolucencies are discovered on panoramic view.


Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin.
Somatostatin significantly suppressed cell growth of the mouse insulinoma-derived cell line MIN6. MIN6 cells exhibited high-affinity binding of somatostatin with 50% inhibitory concentration value of 0.9 nM. RNA blot analysis revealed that MIN6 cells expressed only SSTR3 among the five somatostatin receptors so far identified. Treatment of MIN6 cells with somatostatin significantly reduced the serum-induced c-fos expression levels. On the other hand, somatostatin (100 nM) treatment of MIN6 cells cultured in medium containing 10% serum transiently increased c-fos expression levels to 282 +/- 4.7% and then significantly decreased them to 27 +/- 7.6% of the levels before treatment. Mitogen-activated protein (MAP) kinase activity transiently increased to 656 +/- 91.2% and decreased thereafter to 39 +/- 13.3% of the activity before the addition of somatostatin (100 nM) into the medium. In addition, the stimulatory effect of somatostatin on c-fos expression and MAP kinase activity (early effect) was not altered by pertussis toxin (PTX), whereas the suppressive effect of somatostatin on c-fos expression and MAP kinase activity (late effect) was mitigated by PTX. These findings suggest that an inhibition of c-fos expression mediated by cross talk between PTX-sensitive G protein signaling and receptor tyrosine kinase signaling is one of the mechanisms by which somatostatin inhibits cell growth in MIN6 cells.


Influence of hyperglycemia on insulin's in vivo effects in type II diabetes.
The present study was designed to quantitate the interaction between the decrease in target tissue insulin action seen in subjects with Type II diabetes and the mass action effect of glucose exerted via the prevailing hyperglycemic state. To this end, euglycemic glucose clamp studies were performed in 26 control subjects using insulin infusion rates of 15, 40, 120, 240, and 1,200 mU/M2 per min and in 10 Type II diabetic subjects using insulin infusion rates of 120 and 1,200 mU/M2 per min. The results of these euglycemic studies indicated that insulin-stimulated peripheral glucose disposal was decreased in the Type II diabetics due to a combined receptor (rightward shift in the dose-response curve) and postreceptor defect in insulin action (decreased maximal response), whereas the decrease in insulin-mediated suppression of hepatic glucose output (HGO) was consistent with a defect in insulin binding (rightward shift in dose-response curve). Hyperglycemic glucose clamp studies were also performed in the Type II diabetics at their respective fasting serum glucose levels (mean [+/- SE] 280 +/- 17 mg/dl) employing insulin infusion rates of 15, 40, 120, and 1,200 mU/M2 per min. In the presence of their basal level of hyperglycemia, the noninsulin-dependent diabetes mellitus (NIDDM) subjects exhibited rates of overall glucose disposal that were similar to those observed in control subjects studied at euglycemia at similar steady state insulin concentrations. This suggests that in Type II diabetics, the mass action effect of glucose partially compensates for the marked decrease in insulin-stimulated glucose uptake observed under euglycemic conditions. However, even in the presence of hyperglycemia, insulin levels below 100 microU/ml had little effect and maximally effective insulin levels increased peripheral glucose disposal only 2.8-fold (142 +/- 7-413 +/- 47 mg/M2 per min) above basal in the Type II diabetics, compared with a sixfold increase (75 +/- 4-419 +/- 34 mg/M2 per min) in the control subjects studied at euglycemia. Thus, the severe insulin resistance that is a characteristic feature of NIDDM remains apparent. Basal HGO was elevated in the NIDDM subjects (157 +/- 6 vs. 76 +/- 4 mg/M2 per min for controls) and a high degree of correlation was found between the basal rate of HGO and the fasting glucose level (r = 0.80, P less than 0.01). The presence of hyperglycemia augmented insulin-mediated suppression of HGO, but did not restore it to normal. We concluded that: (a) in the presence of basal hyperglycemia, physiologic insulin levels exerts a diminished effect to suppress HGO and stimulate peripheral glucose disposal in NIDDM; (b) basal HGO is elevated in untreated Type II diabetics, and this may serve to maintain the level of hyperglycemia required to compensate for the decrease in peripheral insulin action; and (c) fasting hyperglycemia exerts a suppressive effect on HGO but does not completely compensate for the decrease in hepatic insulin action in Type II diabetics.


