Evolution of Hematological Parameters During the First 2 Years After Laparoscopic Sleeve Gastrectomy: Results of a Retrospective Study.
Laparoscopic sleeve gastrectomy (LSG) is one of the most effective bariatric surgery methods of treatment for obesity. It can cause nutritional deficiencies and lead to anemia at the same time. The aim of the present study is to retrospectively investigate whether the supplement treatment administration to cases that underwent LSG is sufficient in terms of the hematological parameters. A total of 494 obese patients between 18 and 65 years who underwent LSG were recruited to the study. Vitamin B12, iron, and folic acid replacement therapy are prescribed to all patients who can be followed-up at regular intervals. We compared hemogram, iron studies, vitamin B12, and folic acid values of these patients at preoperative and at first visit (1 month), 3, 6, 12, and 24 months post-surgery. The number of patients with anemia and vitamin B12 and folic acid deficiencies decreased significantly during the follow-up with supplementation. Postoperative leucocyte and thrombocyte levels were significantly lower than the preoperative levels. Our study indicates that the proper supplementation therapy in patients attending regular follow-up helps to keep hematological parameters within the normal range and to improve anemia and deficiencies of vitamin B12 and folic acid. Compliance with follow-up programs is essential after costly and invasive treatments such as sleeve gastrectomy to improve the well-being of patients in the long-term and to maximize compliance.


Extraction and comparison of gene expression patterns from 2D RNA in situ hybridization images.
Recent advancements in high-throughput imaging have created new large datasets with tens of thousands of gene expression images. Methods for capturing these spatial and/or temporal expression patterns include in situ hybridization or fluorescent reporter constructs or tags, and results are still frequently assessed by subjective qualitative comparisons. In order to deal with available large datasets, fully automated analysis methods must be developed to properly normalize and model spatial expression patterns. We have developed image segmentation and registration methods to identify and extract spatial gene expression patterns from RNA in situ hybridization experiments of Drosophila embryos. These methods allow us to normalize and extract expression information for 78,621 images from 3724 genes across six time stages. The similarity between gene expression patterns is computed using four scoring metrics: mean squared error, Haar wavelet distance, mutual information and spatial mutual information (SMI). We additionally propose a strategy to calculate the significance of the similarity between two expression images, by generating surrogate datasets with similar spatial expression patterns using a Monte Carlo swap sampler. On data from an early development time stage, we show that SMI provides the most biologically relevant metric of comparison, and that our significance testing generalizes metrics to achieve similar performance. We exemplify the application of spatial metrics on the well-known Drosophila segmentation network. A Java webstart application to register and compare patterns, as well as all source code, are available from: http://tools.genome.duke.edu/generegulation/image_analysis/insitu firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Facile fabrication of a magnetically smart PTX-loaded Cys-Fe3O4/CuS@BSA nano-drug for imaging-guided chemo-photothermal therapy.
In this study, a multifunctional nano-drug (PTX-loaded Cys-Fe3O4/CuS@BSA nanocomposite), which performs well in hydrophobic drug delivery, magnetic resonance imaging (MRI) and chemo-photothermal combination therapy, has been successfully synthesized via a facile method with several biocompatible agents. The characterization verified that our as-obtained nanocarrier has a preferable average diameter of about 300 nm for cancer therapy, shows a great MRI ability and magnetism performance, and exhibits a favorable in vitro and in vivo photothermal therapeutic efficacy by introducing CuS, and the sustained release of chemotherapeutics could be controlled by pH value and near-infrared laser irradiation has further enhanced the therapeutic performance. Overall, the excellent synergistic effect to inhibit tumor growth effectively realized via imaging-guided combinational chemo-photothermal therapy in the present work, highlights the promise of conquering the limitations of tumor treatments.


Can resveratrol help to maintain metabolic health?
The number of people suffering from metabolic diseases is dramatically increasing worldwide. This stresses the need for new therapeutic strategies to combat this growing epidemic of metabolic diseases. A reduced mitochondrial function is one of the characteristics of metabolic diseases and therefore a target for intervention. Here we review the evidence that mitochondrial function may act as a target to treat and prevent type 2 diabetes mellitus, and, if so, whether these effects are due to reduction in skeletal muscle fat accumulation. We describe how exercise may affect these parameters and can be beneficial for type 2 diabetes. We next focus on alternative ways to improve mitochondrial function in a non-exercise manner. Thus, in 2003, resveratrol (3,5,4'-trihydroxystilbene) was discovered to be a small molecule activator of sirtuin 1, an important molecular target regulating cellular energy metabolism and mitochondrial homoeostasis. Rodent studies have clearly demonstrated the potential of resveratrol to improve various metabolic health parameters. Here we review data in human subjects that is available on the effects of resveratrol on metabolism and mitochondrial function and discuss how resveratrol may serve as a new therapeutic strategy to preserve metabolic health. We also discuss whether the effects of resveratrol are similar to the effects of exercise training and therefore if resveratrol can be considered as an exercise mimetic.


Sputum PCR-single-strand conformational polymorphism test for same-day detection of pyrazinamide resistance in tuberculosis patients.
Pyrazinamide is a first-line drug for treating tuberculosis, but pyrazinamide resistance testing is usually too slow to guide initial therapy, so some patients receive inappropriate therapy. We therefore aimed to optimize and evaluate a rapid molecular test for tuberculosis drug resistance to pyrazinamide. Tuberculosis PCR-single-strand conformational polymorphism (PCR-SSCP) was optimized to test for mutations causing pyrazinamide resistance directly from sputum samples and Mycobacterium tuberculosis isolates. The reliability of PCR-SSCP tests for sputum samples (n = 65) and Mycobacterium tuberculosis isolates (n = 185) from 147 patients was compared with four tests for pyrazinamide resistance: Bactec-460 automated culture, the Wayne biochemical test, DNA sequencing for pncA mutations, and traditional microbiological broth culture. PCR-SSCP provided interpretable results for 96% (46/48) of microscopy-positive sputum samples, 76% (13/17) of microscopy-negative sputum samples, and 100% of Mycobacterium tuberculosis isolates. There was 100% agreement between PCR-SSCP results from sputum samples and Mycobacterium tuberculosis isolates and 100% concordance between 50 blinded PCR-SSCP rereadings by three observers. PCR-SSCP agreement with the four other tests for pyrazinamide resistance varied from 89 to 97%. This was similar to how frequently the four other tests for pyrazinamide resistance agreed with each other: 90 to 94% for Bactec-460, 90 to 95% for Wayne, 92 to 95% for sequencing, and 91 to 95% for broth culture. PCR-SSCP took less than 24 hours and cost approximately $3 to $6, in contrast with the other assays, which took 3 to 14 weeks and cost $7 to $47. In conclusion, PCR-SSCP is a relatively reliable, rapid, and inexpensive test for pyrazinamide resistance that indicates which patients should receive pyrazinamide from the start of therapy, potentially preventing months of inappropriate treatment.


[Sensitized photomodification of DNA with binary systems of oligonucleotide conjugates. III. Double-quantum sensitization].
Site-specific modification of single-stranded DNA by oligonucleotide derivatives of p-azido-O-(4-aminobutyl)tetrafluorobenzaldoxime sensitized by an oligonucleotide derivative of pyrenylethylamine was studied. Upon irradiation with the long-wave UV light (365-390 nm) of a DNA target-oligonucleotide reagent complementary complex, a considerable increase in the rate of sensitized photomodification at the G11 residue of the target relative to the direct photomodification was observed owing to the singlet-single energy transfer from the sensitizer onto the photoreagent. Upon simultaneous irradiation of the complex with UV and visible light in the region of the triplet-triplet absorption of pyrene (360-580 nm), an additional increase in the modification rate and a change in its site-direction (from the G11 to T13 residue) occurred through the two-photon triplet-triplet sensitization. The total extent of the structure photomodification amounted to 80%.


Molecular epidemiology and the genetics of environmental cancer.
Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments.


First-trimester aneuploidy risk assessment: the impact of comprehensive counseling and same-day results on patient satisfaction, anxiety, and knowledge.
We evaluated the added benefit of a comprehensive counseling protocol for first-trimester aneuploidy risk assessment. We performed a prospective cohort study surveying patients referred for first-trimester aneuploidy risk assessment. We compared responses between women who underwent serum testing done in advance of their ultrasound such that their final risk assessment was given to them the same day as their ultrasound (comprehensive) versus women who underwent serum testing the same day as their ultrasound and who therefore received their final risk assessment later (standard). Response rate was 94.8%. The comprehensive group was significantly more likely to receive counseling in accordance with recommended American College of Obstetricians and Gynecologists (ACOG) guidelines, had significantly greater reduction in anxiety and increased satisfaction, and was more likely to report an increased understanding of their results. The comprehensive group scored significantly higher on test-style questions about aneuploidy risk assessment. Comprehensive aneuploidy risk assessment counseling including same-day results is associated with increased patient understanding and satisfaction, decreased anxiety, and increased adherence to ACOG guidelines.


[Immunotherapy advances for lung cancer combined with chronic obstructive pulmonary disease].
Lung cancer is a major public health problem worldwide, with high rates of morbidity and mortality. It often coexists with chronic obstructive pulmonary disease (COPD), the diagnosis and management of which often receives insufficient attention. In particular, the presence of COPD has significant implications for the clinical management of lung cancer patients. This review systematically assesses the influence of COPD on the efficacy of immunotherapy and the occurrence of immune-related adverse events in patients with lung cancer, identifies existing challenges and proposes avenues for future research in this field.


The Bewildering Antitubercular Action of Pyrazinamide.
Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. Defining the mode of action for PZA will open new avenues for rational design of novel therapeutic approaches for the treatment of TB. In this review, we discuss the four prevailing models for PZA action, recent developments in modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.


