Core binding factor cannot synergistically activate the myeloperoxidase proximal enhancer in immature myeloid cells without c-Myb.
The myeloperoxidase (MPO) gene is transcribed specifically in immature myeloid cells and is regulated in part by a 414-bp proximal enhancer. Mutation of a core binding factor (CBF)-binding site at -288 decreased enhancer activity 30-fold in 32D cl3 myeloid cells cultured in granulocyte colony-stimulating factor (G-CSF). A novel functional analysis, linking the CBF-binding site to an enhancer deletion series, located at -147 an evolutionarily conserved c-Myb-binding site which was required for optimal enhancer activity and synergy with CBF in 32D cells. These sites cooperated in isolation and independent of a precise spacing. Deletional analysis carried out in the absence of the c-Myb-binding site at -147 located at -301 a second c-Myb-binding site which also synergized with CBF to activate the enhancer. A GA-rich region at -162 contributed to cooperation with CBF when the adjacent c-Myb-binding site was intact. Mutation of both c-Myb-binding sites in the context of the entire enhancer greatly impaired activation by endogenous CBF in 32D cells. Similarly, activation by c-Myb was impaired in constructs lacking the CBF-binding site. CBF and c-Myb were required for induction of MPO proximal enhancer activity when 32D cells differentiated in response to G-CSF. A fusion protein containing the Gal4 DNA-binding domain and the AML-1B activation domain, amino acids 216 to 480, activated transcription alone and cooperatively with c-Myb in nonmyeloid CV-1 cells. Determining how CBF and c-Myb synergize in myeloid cells might contribute to our understanding of leukemogenesis by the AML1-ETO, AML1-MDS1, CBFbeta-SMMHC, and v-Myb oncoproteins.


Spica cast as an alternative to general anesthesia for lower limb MRI in young children.
The conventional approach for MRI procedures in very young children is to use general anesthesia which comes with inherent risks. Non-pharmacological strategies to reduce anxiety in children have also been described, but they all require patient cooperation. The purpose of the study was to evaluate the ability to complete diagnosis using temporary spica cast immobilization (TSCI) in children less than 3 years old undergoing MRI procedures for lower limb disorders. A retrospective review identified 14 children under 3 years old that had required an MRI for a lower limb disorder, using TSCI. The MRI procedure was performed for evaluation of hip dysplasia, bone infections, limping, evaluation of soft tissue tumor and femoral head osteonecrosis. A spica cast was fitted by the pediatric orthopedic team. The MRI procedure was subsequently performed. Diagnosis was achieved in all cases. The radiologist identified movement artifacts (14 %) that did not impair the image quality enough to prevent interpretation. TSCI is a safe, effective and costless procedure avoiding general anesthesia for young patients under 3 years old who require MRI for pelvis or lower limb disorders. IV.


Measuring HIV Knowledge Among Women Incarcerated in Jail.
Incarcerated women often have arresting behaviors that are also high risk for acquiring HIV, such as drug use and sex work. Little research has been done related to HIV knowledge among women in jail. This study assessed HIV knowledge among English-speaking women 18 years and older detained in a large, Southeastern jail (N = 202). HIV knowledge was assessed using the Brief HIV Knowledge Questionnaire. HIV knowledge scores were significantly lower among women over age 50, F(3, 195) = 7.39, p < .001; those with less than a high school education, F(2, 187) = 4.10, p = .018; and those with no history of sexually transmitted infections, F(1, 200) = 7.66, p = .006. Assessment of HIV knowledge among incarcerated women revealed a need for prevention education.


Association between routine measures of graft function and mortality in heart transplant recipients.
To date, long-term graft dysfunction, an important cause of death after heart transplantation, has been defined as a left ventricular ejection fraction (LVEF) of ≤40% or right atrial pressure (RAP) of ≥15 mm Hg. Empirical associations between measures of cardiac function and mortality post-transplant remain, however, unestablished. We conducted a retrospective two-centre cohort study of consecutive adults who underwent heart transplant between 2002 and 2017. We evaluated the association between LVEF and RAP and mortality, including rejection and cardiac allograft vasculopathy as additional time-dependent covariates using Cox proportional hazard models. We applied restricted cubic splines to both LVEF and RAP. Of 590 eligible heart transplant recipients, of whom 72% were male with a mean age of 49 years, 410 received their transplant at Toronto General Hospital and 180 at Rigshospitalet. We observed a 5% absolute risk increase for 1-year mortality, from 11% to 16%, when the LVEF dropped to 53% (HR 1.71 for LVEF of 53% compared with 60%, 95% CI 1.36 to 2.14) or when the RAP increased to 12 mm Hg (HR 1.49 for RAP of 12 mm Hg compared with 5 mm Hg, 95% CI 1.04 to 2.13). In this study, we observed that small changes in graft function at any time post-transplant are associated with an increased mortality. Our results suggest that the current definition of graft dysfunction may underestimate patient risk of adverse outcomes.


Lactation and interbirth interval in the Senegal galago (Galago senegalensis moholi).
Five years of reproductive data on Galago senegalensis moholi at the Duke University Primate Center were examined to determine the effect of lactation on interbirth interval and its component phases, postpartum anovulatory interval and interval from onset of estrous cycles to conception. Females whose infants died within 3 weeks of birth had significantly shorter interbirth intervals and postpartum anovulatory intervals than did females who raised their infants until weaning.


Clinical photographic observation of plantar corns and callus associated with a nominal scale classification and inter- observer reliability study in a student population.
The management of plantar corns and callus has a low cost-benefit with reduced prioritisation in healthcare. The distinction between types of keratin lesions that forms corns and callus has attracted limited interest. Observation is imperative to improving diagnostic predictions and a number of studies point to some confusion as to how best to achieve this. The use of photographic observation has been proposed to improve our understanding of intractable keratin lesions. Students from a podiatry school reviewed photographs where plantar keratin lesions were divided into four nominal groups; light callus (Grade 1), heavy defined callus (Grade 2), concentric keratin plugs (Grade 3) and callus with deeper density changes under the forefoot (Grade 4). A group of 'experts' assigned from qualified podiatrists validated the observer rated responses by the students. Cohen's weighted statistic (k) was used to measure inter-observer reliability. First year students (unskilled) performed less well when viewing photographs (k = 0.33) compared to third year students (semi-skilled, k = 0.62). The experts performed better than students (k = 0.88) providing consistency with wound care models in other studies. Improved clinical annotation of clinical features, supported by classification of keratin- based lesions, combined with patient outcome tools, could improve the scientific rationale to prioritise patient care. Problems associated with photographic assessment involves trying to differentiate similar lesions without the benefit of direct palpation. Direct observation of callus with and without debridement requires further investigation alongside the model proposed in this paper.


Wolbachia-induced mortality as a mechanism to modulate pathogen transmission by vector arthropods.
Insecticide resistance and absence of clinical cures or vaccines for many vector-borne diseases has stimulated interest in using genetically modified arthropod vectors for disease control. Current transgenic strategies focus on vector susceptibility to pathogen infection, which is an inefficient target for pathogen transmission interference. Manipulation of vector survival is theoretically more effective, resulting in larger reductions in the expected number of human infections. A hypothetical method to manipulate vector survival is to drive mortality-inducing Wolbachia into populations. For varying patterns and degrees of induced mortality, we outline the conditions under which virulent Wolbachia introductions into vector populations are expected to succeed and quantify the resultant reduction in pathogen transmission. The most critical component to the success of this strategy is the pattern of induced mortality. For operationally feasible introductions, induced mortality must be delayed until after vector reproduction begins. If this condition is not met, introduction thresholds become exceedingly high, ranging from approximately 40% to 90% of the total adult population. Delayed induced mortality patterns can reduce introduction thresholds to approximately 15-45% of the total adult population. Reduction in cytoplasmic incompatibility with male age has negligible effects on introduction success regardless of the induced mortality pattern. Under proper circumstances, symbiont-induced manipulation of vector survival can theoretically result in up to 100% reduction in pathogen transmission, depending on Wolbachia parameters, magnitude and pattern of induced mortality, and duration of pathogen incubation in the vector. Our results indicate that a broadening of the current paradigm for genetic manipulation of vectors to parameters other than arthropod vector competence is justified and will reveal new research possibilities for vector-borne disease control.


Hardwood seeding root and nutrient parameters for a model of nutrient uptake.
Use of mechanistic models is an increasingly accepted way to evaluate complex processes. The Barber-Cushman model provides a means to simulate nutrient uptake once information on root system characteristics, nutrient uptake, and soil nutrient supply are developed. Objectives of this study were to determine during a growing season: (i) root growth for 1-yr-old black cherry (Prunus serotina Ehrh.), northern red oak (Quercus rubra L.), and red maple (Acer rubrum L.) seedlings; (ii) net plant increase in N, P, K, Ca, and Mg; (iii) soil solution and solid phase nutrient concentrations; and (iv) the influence of root growth and soil nutrient supply changes on nutrient uptake using the Barber-Cushman model. Seedlings were grown in pots containing A horizon soil from two forest sites. Measurements were made on five occasions during the growing season. Root growth averaged 41.5 cm d-1 for red maple compared with 28.0 and 16.7 cm d-1 for cherry and oak, respectively. Seventy-five percent of root growth occurred at the end of the growing season. Total plant N showed the greatest change (25-58%) due to soil source. Model simulations underestimated observed uptake by 31 to 99%. A clear relationship between soil solution nutrient concentration and plant uptake, an important assumption of the model, was not observed. Results indicate care will need to be exercised in the development and use of root growth and nutrient supply values in mechanistic models.