Effect of Conductivity on In Situ Deactivation of Catechol-Boronate Complexation-Based Reversible Smart Adhesive.
To reduce the need for elevated electrical potential to deactivate catechol-based smart adhesive and preserve its reversibility, conductive 1-pyrenemethyl methacrylate (PyMA) was incorporated into a catechol and phenylboronic acid-containing adhesive coating immobilized on aluminum (Al) discs. Electrochemical impedance spectroscopy (EIS) indicated that incorporation of 26 mol % of PyMA reduced ionic resistance (Rs) and charge-transfer resistance (Rc) of the coating from over 22 Ω/mm2 to 5.9 and 1.2 Ω/mm2, respectively. A custom-built Johnson-Kendall-Roberts (JKR) contact mechanics test setup was used to evaluate the adhesive property of the coating with in situ applied electricity using a titanium (Ti) sphere both as a test substrate as well as the cathode for application of electricity and the Al disc as the anode. The adhesive coating demonstrated over 95% reduction in the adhesive property when electricity (1-2 V) was applied while the adhesive was in direct contact with the Ti surface. The addition of PyMA enables the deactivation of the adhesive using a voltage as low as 1 V. Both cyclic voltammetry (CV) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra confirmed the formation of catechol-boronate complexation through electrochemical stimulation. Breaking the complex with an acidic buffer (pH 3) recovered the catechol for strong wet adhesion and the coating could be repeatedly deactivated and reactivated using low electrical potential for up to five cycles. Incorporation of both conductive PyMA and boronic acid as the temporary protecting group was required to achieve rapidly switchable adhesive that could be deactivated with low applied voltage.


A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice.
Altered nutrients during the in utero (IU) and/or lactation (L) period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD) fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Female wild type (WT) mice were fed either a HFD or control chow (C) prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension) and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT1- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.


[Information on AIDS among persons aged 16-20 years].
In order to illustrate whether the AIDS and "Safe sex" campaigns have influenced young people, an investigation originally made in 1985 was repeated in October 1989; the objects being sexual knowledge, sexual experience and contraception among persons aged 16-20 years. A representative random sample consisting of 359 women (percentage replies 77.9) and 400 men (percentage replies 76.3) who were over 16 but not yet 21 years was interviewed personally by the professional interviewer staff of the Institute for Social Research. A total of 72% (n = 547) had been informed about AIDS at school, most of these were among the youngest participants. Simultaneously, 43% (n = 326) considered that school was the best source of information. School thus appears to be an effective channel of information about AIDS to young people. TV/radio were also found to be important channels of information while only few participants stated that they had received the best information in their homes. The majority of replies to questions about AIDS were in complete agreement with the messages in the informative campaigns. In conclusion, it is stated that the replies were markedly uniform without any obvious connection with sex, age, background or experience. Significantly more of the men, however, considered that their knowledge about AIDS was adequate.


Self-management practices among primary care patients with musculoskeletal pain and depression.
The objective of this study was to assess the effect of clinical depression on pain self-management practices. We employed a cross-sectional analysis of baseline data from the Stepped Care for Affective disorders and Musculoskeletal Pain (SCAMP) study. Participants included 250 patients with pain and comorbid depression and 250 patients with pain only and were enrolled from urban university and VA primary care clinics. Musculoskeletal pain was defined as low back, hip or knee pain present >or=3 months and with at least a moderate, Brief Pain Inventory severity score >or=5. Depression was defined as a PHQ-9 score >or=10. We used multiple logistic and Poisson regression to assess the relationship between individual and combined effects of depression and pain severity on two core pain self-management skills: exercise duration and cognitive strategies. Depressed patients exercised less per week than did nondepressed patients but showed a trend towards more frequent use of cognitive strategies. On multivariable analysis, depression severity substantially decreased the use of exercise as a pain self-management strategy. In contrast, depression and pain severity interacted to increase the use of cognitive strategies. Depression and pain severity have differential effects on self-management practices. Understanding the differences between preferential strategies of pain patients with and without depression may be useful in tailoring pain self-management programs.


Development and application of a new 25,27-bis(L-phenylalaninemethylester-N-carbonylmethoxy)-26,28-dihydroxy-para-tert-butylcalix[4]arene stationary phase.
A 25,27-bis(L-phenylalaninemethylester-N-carbonylmethoxy)-26,28-dihydroxy- para-tert-butylcalix[4]arene-bonded silica gel stationary phase was synthesized, structurally characterized and used for LC. Its separation mechanism was studied and compared with octadecyl-bonded stationary phase, as well as our previously prepared para-tert-butylcalix[4]arene-1,2-crown-4 stationary phase. Meanwhile, the chromatographic behaviors were investigated by using polycyclic aromatic hydrocarbons, monosubstituted benzenes, anilines, phenols, Tanaka tests solutes, fluoroquinolones, and flavonoids as probes. Mechanisms involved in the chromatographic separation included hydrophobic, π-π and π-electron transfer, hydrogen bonding, and inclusion interactions. Moreover, the column was successfully employed for the analysis of the illegal additive of melamine in milk product.


Ethnic Disparity in the Incidence and Outcome of Biliary Atresia in New Zealand.
To determine incidence and outcome of biliary atresia (BA) between ethnic groups in New Zealand (NZ), a retrospective review was undertaken of children with BA born between 2002 and 2014. Prioritized ethnicity was used to determine ethnicity and was compared to population data. Uni- and multivariate analyses were undertaken to determine demographic and biochemical factors associated with outcome. Overall incidence was 1 in 9181 (Māori 1 in 5285; European 1 in 16,228; P < 0.0001). Overall and transplant-free survival rates at 1, 2, and 5 years were 92%, 86%, 82% and 70%, 49%, 30% respectively with Māori having improved transplant-free survival (P < 0.05) despite European children undergoing Kasai earlier (49 vs 63 days). BA is more common in NZ than Europe and North America, which is attributable to a higher incidence in Māori but overall outcome is poorer. Māori have improved transplant-free survival compared to NZ European children but the reason is unknown.