Plant food allergy in patients with pollinosis from the Mediterranean area.
Patients with pollinosis develop symptoms after intake of plant food more often than the general population. In order to study the prevalence of the presentation of allergic symptoms to plant foods in pollinosis, we selected a representative sample of the population from our Mediterranean area. All patients completed a questionnaire, provided a blood sample and underwent a battery of skin and other complementary tests (prick-prick, oral challenge test) when necessary. The pollen counts were obtained from the Elche pollen station. In addition, sera from a subgroup of patients were checked with an allergen molecule panel on an Advia Centaur XP platform. Of the final sample (n = 233), 39.9% of the patients with pollinosis were sensitized and 30.9% had clinical allergy to at least one of the plant foods studied. Regression analysis showed that age and sensitization to the extracts of Platanus acerifolia and Artemisia vulgaris were the most important variables for discriminating between groups. Patients with pollinosis at a risk of allergy to plant foods had significantly higher Pru p 3 values [odds ratio (OR) 3.3; 95% confidence interval (95% CI) 2.3-4.8], and the value increased according to the number of plant food sensitizations. Plant food allergy is more common in patients with pollinosis than in the general population. The use of the London plain tree (P. acerifolia) and mugwort (A. vulgaris) in the skin tests may help identify such patients in our Mediterranean area, but determination of rPru p 3 could also be very useful in patients suspected of having plant food allergy.


Neural activity during the viewing of emotional pictures in veterans with pathological anger and aggression.
Anger and aggression are common mental health problems after military deployment. Anger and aggression have been associated with abnormalities in subcortical and cortical levels of the brain and their connectivity. Here, we tested brain activation during the processing of emotional stimuli in military veterans with and without anger and aggression problems. Thirty military veterans with anger and aggression problems and 29 veterans without a psychiatric diagnosis (all males) participated in this study. During an fMRI scan 32 negative, 32 positive and 32 neutral pictures from the International Affective Picture System were presented in intermixed order. The Aggression group showed heightened activity in brain areas including the supplementary motor area, the cingulum and the parietal cortex, in response to stimuli, regardless of category. Furthermore, the Aggression group showed stronger connectivity between the dorsal anterior cingulate cortex (dACC) and the amygdala during the viewing of negative stimuli, and weaker connectivity between dACC and medial prefrontal cortex during the viewing of positive stimuli. Veterans with anger and aggression problems showed enhanced brain response to all stimuli during the task, irrespective of valence and they rated the pictures more likely as negative. We take this to indicate enhanced preparation for action and attention to the presentation of stimuli that could prove to be threatening. Further, group differences in functional connectivity involving the dACC reveal abnormal processing of stimuli with negative and positive valence. In sum, the results point towards a bias towards an enhanced sensitivity to perceived or potential threat in aggression.


Efficient generation of dopamine neurons from human embryonic stem cells.
In this chapter, we introduce a co-culture protocol for human embryonic stem (hES) cell differentiation in which dopamine (DA) neurons with midbrain-specific markers are efficiently derived. Human ES cells on a feeder layer of stromal cells are induced to differentiate into neuroepithelial or neural precursor cells with embryonic midbrain precursor properties. The resulting neural precursor cells are then selectively expanded and serially passaged to obtain a large, homogeneous population of these cells. Under the conditions for terminal differentiation, the majority of hES-derived neural precursors differentiate into neuronal cells that are positive for DA neuronal markers such as tyrosine hydroxylase (TH) and function in vitro as presynaptic DA neurons.


Hands on Methods for High Resolution Cryo-Electron Microscopy Structures of Heterogeneous Macromolecular Complexes.
Electron microscopy of frozen hydrated samples (cryo-EM) is a powerful structural technique that allows the direct study of functional macromolecular complexes in an almost physiological environment. Protein macromolecular complexes are dynamic structures that usually hold together by an intricate network of protein-protein interactions that can be weak and transient. Moreover, a standard feature of many of these complexes is that they behave as nanomachines able to undergo functionally relevant conformational changes in one or several complex components. Among all the other main structural biology techniques, only cryo-EM has the potential of successfully dealing at the same time with both sample heterogeneity and inherent flexibility. The cryo-EM field is currently undergoing a revolution thanks to groundbreaking technical developments that have brought within our reach the possibility of solving the structure of biological complexes at atomic resolution. These technical developments have been mostly focused on new direct electron detector technology and improved sample preparation methods leading to better image quality. This fact has in turn required the development of new and better image processing algorithms to make the most of the higher quality data. The aim of this review is to provide a brief overview of some reported examples of single particle analysis strategies designed to find different conformational and compositional states within target macromolecular complex and specifically to deal with it to reach higher resolution information. Different image processing methodologies specifically aimed to symmetric or pseudo-symmetric protein complexes will also be discussed.


The Relevance of Simpson Grade Resections in Modern Neurosurgical Treatment of World Health Organization Grade I, II, and III Meningiomas.
The Simpson grading system has played an important role in surgical resections of meningiomas. The aim of this study was to determine if this grading system predicts meningioma recurrence in a modern cohort of patients with tumors of all World Health Organization grades. Adult patients who underwent primary, nonbiopsy resection of a meningioma at a tertiary care institution between 2007 and 2015 were retrospectively reviewed. Stepwise multivariate proportional hazard analyses were used to identify associations with recurrence after resection. Log-rank analyses were used to compare Kaplan-Meier plots for time to recurrence between each Simpson grade. Of 572 patients who met inclusion criteria, 72 (12.6%) presented with recurrence. Factors associated with recurrence after gross total resection (Simpson grades I-III) were non-World Health Organization grade I (hazard ratio [HR] [95% confidence interval (CI)] 6.215 [2.864-12.419], P < 0.0001) and preoperative neurologic deficits (HR [95% CI] 2.862 [1.512-5.499], P = 0.001). Factors associated with recurrence after subtotal resections (Simpson IV) were African American race (HR [95% CI] 2.776 [1.232-5.890], P = 0.02) and parafalcine location (HR [95% CI] 3.956 [1.624-8.775], P = 0.004). Simpson grade was not an independent risk factor for recurrence. Identification and consideration of factors associated with recurrence after gross total or subtotal resections may help guide treatment strategies for patients with meningiomas.


Economic evaluation for first-line anti-hypertensive medicines: applications for the Philippines.
Medicines to control hypertension, a leading cause of morbidity and mortality, are a major component of health expenditures in the Philippines. This study aims to review economic studies for first line anti-hypertensive medical treatment without co-morbidities; and discuss practical, informational and policy implications on the use of economic evaluation in the Philippines. A systematic literature review was performed using the following databases: MEDLINE, EMBASE, BIOSIS, PubMed, The Cochrane Library, Health Economics Evaluations Database (HEED) and the Centre for Reviews and Dissemination - NHS NICE. Six existing economic analytical frameworks were reviewed and one framework for critical appraisal was developed. Out of 1336 searched articles, 12 fulfilled the inclusion criteria. The studies were summarized according to their background characteristics (year, journal, intervention and comparators, objective/study question, target audience, economic study type, study population, setting and country and source of funding/conflict of interest) and technical characteristics (perspective, time horizon, methodology/modeling, search strategy for parameters, costs, effectiveness measures, discounting, assumptions and biases, results, cost-effectiveness ratio, endpoints, sensitivity analysis, generalizability, strengths and limitations, conclusions, implications and feasibility and recommendations). The studies represented different countries, perspectives and stakeholders. Diuretics were the most cost-effective drug class for first-line treatment of hypertension without co-morbidities. Although the Philippine Health Insurance Corporation may apply the recommendations given in previous studies (i.e. to subsidize diuretics, ACE inhibitors and calcium channel blockers), it is uncertain how much public funding is justified. There is an information gap on clinical data (transition probabilities, relative risks and risk reduction) and utility values on hypertension and related diseases from middle- and low- income countries. Considering the national relevance of the disease, a study on the costs of hypertension in the Philippines including in-patient, out-patient, out-of-pocket, local government and national government expenditure must be made. Economic evaluation may be incorporated in health technology assessment, planning, proposal development, research, prioritization and evaluation of health programmes. The approaches will vary depending on the policy questions. The information gap calls for building strong economic evaluative capacity in growing economies.


The Crohn's disease: associated ATG16L1 variant and Salmonella invasion.
A common genetic coding variant in the core autophagy gene ATG16L1 is associated with increased susceptibility to Crohn's disease (CD). The variant encodes an amino acid change in ATG16L1 such that the threonine at position 300 is substituted with an alanine (ATG16L1 T300A). How this variant contributes to increased risk of CD is not known, but studies with transfected cell lines and gene-targeted mice have demonstrated that ATG16L1 is required for autophagy, control of interleukin-1-β and autophagic clearance of intracellular microbes. In addition, studies with human cells expressing ATG16L1 T300A indicate that this variant reduces the autophagic clearance of intracellular microbes. We demonstrate, using somatically gene-targeted human cells that the ATG16L1 T300A variant confers protection from cellular invasion by Salmonella. In addition, we show that ATG16L1-deficient cells are resistant to bacterial invasion. These results suggest that cellular expression of ATG16L1 facilitates bacterial invasion and that the CD-associated ATG16L1 T300A variant may confer protection from bacterial infection.


Pharmacologic purging of malignant T cells from human bone marrow using 9-beta-D-arabinofuranosylguanine.
Arabinosylguanine (araG) is a nucleoside analog that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate, resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymphoblastoid cell lines as well as to freshly isolated leukemia cells from patients with T cell acute lymphoblastic leukemia. In this report, we demonstrate that araG is an effective agent to use for chemoseparation of malignant T lymphoblasts from human bone marrow. When freshly isolated human T leukemia cells or T lymphoblastoid cells were treated with 100 microM araG for 18 hr, up to 6 logs of clonogenic T cells could be eliminated without appreciable toxicity to the normal myeloid, erythroid, and megakaryocytoid clonal progenitor cells. We discuss the use of this agent in ex vivo elimination of residual malignant T cells from marrow of patients requiring myeloablative chemotherapy with autologous bone marrow rescue.