[Study on the determination of trace elements in bitter almond by inductively coupled plasma mass spectrometry].
Samples of bitter almond were digested by microwave digestion, and trace elements amounts of B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Ba and Pb in sample solutions were determined by inductively coupled plasma mass spectrometry (ICP-MS). HNO3 + H2O2 was used to achieve the complete decomposition of the organic matrix in a closed-vessel microwave oven. The working parameters of the instrument were optimized. The result showed that the relative standard deviation (RSD) was less than 4.79% for all the elements, and the recovery was 90.00%-109.30% by adding standard recovery experiment. This method was simple, sensitive and precise and can perform simultaneo multi-elements determination for bitter almond, which could satisfy the sample examination request and provide scientific rationale for determining inorganic elements in bitter almond.


Effectiveness of zonisamide in childhood refractory epilepsy.
Zonisamide (ZNS) is a new generation antiepileptic drug (AED) used in refractory epilepsy. This study assessed the effectiveness and reliability of ZNS in childhood refractory epilepsy. Sixty-eight epilepsy patients who were followed up in the paediatric neurology clinic, between 2013 and 2019, and in whom add-on therapy ZNS had been added as their seizures had continued despite multiple drugs being used, were included in this retrospective study. Their demographic findings, seizure aetiology, pre-treatment and post-treatment electroencephalography findings, treatment responses and any side effects of the drugs given were assessed in these patients. There were 46 (67.6%) patients in the refractory generalized epilepsy (RGE) group using multiple AEDs and 22 (32.35%) patients in the refractory focal epilepsy (RFE) group. Of these patients, 12 (17.65%) were being followed up for idiopathic epilepsy and 8 (11.76%) were being followed up for epilepsy of unknown aetiology. Twenty-two (32.36%) patients were followed up for structural abnormality, 8 patients (11.77%) were followed up for genetic disease, 4 patients (5.88%) were followed up for infectious sequel, 14 patients (20.59%) were followed up for metabolic reasons. In the RGE group, a more than 50% reduction was found in the seizures of 26 (56.5%) patients, while the seizures of 7 (15.2%) patients were found to have terminated completely. In the RFE group, a more than 50% reduction was found in the seizures of 19 (86.4%) patients, while the seizures of 2 (9.1%) patients were found to have terminated completely. The termination or a more than 50% reduction in seizures in 4 of the 6 patients followed up for a diagnosis of tuberous sclerosis complex (TSC) was significant. ZNS is an effective and reliable option as an add-on therapy in paediatric refractory epilepsy, especially in focal epilepsy. It can also be considered for treatment in TSC patients.


Antipsychotic-induced parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders.
In view of the significant cognitive deficits in schizophrenia and their impact on patients' social and occupational functioning, and considering that the influence potential influence of antipsychotic-induced extrapyramidal symptoms on cognition in schizophrenia remains poorly understood, the current study sought to identify the clinical, socio-demographic and neurologic predictors of the cognitive performance of schizophrenia patients. Eighty-two schizophrenia-spectrum (DSM-IV criteria) outpatients were recruited. Psychiatric symptoms were evaluated with the Positive And Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Extrapyramidal symptoms were evaluated with the Extrapyramidal Symptoms Rating Scale, while spatial working, planning abilities and visual paired associates learning were evaluated with the CAmbridge Neuropsychological Tests Automated Battery. The Stroop test was also administered. Multivariate hierarchic linear regression analyses were performed. We found that negative symptoms were associated with cognitive flexibility, planning, visual learning and working memory performance in schizophrenia. Age, sex, number of hospitalizations and antipsychotic type also emerged as significant predictors. More importantly, we found a significant association between antipsychotic-induced parkinsonism and working memory performance. The fact that negative symptoms and socio-demographic variables predicted cognitive performance in schizophrenia is consistent with the previous literature on the topic. The finding of an association between parkinsonism and working memory may have clinical implications, since working memory deficits are considered putative endophenotypes of schizophrenia and are known to impair patients' social and occupational functioning. Our results will need to be replicated in longitudinal studies involving larger samples of patients.


Joint WFH-ISTH session: issues in clinical trial design.
Haemophilia therapy is experiencing an unprecedented expansion in the number and novelty of clotting factor concentrates. Every product must be licensed by regulatory authorities, primarily on the basis of its safety and efficacy profiles. The low prevalence of haemophilia, and other inherited bleeding disorders, presents a significant challenge to patient recruitment for preauthorization clinical trials, especially given the low frequency of inhibitory antibodies, the major adverse event related to clotting factor exposure. Other challenges include a lack of harmonization between the major regulatory authorities in certain key areas, the selection of laboratory monitoring methodologies and the difficulty in obtaining high-quality phase IV safety data following authorization. These aspects will be reviewed in this session, which will also highlight the roles played by the World Federation of Hemophilia and International Society on Thrombosis and Haemostasis in the promotion of these discussions.


The effects of physical exercise on metabolic rate and dietary-induced thermogenesis.
1. The energy metabolism of ad lib.-fed adult male Wistar rats receiving daily running exercise (0.9 km/d; 8 degrees incline) on a motor-driven treadmill, over a period of 56 d, was compared with that of sedentary ad lib.-fed rats and sedentary restricted-fed rats of similar body-weight (approximately 420 g). 2. The metabolizable energy of the diet (Oxoid 41 B) was 11.44 +/- 0.05 kJ/g. This value was not affected by restricted feeding (70% ad lib.), exercise training or exercise itself. 3. Exercise-trained rats ate 5% more food than the sedentary ad lib.-fed rats but their equilibrium body-weight was 60 g lower than that of the latter group. 4. Resting metabolic rate, measured over 22 h in a respiration chamber was increased by 10% in exercise-trained animals. 5. Feeding increased energy expenditure (dietary-induced thermogenesis) and this effect was potentiated by performance of an exercise task. 6. Exercise-trained rats exhibited anticipatory rises in energy expenditure (approximately 40%) when placed on a stationary treadmill. 7. Treadmill work increased energy expenditure by a factor of 1.9-2.4. 8. The energy cost of the exercise, determined by respiration calorimetry was 66-80 J/g per km. These energy costs did not account for all the differences observed in food energy consumption of exercise-trained and sedentary rats of equal body-weight. 9. It is concluded that regular physical exercise increases energy expenditure by factors additional to the energy requirement directly related to the physical work. These factors include an increased resting metabolic rate in exercise-trained rats, increased dietary thermogenesis induced by exercise and anticipatory increases in energy metabolism during the period preceding exercise.


A molecularly imprinted polymer as an antibody mimic with affinity for lysine acetylated peptides.
Lysine acetylation is a widespread protein post-translational modification (PTM) that plays a central role in diverse physiological processes. The study on the scope and pattern of lysine acetylation is an important subject in the proteomic research. However, identification of lysine acetylation from biological sources is a great challenge due to the low abundance in the massive background of unmodified proteins and the dynamic fashion of the modifications. In this research, a novel molecularly imprinted polymer (MIP) with high affinity for peptides containing acetylated lysine (Kac) has been synthesized by the combination of an epitope and surface-confined imprinting strategy. A dipeptide: KacA, containing acetylated lysine and alanine residues, was used as the template and immobilized on the sacrificial silica support. After hierarchical imprinting and removal of silica, the surface-confined cavities were created on the resulting KacA-MIP material. The equilibrium binding and HPLC experiments demonstrated that the KacA-MIP has good selectivity and epitope affinity. It can differentiate Lys-acetylated peptides (Kac-peptides) from their native structures and has higher affinity for Kac-peptides with different sequences. The selectivity of the MIP was also proved by its ability in the extraction of Kac-peptides from spiked histone digest and by its enrichment performance in the whole cell lysates. The study developed a method of MIP preparation with affinity for PTM peptide based on recognition of peptide side chains. It also indicated that the MIP has potential to be used as an antibody mimic in the PTM analysis.


Mode and tempo in the evolution of socio-political organization: reconciling 'Darwinian' and 'Spencerian' evolutionary approaches in anthropology.
Traditional investigations of the evolution of human social and political institutions trace their ancestry back to nineteenth century social scientists such as Herbert Spencer, and have concentrated on the increase in socio-political complexity over time. More recent studies of cultural evolution have been explicitly informed by Darwinian evolutionary theory and focus on the transmission of cultural traits between individuals. These two approaches to investigating cultural change are often seen as incompatible. However, we argue that many of the defining features and assumptions of 'Spencerian' cultural evolutionary theory represent testable hypotheses that can and should be tackled within a broader 'Darwinian' framework. In this paper we apply phylogenetic comparative techniques to data from Austronesian-speaking societies of Island South-East Asia and the Pacific to test hypotheses about the mode and tempo of human socio-political evolution. We find support for three ideas often associated with Spencerian cultural evolutionary theory: (i) political organization has evolved through a regular sequence of forms, (ii) increases in hierarchical political complexity have been more common than decreases, and (iii) political organization has co-evolved with the wider presence of hereditary social stratification.


Dissecting T cell lineage relationships by cellular barcoding.
T cells, as well as other cell types, are composed of phenotypically and functionally distinct subsets. However, for many of these populations it is unclear whether they develop from common or separate progenitors. To address such issues, we developed a novel approach, termed cellular barcoding, that allows the dissection of lineage relationships. We demonstrate that the labeling of cells with unique identifiers coupled to a microarray-based detection system can be used to analyze family relationships between the progeny of such cells. To exemplify the potential of this technique, we studied migration patterns of families of antigen-specific CD8(+) T cells in vivo. We demonstrate that progeny of individual T cells rapidly seed independent lymph nodes and that antigen-specific CD8(+) T cells present at different effector sites are largely derived from a common pool of precursors. These data show how locally primed T cells disperse and provide a technology for kinship analysis with wider utility.