Kindergarten readiness after prematurity: Integrating health, development, and behavioral functioning to optimize educational outcomes of vulnerable children.
In the past 20 years, many advances (e.g., maternal steroids and surfactant) have changed the course of neonatal medicine. As a result, extremely preterm infants survive medical complications that were previously fatal. Once they are discharged from the neonatal intensive care unit, preterm infants may continue to experience a spectrum of medical and developmental challenges, and their families are faced with the potentially daunting task of nurturing a vulnerable child. Families may be referred to multiple systems of care, including primary care physicians, pediatric subspecialists, and early intervention services. The ultimate goal for preterm infants is to optimize their motor, communicative, social-emotional, and adaptive development as well as to promote their learning at home, at school, and in the community. As children transition to school, key indicators of their functional status include the amount of developmental, educational, habilitative, and behavioral supports they require to participate in learning activities with their peers. Success may be measured by whether preterm infants are ready for large-group learning with peers and the extent of supports required to make this important transition. The purpose of this review is to describe what is known about certain indicators of school readiness in preterm infants, including neurodevelopmental impairments, social-emotional skills, and social factors. We conclude with guidelines for using this transition as an important indicator of developmental trajectories that may help us to better understand risk and resilience in this vulnerable population of children.


Advanced trauma life support, 8th edition, the evidence for change.
The American College of Surgeons Committee on Trauma's Advanced Trauma Life Support Course is currently taught in 50 countries. The 8th edition has been revised following broad input by the International ATLS subcommittee. Graded levels of evidence were used to evaluate and approve changes to the course content. New materials related to principles of disaster management have been added. ATLS is a common language teaching one safe way of initial trauma assessment and management.


High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive non-Hodgkin lymphoma (NHL) in adults.
High-dose chemotherapy with autologous stem cell support (HDT) has been proven effective in relapsed aggressive non-Hodgkin lymphoma (NHL). However, conflicting results of HDT as part of first-line treatment have been reported in randomised controlled trials (RCTs). We undertook a systematic review and meta-analysis to assess the effects of such treatment. To determine whether high-dose chemotherapy with autologous stem cell transplantation as part of first-line treatment improves survival in patients with aggressive non-Hodgkin lymphoma. MEDLINE, EMBASE, Cancer Lit, the Cochrane Library and smaller databases, Internet-databases of ongoing trials, conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology were searched. We included full-text, abstract publications and unpublished data. Randomised controlled trials comparing conventional chemotherapy versus high-dose chemotherapy in the first-line treatment of adults with aggressive non-Hodgkin lymphoma were included in this review. Eligibility and quality assessment, data extraction and analysis were done in duplicate. All authors were contacted to obtain missing data and asked to provide individual patient data. Fifteen RCTs including 3079 patients were eligible for this meta-analysis. Overall treatment-related mortality was 6.0% in the HDT group and not significantly different compared to conventional chemotherapy (OR 1.33 [95% CI 0.91 to 1.93], P=0.14). 13 studies including 2018 patients showed significantly higher CR rates in the group receiving HDT (OR 1.32, [95% CI 1.09 to 1.59], P=0.004). However, HDT did not have an effect on OS, when compared to conventional chemotherapy. The pooled HR was 1.04 ([95% CI 0.91 to 1.18], P=0.58). There was no statistical heterogeneity among the trials. Sensitivity analyses underlined the robustness of these results. Subgroup analysis of prognostic groups according to IPI did not show any survival difference between HDT and controls in 12 trials (low and low-intermediate risk IPI: HR 1.41[95% CI 0.95 to 2.10], P=0.09; high-intermediate and high risk IPI: HR 0.97 [95% CI 0.83 to 1.13], P=0.71. Event-free survival (EFS) also showed no significant difference between HDT and CT (HR 0.93, [95% CI 0.81 to 1.07], P=0.31). Other possible risk factors such as the proportion of patient with diffuse large cell lymphoma, protocol adherence, HDT strategy, response status before HDT, conditioning regimens and methodological issues were analysed in sensitivity analyses. However, there was no evidence for an association between these factors and the results of our analyses. . Despite higher CR rates, there is no benefit for high-dose chemotherapy with stem cell transplantation as a first line treatment in patients with aggressive NHL.