ENCODE tiling array analysis identifies differentially expressed annotated and novel 5' capped RNAs in hepatitis C infected liver.
Microarray studies of chronic hepatitis C infection have provided valuable information regarding the host response to viral infection. However, recent studies of the human transcriptome indicate pervasive transcription in previously unannotated regions of the genome and that many RNA transcripts have short or lack 3' poly(A) ends. We hypothesized that using ENCODE tiling arrays (1% of the genome) in combination with affinity purifying Pol II RNAs by their unique 5' m⁷GpppN cap would identify previously undescribed annotated and unannotated genes that are differentially expressed in liver during hepatitis C virus (HCV) infection. Both 5'-capped and poly(A)+ populations of RNA were analyzed using ENCODE tiling arrays. Sixty-four annotated genes were significantly increased in HCV cirrhotic as compared to control liver; twenty-seven (42%) of these genes were identified only by analyzing 5' capped RNA. Thirty-one annotated genes were significantly decreased; sixteen (50%) of these were identified only by analyzing 5' capped RNA. Bioinformatic analysis showed that capped RNA produced more consistent results, provided a more extensive expression profile of intronic regions and identified upregulated Pol II transcriptionally active regions in unannotated areas of the genome in HCV cirrhotic liver. Two of these regions were verified by PCR and RACE analysis. qPCR analysis of liver biopsy specimens demonstrated that these unannotated transcripts, as well as IRF1, TRIM22 and MET, were also upregulated in hepatitis C with mild inflammation and no fibrosis. The analysis of 5' capped RNA in combination with ENCODE tiling arrays provides additional gene expression information and identifies novel upregulated Pol II transcripts not previously described in HCV infected liver. This approach, particularly when combined with new RNA sequencing technologies, should also be useful in further defining Pol II transcripts differentially regulated in specific disease states and in studying RNAs regulated by changes in pre-mRNA splicing or 3' polyadenylation status.


Bulgarian Jews in Israel: genetic blood markers. Red-cell antigens, serum proteins and red-cell isozymes.
Two hundred and sixteen unrelated Bulgarian Jews were typed for the following genetic systems: ABO, MNS, Rh, Kell and Duffy of the blood groups; ADA, AK1, ACP1, ESD, GLO, PGD, PGM1 and PGM2 of the red-cell enzymes, and for the serum proteins HP, GC and PI. A comparison of observed gene frequencies with those of two other Sephardi Jewish groups, from Libya and Morocco, disclosed significant heterogeneity in several systems. This was mostly due to Moroccan Jews differing from Bulgarian or from both the Libyan and Bulgarian Jews. A comparison of gene frequencies in Bulgarian Jews with those in Oriental Jews from Iraq and in Ashkenazi Jews from Poland disclosed a similarity between the three groups in Rh, ADA, GLO, PGM1 and HP. The frequencies for the above systems in the three groups were closer to those of Middle Easterners than to those of Europeans. A different pattern was observed for GC and PI, in which Bulgarian resembled Polish Jews and differed significantly from Iraqi Jews. This probably reflects an outcome of convergent adaptive processes.


Binary mixtures of locally coupled mobile oscillators.
Synchronized behavior in a system of coupled dynamic objects is a fascinating example of an emerged cooperative phenomena which has been observed in systems as diverse as a group of insects, neural networks, or networks of computers. In many instances, however, the synchronization is undesired because it may lead to system malfunctioning, as in the case of Alzheimer's and Parkinson's diseases, for example. Recent studies of static networks of oscillators have shown that the presence of a small fraction of so-called contrarian oscillators can suppress the undesired network synchronization. On the other hand, it is also known that the mobility of the oscillators can significantly impact their synchronization dynamics. Here, we combine these two ideas-the oscillator mobility and the presence of heterogeneous interactions-and study numerically binary mixtures of phase oscillators performing two-dimensional random walks. Within the framework of a generalized Kuramoto model, we introduce two phase-coupling schemes. The first one is invariant when the types of any two oscillators are swapped, while the second model is not. We demonstrate that the symmetric model does not allow for a complete suppression of the synchronized state. However, it provides means for a robust control of the synchronization timescale by varying the overall number density and the composition of the mixture and the strength of the off-diagonal Kuramoto coupling constant. Instead, the asymmetric model predicts that the coherent state can be eliminated within a subpopulation of normal oscillators and evoked within a subpopulation of the contrarians.


The clinical association between Periodontitis and COVID-19.
The study aimed to clinically assess the association between periodontitis and COVID-19-related outcomes. Data pertaining to patient demographics, medical history, blood parameters, periodontal clinical examination and aMMP-8 point-of-care diagnostics (both site-level and patient-level) was recorded for eighty-two COVID-19-positive patients. COVID-19-related outcomes such as COVID-19 pneumonia, death/survival, types of hospital admission and need of assisted ventilation were also assessed. Males were predominantly afflicted with COVID-19, with advanced age exhibiting a greater association with the presence of periodontitis. Higher severity of periodontitis led to 7.45 odds of requiring assisted ventilation, 36.52 odds of hospital admission, 14.58 odds of being deceased and 4.42 odds of COVID-19-related pneumonia. The aMMP-8 mouthrinse kit was slightly more sensitive but less specific than aMMP-8 site-specific tests. Based on the findings of the present study, periodontitis seems to be related to poorer COVID-19-related outcomes. However, within the constraints of this work, a direct causality may not be established. Periodontitis, by means of skewing the systemic condition for a number of comorbidities, may eventually influence COVID-19 outcomes in an indirect manner. The study is the first to clinically, and by means of a validated point-of-care diagnostic methodology, assess the association between periodontal health and COVID-19-related outcomes. Assessment of the periodontal status of individuals can aid in the identification of risk groups during the pandemic along with reinforcing the need to maintain oral hygiene and seeking periodontal care.


S-Nitrosylation: An Emerging Paradigm of Redox Signaling.
Nitric oxide (NO) is a highly reactive molecule, generated through metabolism of L-arginine by NO synthase (NOS). Abnormal NO levels in mammalian cells are associated with multiple human diseases, including cancer. Recent studies have uncovered that the NO signaling is compartmentalized, owing to the localization of NOS and the nature of biochemical reactions of NO, including S-nitrosylation. S-nitrosylation is a selective covalent post-translational modification adding a nitrosyl group to the reactive thiol group of a cysteine to form S-nitrosothiol (SNO), which is a key mechanism in transferring NO-mediated signals. While S-nitrosylation occurs only at select cysteine thiols, such a spatial constraint is partially resolved by transnitrosylation, where the nitrosyl moiety is transferred between two interacting proteins to successively transfer the NO signal to a distant location. As NOS is present in various subcellular locales, a stress could trigger concerted S-nitrosylation and transnitrosylation of a large number of proteins involved in divergent signaling cascades. S-nitrosylation is an emerging paradigm of redox signaling by which cells confer protection against oxidative stress.


A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in Schizophrenia.
Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with atypical antipsychotic drugs. The cannabinoid receptor 1 (CNR1) is expressed centrally in the hypothalamic region and associated with appetite and satiety, as well as peripherally. An antagonist of CNR1 (rimonabant) has been effective in causing weight loss in obese patients indicating that CNR1 might be important in antipsychotic-induced weight gain. Twenty tag SNPs were analyzed in 183 patients who underwent treatment (with either clozapine, olanzapine, haloperidol, or risperidone) for chronic schizophrenia were evaluated for antipsychotic-induced weight gain for up to 14 weeks. The polymorphism rs806378 was nominally associated with weight gain in patients of European ancestry treated with clozapine or olanzapine. 'T' allele carriers (CT+TT) gained more weight (5.96%), than the CC carriers (2.76%, p=0.008, FDR q-value=0.12). This translated into approximately 2.2 kg more weight gain in patients carrying the T allele than the patients homozygous for the CC genotype (CC vs CT+TT, 2.21+/-4.51 vs 4.33+/-3.89 kg; p=0.022). This was reflected in the allelic analysis (C vs T allele, 3.84 vs 5.83%, p=0.035). We conducted electrophoretic mobility shift assays which showed that the presence of the T allele created a binding site for arylhydrocarbon receptor translocator (ARNT), a member of the basic helix-loop-helix/Per-Arnt-Sim protein family. In this study, we provide evidence that the CNR1 gene may be associated with antipsychotic-induced weight gain in chronic schizophrenia patients. However, these observations were made in a relatively small patient population; therefore these results need to be replicated in larger sample sets.


Myocardial impairment in chronic hypoxia is abolished by short aeration episodes: involvement of K+ATP channels.
In vivo exposure to chronic hypoxia is considered to be a cause of myocardial dysfunction, thereby representing a deleterious condition, but repeated aeration episodes may exert some cardioprotection. We investigated the possible role of ATP-sensitive potassium channels in these mechanisms. First, rats (n = 8/group) were exposed for 14 days to either chronic hypoxia (CH; 10% O(2)) or chronic hypoxia with one episode/day of 1-hr normoxic aeration (CH+A), with normoxia (N) as the control. Second, isolated hearts were Langendorff perfused under hypoxia (10% O(2), 30 min) and reoxygenated (94% O(2), 30 min) with or without 3 microM glibenclamide (nonselective K(+)(ATP) channel-blocker) or 100 microM diazoxide (selective mitochondrial K(+)(ATP) channel-opener). Blood gasses, hemoglobin concentration, and plasma malondialdehyde were similar in CH and CH+A and in both different from normoxic (P < 0.01), body weight gain and plasma nitrate/nitrite were higher in CH+A than CH (P < 0.01), whereas apoptosis (number of TUNEL-positive nuclei) was less in CH+A than CH (P < 0.05). During in vitro hypoxia, the efficiency (ratio of ATP production/pressure x rate product) was the same in all groups and diazoxide had no measurable effects on myocardial performance, whereas glibenclamide increased end-diastolic pressure more in N and CH than in CH+A hearts (P < 0.05). During reoxgenation, efficiency was markedly less in CH with respect to N and CH+A (P < 0.0001), and ratex pressure product remained lower in CH than N and CH+A hearts (P < 0.001), but glibenclamide or diazoxide abolished this difference. Glibenclamide, but not diazoxide, decreased vascular resistance in N and CH (P < 0.005 and < 0.001) without changes in CH+A. We hypothesize that cardioprotection in chronically hypoxic hearts derive from cell depolarization by sarcolemmal K(+)(ATP) blockade or from preservation of oxidative phosphorylation efficiency (ATP turnover/myocardial performance) by mitochondrial K(+)(ATP) opening. Therefore K(+)(ATP) channels are involved in the deleterious effects of chronic hypoxia and in the cardioprotection elicited when chronic hypoxia is interrupted with short normoxic aeration episodes.