Wavelength dependent UV inactivation and DNA damage of adenovirus as measured by cell culture infectivity and long range quantitative PCR.
Adenovirus is regarded as the most resistant pathogen to ultraviolet (UV) disinfection due to its demonstrated resistance to monochromatic, low-pressure (LP) UV irradiation at 254 nm. This resistance has resulted in high UV dose requirements for all viruses in regulations set by the United States Environmental Protection Agency. Polychromatic, medium-pressure (MP) UV irradiation has been shown to be much more effective than 254 nm, although the mechanisms of polychromatic UV inactivation are not completely understood. This research analyzes the wavelength-specific effects of UV light on adenovirus type 2 by analyzing in parallel the reduction in viral infectivity and damage to the viral genome. A tunable laser from the National Institute of Standards and Technology was used to isolate single UV wavelengths. Cell culture infectivity and PCR were employed to quantify the adenoviral inactivation rates using narrow bands of irradiation (<1 nm) at 10 nm intervals between 210 and 290 nm. The inactivation rate corresponding to adenoviral genome damage matched the inactivation rate of adenovirus infectivity at 253.7 nm, 270 nm, 280 nm, and 290 nm, suggesting that damage to the viral DNA was primarily responsible for loss of infectivity at those wavelengths. At 260 nm, more damage to the nucleic acid was observed than reduction in viral infectivity. At 240 nm and below, the reduction of viral infectivity was significantly greater than the reduction of DNA amplification, suggesting that UV damage to a viral component other than DNA contributed to the loss of infectivity at those wavelengths. Inactivation rates were used to develop a detailed spectral sensitivity or action spectrum of adenovirus 2. This research has significant implications for the water treatment industry with regard to polychromatic inactivation of viruses and the development of novel wavelength-specific UV disinfection technologies.


[Yersinia lipopolysaccharide and its biological activity].
The data on the structure and biological activity of the lipopolysaccharide (LPS) of Yersinia as an important virulence factor are analyzed. The biological effects of LPS are characterized by dose dependence: small doses stimulate the intensity of phagocytosis, while large doses decrease phagocytic activity and produce cytotoxic effect. Yersinia LPS plays an important role in the development of such consequences of yersiniosis as reactive arthritis, erythema nodosum, Reiter's syndrome. Yersinia LPS is a widespread component for the diagnostics of yersiniosis and pseudotuberculosis.


Development of the pedestrian anger expression inventory.
There has been extensive research into road user behavior, although how pedestrians express their anger has yet to be explored. This is important given the high vulnerability of pedestrians and the additional risks that angry people often undertake. The present study developed a tool to measure one's tendency to engage in aggressive acts while walking: The pedestrian anger expression inventory (PAX). The survey consisted of 37 items adapted from the Driving Anger Expression Inventory as well as a subset of items from the Pedestrian Behavior Questionnaire. Ten items from the Trait Anger Scale (TAS) questionnaire were also used to assess the general anger tendencies of individuals. A total of 475 participants from Tehran provided complete responses to a questionnaire administered via paper and pencil. A Principal Component Analysis showed a 30-item, 3-factor model describing three ways of expressing anger: 1) Anger Expression-In (internalizing anger), 2) Anger Expression-Out (in the form of aggression), and 3) Adaptive/Constructive Expression (dealing with anger in a constructive way). Hierarchical linear regression showed that trait anger was a significant predictor of pedestrian anger expression, above other demographic variables (age and gender). However, age and gender remained significant predictors of pedestrian anger. As age increased, the tendency to become angry while walking decreased. Male pedestrians were also significantly more likely to express their anger aggressively than female pedestrians. In this study, we developed a questionnaire to measure anger expression in pedestrians, highlighting three broad ways pedestrians deal with their anger (internally, externally, or constructively). This questionnaire was used in Iran and therefore, further research is required to validate these tools among different samples and populations.


Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial.
Multiple Sclerosis (MS) is a prevalent inflammatory disease in which the immune system plays an essential role in the damage, inflammation, and demyelination of central nervous system neurons (CNS). The cannabinoid receptor type 2 (CB2) agonists possess anti-inflammatory effects against noxious stimuli and elevate the neuronal survival rate. We attempted to analyze the protective impact of low doses of β-Caryophyllene (BCP) in experimental autoimmune encephalomyelitis (EAE) mice as a chronic MS model. Immunization of female C57BL/6 mice was achieved through two subcutaneous injections into different areas of the hind flank with an emulsion that consisted of myelin Myelin oligodendrocyte glycoprotein (MOG)35-55 (150 µg) and complete Freund's adjuvant (CFA) (400 µg) with an equal volume. Two intraperitoneal (i.p.) injections of pertussis toxin (300 ng) were performed on the animals on day zero (immunizations day) and 48 h (2nd day) after injection of MOG + CFA. The defensive effect of low doses of BCP (2.5 and 5 mg/kg/d) was investigated in the presence and absence of a CB2 receptor antagonist (1 mg/kg, AM630) in the EAE model. We also examined the pro/anti-inflammatory cytokine levels and the polarization of brain microglia and spleen lymphocytes in EAE animals. According to our findings, low doses of BCP offered protective impacts in the EAE mice treatment in a CB2 receptor-dependent way. In addition, according to results, BCP decreased the pathological and clinical defects in EAE mice via modulating adaptive (lymphocytes) and innate (microglia) immune systems from inflammatory phenotypes (M1/Th1/Th17) to anti-inflammatory (M2/Th2/Treg) phenotypes. Additionally, BCP elevated the anti-inflammatory cytokine IL-10 and reduced blood inflammatory cytokines. BCP almost targeted the systemic immune system more than the CNS immune system. Thus, a low dose of BCP can be suggested as a therapeutic effect on MS treatment with potent anti-inflammatory effects and possibly lower toxicity.


Standardized amino acid digestibility in cecectomized roosters and lysine bioavailability in chicks fed distillers dried grains with solubles.
This study was conducted to compare the concentration of standardized digestible (SDD) Lys and relative bioavailable Lys in 7 sources of corn distillers dried grains with solubles (DDGS). A second objective was to evaluate 2 in vitro methods, reactive Lys and color score, to predict the concentration of SDD Lys and bioavailable Lys in DDGS. Seven sources of DDGS were fed to cecectomized roosters, and digestibility of amino acids was measured using the total excreta collection method. To measure the relative bioavailable Lys in DDGS, a standard curve (r(2) = 0.96, P < 0.01) was constructed from 9-d weight gain of young chicks fed a Lys-deficient basal diet or diets containing increasing concentrations of l-Lys-HCl. Seven additional diets were formulated by adding each of the 7 sources of DDGS to the basal diet, and total weight gain of chicks was measured. Weight gain of chicks fed each DDGS-containing diet was then compared with the standard curve to calculate the bioavailable Lys and bioavailability of Lys in each source of DDGS. All DDGS sources were analyzed for reactive Lys using the guanidination procedure, and a Hunterlab color score was used to measure the degree of lightness (L), redness (a), and yellowness (b). Results showed that the mean SDD Lys values and the mean relative bioavailability of Lys were 61.4 and 69.0%, respectively. Differences between the concentration of SDD Lys and the concentration of bio-available Lys were not observed in 5 of 7 sources of DDGS. The concentration of SDD Lys was correlated (r(2) = 0.84, P < 0.05) with the concentration of reactive Lys in DDGS. Greater Hunterlab L scores were associated with a greater (r(2) = 0.90, P < 0.05) concentration of bioavailable Lys in DDGS. In conclusion, the concentration of SDD Lys in DDGS does not overestimate the concentration of bioavailable Lys for poultry. Values for reactive Lys may be used to estimate the concentration of SDD Lys, whereas Hunterlab L may be used to estimate the concentration of bioavailable Lys in DDGS.


Probing hysteresis during sorption of cyclohexane within mesoporous silica using NMR cryoporometry and relaxometry.
The conventional data analysis methods for obtaining a pore size distribution (PSD) from gas sorption data make several critical assumptions that impact significantly on the accuracy of the PSD thereby obtained. In particular, assumptions must be made concerning the nature of the pore-filling or emptying process in adsorption, or desorption, respectively. The possibility of pore-pore interactions is also generally neglected. In this work, NMR cryoporometry and relaxometry have been used to study the adsorption and desorption of cyclohexane within a mesoporous, sol-gel silica catalyst support pellet with the aim of assessing the impact of the aforementioned problems for gas sorption PSDs and developing solutions. The advanced melting effect makes cryoporometry a particularly sensitive probe of adsorbate ganglia spatial distribution. It has been demonstrated that utilising gas sorption scanning curves provided insufficient additional information to alleviate the aforementioned problems with interpreting gas sorption data. The NMR data has shown how the nature of the sorption hysteresis changed with amount adsorbed, due to detectable variations in the mechanisms of pore-filling and emptying along the isotherm. Hence, relating a particular condensation or evaporation pressure to a specific characteristic pore size is not as straightforward as assumed in typical pore size analysis software. However, the NMR techniques reveal the additional information required to improve pore size estimates from gas sorption for disordered solids.


Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy.
To analyze the genetic abnormality in a Japanese patient with adult-type metachromatic leukodystrophy (MLD), we first elucidated the genomic organization of the human arylsulfatase A (ASA) gene and then compared the nucleotide sequences of exons and splice junctions of the mutant ASA gene to those of a normal control. We have identified a new mutation, a G-to-A transition in exon 2, which results in amino acid substitution of Asp for 99Gly. In a transient expression study, COS cells transfected with the mutant cDNA carrying 99Gly----Asp did not show an increase of ASA activity, which confirms that the mutation is a cause of adult-type MLD.


Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo.
Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.