Effects of prepartum ingestion of Ipomoea carnea on postpartum maternal and neonate behavior in goats.
Ipomoea carnea is a toxic plant that grows in tropical areas, and is readily consumed by grazing goats. The plant contains the alkaloids swainsonine and calystegines, which inhibit cellular enzymes and cause systematic cell death. This study evaluated the behavioral effects on dams and kids of prenatal ingestion of this plant. Freshly harvested leaves of I. carnea (10 g/kg body weight) were fed daily to nine pregnant goats from the fifth to the 16th week of gestation; five pregnant goats were controls. Dam and kid behavior were evaluated during 2-hr postpartum. Further evaluation of the offspring was performed using various tests after birth: (1) reaching and discriminating their dam from an alien doe (two tests at 12-hr postpartum), and (2) navigating a progressive maze (2, 4, and 6 days postpartum). Postnatal (n = 2) and fetal (n = 2) mortality were observed in the treated group. Intoxicated kids had difficulty in standing at birth, and only one was able to suckle within 2 hr of birth. Treated kids were slower than controls to arrive at their dam in the discrimination test; treated kids often (seven of nine completed tests) incorrectly chose the alien dam (controls: 0/10 tests). During some runs on days 2, 4, and 6 postpartum, treated kids were slower to leave the starting point of the maze, and were slower to arrive at the dam on all test days. This study suggests that the offspring of pregnant goats given I. carnea during gestation have significant behavioral alterations and developmental delays.


Possible role of the leptin system in controlling puberty in the male chub mackerel, Scomber japonicus.
Leptin directly regulates kisspeptin neurons in the hypothalamus and gonadotropin secretion from the pituitary, making it a central player in the onset of mammalian puberty. Recently, we identified two leptin genes (lepa and lepb) and a single leptin receptor (lepr) in the marine perciform fish chub mackerel; however, the expression of these genes did not correlate with the expression of important reproductive genes or ovarian stage during female puberty. Here, we expand upon these initial observations by evaluating the expression of lepa, lepb, and lepr during pubertal transition and under differential feeding conditions in the male chub mackerel. Reverse transcription-polymerase chain reaction (RT-PCR) showed that lepa was primarily expressed in the liver of pubertal and gonadal recrudescence adults, as well as in the brain of adult fish; lepb was primarily expressed in the brain of all fish tested; and lepr was widely expressed in a variety of tissues. qRT-PCR analyses revealed significant increases in the hepatic expression of lepa in accordance with testicular stage, whereas pituitary follicle-stimulating hormone (fshβ) expression increased in unison with hepatic lepa. In contrast, expression of both brain lepa and lepb dramatically decreased during pubertal transition, with brain kisspeptin 1 (kiss1) expression strongly correlating with leptin expression patterns. In pre-pubertal males, lepa, lepb, and lper gene expression in the brain, pituitary gland, and liver decreased in fish given a high feed diet, relative to the controlled feeding group. Taken together, these results indicate high sexual specificity of leptin expression, suggesting a possible role for leptin signaling in endocrine and neuroendocrine functions during spermatogenesis in the pubertal male chub mackerel.


Liquid chromatographic method for fumonisin B1 in sorghum syrup and corn-based breakfast cereals.
The fungus Fusarium verticillioides has been found on corn and sorghum, so it is possible that one or more of these toxins may be found in corn products such as breakfast cereals and syrup prepared from sorghum. Published methods when applied to syrups spiked with fumonisins gave low recoveries, less than 50%. A method was therefore developed which would be applicable to the syrup and breakfast cereals as well. Test samples were extracted with methanol-0.1 M sodium phosphate buffer (pH3) (1 + 1). The extract was diluted with water and applied to a 1 g C18 column. The column was washed with acetonitrile-water (2 + 8). Fumonisin B1 (FB1) was eluted with acetonitrile-trifluoroacetic acid (1000 + 1). The purified extract was evaporated and the toxin was derivatized with ophthaldialdehyde mercaptoethanol. The reaction mixture was resolved on a C18 liquid chromatographic column using acetonitrile-water-acetic acid (500 + 550 + 10.5) as the mobile phase at 37 degrees C, and FB1 measured with a fluorescence detector (excitation 335 nm, emission 440 nm). Recoveries of FB1 added to samples of sorghum syrup at levels ranging from 0.1 to 1.0 microgram/g were 94-132%. Recoveries of FB1 added to samples of breakfast cereal (corn flakes) at levels ranging from 0.2 to 1.6 micrograms/g were 96-100%. The method was applied to the analysis of 35 samples of sorghum syrup collected from 15 states in the US. One sample was found to contain FB1 at 0.12 microgram/g. A total of 32 samples of breakfast cereals collected by the Food and Drug Administration inspectors from grocery stores around the Kansas City area were analysed; no FB1 was found in the breakfast cereals (< 0.01 microgram/g). Results of this study indicated that FB1 possibly is not a problem in sorghum syrup and corn-based breakfast cereals in the US.