Sixty-five-year old final clarifier performance rivals that of modern designs.
The Stickney plant of the Metropolitan Wastewater Reclamation District of Greater Chicago (MWRDGC), one of the largest wastewater treatment plants in the world, treats an average dry weather flow of 22 m3/s and a sustained wet weather flow of 52 m3/s that can peak to 63 m3/s. Most of the inner city of Chicago has combined sewers, and in order to reduce pollution through combined sewer overflows (CSO), the 175 km Tunnel and Reservoir Plan (TARP) tunnels, up to 9.1 m in diameter, were constructed to receive and convey CSO to a reservoir from where it will be pumped to the Stickney treatment plant. Pumping back storm flows will result in sustained wet weather flows over periods of weeks. Much of the success of the plant will depend on the ability of 96 circular final clarifiers to produce an effluent of acceptable quality. The nitrifying activated sludge plant is arranged in a plug-flow configuration, and some denitrification takes place as a result of the high oxygen demand in the first pass of the four-pass aeration basins that have a length to width ratio of 18:1. The SVI of the mixed liquor varies between 60 and 80 ml/g. The final clarifiers, which were designed by the District's design office in 1938, have functioned for more than 65 years without major changes and are still producing very high-quality effluent. This paper will discuss the design and operation of these final clarifiers and compare the design with more modern design practices.


[A data base of a thoracic and cardiovascular department: information on 1001 patients].
The Authors illustrate the results derived from a data base of a thoracic and cardiovascular Department, comprehensive of 1001 patients (464 M and 537 F, average age 71, minimum age 18 and maximum age 101). The conducted analysis results in several considerations: the cause of patient's hospitalization was not relevant to the direct expertise of the Department in the 27,5% of the cases and the profile of the typical-patient is of an elderly person (73% of the cases over 65 years old), basically overweight or obese (35% of the cases with BMI > 25) and with medium-low cultural level (70% of the cases not over middle school); moreover our patients, although under poly-therapy before hospitalization, were discharged with a number of prescribed medicines even more plentiful. The data base of the Department proved to be a useful tool both to instantaneously monitor the departmental activity and also to rationalize the pharmacological therapies.


Human papillomavirus 16 E7 protein is associated with the nuclear matrix.
The cellular localization of the human papillomavirus (HPV)-16 E7 gene product in the cell lines CaSki and SiHa has been determined by both biochemical and immunocytochemical methods. These measurements show E7 to be localized in the cell nucleus, specifically with the nonchromatin nuclear structure or nuclear matrix. This localization of E7 required an unambiguous fractionation of the nuclear constituents. This was achieved by using a gentle sequential fractionation procedure to prepare the scaffold consisting of the nuclear matrix and intermediate filaments (NM-IF). Chromatin was cleaved with nuclease and the resulting nucleosomes eluted with 0.25 M ammonium sulfate. Immunostaining of cells after this extraction procedure with monoclonal antibodies (mAbs) to E7 revealed a fine grained, punctate nuclear fluorescence in CaSki and SiHa, which was absent in normal cervical keratinocytes and the HPV-negative cell line C33.1. Western blots of cell fractions with these mAbs showed that E7 was localized in the NM-IF fraction in SiHa and CaSki but was not detected in HPV-negative cells. A second protein of slightly higher mobility is identified by these antisera in HPV-16-containing cells. The data suggest that the previous inability to directly visualize E7 by immunocytology is due to the masking of epitopes by cellular components and not to low levels of protein.


Accessibility of myofilament cysteines and effects on ATPase depend on the activation state during exposure to oxidants.
Signaling by reactive oxygen species has emerged as a major physiological process. Due to its high metabolic rate, striated muscle is especially subject to oxidative stress, and there are multiple examples in cardiac and skeletal muscle where oxidative stress modulates contractile function. Here we assessed the potential of cysteine oxidation as a mechanism for modulating contractile function in skeletal and cardiac muscle. Analyzing the cysteine content of the myofilament proteins in striated muscle, we found that cysteine residues are relatively rare, but are very similar between different muscle types and different vertebrate species. To refine this list of cysteines to those that may modulate function, we estimated the accessibility of oxidants to cysteine residues using protein crystal structures, and then sharpened these estimates using fluorescent labeling of cysteines in cardiac and skeletal myofibrils. We demonstrate that cysteine accessibility to oxidants and ATPase rates depend on the contractile state in which preparations are exposed. Oxidant exposure of skeletal and cardiac myofibrils in relaxing solution exposes myosin cysteines not accessible in rigor solution, and these modifications correspond to a decrease in maximum ATPase. Oxidant exposure under rigor conditions produces modifications that increase basal ATPase and calcium sensitivity in ventricular myofibrils, but these effects were muted in fast twitch muscle. These experiments reveal how structural and sequence variations can lead to divergent effects from oxidants in different muscle types.


Radical mediators and mitogen-activated protein kinase signaling in oxygen-dependent radiosensitivity of human tumor cell lines.
Oxygen enhancement of tumor radiosensitivity is attributed to DNA damage by reactive oxygen species. The mechanism remains unclear but may involve mitochondria as major sources of oxygen and nitrogen radicals as well as central effectors of energy homeostasis and apoptosis. Here we used dihydrorhodamine and 2',7'-dichlorodihydrofluorescein to compare mitochondrial and total cell generation, respectively, of reactive oxygen or nitrogen species in cells irradiated at 5 Gy. Irradiation in the presence of oxygen selectively stimulated mitochondrial radical production in HeLa and MeWo cells, but in MCF7 cells radical production was more generalized. In all three cell lines oxygen impaired cell proliferation as measured by resazurin reduction 7 days after irradiation. Antioxidants N-acetylcysteine, ascorbic acid, and melatonin largely prevented dye oxidation during normoxic irradiation yet had no effect on oxygen-dependent irradiation injury. However, NO synthase inhibitor N(G)-monomethyl-L-arginine protected HeLa and MCF7 though not MeWo cells, consistent with their different levels of constitutive NO generation. SB203580 inhibition of p38 MAPK appreciably protected HeLa and marginally protected MCF7 cells against oxygen-dependent irradiation injury, while the less specific JNK/SAPK inhibitor SP600125 and ERK inhibitor U0126 had no effect. None of the inhibitors affected MeWo radiosensitivity. Therefore oxygen-enhanced radiosensitivity in these tumor cell lines does not depend on extensive production of oxygen radicals and is cell-type dependent. NO mediates oxygen-dependent injury in HeLa and MCF7 cells, by p38-dependent and MAPK-independent mechanisms, respectively. In MeWo cells this oxygen-enhanced radiosensitivity is independent of both NO and MAPK signaling.


Ectopic "high" origin of both coronary arteries from the left aortic wall: anatomic and postmortem angiographic findings.
Anatomic and postmortem angiographic findings of a previously unreported case of ectopic origins and unusual courses of the right coronary (RC) artery and the left coronary (LC) artery were demonstrated. This specimen was unique among 450 angiographies and 60 corrosion castings of the human hearts examined in this study. The ostium of the RC artery was pocket-like, located in the left aortic wall at roughly 180 degrees to the long axis of the ascending aorta and 19 mm above the rim of the sinotubular junction (SJ). Initially, the RC runs to the right and downward, passing high in the cleft between the aorta and the pulmonary trunk, thereby avoiding a possible compression from them. The ostium of the LC faced upward and originated from the left aortic wall 7 mm above the SJ. The LC ran to the left and downwards for 16 mm until its division. Histologically, the first 11 mm of the RC were elastic. This observation, together with its high course between the great vessels, combined to make this case benign. The best x-ray projections to show the characteristic findings of the present case were anteroposterior and lateral, which were of practical importance for the correct determination and interpretation of this case. The cardiac surgeon should be aware that high cannulation will be required to locate the RC to avoid accidentally cross-clamping or transecting the vessel during surgery where this anomaly may be encountered.


Colour Preference to Emotions in Relation to the Anxiety Level among School Children in Puducherry - A Cross-Sectional Study.
Dental setting plays an important role in child's behavior and cooperation to the planned dental treatment. Adding attractive colours to the dental environment and by incorporating colourful equipments can make the child feel good and be at ease. This study tries to convey the relationship between colours and dental anxiety among children. To evaluate the colour preference to emotions in relation to children's age, gender and anxiety level. A total of 382 children aged 6-12 years were randomly selected from schools in and around Puducherry. Modified dental anxiety scale was recorded by a calibrated examiner. Each question was scored from one (not anxious) to five (extremely anxious); such that the total score ranges from 5 to 25, wherein a score of 15 or more was considered to be anxious. Based on this, children were divided into anxious and non-anxious groups. All the children were provided with eight different coloured crayon pencils and were asked to shade two cartoon emoticons indicating happiness and sadness with their preferred colour. Values were tabulated and statistically analyzed to evaluate the association between the variables using Z test, Chi-square, Chi-square goodness of fit and odds ratio. (p≤0.05 was considered statistically significant). Among 382 children, 77% (294) were graded as anxious and 23% (88) as non- anxious. For positive emotion (happiness), 31.2% (119) children preferred blue followed by pink 29.3% (112). For negative emotion (sadness), 52.1% (199) of children preferred black and 46.9% (179) preferred red. Association between colour and emotion was highly significant (p= 0.005). From the colours preferred by the children in our study, it can be concluded that colours like blue and pink in the dental set-up could enhance a positive attitude while black and red could develop a negative outlook in their mind.