Conscious sedation and analgesia for oocyte retrieval during in vitro fertilisation procedures.
Various methods of sedation and analgesia have been used for pain relief during oocyte recovery in IVF/ICSI procedures. The choice of agents has also been influenced by quality of analgesia as well as by concern about possible detrimental effects on reproductive outcome. To assess the efficacy of conscious sedation and analgesia versus alternative methods on pregnancy outcomes and pain relief in patients undergoing transvaginal oocyte retrieval. We searched the Specialised Register of the Menstrual Disorders and Subfertility Group, The Central Register of Controlled Trials (CENTRAL) , MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), the National Research Register, and Current Controlled Trials. There was no language restriction. All references in the identified trials and background papers were checked and authors contacted to identify relevant published and unpublished data. Only randomised controlled trials comparing conscious sedation and analgesia versus alternative methods for pain relief during oocyte recovery were included. Two reviewers independently scanned abstracts of the reports identified by electronic searching to identify relevant papers, extracted data and assessed trial quality. Interventions were classified and analysed under broad categories/strategies of pain relief comparing conscious sedation/analgesia with alternative methods and administration protocols. Our search strategy identified 390 potentially eligible reports and 12 papers met our inclusion criteria. There were no significant differences in clinical pregnancy rates per woman and patient satisfaction between the methods compared. Women's perception of pain showed conflicting results. Due to considerable heterogeneity, in terms of types and dosages of sedation or analgesia used, and tools used to assess the principal outcomes of pain and satisfaction, a meta-analysis of all the studies was not attempted. Of the three trials which compared the effect of conventional medical analgesia plus paracervical block versus electro-acupuncture plus paracervical block, there was no significant difference in clinical pregnancy rates per woman in the two groups (OR 1.01; 95% CI 0.73 to 1.4). For intra-operative pain score as measured by visual analogue scale (VAS), there was a significant difference (WMD -4.95; 95% CI -7.84 to -2.07), favouring conventional medical analgesia plus paracervical block . There was also a significant difference in intra-operative pain by VAS between patient-controlled sedation and physician-administered sedation (WMD 5.98; 95% CI 1.63 to 10.33), favouring physician -administered sedation. However, as different types and dosages of sedative and analgesic agents were used in these trials, these data should be interpreted with caution. For the rest of the trials, a descriptive summary of the outcomes was presented. There is insufficient evidence to determine the effect of different methods of pain relief when compared with conscious sedation and analgesia used during oocyte recovery. In this review, no one particular pain relief method or delivery system appeared to be better than the other. In future, greater consensus is needed to determine both the tools used to evaluate pain and the timing of pain evaluation during and after the procedure. Pain assessment using both subjective and objective measures may merit consideration. In addition, future trials should include intra- and post-operative adverse respiratory and cardiovascular events as outcomes.


HOXB4 can enhance the differentiation of embryonic stem cells by modulating the hematopoietic niche.
Hematopoietic differentiation of embryonic stem cells (ESCs) in vitro has been used as a model to study early hematopoietic development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells (HPCs) where it promotes self-renewal, but it is also expressed in the primitive streak of the gastrulating embryo. This led us to hypothesize that HOXB4 might modulate gene expression in prehematopoietic mesoderm and that this property might contribute to its prohematopoietic effect in differentiating ESCs. To test our hypothesis, we developed a conditionally activated HOXB4 expression system using the mutant estrogen receptor (ER(T2)) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ESCs led to an increase in hematopoietic differentiation. Expression profiling revealed an increase in the expression of genes associated with paraxial mesoderm that gives rise to the hematopoietic niche. Therefore, we considered that HOXB4 might modulate the formation of the hematopoietic niche as well as the production of hematopoietic cells per se. Cell mixing experiments supported this hypothesis demonstrating that HOXB4 activation can generate a paracrine as well as a cell autonomous effect on hematopoietic differentiation. We provide evidence to demonstrate that this activity is partly mediated by the secreted protein FRZB.


Direct infusion mass spectrometry of oxylipin-containing Arabidopsis membrane lipids reveals varied patterns in different stress responses.
Direct infusion electrospray ionization triple quadrupole precursor scanning for three oxidized fatty acyl anions revealed 86 mass spectral peaks representing polar membrane lipids in extracts from Arabidopsis (Arabidopsis thaliana) infected with Pseudomonas syringae pv tomato DC3000 expressing AvrRpt2 (PstAvr). Quadrupole time-of-flight and Fourier transform ion cyclotron resonance mass spectrometry provided evidence for the presence of membrane lipids containing one or more oxidized acyl chains. The membrane lipids included molecular species of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, digalactosyldiacylglycerol, monogalactosyldiacylglycerol, and acylated monogalactosyldiacylglycerol. The oxidized chains were identified at the level of chemical formula and included C(18)H(27)O(3) (abbreviated 18:4-O, to indicate four double bond equivalents and one oxygen beyond the carbonyl group), C(18)H(29)O(3) (18:3-O), C(18)H(31)O(3) (18:2-O), C(18)H(29)O(4) (18:3-2O), C(18)H(31)O(4) (18:2-2O), and C(16)H(23)O(3) (16:4-O). Mass spectral signals from the polar oxidized lipid (ox-lipid) species were quantified in extracts of Arabidopsis leaves subjected to wounding, infection by PstAvr, infection by a virulent strain of P. syringae, and low temperature. Ox-lipids produced low amounts of mass spectral signal, 0.1% to 3.2% as much as obtained in typical direct infusion profiling of normal-chain membrane lipids of the same classes. Analysis of the oxidized membrane lipid species and normal-chain phosphatidic acids indicated that stress-induced ox-lipid composition differs from the basal ox-lipid composition. Additionally, different stresses result in the production of varied amounts, different timing, and different compositional patterns of stress-induced membrane lipids. These data form the basis for a working hypothesis that the stress-specific signatures of ox-lipids, like those of oxylipins, are indicative of their functions.


Echocardiography in the emergency room: is it feasible, beneficial, and cost-effective?
Echocardiography in the emergency room presents exciting practice possibilities that can facilitate prompt and reliable diagnostic evaluations in patients with suspected cardiovascular emergencies. Echocardiography has the diagnostic potentials to evaluate the entire spectrum of cardiovascular abnormalities short of delineating coronary anatomy and evaluation of the conduction system. By reliably assessing the global and regional function, visualizing the cardiovascular structures from multiple tomographic planes, and quantitating hemodynamic abnormalities, echocardiography should be able to assist emergency room physician's evaluation and triage of the patients with chest pain syndrome, unexplained dyspnea, hypotension, shock, chest trauma, and cardiac arrest, whereby hopefully minimizing the unnecessary admission to the hospital and facilitating inhospital evaluation of the admitted patients with echocardiographic information. However, the optimal echocardiography practice in the emergency room requires well trained sonographers and echocardiographers who can respond to the clinical needs at anytime. Whether an emergency room physician can perform and interpret echocardiographic examinations satisfactorily will depend on his/her level of training and continuing education in this area. Currently, there is no established guideline for performing echocardiography in the emergency room. Further clinical investigations are necessary to define the most optimal and economical utilization of this versatile imaging and hemodynamic diagnostic modality in the emergency room.


Laser in situ keratomileusis for primary and secondary mixed astigmatism.
To evaluate and compare the efficacy, predictability, and safety of LASIK in the correction of primary and secondary mixed astigmatism after previous LASIK surgery. Retrospective, comparative case series. The retrospective study included 118 eyes having LASIK with the LADARVison 4000 excimer laser (Alcon Surgical, Orlando, Florida) to correct mixed astigmatism. The eyes were divided into two groups: in group A (n = 64), LASIK was for primary mixed astigmatism and in group B (n = 54), LASIK was for secondary mixed astigmatism. Mean follow-up was 10.6 +/- 5.90 months. Overall, the postoperative UCVA was 20/20 in 51% of eyes and 20/40 or better in 97% of eyes at the last visit. The mean refractive cylinder was -2.18 +/- 0.94 D preoperatively and -0.56 +/- 0.56 D postoperatively. Sixty-one percent of eyes had a refractive cylinder of 0.50 D or less. One eye lost 2 lines of BSCVA (0.8%). None of the eyes had postoperative BSCVA worse than 20/25. The difference of preoperative cylinder was significant between group A and group B (P = .000). However, there was no statistical difference of postoperative refraction and UCVA between these two groups. At 12 months, the mean vector magnitude achieved was 93% of intended cylinder correction with a mean angle of error of -3.0 +/- 16 degrees. LASIK is a safe, effective, and predictable procedure to treat both primary and secondary mixed astigmatism. Nomogram adjustment with spherical and astigmatism components individually may improve refractive outcomes.


Interfaces and the edge percolation map of random directed networks.
The traditional node percolation map of directed networks is reanalyzed in terms of edges. In the percolated phase, edges can mainly organize into five distinct giant connected components, interfaces bridging the communication of nodes in the strongly connected component and those in the in and out components. Formal equations for the relative sizes in the number of edges of these giant structures are derived for arbitrary joint degree distributions in the presence of local and two-point correlations. The uncorrelated null model is fully solved analytically and compared against simulations, finding an excellent agreement. Interfaces, and their particular conformations giving place from "hairy ball" percolation landscapes to bottleneck straits, could bring new light to the discussion of how a structure is interwoven with functionality in flow networks.


Visceral and Cutaneous Leishmaniases in a City in Syria and the Effects of the Syrian Conflict.
War provides ideal grounds for the outbreak of infectious diseases, and the Syrian war is not an exception to this rule. Following the civil crisis, Syria and refugee camps of neighboring countries witnessed an outbreak of leishmaniasis. We accessed the database of the central leishmaniasis registry in Latakia city and obtained the leishmaniasis data of the period 2008-2016. Our data showed that the years 2013 and 2014 recorded a surge in the number of both cutaneous leishmaniases (CL) and visceral leishmaniasis (VL) cases. This surge coincided with the massive internal displacement waves that struck Latakia governorate during that time. Subsequently, after 2015, the number of recorded CL and VL cases gradually decreased. This drop coincided with a reduced influx of internally displaced persons into Latakia governorate. Our report depicts the effects of the Syrian crisis on the epidemiology of leishmaniasis by outlining the experience of Latakia governorate. Similar results may have occurred in other refugee-hosting Syrian governorates.