Endothelial responses to oxidized lipoproteins determine genetic susceptibility to atherosclerosis in mice.
Oxidized LDL has been found within the subendothelial space, and it exhibits numerous atherogenic properties, including induction of inflammatory genes. We examined the possibility that variations in endothelial response to minimally modified LDL (MM-LDL) constitute one of the genetic components in atherosclerosis. By a novel explant technique, endothelial cells (ECs) were isolated from the aorta of inbred mouse strains with different susceptibilities to diet-induced atherosclerosis. Responses to MM-LDL were evaluated by examining the expression of inflammatory genes involved in atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and macrophage-colony-stimulating factor (M-CSF), an oxidative stress gene, heme oxygenase-1 (HO-1), and other, noninflammatory, genes. ECs from the susceptible mouse strain C57BL/6J exhibited dramatic induction of MCP-1, M-CSF, and HO-1, whereas ECs from the resistant strain C3H/HeJ showed little or no induction. In contrast, ECs from the 2 strains responded similarly to lipopolysaccharide. These data provide strong evidence that genetic factors in atherosclerosis act at the level of the vessel wall.


Simultaneous estimation of physiological parameters and the input function--in vivo PET data.
Dynamic imaging with positron emission tomography (PET) is widely used for the in vivo measurement of regional cerebral metabolic rate for glucose (rCMRGlc) with [18F]fluorodeoxy-D-glucose (FDG) and is used for the clinical evaluation of neurological disease. However, in addition to the acquisition of dynamic images, continuous arterial blood sampling is the conventional method to obtain the tracer time-activity curve in blood (or plasma) for the numeric estimation of rCMRGlc in mg glucose/100-g tissue/min. The insertion of arterial lines and the subsequent collection and processing of multiple blood samples are impractical for clinical PET studies because it is invasive, has the remote, but real potential for producing limb ischemia, and it exposes personnel to additional radiation and risks associated with handling blood. In this paper, based on our previously proposed method for extracting kinetic parameters from dynamic PET images, we developed a modified version (post-estimation method) to improve the numerical identifiability of the parameter estimates when we deal with data obtained from clinical studies. We applied both methods to dynamic neurologic FDG PET studies in three adults. We found that the input function and parameter estimates obtained with our noninvasive methods agreed well with those estimated from the gold standard method of arterial blood sampling and that rCMRGlc estimates were highly correlated (r = 0.973). More importantly, no significant difference was found between rCMRGlc estimated by our methods and the gold standard method (P > 0.16). We suggest that our proposed noninvasive methods may offer an advance over existing methods.


Effects of hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume.
The effects of long-term hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume were studied in eight conscious dogs over a 34-day period. Plasma protein concentration (PPC) was decreased by daily plasmapheresis, and the effects of decreasing and increasing sodium intake were measured. By the 12th day of plasmapheresis, during which sodium intake was 30 meq/day, PPC had decreased to 2.5 g/dl from a control value of 7.2 g/dl, mean arterial pressure had decreased to 78% of control, glomerular filtration rate (GFR) was 75.2% of control, and urinary sodium excretion was decreased. By day 18 of plasmapheresis, estimated renal plasma flow (ERPF) was decreased to 60% of control due to the decreased arterial pressure and an increase in renal vascular resistance. Also, plasma renin activity and plasma aldosterone concentration were both increased, and the relationship between mean arterial pressure and urinary sodium excretion was distinctly shifted to the left along the arterial pressure axis. In contradistinction to acute experiments, chronic hypoproteinemia results in decreases in GFR, ERPF, and urinary sodium excretion and has marked effects on both fluid volume and arterial pressure regulation.


Improving drug delivery to primary and metastatic brain tumors: strategies to overcome the blood-brain barrier.
Brain tumor diagnosis has an extremely poor prognosis, due in part to the blood-brain barrier (BBB) that prevents both early diagnosis and effective drug delivery. The infiltrative nature of primary brain tumors and the presence of micro-metastases lead to tumor cells that reside behind an intact BBB. Recent genomic technologies have identified many genetic mutations present in glioma and other central nervous system (CNS) tumors, and this information has been instrumental in guiding the development of molecularly targeted therapies. However, the majority of these agents are unable to penetrate an intact BBB, leading to one mechanism by which the invasive brain tumor cells effectively escape treatment. The diagnosis and treatment of a brain tumor remains a serious challenge and new therapeutic agents that either penetrate the BBB or disrupt mechanisms that limit brain penetration, such as endothelial efflux transporters or tight junctions, are required in order to improve patient outcomes in this devastating disease.


Investigation of the efficacy of a dietetic food in the management of chronic enteropathies in dogs.
Chronic enteropathies (CEs) are a common cause of morbidity in dogs. CEs are diagnosed in dogs with chronic gastrointestinal clinical signs (>3 weeks), inflammatory changes on intestinal biopsies and where no other underlying cause is determined based on a thorough, standardised diagnostic work-up. Based on response to therapy, CEs are subclassified into food-responsive, antibiotic-responsive or steroid-responsive enteropathies. A significant proportion of dogs with a CE are food-responsive; however, there are limited peer-reviewed publications describing the clinical efficacy of the commercially available diets used to treat CE. In this study, the authors evaluated the response of 15 dogs with a CE to a commercially available dietetic food (Hill's Prescription Diet i/d Sensitive Canine Dry). The dogs underwent a standard diagnostic evaluation and did not receive concurrent anthelmintic, antibiotic, glucocorticoid or gastroprotectant therapies. The clinical efficacy of the dietary treatment was assessed by comparing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) before and a median of 13 days after dietary therapy. The authors found that the CIBDAI significantly decreased following the introduction of the dietetic food (median CIBDAI score pretreatment 9, post-treatment 2; P<0.0005). This study demonstrates that this dietetic food can be used to successfully manage CE in dogs.