Blood gas analysis of bovine fetal capillary blood during stage II labor.
The aim of this study was to determine whether blood gas variables in fetal capillary blood during the last 30 min of stage II labor can be used to diagnose fetal asphyxia. Twenty-five newborn calves were used to investigate the correlation between capillary blood gas values obtained from the dorsolateral aspect of the distal pastern and those in arterial and venous blood. The pH, partial pressure of oxygen, partial pressure of carbon dioxide, concentration of bicarbonate, base excess and oxygen saturation were determined. The bicarbonate concentration (arterial, r=0.759; venous, r=0.766; both P<0.0001) and base excess (arterial, r=0.730; venous, r=0.807; both P<0.0001) had the highest correlations. Fetal capillary blood was collected during the last 30 min of stage II labor and the results of blood gas analysis were compared with those of arterial and venous blood collected immediately after birth in 38 calves. The pH (arterial, r=0.806; venous, r=0.885; both P<0.0001) and base excess (arterial, r=0.822; venous, r=0.871; both P<0.0001) had the highest correlations. The pH and base excess were significantly lower after birth than during the last 30 min of stage II labor. The severity of fetal acidosis during stage II labor can be easily and reliably determined using the pH or base excess of fetal capillary blood.


Changes in popular attitudes and beliefs about tranquilizers. 1970-1979.
In nationwide surveys of the extent and nature of psychotherapeutic drug use conducted in 1970 and 1979, respondents were also questioned about their knowledge of tranquilizers and attitudes toward the use of these medications in general and in specific situations. In both 1970 and 1979, most Americans believed that tranquilizers were effective; by 1979, however, we found a sharp increase in the proportion of respondents who believed that these medications were overprescribed. Reservations about the effects of tranquilizers on health, mood, and behavior had also become more widespread by 1979. In both 1970 and 1979, however, respondents were generally more accepting of tranquilizer use when presented with practical situations pitting benefit against risk. A majority condoned the use of tranquilizers in situations involving pronounced impairment.


[A randomised clinical trial on the effectiveness of a re-integration training after short-term inpatient psychotherapy].
Standardised evaluation studies performed in the Netherlands in a large number of inpatient and day-treatment hospitals providing psychotherapy have shown significant symptomatic improvements in patients between the date of entry to the studies and follow-up after one year. However, the work situation of ex-patients hardly changed and a large number of patients were still receiving psychotherapy. To examine the effectiveness of a specifically designed course of re-integration training. A group of 128 patients were assigned randomly either to a re-integration training course aimed at improved functioning at work and improved relationships, or to booster sessions. Outcome measures were symptom level, work status, absence from work, and further psychotherapy. results After two years the number of patients in paid employment remained the same (76%) in the re-integration training course and increased from 67 to 87% in the booster sessions. Attendance was significantly higher in the booster sessions than in the re-integration training. There were no differences in the other outcome measures. We conclude that re-integration training was no more effective than the booster sessions. Our hypothesis is that continuity of care (therapists plus programme) explains the favourable result of the booster sessions.


Lack of genetic differentiation in aggressive and secondary bark beetles (Coleoptera: Curculionidae, Scolytinae) from Arizona.
Bark beetles (Coleoptera: Curculionidae, Scolytinae) play an important role as disturbance agents in ponderosa pine (Pinus ponderosa Douglas ex Lawson) forests of Arizona. However, from 2001 to 2003, elevated bark beetle activity caused unprecedented levels of ponderosa pine mortality. A better understanding of the population structure of these species will facilitate analysis of their dispersal patterns and improve management strategies. Here, we use fluorescently labeled amplified fragment length polymorphism (fAFLP) analysis to resolve genetic variation among and within sampling locations in northcentral Arizona of Ips pini (Say), Dendroctonus brevicomis LeConte, and D. frontalis Zimmermann. We generated genetic fingerprints for >500 beetle specimens and analyzed genetic diversity. For all species, gene flow estimates among sampling locations were high, and significant population subdivision was not discernible across a large portion of ponderosa pine forests in Arizona. However, a weak relationship was detected with I. pini population structure and elevation. Because of the lack of genetic differentiation detected throughout the large study area, our findings suggest these insects are capable of long distance dispersal and exhibit a high degree of gene flow across a broad region. We conclude that our results are consistent with strong dispersal patterns and large population sizes of all three species.


Laser-driven proton oncology--a unique new cancer therapy?
In 2000, the University of Strathclyde, collaborating with the Rutherford Appleton Laboratory, organized the first workshop dealing with the potential of high-power laser technology in medicine. Two areas of potential were identified: firstly the production of positron emission tomography (PET) isotopes; and secondly, the potential for laser-accelerated proton and heavy ion beams for therapy. The attendees, mainly clinicians and radiation physicists, emphasised that the laser community should concentrate on developing laser and target technology for therapy rather than isotope production because of the potential advantages over conventional accelerator technology for that purpose. On the 30 March 2007, the universities of Strathclyde and Paisley organized a follow-up meeting to identify the progress made in laser-driven proton and ion beam technology with applications leading to proton and ion beam therapy for deep-seated tumours. The meeting was supported by the Scottish Universities Physics Alliance (SUPA)--an organization set up in Scotland to bring together all of the physics departments collaborating with life scientists to work on ground-breaking new science which no single university could attempt. This is a summary of the meeting.


Individual adenovirus type 5 early region 1A gene products elicit distinct alterations of cellular morphology and gene expression.
Adenovirus early region 1A (E1A), which gives rise to three overlapping transcripts, was inserted into a murine leukemia virus-derived vector, and recombinant viruses were used to prepare permanent cell lines of NIH 3T3 cells containing DNA copies of the individual 13S, 12S, and 9S mRNAs. Integrated proviral copies of the recombinant genomes were rescued as bacterial plasmids from each of the cell lines, and the DNA sequence of E1A was demonstrated to be a precise copy of the individual transcripts. The DNA copies were shown to be expressed as part of the full-length retroviral transcript by S1 nuclease analysis, and the synthesis of their encoded polypeptides was demonstrated by immunoprecipitation. Those cell lines expressing the polypeptide encoded by the 13S transcript were shown to contain that function required for regulating the accumulation of mRNAs from adenovirus early genes by their ability to complement the adenovirus type 5 E1A deletion mutant dl312. Cell lines expressing polypeptides encoded by the 13S, 12S, and 9S transcripts showed characteristic alterations in morphology. Two-dimensional gel electrophoresis of total cellular protein derived from the three cell lines demonstrated that each E1A gene product elicits specific alterations in the patterns of proteins expressed. Studies of the expression of two specific genes, those encoding fibronectin and collagen type 1, indicated that the observed alteration in levels of the two proteins results from a reduction in RNA levels induced by E1A functions.


Imprinting of nanoparticles in thin films: Quo Vadis?
Nanomaterials, and especially nanoparticles, have been introduced to almost any aspect of our lives. This has caused increasing concern as to their toxicity and adverse effects on the environment and human health. The activity of nanoparticles, including their nanotoxicity, is not only a function of the material they are made of but also their size, shape, and surface properties. It is evident that there is an unmet need for simple approaches to the speciation of nanoparticles, namely to monitor and detect them based on their properties. An appealing method for such speciation involves the imprinting of nanoparticles in soft matrices. The principles of imprinting nanoparticles originate from the molecularly imprinted polymer (MIP) approach. This review summarizes the current status of this emerging field, which bridges between the traditional MIP approach and the imprinting of larger entities such as viruses and bacteria. The concepts of nanoparticle imprinting and the requirement of both physical and chemical matching between the nanoparticles and the matrix are discussed and demonstrated.


[The relationship between bacterial sputum analysis and infection].
Sputum specimens were examined microscopically for the presence of squamous epithelial cell (SECs) and leucoctyes. Where less than 10 SECs and more than 25 leucocytes per low-power field were present, pathogenic organisms were isolated from 84% of patients with pulmonary infections. Sputum specimens which did not comply with these requirements showed a weaker correlation and more non-pathogenic organisms of the buccal cavity were isolated. The bacteriological isolates in sputum specimens and the clinical conditions with which they were associated in this series, are described.


[Effects of insulin and somatomedin C on the function of cultured Leydig cells].
Porcine cultured Leydig cells (LC) lose hCG receptors and hCG responsiveness (cAMP and testosterone) when they are cultured for three days in a defined medium without insulin or somatomedin C (Sm-C) (Insulin-like growth factor I). In the presence of insulin (50 ng/ml) or of Sm-C (10 ng/ml) the loss of the hCG receptor number and the decreased cAMP response to hCG were prevented, but the steroidogenic response to hCG was only partially prevented. This parameter became normal when cells were pretreated with either Sm-C (10 ng/ml) plus insulin (50 ng/ml) or with insulin alone at high concentrations (5 micrograms/ml). These results indicate that both Sm-C and insulin acting through their own receptors increase Leydig cell steroidogenic capacity by increasing hCG receptor number and improving some step beyond cAMP formation.