Vaccine-related major cutaneous reaction size correlates with cellular-mediated immune responses after tularaemia immunisation.
Francisella tularensis, the causative agent of tularaemia, is an exceptionally infectious bacterium, potentially fatal for humans if left untreated and with the potential to be developed as a bioweapon. Both natural infection and live-attenuated vaccine strain (LVS) confer good protection against tularaemia. LVS vaccination is traditionally administered by scarification, and the formation of a cutaneous reaction or take at the vaccination site is recognised as a clinical correlate of protection. Although previous studies have suggested that high antibody titres following vaccination might serve as a useful surrogate marker, the immunological correlates of protection remain unknown. We investigated the host T-cell-mediated immune (T-CMI) responses elicited following immunisation with LVS vaccine formulated by the DynPort Vaccine Company (DVC-LVS) or the United States Army Medical Research Institute of Infectious Diseases (USAMRIID-LVS). We compared T-CMI responses prompted by these vaccines and correlated them with take size. We found that both LVS vaccines elicited similar T-CMI responses. Interestingly, take size associated with the T cells' ability to proliferate, secrete IFN-γ and mobilise degranulation, suggesting that these responses play an essential role in tularaemia protection. These results renew the appreciation for vaccination through the scarification as a prime route of inoculation to target pathogens driving specific T-CMI responses and provide further evidence that T-CMI plays a role in protection from tularaemia.


Comparative and genetic analysis of the four sequenced Paenibacillus polymyxa genomes reveals a diverse metabolism and conservation of genes relevant to plant-growth promotion and competitiveness.
Members of the genus Paenibacillus are important plant growth-promoting rhizobacteria that can serve as bio-reactors. Paenibacillus polymyxa promotes the growth of a variety of economically important crops. Our lab recently completed the genome sequence of Paenibacillus polymyxa CR1. As of January 2014, four P. polymyxa genomes have been completely sequenced but no comparative genomic analyses have been reported. Here we report the comparative and genetic analyses of four sequenced P. polymyxa genomes, which revealed a significantly conserved core genome. Complex metabolic pathways and regulatory networks were highly conserved and allow P. polymyxa to rapidly respond to dynamic environmental cues. Genes responsible for phytohormone synthesis, phosphate solubilization, iron acquisition, transcriptional regulation, σ-factors, stress responses, transporters and biomass degradation were well conserved, indicating an intimate association with plant hosts and the rhizosphere niche. In addition, genes responsible for antimicrobial resistance and non-ribosomal peptide/polyketide synthesis are present in both the core and accessory genome of each strain. Comparative analyses also reveal variations in the accessory genome, including large plasmids present in strains M1 and SC2. Furthermore, a considerable number of strain-specific genes and genomic islands are irregularly distributed throughout each genome. Although a variety of plant-growth promoting traits are encoded by all strains, only P. polymyxa CR1 encodes the unique nitrogen fixation cluster found in other Paenibacillus sp. Our study revealed that genomic loci relevant to host interaction and ecological fitness are highly conserved within the P. polymyxa genomes analysed, despite variations in the accessory genome. This work suggets that plant-growth promotion by P. polymyxa is mediated largely through phytohormone production, increased nutrient availability and bio-control mechanisms. This study provides an in-depth understanding of the genome architecture of this species, thus facilitating future genetic engineering and applications in agriculture, industry and medicine. Furthermore, this study highlights the current gap in our understanding of complex plant biomass metabolism in Gram-positive bacteria.


[Analysis of the results of serum studies of children and adults for antibodies to the poliomyelitis virus in a multiyear effort at vaccinal prevention of this infection].
The results of testing the blood sera of children and adults for the presence of antibodies to poliomyelitis have shown the low level of immunity to this infection. The authors believe that the main reasons of the tendency towards the decrease in immunity to poliomyelitis, observed in recent years, are the drawbacks of the vaccinal prevention of this infection and the absence of a differentiated approach to the choice of immunization methods under concrete conditions. Mass immunization against poliomyelitis is recommended, especially in the southern and south-eastern regions of the U.S.S.R.


Infectious etiologies among post-donation deferrals in a military blood donation center.
The burden of transfusion-transmitted infections among blood recipients remains low due to extensive pre- and post-donation screening. However, the military has the unique challenge of providing blood in austere environments with limited testing capabilities. This study evaluates the infectious etiologies of deferred blood donors at a large military blood donation center. All blood donors at the Armed Service Blood Bank Center, San Antonio, between 2017 and 2022 with positive post-donation screening for hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV-I/II), Zika (2018-2021), West Nile virus, Trypanosoma cruzi, Treponema pallidum, or Babesia microti (2020-2022) were evaluated. Donors were deferred based on Food and Drug Administration (FDA) guidance. Two-hundred and thirteen (213) donors met FDA criteria for deferral. T. pallidum (n = 45, 50.3 per 100,000), HCV (n = 34, 38.0 per 100,000), and HBV (n = 19, 21.2 per 100,000) were the most common pathogens among those with both positive screening and confirmatory testing. The majority of HIV (95%), Chagas (78%), HTLV-I/II (50%) deferrals were due to indeterminate confirmatory tests following initial positive screens. The majority of deferrals for HBV were for a second occurrence of a positive screen despite negative confirmatory testing. The rates of post-donation deferral for transfusion-transmissible infections were low in this military cohort. Our findings suggest that donor testing in deployed service members should focus on HBV, HCV, and T. pallidum and highlight the need for better diagnostics for HIV, Chagas, and HTLV-I/II.


Common use of prescription off-label acne therapy in children younger than 12 years old.
Acne is occurring more frequently in younger age groups, but most available treatments are considered off-label in young children. As the epidemiology of acne has changed to include younger children over the past 20 years, neither regulators, pharmaceutical companies, nor clinicians have understood the need or value of obtaining regulatory sanctions for problems physicians have managed using clinical judgment. The objective of this study was to analyze the frequency of off-label acne treatment according to age and other demographic factors. We searched the National Ambulatory Medical Care Survey from 1993 to 2010 for visits in children younger than 12 years of age for the diagnosis of International Classification of Diseases, Ninth Revision, code 706.1. We tabulated leading acne treatments and assessed factors associated with off-label prescribing. Off-label but appropriate acne treatments were used in 29% of acne visits for children younger than 12 years of age. Dermatologists were more likely than pediatricians to prescribe off-label treatment (p < 0.001). The most frequently used off-label treatments were topical retinoids, followed by oral antibiotics. There was no significant trend in the rate of off-label prescribing over time (p = 0.40). Off-label treatment is well within the standard of care for young children with acne. More data on the use of topical retinoids in young children will improve our understanding of their use, which may help optimize treatment outcomes for children with acne.


Oral hygiene behaviors and caries experience in Northwest PRECEDENT patients.
To investigate the association between oral hygiene behaviors (toothbrushing, water rinsing after brushing, interproximal cleaning, and adjunctive use of fluoride products) and recent caries (past 24 months) in a random sample of patients in Northwest PRECEDENT practices. Practitioner-members of Northwest PRECEDENT, a dental practice-based research network, conducted a longitudinal study on caries risk assessment. At baseline, patients completed a questionnaire on oral self-care, snacking, health, and socio-demographics. A dental examination recorded readily visible heavy plaque and decayed, missing, and filled teeth; chart review captured new caries and treatments in the previous 24 months. Bivariate and multiple generalized estimating equations (GEE) log-linear regression models stratified by age-groups were used to relate oral hygiene behaviors to the primary outcome of mean dental caries in the past 24 months on data from 1400 patients in 63 practices. The primary exposure of interest was fluoride toothbrushing frequency. Fluoride toothbrushing once per day or twice or more per day by patients 9-17 was significantly associated with a 50% lower mean caries rate compared with fluoride toothbrushing less than once per day, after adjustment for covariates [rate ratios (RR) = 0.5; 95% confidence intervals (CI) = 0.3-0.8]. After adjustment, for patients 18-64, fluoride toothbrushing two or more times per day was significantly associated with a 40% lower recent mean caries rate (RR = 0.6; 95% CI = 0.4-0.9); in patients 65+, twice a day or more fluoride toothbrushing was not associated with lower caries rates (RR = 1.1; 95% CI = 0.7-1.8). Of the other oral hygiene variables, after adjustment, patients 18-64 who rinsed with water after brushing had a 40% lower mean caries rate compared with no rinsing (RR = 0.6; 95% CI = 0.4-0.9) and the presence of readily visible heavy plaque was significantly associated with an increase in the mean caries rate for patients 18-64 (RR = 1.6; 95% CI = 1.2-2.2) and 65+ (RR = 2.5; 95% CI = 1.8-3.5). In the present study, the frequency of fluoride toothbrushing and the presence of readily visible heavy plaque were the factors most strongly associated with mean caries rate. In young patients with permanent dentition, the daily application of fluoride toothpaste appears more important than emphasis on thorough plaque removal. While for adults, the protective effect of twice daily fluoride toothbrushing disappears with advancing age and the presence of readily visible heavy plaque becomes increasingly associated with caries risk.