Effect of soybean meal substitution by different concentrations of sunflower meal on egg quality traits of white and coloured dwarf dam lines.
1. The effect of soybean meal substitution by different concentrations of sunflower meal on egg quality traits of white and coloured dwarf dam lines was investigated. 2. A total of 144 dwarf hens (38 weeks of age) from the same hatch were randomly divided into 12 groups of 12 birds (4 dietary treatments x 3 replicates). 3. A 2 x 4 factorial design was used to study the effect of 2 lines (Factor A) and substitution of soybean meal (SBM) with 4 concentrations (0, 10, 15 and 20%) of sunflower meal (SFM) [Factor B] on egg quality traits of dwarf dam line hens. 4. All the diets were designed to be isocaloric (113 MJ ME/kg) and isonitrogenous (180 g/kg crude protein) The duration of the experiment was 12 weeks. 5. Analysis of variance indicated a highly significant line effect. There were non-significant effects of substitution of soybean meal with different concentrations of sunflower meal on egg quality traits except for Haugh unit. 6. White plumaged dwarf broiler breeder dam line produced significantly fewer, but larger, eggs than coloured dwarf dam line hens.


Cognitive Distortions, Humor Styles, and Depression.
Cognitive distortions are negative biases in thinking that are theorized to represent vulnerability factors for depression and dysphoria. Despite the emphasis placed on cognitive distortions in the context of cognitive behavioural theory and practice, a paucity of research has examined the mechanisms through which they impact depressive symptomatology. Both adaptive and maladaptive styles of humor represent coping strategies that may mediate the relation between cognitive distortions and depressive symptoms. The current study examined the correlations between the frequency and impact of cognitive distortions across both social and achievement-related contexts and types of humor. Cognitive distortions were associated with reduced use of adaptive Affiliative and Self-Enhancing humor styles and increased use of maladaptive Aggressive and Self-Defeating humor. Reduced use of Self-Enhancing humor mediated the relationship between most types of cognitive distortions and depressed mood, indicating that distorted negative thinking may interfere with an individual's ability to adopt a humorous and cheerful outlook on life (i.e., use Self-Enhancing humor) as a way of regulating emotions and coping with stress, thereby resulting in elevated depressive symptoms. Similarly, Self-Defeating humor mediated the association of the social impact of cognitive distortions with depression, such that this humor style may be used as a coping strategy for dealing with distorted thinking that ultimately backfires and results in increased dysphoria.


Induction of arginase II mRNA by nitric oxide using an in vitro model of gyrate atrophy of choroid and retina.
The authors previously reported ornithine cytotoxicity in ornithine-δ-aminotransferase (OAT)-deficient human retinal pigment epithelial (RPE) cells as an in vitro model of gyrate atrophy of the choroid and retina (GA). Given that RPE cells are severely damaged by arginine combined with ornithine, they investigated the role of arginine metabolism using that in vitro model. Human telomerase reverse transcriptase (hTERT)-RPE cells were incubated with ornithine or other agents in the presence of 5-fluoromethylornithine (5-FMO), an OAT-specific inhibitor. mRNA expression was determined by quantitative real-time polymerase chain reaction, and the concentration of nitric oxide (NO) was quantified using a Griess assay. Furthermore, cytotoxicity was examined by morphologic observations and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays, with the effect of arginase II examined using short interfering (si) RNA for arginase II and S-(2-boronoethyl)-L-cysteine (BEC), an arginase inhibitor. NO production in 5-FMO-treated hTERT-RPE cells was increased by ornithine, and the NO donors S-nitroso-N-acetyl-DL-penicillamine (SNAP) and S-nitrosoglutathione induced cytotoxicity. Ornithine increased the expression of arginase II mRNA in 5-FMO-treated cells. Arginase II upregulation was partially inhibited by an NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, which was mimicked by SNAP. Arginase II siRNA and BEC enhanced ornithine cytotoxicity, and arginase II silencing resulted in a further increase in NO production. These results demonstrate that NO is produced in our in vitro GA model, which induced cytotoxicity of RPE cells and upregulation of arginase II. NO may be involved in RPE degeneration in GA through the regulation of arginase II mRNA expression.


[Surgical procedure in medical fractures of the femoral neck in the middle-aged and elderly].
The treatment of 615 elderly and senile patients with medial fractures of the femoral neck is analyzed. The average age of the patients was 76. In spite of the age and concomitant diseases, 487 patients were subjected to operations. The character of the operation depended on the kind of fracture. Remote results were studied in 210 patients within the period of 5 years. Union of fractures was observed in 200 patients.