Implementing Shared Decision-Making for Multiple Sclerosis: The MS-SUPPORT Tool.
Disease modifying therapies (DMTs) offer opportunities to improve the course of multiple sclerosis (MS), but decisions about treatment are difficult. People with multiple sclerosis (pwMS) want more involvement in decisions about DMTs, but new approaches are needed to support shared decision-making (SDM) because of the number of treatment options and the range of outcomes affected by treatment. We designed a patient-centered tool, MS-SUPPORT, to facilitate SDM for pwMS. We sought to evaluate the feasibility and impact of MS-SUPPORT on decisions about disease modifying treatments (DMTs), SDM processes, and quality-of-life. This multisite randomized controlled trial compared the SDM intervention (MS-SUPPORT) to control (usual care) over a 12-month period. English-speaking adults with relapsing MS were eligible if they had an upcoming MS appointment and an email address. To evaluate clinician perspectives, participants' MS clinicians were invited to participate. Patients were referred between November 11, 2019 and October 23, 2020 by their MS clinician or a patient advocacy organization (the Multiple Sclerosis Association of America). MS-SUPPORT is an online, interactive, evidence-based decision aid that was co-created with pwMS. It clarifies patient treatment goals and values and provides tailored information about MS, DMTs, and adherence. Viewed by patients before their clinic appointment, MS-SUPPORT generates a personalized summary of the patient's treatment goals and preferences, adherence, DMT use, and clinical situation to share with their MS clinician. Outcomes (DMT utilization, adherence, quality-of-life, and SDM) were assessed at enrollment, post-MS-SUPPORT, post-appointment, and quarterly for 1 year. Participants included 501 adults with MS from across the USA (84.6% female, 83% white) and 34 of their MS clinicians (47% neurologists, 41% Nurse Practitioners, 12% Physician Assistants). Among the 203 patients who completed MS-SUPPORT, most (88.2%) reported they would recommend it to others and that it helped them talk to their doctor (85.2%), understand their options (82.3%) and the importance of taking DMTs as prescribed (82.3%). Among non-users of DMTs at baseline, the probability ratio of current DMT use consistently trended higher over one-year follow-up in the MS-SUPPORT group (1.30 [0.86-1.96]), as did the cumulative probability of starting a DMT within 6-months, with shorter time-to-start (46 vs 90 days, p=0.24). Among the 222 responses from 34 participating clinicians, more clinicians in the MS-SUPPORT group (vs control) trended towards recommending their patient start a DMT (9 of 108 (8%) vs 5 of 109 (5%), respectively, p=0.26). Adherence (no missed doses) to daily-dosed DMTs was higher in the MS-SUPPORT group (81.25% vs 56.41%, p=.026). Fewer patients forgot their doses (p=.046). The MS-SUPPORT group (vs control) reported 1.7 fewer days/month of poor mental health (p=0.02). MS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool.


Coeliac disease.
Coeliac disease is an immune-mediated enteropathy against dietary gluten present in wheat, rye and barley and is one of the most common lifelong food-related disorders worldwide. Coeliac disease is also considered to be a systemic disorder characterized by a variable combination of gluten-related signs and symptoms and disease-specific antibodies in addition to enteropathy. The ingestion of gluten leads to the generation of harmful gluten peptides, which, in predisposed individuals, can induce adaptive and innate immune responses. The clinical presentation is extremely variable; patients may have severe gastrointestinal symptoms and malabsorption, extraintestinal symptoms or have no symptoms at all. Owing to the multifaceted clinical presentation, diagnosis remains a challenge and coeliac disease is heavily underdiagnosed. The diagnosis of coeliac disease is achieved by combining coeliac disease serology and small intestinal mucosal histology during a gluten-containing diet. Currently, the only effective treatment for coeliac disease is a lifelong strict gluten-free diet; however, the diet is restrictive and gluten is difficult to avoid. Optimizing diagnosis and care in coeliac disease requires continuous research and education of both patients and health-care professionals.


[The role of the hormones-cyclases system in the pathogenesis of erosive gastric and duodenal affections].
As a result of a complex survey of 120 patients with erosive gastroduodenal affections, significant abnormalities of the aggressive-protective balance of the mucous coat of the stomach were discovered. In addition to affections of local protection factors, the change of the hormonal status characterized by hypercortisolemia, hyperinsulinemia, hypergastrinemia and increased level of such cyclic nucleotides as cAMP and cGMP was revealed. The dependence of the mucus-producing function, lysozyme activity and acid production on the level of blood hormones was discovered. Alternate dependencies of cortisol, insulin and gastrin levels on cAMP and cGMP levels as well as alternate impact of cAMP and cGMP on acid-producing gastric cells were established.


Reducing the flavour of oral lidocaine: randomized controlled trial assessing the efficacy of mint-flavoured mouthwash.
To test the hypothesis that using an alcohol-based, mint-flavoured oral mouthwash prior to applying oral lidocaine spray will result in an improvement in the unpleasant taste of the lidocaine. A double-blind, randomized, controlled trial using a crossover design. A tertiary care hospital. Fifteen able-bodied volunteers rinsed for 30 seconds with either a mint-flavoured, alcohol-based mouthwash (treatment) or plain water (placebo) prior to the administration of topical lidocaine spray. All subjects received both the treatment and the placebo; however, the order of exposure was randomized. Subjects completed two 100 mm visual analogue scales (VASs). The first assessed the overall satisfaction with the taste of the lidocaine. This consisted of a 100 mm VAS with 0 defined as the "most unpleasant taste" and 100 mm defined as the "most pleasant taste," whereas 50 mm was defined as neutral or no taste. The second VAS assessed subjective analgesia after lidocaine administration. There was a statistically significant improvement in the taste of oral lidocaine after administering the treatment intervention (p = .003). There was a reduction in subjective analgesia, which did not reach statistical significance (p = .03). Use of the oral mouthwash reduced the perception of the negative flavour of the lidocaine from 20.77 (13.2) mm to 50.2 (12.84) mm as assessed by the VAS. A brief rinse with a mint-flavoured, alcohol-based mouthwash prior to administration of topical lidocaine resulted in a significant improvement in the perceived flavour of topical lidocaine with a minimal reduction in subjective analgesia.


Penalized least squares regression methods and applications to neuroimaging.
The goals of this paper are to review the most popular methods of predictor selection in regression models, to explain why some fail when the number P of explanatory variables exceeds the number N of participants, and to discuss alternative statistical methods that can be employed in this case. We focus on penalized least squares methods in regression models, and discuss in detail two such methods that are well established in the statistical literature, the LASSO and Elastic Net. We introduce bootstrap enhancements of these methods, the BE-LASSO and BE-Enet, that allow the user to attach a measure of uncertainty to each variable selected. Our work is motivated by a multimodal neuroimaging dataset that consists of morphometric measures (volumes at several anatomical regions of interest), white matter integrity measures from diffusion weighted data (fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity) and clinical and demographic variables (age, education, alcohol and drug history). In this dataset, the number P of explanatory variables exceeds the number N of participants. We use the BE-LASSO and BE-Enet to provide the first statistical analysis that allows the assessment of neurocognitive performance from high dimensional neuroimaging and clinical predictors, including their interactions. The major novelty of this analysis is that biomarker selection and dimension reduction are accomplished with a view towards obtaining good predictions for the outcome of interest (i.e., the neurocognitive indices), unlike principal component analysis that are performed only on the predictors' space independently of the outcome of interest.


Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).
Earlier studies from our laboratory demonstrated that the terpolymer of L-glutamic acid, L-alanine, and L-tyrpsine (GAT) stimulated the development of T cells capable of specifically suppressing the antibody responses in vivo and in vitro of nonresponder strains (bearing the H-2(s), H-2(q), and H-2(p) haplotypes) to GAT complexed with an immunogenic carrier, methylated bovine serum albumin, MBSA (1,2). We then extended these findings to another antigen, the copolymer of L-glutamic acid and L-tyrosine (GT). None of 19 inbred or congenic resistant mouse strains developed antibody responses to GT after immunization with this synthetic polypeptide in adjuvants. All the strains investigated, however, developed IgG plaque-forming cells (PFC) primary responses to GT complexed with MBSA (3). This permitted us to determine that: (a) preimmunization with GT suppressed the response to GT-MBSA in certain but not in all strains; (b) the suppression could be transferred by thymocytes and spleen cells from GT-primed animals; (c) the development of GT-specific suppressor cells is under dominant control of H-2- linked gene(s) which have been designated specific immune suppressor genes (Is genes); (d) the Is genes are antigen specific since GAT-MBSA responses are suppressed by GAT in strains carrying the H-2(q) haplotype, while GT-MBSA responses are not suppressed by the related polymer GT in these same strains (3,4). The experiments reported in this study map the Is genes responsible for GT-specific suppression within the H-2 complex. The data indicate that the K and D loci are not concerned with GT-specific suppression, and that this phenomenon is controlled by complementing or interacting genes which map on either side of cross-over events between the IB and IC subregions.


A Nanofocused Light on Stradivari Violins: Infrared s-SNOM Reveals New Clues Behind Craftsmanship Mastery.
It is well-known that all the phases of the manufacturing influence the extraordinary aesthetic and acoustic features of Stradivari's instruments. However, these masterpieces still keep some of their secrets hidden by the lack of documentary evidence. In particular, there is not a general consensus on the use of a protein-based ground coating directly spread on the wood surface by the Cremonese Master. The present work demonstrates that infrared scattering-type scanning near-fields optical microscopy (s-SNOM) may provide unprecedented information on very complex cross-sectioned microsamples collected from two of Stradivari's violins, nanoresolved chemical sensitivity being the turning point for detecting minute traces of a specific compound, namely proteins, hidden by the matrix when macro or micro sampling approaches are exploited. This nanoresolved chemical-sensitive technique contributed new and robust evidence to the long-debated question about the use of proteinaceous materials by Stradivari.