Somatosensory and Gustatory Profiling in the Orofacial Region.
Quantitative sensory testing (QST) is a standard procedure in medicine to describe sensory patterns in various pathologies. The aim of this prospective clinical study was to define reference values of the trigeminal nerve (V3), including taste qualities, to create a compatibility for sensory loss or gain in pathologies. Fifty-one patients were included, and a standardized testing battery with 11 QST parameters according to the German Research Network on Neuropathic Pain (DFNS) was applied complemented by quantitative gustatory assessments. Significant somatosensory differences were found between the test sites (MDT at the chin, WDT at the lower lip) but no effect was detected for gender, age, and between body types. Taste sensitivity was dependent on concentration, gender (females being more sensitive) and increasing age (for bitter and sour taste). We provide reference values for somatosensory and gustatory testing of the facial area. Our data facilitate the detection of neurosensory abnormalities in the orofacial region. This might also serve as a control setting for COVID-19.


Relative yield loss calculations in wheat (Triticum durum Desf. cv. Camacho) due to ozone exposure.
In this work, an estimation of the relative yield losses of wheat due to ozone exposure is made by means of two approaches proposed by the CLRTAP (Convention on Long Range Transboundary Air Pollution): the exposure-response approach, which deals with the exposure of plants to ozone during a certain time, and the accumulated uptake approach, which, besides ozone exposure, deals with the velocity of absorption of the contaminant and the environmental factors that modulate that absorption. Once the relative yield losses are calculated by means of the two approaches, the aim is to establish which index (the exposure-response index or the accumulated uptake index) best characterizes the response of wheat plants to ozone. The relative yield losses are compared considering two watering regimes: well watered and nonwatered. The results obtained show that the relative yield losses in wheat due to ozone exposure are much more strongly linked to the real quantity of ozone absorbed by plants than to the environmental ozone exposure, which means that the accumulated uptake approach is much more realistic than the exposure-response approach. Relative yield loss estimations were higher in a crop with no watering; 3% of relative yield losses more than a crop watered until field capacity.


Adaptive strategies of Scots pine under shade: Increase in lignin synthesis and ecotypic variation in defense-related gene expression.
Shade is a stressful condition for plants characterized by low Red:Far-Red (R:FR) ratio. The northern latitudes in Sweden daily receive more hours of FR-enriched light (twilight) or shade-like conditions compared to southern forests during the growing season. Scots pine (Pinus sylvestris L.) is a shade-intolerant species. Yet, it is well adapted to this latitudinal variation in light, which is evident by a northward increase in FR requirement to maintain growth. Shade adversely affects plant growth; it makes the plant weak and, therefore, susceptible to pathogen attack. Lignin is involved in plant protection against pathogen invasion mainly by forming a physical barrier. We studied lignin synthesis and expression of defense-related genes (growth-defense trade-offs) under a low R:FR (shade) ratio in Scots pine. A higher number of immunity/defense-related genes were up-regulated in response to shade in northern populations compared to southern ones, which can be viewed as a local adaptation to light quality for optimal growth and survival. Light quality regulates lignin metabolism; light stimulates lignin synthesis, while shade causes a decrease in lignin synthesis in most angiosperms. In contrast, Scots pine shows an increase in lignin synthesis supported by the higher expression of a few key genes in the lignin biosynthetic pathway, a novel finding reported by our study. These findings can be applied to future breeding strategies in forestry to produce disease-resilient trees.


Accidents and injuries in patients with epilepsy.
People with pilepsy are thought to be at an increased risk of accidents and injuries. This results in stigmatization of patients with epilepsy and contributes to a number of limitations in their daily living activities. However, even with differing results, several observational studies (including a large multicenter European survey) report that most accidental injuries are minor and are mostly caused by an epileptogenic clinical condition, an associated handicap or the recurrence of seizures. Domestic, street and work accidents are, in decreasing order, the most common places for such injuries to occur. Contusions and wounds are the most common injuries, followed by abrasions, fractures, brain concussions, sprains/strains and burns. Associated handicaps and comorbidity, where present, as well as antiepileptic drugs, may cause accidents and injuries by impairing cognitive functions and increasing the patient's susceptibility to suffer from the complications of injuries. Patients with epilepsy are also at a slightly higher risk of accidental death than the general population; accidental causes include fires and flames, drowning, suffocation, foreign bodies, falls, suicide and transport accidents. When epileptogenic conditions and seizure-related events are excluded, patients with epilepsy are only at a slightly greater risk of accidents and injuries than the general population.


Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes.
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has previously been shown in HD, and furthermore dopamine is thought to be implicated in cognition, behavioral and motor disturbances. A substantiated inverse correlation between motor onset and the elongated CAG repeat in the HTT has been established. This relation does not account for the full variability of the motor onset, and efforts have been put into finding genetic modifiers of motor onset, however, mostly with unsuccessful outcome. In this study, we took an alternative approach focusing on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms in a well-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance in HD, and point toward more personalized treatment modalities of HD in the future.


[Comparative evaluation of subjective dyspnea sensation in patients with various diseases].
Results of examination of 180 patients with various diseases (COPD, bronchial asthma, idiopathic interstitial pneumonia, chronic heart failure, obesity) are presented. They suggest qualitative and quantitative differences between dyspnea sensation that may be used for differential diagnostics of the above conditions.


Untargeted metabolomics identifies enterobiome metabolites and putative uremic toxins as substrates of organic anion transporter 1 (Oat1).
Untargeted metabolomics on the plasma and urine from wild-type and organic anion transporter-1 (Oat1/Slc22a6) knockout mice identified a number of physiologically important metabolites, including several not previously linked to Oat1-mediated transport. Several, such as indoxyl sulfate, derive from Phase II metabolism of enteric gut precursors and accumulate in chronic kidney disease (CKD). Other compounds included vitamins (pantothenic acid, 4-pyridoxic acid), urate, and metabolites in the tryptophan and nucleoside pathways. Three metabolites, indoxyl sulfate, kynurenine, and xanthurenic acid, were elevated in the plasma and interacted strongly and directly with Oat1 in vitro with IC50 of 18, 12, and 50 μM, respectively. A pharmacophore model based on several identified Oat1 substrates was used to screen the NCI database and candidate compounds interacting with Oat1 were validated in an in vitro assay. Together, the data suggest a complex, previously unidentified remote communication between the gut microbiome, Phase II metabolism in the liver, and elimination via Oats of the kidney, as well as indicating the importance of Oat1 in the handling of endogenous toxins associated with renal failure and uremia. The possibility that some of the compounds identified may be part of a larger remote sensing and signaling pathway is also discussed.


The WHO near miss criteria are appropriate for admission of critically ill pregnant women to intensive care units in China.
Evaluation of the severity of the pregnant women with suitable admission to the Intensive Care Unit (ICU) is very important for obstetricians. By now there are no criteria for critically ill obstetric patients admitted to the ICU. In this article, we investigated the admission criteria of critically ill patients admitted to the ICU in order to provide a referral basis of reasonable use of the ICU. A retrospective analysis of critically ill pregnant women admitted to the ICU in Perking University Third Hospital in China in the last 6 years (from January 2006 to December 2011) was performed, using acute physiology and chronic health evaluation II (APACHE-II), Marshall and WHO near miss criteria to assess the severity of illness of patients. There were 101 critically ill pregnant patients admitted to the ICU. Among them, 25.7% women were complicated with internal or surgical diseases, and 23.8% women were patients of postpartum hemorrhage and 23.8% women were patients of pregnancy-induced hypertension. Sixty-nine cases (68.3%) were administrated with adjunct respiration with a respirator. Sixteen cases (15.8%) required 1-2 types of vasoactive drugs. Fifty-five cases (54.5%) required a hemodynamic monitoring. Seventy-three cases (72.3%) had multiple organ dysfunctions (MODS). The average duration in ICU was (7.5 ± 3.0) days. A total of 12.9%, 23.8% and 74.3% of women were diagnosed as critically ill according to the APACHE-II, Marshall and WHO near miss criteria, respectively. The rate was significantly different according to the three criteria (P < 0.01). The WHO near miss criteria can correctly reflect the severity of illness of pregnant women, and the WHO near miss criteria are appropriate for admission of critically ill pregnant women to ICU in China.


Cell Nuclei Segmentation With Dynamic Token-Based Attention Network.
Cell nuclei segmentation is crucial for analyzing cell structure in different tasks, i.e., cell identification, classification, etc., to treat various diseases. Several convolutional neural network-based architectures have been proposed for segmenting cell nuclei. Although these methods show superior performance, they lack the ability to predict reliable masks when using biomedical image data. This paper proposes a novel Dynamic Token-based Attention Network (DTA-Net). Combining convolutional neural networks (CNN) with a vision transformer (ViT) allows us to capture detailed spatial information from images efficiently by encoding local and global features. Dynamic Token-based Attention (DTA) module calculates attention maps keeping the overall computational and training costs minimal. For the nuclei segmentation task on the 2018 Science Bowl dataset, our proposed method outperformed SOTA networks with the highest Dice similarity score (DSC) of 93.02% and Intersection over Union (IoU) of 87.91% without using image pre- or post-processing techniques. The results showed that high-quality segmentation masks could be obtained by configuring a ViT in the most straight forward manner.Clinical relevance- In this work, the segmentation of cell nuclei in microscopy images is carried out automatically, irrespective of their appearance, density, magnification, illumination, and modality.