Cardiovascular consequences of extreme prematurity: the EPICure study.
The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation. Age and sex-matched classmates were recruited as controls. Information concerning perinatal and maternal history was collected, and current anthropometric characteristics were measured in 219 children born extremely preterm and 153 classmates. A subset of the extremely preterm children (n = 68) and classmates (n = 90) then underwent detailed haemodynamic investigations, including measurement of supine blood pressure (BP), aortic pulse wave velocity (aPWV, a measure of aortic stiffness) and augmentation index (AIx, a measure of arterial pressure wave reflections). Seated brachial systolic and diastolic BP were not different between extremely preterm children and classmates (P = 0.3 for both), although there was a small, significant elevation in supine mean and diastolic BP in the extremely preterm children (P < 0.05 for both). Arterial pressure wave reflections were significantly elevated in the extremely preterm children (P < 0.001) and this persisted after adjusting for confounding variables. However, aortic stiffness was not different between the groups (P = 0.1). These data suggest that extreme prematurity is associated with altered arterial haemodynamics in children, not evident from the examination of brachial BP alone. Moreover, the smaller, preresistance and resistance vessels rather than large elastic arteries appear to be most affected. Children born extremely preterm may be at increased future cardiovascular risk.


Evaluation of a screw insertion landmark for a minimally invasive repair technique in induced bilateral sacroiliac luxation in feline cadavers.
The aim of this study was to describe an alternative landmark for screw insertion into the body of the ilium with bilateral sacroiliac luxation in cats. Seven cat cadavers with artificially induced bilateral sacroiliac luxation were used. The screw insertion point was determined using the caudal iliac crest and cranial acetabular rim. These two points make the first guideline; a second guideline ran perpendicular to the caudal iliac crest point. The screw insertion point was halfway along the second guideline across the ilium body. Surgery was performed in a minimally invasive manner using fluoroscopy. Postoperative radiographs and CT were performed. In the postoperative evaluation, the sacroiliac joint reduction percentage was almost 90% and there was no significant difference in pelvic canal diameter ratio before and after surgery. Screw depth/sacral width was >60% in all cadavers. On CT, the angle between the screw and sacrum wing was within the normal range of 96.24° to the left and 98.65° to the right, except in one case. In previous studies, surgical repair was based on having an intact contralateral ilium. However, this method is not applicable to patients with bilateral sacroiliac luxation and is mostly performed using open reduction methods. The screw insertion point suggested in this study offers a potential alternative repair technique for patients with bilateral sacroiliac luxation.


Targeting HDAC3 in the DBA/2J spontaneous mouse model of glaucoma.
High intraocular pressure (IOP) is the most common risk factor associated with glaucoma in humans. While lowering IOP is effective at reducing the rate of retinal ganglion cell (RGC) loss, to date, no treatment exists to directly preserve these cells affected by damage to the optic nerve. Recently, histone deacetylase-3 (HDAC3) has become a potential therapeutic target because it plays an important role in the early nuclear atrophic events that precede RGC death. Conditional knockout or inhibition of HDAC3 prevents histone deacetylation, heterochromatin formation, apoptosis, and eventual RGC loss following acute optic nerve injury. Using these approaches to repress HDAC3 activity, we tested whether targeting HDAC3 protects RGCs from ganglion cell-specific BRN3A expression loss, total somatic cell loss, and optic nerve degeneration in the DBA/2J mouse model of spontaneous glaucoma. Targeted ablation of Hdac3 activity did not protect RGCs from axonal degeneration or somatic cell death in the DBA/2J mouse model of glaucoma. However, inhibition of HDAC3 activity using RGFP966 conferred mild protection against somatic cell loss in the ganglion cell layer in aged DBA/2J mice. Further experimentation is necessary to determine whether other class I HDACs may serve as potential therapeutic targets in chronic models of glaucoma.


Mother-child interaction in autistic and nonautistic children: characteristics of maternal approach behaviors and child social responses.
The nature of mother-child interaction in autism and the maternal approach characteristics that elicit social response in children with autism were examined in two studies. Mother-child play sessions of 24 preschool children with autism and 24 typically developing preschoolers were compared in Study 1, and play sessions of 9 mothers with their autistic child and with their nonautistic child were compared in Study 2. Mother-child interactions were coded using the Approach Withdrawal Interaction Coding System to quantify maternal approach behaviors and child responses. Results of Study 1 indicate that, although the quantity of approaches did not differ between mothers with their autistic children and mothers with their nonautistic children, there were qualitative differences. Mothers used more physical contact, more high-intensity behaviors, and fewer social verbal approaches with autistic children. Results of Study 2 replicated these findings with mothers showing a similar pattern of approach toward their autistic children but not their nonautistic children. Although autistic children displayed lower contingency to maternal approaches in general, they showed greater responsiveness to approaches involving increased physical proximity and/or containing nonverbal object use. Mothers socially engaged both autistic and nonautistic children. The implications for parent training and intervention are discussed.