Comparison of luteinizing hormone surge responses to ovarian steroids in cyclic and spontaneously persistent estrous rats of middle age.
Female rats of the Charles River CD strain, when 6 to 12 months old, present spontaneous persistent estrus (SPE) in increasing numbers, while others remain cyclic. Apparently as a prelude to SPE, some rats still cycling will fail to ovulate early in response to estrogen or progesterone administration during diestrus. When estradiol benzoate (EB) was given on Day 2 of the 5-day cycle or when progesterone was given on Day 3, the luteinizing hormone (LH) surges, if they occurred at all, tended to be much smaller than the normal surge of proestrus. The normal surges could be equalled only when EB was given on Day 2 and followed by progesterone on Day 3. In SPE rats, progesterone treatment usually induces ovulation only after SPE has been interrupted for a few days and the rat has returned to proestrus-estrus. LH surges induced in that way by progesterone were usually substantial. Thus, the ability of the LH-release apparatus to function had returned within 1 week after interruption of the persistent estrogenic status. Comparison were made of LH surge responses to EB administration in cyclic and SPE rats during pseudopregnancies produced by cervical stimulation (after LH injection of SPE rats) or by daily injection of progesterone. In previously cyclic rats, proestrus-like surges of LH were registered consistently, while in previously SPE rats the levels attained were generally lower. Unexpectedly, if rats were castrated when daily progesterone treatment started, few produced large amounts of LH. This was especially true in the SPE group, 14 of 20 rats failing to show any LH surge. Hence, although capacity to produce the LH surge in response to estrogen + progesterone can return within a few days after SPE cases, some unknown ovarian activity plays an important role. Such activity may also take part in the normal cycle.


The dissociation between the P3a event-related potential and behavioral distraction.
Unexpected novel sounds can capture our attention and impair performance. Recent behavioral research revealed that only novel sounds that provided target-related (but not task-related) information impaired performance. This poses the question of the automaticity of novelty processing and its expression at the behavioral level. In an auditory-visual oddball paradigm, the informational content of sounds regarding the time and probability of target occurrence was varied. Independent from the informational content, novel, and deviant sounds elicited the P3a, an ERP-component related to novelty processing. In contrast, impaired performance was only observed if target-related information was provided. Results indicate that distractor sounds are automatically evaluated as potentially significant, but that the consequences for behavior depend on further processes such as the processing of the given information.


Mercury contamination in the recently described Brazilian white-tail dogfish Squalus albicaudus (Squalidae, Chondrichthyes).
The recently described Squalus albicaudus is a mesopredator shark and, as such, exposed to mercury biomagnification processes. Therefore, this study aimed to assess total Hg (THg) concentrations in S. albicaudus, a deep-water species, sampled off Southeastern Brazil and discuss ecological, reproductive, human consumption and conservation implications. Thirty-two individuals were sampled off the coast of Rio de Janeiro, including 13 gravid females carrying 34 embryos. Muscle THg concentrations were higher in all sex classes compared to liver, gonads and brain. The last three, in turn, presented THg concentrations above toxic biota thresholds. Significant correlations were observed between muscle and brain and liver, indicating systemic Hg contamination and inter-organ transport and distribution. In addition, correlations observed between organs strongly support efficient Hg blood-brain barrier crossing and maternal transfer. Maternal THg transfer was observed, with embryo THg also above toxic thresholds for fish. THg levels in muscle and liver, as well as embryos, were higher compared to other Squalus species worldwide. Hg contamination off the coast of Rio de Janeiro is of significant concern and should be further assessed. Potential human consumption risks are noted, as muscle THg concentrations were above maximum permissible levels set by regulatory agencies.


Locomotion characteristics of dairy cows walking on pasture and the effect of artificial flooring systems on locomotion comfort.
The locomotion comfort of dairy cows depends on the floor of the walking alleys. Optimal locomotion comfort is given when cows walk on pasture, allowing freedom from discomfort and pain and the expression of normal behavior. This study examined the characteristics of locomotion behavior on pasture (gold standard with optimal locomotion comfort) and compared it with behaviors of cows walking on mastic asphalt or solid rubber mats before and after a routine claw trimming session. Our hypotheses were (1) that gait variables were different on pasture versus mastic asphalt and on mastic asphalt versus rubber, and (2) that claw trimming had an effect on gait variables of cows walking on mastic asphalt. Twenty-four dairy cows kept in a tiestall facility were enrolled in this experimental trial. The pedogram was measured using 2 standalone 3-dimensional accelerometers (400 Hz), attached to the metatarsus of both hind limbs. The extracted pedogram variables included temporal events (kinematic outcome = gait cycle and stance-phase and swing-phase durations) and peaks (kinetic outcome = foot load, toe-off). The cows were further video-recorded to calculate walking speed and stride length. Locomotion score was performed on mastic asphalt to enroll only nonlame cows (locomotion score <3). For comparison between different floor types, repeated-measures ANOVA was performed with the cow as a subject variable, session time of measurement as within-subject variable, and flooring type as a fixed effect. Three separate analyses were performed: pasture versus mastic asphalt (analysis I), solid rubber versus mastic asphalt (analysis II), and the effect of claw trimming on the kinematic and kinetic variables on mastic asphalt (analysis III). All tested gait variables were significantly different between pasture and mastic asphalt floor. The optimal characteristics of locomotion comfort on pasture included shorter duration of gait cycle, longer stance-phase duration, shorter swing-phase duration, higher walking speed, longer stride length, and higher peaks of foot load and toe-off. However, gait variables of cows walking on rubber mats did not show any significant difference compared with the mastic asphalt floor; only stride length tended to be longer on rubber mats. In addition, the stance- and swing-phase durations significantly improved shortly after trimming. The left-right differences of the stance- and swing-phase durations tended to decrease after claw trimming when cows walked on asphalt floor. The results of this study show that solid rubber flooring does not result in significant improvement of the evaluated variables of locomotion comfort compared with mastic asphalt.


Somatic hypermutation: mutations 3' of rabbit VDJ H-chain genes.
VDJ genes of rabbit B cells are diversified by a somatic gene conversion-like mechanism in which V(H) gene segments 5' of the VDJ gene serve as donors. To assess whether somatic mutation also contributes to Ab diversification in the rabbit, we searched for mutations 3' of VDJ genes because mutations in this region presumably result from somatic mutation rather than gene conversion. We PCR-amplified and cloned the region extending 534 bp 3' of VDJ genes from splenic DNA of young and adult rabbits. Results of nucleotide sequence analysis of the clones revealed a high mutation frequency (2.4%) within the first 120 bp downstream of VDJ genes. This frequency decreased rapidly with increasing distance 3' of the VDJ genes. The mutations demonstrated both strand bias and dinucleotide preferences characteristic of somatic hypermutation. We conclude that Ab diversity in rabbit is generated not only by somatic gene conversion but also by somatic hypermutation.


Rapid Isolation of Extracellular Vesicles Using a Hydrophilic Porous Silica Gel-Based Size-Exclusion Chromatography Column.
Extracellular vesicles (EVs) are nanoscale lipid bilayer vesicles released by almost all cell types and can be found in biological fluids, such as blood and urine. EVs play an important role in various physiological and pathological processes via cell-cell communication, highlighting their potential applications as diagnostic markers for diseases and therapeutic drug delivery carriers. Although various methods have been developed for the isolation of EVs from biological fluids, most of them exhibit major limitations, including low purity, long processing times, and high cost. In this study, we developed a size-exclusion chromatography (SEC) column device using hydrophilic porous silica gel (PSG). Owing to the resistance to pressure of the device, a rapid system for EV isolation was developed by connecting it to a flash liquid chromatography system furnished with a UV detector and a fraction collector. This system can be used for the real-time monitoring of eluted EVs by UV absorption without further analysis and separation of high-purity EVs from urine samples with high durability, reusability, and reproducibility. In addition, there were no significant differences between the PSG column- and conventional SEC column-isolated EVs in the proteome profiles and cellular uptake activities, suggesting the good quality of the EVs isolated by the PSG column. These findings suggest that the PSG column device offers an effective and rapid method for the isolation of intact EVs from biological fluids.


Emotional Picture Perception: Repetition Effects in Free-Viewing and during an Explicit Categorization Task.
Several studies have found that, despite a decrease in the overall amplitude of the late positive potential (LPP) with repeated presentation of the same picture, emotional stimuli continue to elicit a larger LPP than neutral ones. These findings seem to support the hypothesis that the affective modulation of the LPP reflects a mandatory process and does not rely on stimulus novelty. However, in these studies participants were asked to merely look at the pictures, without carrying out any additional task (free-viewing), making picture emotionality the most salient aspect of the stimulus, despite its repetition. The current study aimed to examine the impact of an explicit categorization task on the emotional processing of repeated pictures. To this purpose, ERPs to novel and repeated pictures were measured during free-viewing as well as during an explicit categorization task, where the emotional content of the pictures was task-irrelevant. The within-subject comparison between the free-viewing and task context revealed that the overall LPP habituated more rapidly in the free-viewing condition, but, more importantly, the LPP affective modulation was unaffected by task requirements during both novel and repeated presentations. These results suggest that the affective modulation of the LPP reflects an automatic engagement of cortico-limbic motivational systems, which continues to take place regardless of stimulus novelty and task context.