Teaching subfascial perforator veins surgery: survey on a 2-day hands-on course.
The present paper describes a training method with objective evaluation to enhance video-assisted surgical skills in subfascial endoscopic perforator veins surgery (SEPS). Training was scheduled during a 2-day intensive course. Hands-on exercises were performed (i) on a simulator to assess whether specific training exercises were helpful in attainment of skills; (ii) on a known animal model that uses the swine abdominal wall and which allows practice in endoscopic dissection and perforator veins (PV) using appropriate instrumentation in an environment that is a reasonable surrogate for the human calf; and (iii) assisting a senior surgeon performing SEPS. Thirty surgeons without experience in SEPS were trained to perform a sequence of standardized drills connected with the SEPS technique. The SEPS simulator consisted of an artificially constructed subfascial space of the leg in which false perforator veins had to be localized, and cut. The participants performed a sequence of drills three times in order to improve their dexterity. The same exercises were then performed on a swine model. The model consisted of the arteries and veins penetrating the rectus fascia and passing into the overlying cutaneous trunci muscle and hypodermis on either side of the midline between the arch of the ribs cranially and the umbilicus caudally. Trainees were required to achieve operative space in the animal subcutaneous fat, to reach and identify the "perforating" subcutaneous vessels, and to interrupt some of them with a 5-mm clamp coagulator ultrasonic scalpel. The time required to perform each dexterity drill was recorded in seconds. Finally, the day after, trainees were asked to drive the senior operator during clinical SEPS performed on eight patients, suggesting the following manoeuvres in order to: (i) enter the subfascial space of the leg; (ii) make operative space; (iii) identify the incompetent perforator vein(s); and (iv) coagulate and divide them with the ultrasonic scalpel. Each of these four steps scored 1 point. All the trainees showed a steady improvement in skill acquisition on the SEPS simulator (P < 0.001), and on the animal model with the single-port technique (P < 0.001). These results reflect positively on the animal model using the dual-port technique, and on the scores achieved in the operating theatre during clinical SEPS. The validity of the 2-day course was demonstrated by significant improvement in performance with increasing skill on the training models, and in clinical practice.


Outbreeding and lack of temporal genetic structure in a drone congregation of the neotropical stingless bee Scaptotrigona mexicana.
Drone aggregations are a widespread phenomenon in many stingless bee species (Meliponini), but the ultimate and proximate causes for their formation are still not well understood. One adaptive explanation for this phenomenon is the avoidance of inbreeding, which is especially detrimental for stingless bees due to the combined effects of the complementary sex-determining system and the small effective population size caused by eusociality and monandry. We analyzed the temporal genetic dynamics of a drone aggregation of the stingless bee Scaptotrigona mexicana with microsatellite markers over a time window of four weeks. We estimated the drones of the aggregation to originate from a total of 55 colonies using sibship re-construction. There was no detectable temporal genetic differentiation or sub-structuring in the aggregation. Most important, we could exclude all colonies in close proximity of the aggregation as origin of the drones in the aggregation, implicating that they originate from more distant colonies. We conclude that the diverse genetic composition and the distant origin of the drones of the S. mexicana drone congregation provides an effective mechanism to avoid mating among close relatives.


Genetic and developmental analysis of the locus vnd in Drosophila melanogaster.
Genetic and developmental analysis of an X-linked vital locus vnd was undertaken. Embryos hemizygous for the original allele vnd did not hatch and exhibited a disorganized ventral nervous system (VNS). The mutation maps in the region 1B6-7 to 1B9-10, a subregion of an area previously shown to be essential to normal neural development. In this paper, we report isolation of five new alleles at the locus vnd. Genetic complementation analysis of all mutations at the vnd locus, with lethal alleles at adjacent loci, indicates that all lesions at the locus vnd affect only one vital gene function in the region. Four of the five alleles are embryonic lethal; one allele is subvital and behaves like an hypomorphic mutation. Hemizygous embryos for three of the four embryonic lethal alleles were inspected in histological sections; all exhibited disorganized VNS similar to the original allele. The developmental analysis in gynandromorphic genetic mosaics shows that (1) vnd+ gene function is not essential in most imaginal-disc cell derivatives, (2) only about 30% of the mosaic zygotes survive as adults, (3) mosaic zygotes with mutant tissue close to the head cuticle are least likely to survive, and (4) mutant tissue in the thoracic ganglion in the adult is not necessarily lethal. The mosaic data are consistent with the vnd+ gene function being necessary in neural cells derived from the anterioventral region of the blastoderm.


A neural network underlying intentional emotional facial expression in neurodegenerative disease.
Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls) were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM) across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.


Biodegradable Hydrogel Scaffolds Based on 2-Hydroxyethyl Methacrylate, Gelatin, Poly(β-amino esters), and Hydroxyapatite.
New composite 3D scaffolds were developed as a combination of synthetic polymer, poly(2-hydroxyethyl methacrylate) (PHEMA), and a natural polymer, gelatin, with a ceramic component, nanohydroxyapatite (ID nHAp) dopped with metal ions. The combination of a synthetic polymer, to be able to tune the structure and the physicochemical and mechanical properties, and a natural polymer, to ensure the specific biological functions of the scaffold, with inorganic filler was applied. The goal was to make a new material with superior properties for applications in the biomedical field which mimics as closely as possible the native bone extracellular matrix (ECM). Biodegradable PHEMA hydrogel was obtained by crosslinking HEMA by poly(β-amino esters) (PBAE). The scaffold's physicochemical and mechanical properties, in vitro degradation, and biological activity were assessed so to study the effects of the incorporation of nHAp in the (PHEMA/PBAE/gelatin) hydrogel, as well as the effect of the different pore-forming methods. Cryogels had higher elasticity, swelling, porosity, and percent of mass loss during degradation than the samples obtained by porogenation. The composite scaffolds had a higher mechanical strength, 10.14 MPa for the porogenated samples and 5.87 MPa for the cryogels, but a slightly lower degree of swelling, percent of mass loss, and porosity than the hybrid ones. All the scaffolds were nontoxic and had a high cell adhesion rate, which was 15-20% higher in the composite samples. Cell metabolic activity after 2 and 7 days of culture was higher in the composites, although not statistically different. After 28 days, cell metabolic activity was similar in all scaffolds and the TCP control. No effect of integrating nHAp into the scaffolds on osteogenic cell differentiation could be observed. Synergetic effects occurred which influenced the mechanical behavior, structure, physicochemical properties, and interactions with biological species.


Repression of sucrose/ultraviolet B light-induced flavonoid accumulation in microbe-associated molecular pattern-triggered immunity in Arabidopsis.
Recognition of microbe-associated molecular patterns (MAMPs) leads to the generation of MAMP-triggered immunity (MTI), which restricts the invasion and propagation of potentially infectious microbes. It has been described that the perception of different bacterial and fungal MAMPs causes the repression of flavonoid induction upon light stress or sucrose application. However, the functional significance of this MTI-associated signaling output remains unknown. In Arabidopsis (Arabidopsis thaliana), FLAGELLIN-SENSING2 (FLS2) and EF-TU RECEPTOR act as the pattern recognition receptors for the bacterial MAMP epitopes flg22 (of flagellin) and elf18 (of elongation factor [EF]-Tu), respectively. Here, we reveal that reactive oxygen species spiking and callose deposition are dispensable for the repression of flavonoid accumulation by both pattern recognition receptors. Importantly, FLS2-triggered activation of PATHOGENESIS-RELATED (PR) genes and bacterial basal defenses are enhanced in transparent testa4 plants that are devoid of flavonoids, providing evidence for a functional contribution of flavonoid repression to MTI. Moreover, we identify nine small molecules, of which eight are structurally unrelated, that derepress flavonoid accumulation in the presence of flg22. These compounds allowed us to dissect the FLS2 pathway. Remarkably, one of the identified compounds uncouples flavonoid repression and PR gene activation from the activation of reactive oxygen species, mitogen-activated protein kinases, and callose deposition, corroborating a close link between the former two outputs. Together, our data imply a model in which MAMP-induced repression of flavonoid accumulation serves a role in removing the inherent inhibitory action of flavonoids on an MTI signaling branch.


A genomics approach to understanding host response during dengue infection.
Dengue infection results in a wide clinical spectrum, ranging from asymptomatic, through fever (DF), to the life threatening complications haemorrhagic fever (DHF) and shock syndrome (DSS). Although we now understand that factors such as repeat infections and the type or magnitude of the host response are important in determining severity, the mechanisms of these actions remain largely unknown. Understanding this host-pathogen interaction may enable outcome prediction and new therapy options. Developments in biology now allow a 'systems approach' to be applied to this problem, utilizing whole genomes of both human and virus, in vitro and in vivo to enable a more complete picture of their interplay to be built up. We have developed a chip-based approach to viral sequencing, to increase efficiency and enable large numbers ofgenomes to be completed, together with a web-based interpretation tool. We have also applied human whole genome expression arrays (24000 genes) to characterize the types of host response made to infection and plan to investigate the role of host variation using human whole genome genetic association studies in the future. These technologies have identified novel host pathways involved in viral replication in vitro, and also host immune responses, such as the interferon signalling pathway, that are influenced by viral sequence. This data will be further refined through interlinking with similar data obtained from a large study of dengue patients, initiated in Singapore, that is able to look at the early host response to infection.


[Gastrin and its role in the development of ulcer disease].
Helicobacter pylori infected patients have increased gastrin release which shows a marked fall after cure of the infection. Recent studies indicate that inflammatory cells and cytokines play an important role in the pathogenesis of Helicobacter-associated hypergastrinemia. Views differ regarding the impact of gastrin on acid secretion. Current evidence suggests that gastrin is responsible for at least some of the increased acid secretion seen in duodenal ulcer patients.


[NO-therapy in the treatment of purulent and necrotic lesions of lower extremities in diabetic patients].
NO-therapy with "Plazon" system was used in complex treatment of purulent and necrotic lesions of the lower extremities in 65 diabetic patients. Efficacy was evaluated with clinical, cytological and bacteriological studies. All the phases of wound process were shorter when NO-therapy was used. Complex treatment with NO-therapy led to faster (2 times) epithelization of diabetic ulcers compared with continual treatment.


Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector.
Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack type VII collagen and therefore have severely impaired dermal-epidermal stability causing recurrent skin and mucosal blistering. There is currently no specific approved treatment for RDEB. We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice. We obtained 50% transduction efficiency in primary human RDEB fibroblasts with an average low copy number (range = 1-2) of integrated provirus. Transduced fibroblasts showed strong type VII collagen re-expression, improved adhesion properties, normal proliferative capabilities, and viability in vitro. We show that a single intradermal injection of 3 × 10(6) genetically corrected RDEB fibroblasts beneath RDEB skin equivalents grafted onto mice allows type VII collagen deposition, anchoring fibril formation at the dermal-epidermal junction, and improved dermal-epidermal adherence 2 months after treatment, supporting functional correction in vivo. Gene-corrected fibroblasts previously showed no tumorigenicity. These data show the efficacy and safety of gene-corrected fibroblast therapy using a self-inactivating vector that has now been good manufacturing grade-certified and pave the way for clinical translation to treat nonhealing wounds in RDEB patients.


[Cheiromegaly and podomegaly associated with primary progressive multiple sclerosis: a case report].
Cheiromegaly is an extremely rare syndrome characterized by unilateral hand hypertrophy with hyperhydrosis. Unilateral foot hypertrophy has been described as podomegaly. Cheiromegaly/podomegaly is usually seen in patients with syringomyelia. Although the underlying pathophysiology remains unknown, it is speculated that chronic cervical cord injury including central descending sympathetic tract is essential for development of this syndrome. We report a cheiromegaly/podomegaly in a case with primary progressive multiple sclerosis. This 29-year-old woman developed cheiromegaly and podomegaly in her right hand and foot associated with chronic progressive cervical myelopathy. At age two, she developed transient paraparesis with full recovery, suggesting her symptomatic onset of her longstanding illness. At age 10, she had left leg weakness, and gradually worsened. On admission at age 29, she had muscular weakness in her left upper and both lower extremities. Sensory impairment was seen below her 5th cervical and 6th thoracic dermatome level. Her deep tendon reflexes were exaggerated in all extremities with bilateral Babinski's signs. MR imaging showed multiple plaques in the white matter of the brain associated with cervical spinal cord lesions. Taken together with the presence of oligoclonal band IgG in the cerebrospinal fluid, this patient met the criteria of multiple sclerosis. This is the first report presenting cheiromegaly/podomegaly not associated with syringomyelia, but with multiple sclerosis. It is suggested that cheiromegaly/podomegaly in present case may be caused by chronic cervical cord injury affecting descending central sympathetic tract associated with primary progressive multiple sclerosis.


Cross-sectional and longitudinal associations between total and regional white matter hyperintensity volume and cognitive and motor function in Parkinson's disease.
White matter hyperintensities (WMH) are frequently observed on T2-weighted brain magnetic resonance imaging studies of healthy older adults and have been linked with impairments in balance, gait, and cognition. Nonetheless, few studies have investigated the longitudinal effects of comorbid WMH on cognition and motor function in Parkinson's disease. The Lesion Segmentation Tool for Statistical Parametric Mapping was used to obtain total lesion volume and map regional WMH probabilities in 29 PD and 42 control participants at two study visits 18 months apart. Both cross-sectional and longitudinal comparisons were made between composite scores in the domains of executive function, memory, and language, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. We found no difference between disease and control groups in total WMH volume or progression during the study. Greater regional and global WMH at baseline was more strongly associated with lower executive function in PD subjects than in controls. Increased regional WMH was also more strongly associated with impaired memory performance in PD relative to controls. Longitudinally, no associations between cognitive change and total or regional WMH progression were detected in either group. A positive relationship between baseline regional WMH and total UPDRS scores was present in the control group, but not PD. However, greater WMH increase was associated with a greater increase in UPDRS motor sub-scores in PD. These findings suggest that although PD patients do not experience greater mean WMH load than normal aged adults, comorbid WMH do exacerbate cognitive and motor symptoms in PD.


Comparison of different analytical methods for assessing total antioxidant capacity of human serum.
Three assays were compared for the determination of total antioxidant capacity in human serum: the oxygen radical absorbance capacity (ORAC) assay, the Randox Trolox-equivalent antioxidant capacity (Randox-TEAC) assay, and the ferric reducing ability (FRAP) assay. There was a weak but significant linear correlation between serum ORAC and serum FRAP. There was no correlation either between serum ORAC and serum TEAC or between serum FRAP and serum TEAC. The effect of dilution on the serum TEAC value and the use of inhibition percentage at a fixed time, without considering the length of inhibition time in the quantitation of results, adversely affected the Randox-TEAC assay. The FRAP assay is simple and inexpensive but does not measure the SH-group-containing antioxidants. The ORAC assay has high specificity and responds to numerous antioxidants. By utilizing different extraction techniques in the ORAC assay, one can remove serum proteins and also make some gross differentiation between aqueous and lipid-soluble antioxidants. However, the ORAC assay requires approximately 60 min more than the FRAP or Randox-TEAC assay to quantitate results.


In Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects.
The detection of Cu2+ in living plants and animals is of great importance for environment monitoring and disease diagnosis. Here, a near-infrared (NIR) turn-on photoacoustic (PA) probe (denoted as LET-2) is developed for Cu2+ detection in living subjects, such as soybean sprouts and mice. The absorbance band of LET-2 shifts from 625 to 715 nm after the interaction with Cu2+ , thus producing strong PA signal output at 715 nm (PA715 ) as an indicator. The PA715 value is increased as a function of the concentration of Cu2+ (0 × 10-6 -20 × 10-6 m), with a calculated limit of detection of 10.8 × 10-9 m. More importantly, both in vitro and in vivo studies in soybean sprouts and mice indicate that the as-prepared LET-2 PA probe is highly sensitive and selective for Cu2+ detection. These findings provide a solution for in vivo detection of metal ions by using chemoselective PA probes.


Abnormal cerebral hemodynamics in preterm infants with patent ductus arteriosus.
Blood flow patterns in the anterior cerebral arteries were studied in eight preterm infants with patent ductus arteriosus and left-to-right shunts. A noninvasive Doppler technique was used to obtain the blood flow patterns and to calculate a pulsatility index. Advancing diastolic blood flow was decreased in all eight infants, and two demonstrated retrograde anterior cerebral artery flow during diastole. Following ductal closure, the diastolic flow in the anterior cerebral arteries increased significantly, reaching levels seen in normal infants. These observations demonstrate that infants with patent ductus arteriosus and left-to-right shunts may have abnormal cerebral hemodynamics which return to normal following ductal closure.


Methicillin-Resistant Staphylococcus aureus-Associated Diarrhea in a Critically Ill Burn Patient.
Described in surgical patients after antibiotic use in the 1950s and 1960s, Staphylococcus aureus (S. aureus) enterocolitis is a rare form of nosocomial diarrhea. However, S. aureus is not routinely tested like Clostridium difficile (C. difficile). We report a case of methicillin-resistant S. aureus (MRSA) enterocolitis found on stool culture in a 22-week pregnant female with a previously negative nasal MRSA culture, and a total burn surface area greater than 60%. She also developed necrotizing MRSA pneumonia and bacteremia. After starting broad-spectrum antibiotic for the necrotizing pneumonia with subsequent acute respiratory distress syndrome, the patient exhibited large voluminous diarrhea that tested positive for MRSA and negative for C. difficile in the stool culture. Similar to other reports of high-volume diarrhea, the diarrhea resolved quickly with enteral vancomycin. S. aureus should be considered along with C. difficile during the workup of nosocomial diarrhea, especially with exposure to broad-spectrum antibiotics in the critically ill patient.


Switchable generation of azimuthally- and radially-polarized terahertz beams from a spintronic terahertz emitter.
We propose and demonstrate a method of generating two fundamental terahertz cylindrical vector beams (THz-CVBs), namely the azimuthally- and radially-polarized THz pulses, from a spintronic THz emitter. We begin by presenting that the spintronic emitter generates the HE21 mode, a quadrupole like polarization distribution, when placed between two magnets with opposing polarity. By providing an appropriate mode conversion using a triangular Si prism, we show both from experiment and numerical calculation that we obtain azimuthal and radial THz vector beams. The proposed method facilitates the access of CVBs and paves the way toward sophisticated polarization control in the THz regime.


Coagulation factor VIII. Localization in the aqueous outflow pathways.
Antihemophilic factor A-von Willebrand factor (AHF-vWF) is a protein involved in the first phase of blood coagulation and in the mechanism of platelet adhesion. The localization of this protein has been studied in the anterior segment of fetal and adult human eye by a direct immunofluorescence method. It was found that AHF-vWF is present in the wall of aqueous outflow pathways but not in that of Schlemm canal. As it has fibrinolytic activity in the endothelium of Schlemm canal, this structure can be expected to be especially well protected against fibrin deposition and occlusion by platelets and thrombi. The ciliary processes of the adult eye had no AHF-vWF activity. Instead, fluorescein isothiocyanate-fluorescence could be seen in the vessel wall of the ciliary processes of the fetal eye. This difference may be connected with the function of aqueous secretion.


[The initial trial of the clinical use of FK-1 glue in surgical interventions].
The article presents results of a comparative clinical trial of the preparation "fibrinous glue" (FK-1) and "Beriplast" in operations on the lungs for hermetization of the wound and the lung as well as in reconstructive plastic gynecological operations. Intraoperative hermetization in operations on the lungs was obtained in 67% of the cases when using "FK-1" and in 64% with "Beriplast". In all the cases the lung was spread during 12 hours after operation. The visual intraoperative assessment of using "FK-1" and control laparoscopy on the 4th-5th days after operation showed its good effect in gynecological procedures. Clinical trials of the new domestic fibrinous glue "FK-1" in surgical and gynecological clinics confirmed its high medical effectiveness.