Chemical constituents of Helichrysum italicum (Roth) G. Don essential oil and their antimicrobial activity against Gram-positive and Gram-negative bacteria, filamentous fungi and Candida albicans.
The aerial parts of Helichrysum italicum (Roth) G. Don were subjected to hydrodistillation to obtain essential oils which had been analyzed by gas chromatography and gas chromatography coupled with mass spectrometry and tested for antimicrobial activity against 12 bacteria, two yeasts and four fungi by agar diffusion method. The essential oil yielded 0.44% (v/w) and 67 compounds accounting for 99.24% of the oil were identified with a high content of oxygenated sesquiterpenes (61.42%). The most oxygenated sesquiterpene compounds were α-Cedrene (13.61%), α-Curcumene (11.41%), Geranyl acetate (10.05%), Limonene (6.07%), Nerol (5.04%), Neryl acetate (4.91%) and α-Pinene (3.78%). The antimicrobial activity of the essential oil was assayed by using the disk diffusion method on Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538, Micrococcus luteus ATCC 4698, Klebsiella pneumonia ATCC 4352, Enterococcus cereus ATCC 2035, Bacillus cereus ATCC 10876, Staphylococcus epidermidis ATCC 12228, Bacillus subtilis ATCC 9372, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 49452, Proteus mirabilis ATCC 35659, Listeria monocytogenes ATCC 15313 and yeasts Candida albicans ATCC 10231, Saccharomyces cerevisiae ATCC 9763 and fungi, Fusarium solani var. coeruleum, Aspergillus niger, Alternaria alternata, Ascochyta rabiei. H. italicum inhibited the growth of all the tested microorganisms except three bacteria, E. coli ATCC 25922, K. pneumonia ATCC 4352 and L. monocytogenes ATCC 15313. The most sensitive bacterium was E. cereus ATCC 2035 with minimum inhibitory and bactericidal concentrations of 0.79 μg ml-1. A minimum fungistatic and fungicide concentration of 6.325 μg ml-1 and 12.65 μg ml-1 respectively was obtained with C. albicans ATCC 10231 and S. cerevisiae ATCC 9763. However the four fungi were more resistant with fungistatic minimum concentration ranging from 6.325 μg ml-1 to 50.6 μg ml-1 and a fungicide minimum concentration of 50.6 μg ml-1. This antimicrobial activity could be attributed to the essential oil chemical composition. Thus this study represents a first step in the study of the chemical composition of H. italicum (Roth) G. Don collected from north Algeria and its antimicrobial properties.


Preliminary characterization of two types of suppressor cells in the human uterus.
Survival of the mammalian fetus in an immunologically hostile host has been shown to be determined by the properties of the tissue at the maternal-fetal interface. Suppressor cells have been found in the decidua in both murine and human systems. This study was carried out to further characterize these cells and to determine whether they were present in abnormal early pregnancies and in the endometrium at the time of implantation. Suppressor cells appear in the endometrium after ovulation, and their activity is present in the decidua of successful pregnancies but is absent in missed abortions. Two types of cells have been identified. An early phase large cell appears to be hormone dependent, and later phase small cell appears to be trophoblast dependent. This would suggest that suppressor cells may play a role in protecting the fetal allograft, from the time of implantation, against maternal immunity, thereby allowing a pregnancy to succeed.


[Functional asymmetry of the cerebral hemispheres during visual perception in schizophrenics with productive and negative symptoms].
To study the characteristics of the interhemispherical interaction, tachistoscopic unilateral presentation of verbal stimuli (letters) was used. Three groups of patients were examined: 27 schizophrenic patients with symptoms of an emotional-volitional defect; 23 with the syndrome of psychic automatism in the framework of schizophrenia, and 20 mentally normal subjects. Subjects from different groups presented significant differences in the nature of recognition of stimuli addressed to the right or left hemisphere. These differences are considered from the standpoint of impairment of the interhemispherical interaction in schizophrenia, which is in agreement with the existing model ideas about the visual recognition through the combined work of both brain hemispheres and relative functional specialization of each of them. To explain a possible link of the defect of the interhemispherical interaction and psychopathological symptomatology in schizophrenia, a hypothesis is advanced according to which this defect leads to changes in the time structure of reflection serving as a form of correlation between the immediately percepted things and the past experience of the patients.


Endemic infection in surgical wards.
Endemic infection in male surgical wards has been studied during three periods. There was some infection due to gram-negative bacilli, though Staphylococcus aureus remained as the single most important pathogen even in the absence of epidemic spread. Beta haemolytic streptococci were isolated in large numbers from the lesions of four patients with deep wound infection. Changes introduced in the pattern of post-operative care reduced sepsis due to Staph. aureus, reduced the severity of wound infection and apparently decreased the need for antibiotic therapy. Patients who became infected were retained in hospital longer than those who escaped clinically apparent infection.