Quantification of bacterial transcripts during infection using competitive reverse transcription-PCR (RT-PCR) and LightCycler RT-PCR.
Bacteria have evolved sophisticated regulatory circuits to modulate their gene expression in response to disparate environments. In order to monitor bacterial gene expression and regulation in the host, methods for direct transcript analysis from clinical specimens are needed. For most bacterial infections, amplification of the mRNAs of interest is necessary due to the low numbers of cells present and the low levels of specific transcripts. Here we compare two methods of quantitative reverse transcription-PCR (RT-PCR)-competitive RT-PCR using a one-tube system followed by standard gel analysis and the real-time detection of PCR product formation by fluorescence resonance energy transfer technology using the LightCycler unit. We isolated Staphylococcus aureus RNA directly from clinical specimens obtained from cystic fibrosis patients with chronic S. aureus lung infection and from an animal model of foreign-body infection with no further cultivation of the bacteria. Competitive RT-PCR and LightCycler RT-PCR were tested for their ability to quantify the transcription of a constitutively expressed gyrase gene (gyr) and a highly regulated alpha-toxin gene (hla) of S. aureus. Reproducible results were obtained with both methods. A sensitivity of 10(4) (gyr) and 10(3) (hla) copies, respectively, was reached, which was sufficient for the quantification of transcripts during bacterial infection. Overall, the competitive RT-PCR is a robust technique which does not need special RNA purification. On the negative side, it is labor intensive and time consuming, thus limiting the numbers of samples which can be analyzed at a given time. LightCycler RT-PCR is very susceptible to even traces of inhibitors, but it allows high-throughput processing of samples.


[Traffic-related injuries in children at Trieste, 1984-1986].
Traffic-related injuries to children are poorly known in our country, in spite of their role in mortality and morbidity. Being that they are rather different from those reported in the adults, their study is useful in identifying risks and elaborating prevention strategies. This paper reports epidemiologic and clinical data on 1050 children under 16, referred to our hospital because of road traffic accidents. The study has been prospectively carried out during 1984-86; injuries severity was assessed according to the Abbreviated Injury Scale. Incidence rates resulted to increase with the age, highest values being observed for 15 year old children, due to motorcycle use. Patterns and severity of the injuries were significantly different according to the age and the group of injured subjects. Younger children as pedestrians and 14-15 y.o. motorcyclists resulted to be more involved than car passengers and bicyclists. At a telephone inquiry after 6-12 months sequelae resulted in 20-40% out of 482 children, according to different AIS Score.


Period coded phase shifting strategy for real-time 3-D structured light illumination.
Phase shifting structured light illumination for range sensing involves projecting a set of grating patterns where accuracy is determined, in part, by the number of stripes. However, high pattern frequencies introduce ambiguities during phase unwrapping. This paper proposes a process for embedding a period cue into the projected pattern set without reducing the signal-to-noise ratio. As a result, each period of the high frequency signal can be identified. The proposed method can unwrap high frequency phase and achieve high measurement precision without increasing the pattern number. Therefore, the proposed method can significantly benefit real-time applications. The method is verified by theoretical and experimental analysis using prototype system built to achieve 120 fps at 640 × 480 resolution.


[Effect of the short-term exposure to negative air ions on individuals with vegetative disorders].
The humans with vegetative disorder have been under the short-time exposition to negatively charged air ions, produced by Tchizhevski aeroionizer "Elion-132". The state of vegetative nervous system and some other physiological systems and organs of treated humans were estimated by acupuncture R. Voll method. It was found, that treatment by negatively charged air ions leads to the normalization of the state of mentioned above acupuncture points in the most (87%) of the tested humans with vegetative disorder. In 13% of tested persons these indicators became worse after this procedure. In the each case the changes in the state of different acupuncture points had the single-directed character. The suggestion was made, that vegetative nervous system plays the important role in the formation of organism's integrated reaction to the action of negatively charged air ions.


Polymorphisms of the dopamine transporter gene: influence on response to methylphenidate in attention deficit-hyperactivity disorder.
Attention deficit-hyperactivity disorder (ADHD) is a very common and heterogeneous childhood-onset psychiatric disorder, affecting between 3% and 5% of school age children worldwide. Although the neurobiology of ADHD is not completely understood, imbalances in both dopaminergic and noradrenergic systems have been implicated in the origin and persistence of core symptoms, which include inattention, hyperactivity, and impulsivity. The role of a genetic component in its etiology is strongly supported by genetic studies, and several investigations have suggested that the dopamine transporter gene (DAT1; SLC6A3 locus) may be a small-effect susceptibility gene for ADHD. Stimulant medication has a well-documented efficacy in reducing ADHD symptoms. Methylphenidate, the most prescribed stimulant, seems to act mainly by inhibiting the dopamine transporter protein and dopamine reuptake. In fact, its effect is probably related to an increase in extracellular levels of dopamine, especially in brain regions enriched in this protein (i.e. striatum). It is also important to note that dopamine transporter densities seem to be particularly elevated in the brain of ADHD patients, decreasing after treatment with methylphenidate. Altogether, these observations suggest that the dopamine transporter does play a major role in ADHD. Among the several polymorphisms already described in the SLC6A3 locus, a 40 bp variable number of tandem repeats (VNTR) polymorphism has been extensively investigated in association studies with ADHD. Although there are some negative results, the findings from these reports indicate the allele with ten copies of the 40 bp sequence (10-repeat allele) as the risk allele for ADHD. Some investigations have suggested that this polymorphism can be implicated in dopamine transporter gene expression in vitro and dopamine transporter density in vivo, even though it is located in a non-coding region of the SLC6A3 locus. Despite all these data, few studies have addressed the relationship between genetic markers (specifically the VNTR) at the SLC6A3 locus and response to methylphenidate in ADHD patients. A significant effect of the 40 bp VNTR on response to methylphenidate has been detected in most of these reports. However, the findings are inconsistent regarding both the allele (or genotype) involved and the direction of this influence (better or worse response). Thus, further investigations are required to determine if genetic variation due to the VNTR in the dopamine transporter gene is able to predict different levels of clinical response and palatability to methylphenidate in patients with ADHD, and how this information would be useful in clinical practice.


Acute pan-dysautonomia as well as central nervous system involvement and peripheral neuropathies in a patient with systemic lupus erythematosus.
A 32-year-old woman was diagnosed with leucopenia in 2002, being antinuclear antibody, anti-DNA antibody, and antiphospholipid antibody positive, and she was administered low-dose aspirin. In July 2006, she was admitted to our hospital because of pyrexia and abdominal pain. Examination revealed paralytic ileus, absence of the pupillary light reflex, dyshidrosis and anuresis. In addition, with high-level interleukin-6 in cerebrospinal fluid, the sensory nerve conduction velocity was derivation impotence. She was subsequently diagnosed with systemic lupus erythematosus (SLE) with central nervous system involvement, peripheral neuropathy as well as acute pan-dysautonomia. After pulse corticosteroid therapy, paralytic ileus was improved, however, the urination disorder persisted, and syncope due to orthostatic hypotension became marked. Plasma exchange and a second course of pulse corticosteroid therapy were performed, and were ineffective, whereas intravenous cyclophosphamide was effective. This patient is a rare case of central nervous system, peripheral neuropathy as well as acute pan-dysautonomia with SLE.


Two-Thirds of Survey Respondents in Southern Sweden Used Complementary or Alternative Medicine in 2015.
Research has long suggested that a large and possibly growing number of people use complementary or alternative medicine (CAM). However, in many countries, such as Sweden, national and regional research on CAM use is still very limited. Existing prevalence studies are few and characterized by low comparability. This study aims to contribute towards addressing this knowledge gap. A web-based survey measured the use of and attitude towards CAM and conventional medicine in the southernmost Swedish province of Scania, while taking part in the development of a measurement tool for the standardized study of CAM use within the European Union (EU; I-CAM-Q). 71% of the respondents (n = 1,534) reported having used some form of CAM in the past year. CAM consumption here includes visits to CAM providers, use of natural remedies, and use of self-help methods. Reported use was more common among women, younger age groups, and people with tertiary education. 69% of the respondents stated that collaboration between conventional medicine and complementary medicine should increase. The survey's response rate was 31%. The study confirms that CAM forms a considerable part of the health care offered to and used by the population. In the face of the existing lack of national and regional data on CAM usage, it affirms the importance of furthered investigation of CAM consumption, policy, practice, regulation, and education.


Relation of risk factor levels in young adulthood to parental history of disease. The CARDIA study.
The relation between self-reported parental disease and risk factor levels was examined in 2,637 black and 2,478 white men and women aged 18-30 years at the Coronary Artery Risk Development in Young Adults (CARDIA) Study baseline examination (1985-1986). The prevalence of parental disease (at least one parent) in white versus black participants was 44% and 56% for hypertension, 47% and 44% for obesity, 16% and 13% for myocardial infarction, 11% and 17% for diabetes, and 6% and 10% for stroke, respectively. Among these young adults, parental hypertension was associated with higher sex- and age-adjusted systolic and diastolic blood pressure levels. Parental myocardial infarction was associated with higher plasma cholesterol, higher blood pressure levels, and lower high density lipoprotein cholesterol levels in white participants. Parental diabetes was associated with higher fasting blood glucose and insulin levels in all race-sex groups and with higher triglycerides and lower high density lipoprotein cholesterol in black participants only. Parental history of obesity was related to less favorable age- and sex-adjusted lipid levels in white participants and higher blood pressure levels in black participants. Parental history of stroke was associated with higher systolic blood pressure levels in black participants. In general, these differences across family history were predicted only in part by obesity. The prevalence of more than one disease reported in parents occurred more frequently than would have been expected due to chance alone. These associations between parental disease and risk factors in their adult children probably reflects the impact of both environmental and genetic factors. Parental history may be a useful marker for high risk individuals.


Quality of life of children with atopic dermatitis and their families.
Over the last few years major advances have been made in the conceptualization of quality of life and new instruments have been developed for assessing the construct in paediatric atopic dermatitis. This review looks at these developments and reports on recently published articles on the impact of the condition on affected children and other members of their family. During the period of the review only one article addressing the impact of treatment for paediatric atopic dermatitis on quality of life could be found. This showed the benefits to the quality of life of parents of treating their children with pimecrolimus cream. Given the prevalence of paediatric atopic dermatitis and its impact on affected children and their families it is surprising that so little attention has been devoted to the impact of treatment on quality of life. Where standardized measures are included in studies they generally assess outcomes that are of interest to physicians rather than to patients and their carers.