Dispersal of deep-sea larvae from the intra-American seas: simulations of trajectories using ocean models.
Using data on ocean circulation with a Lagrangian larval transport model, we modeled the potential dispersal distances for seven species of bathyal invertebrates whose durations of larval life have been estimated from laboratory rearing, MOCNESS plankton sampling, spawning times, and recruitment. Species associated with methane seeps in the Gulf of Mexico and/or Barbados included the bivalve "Bathymodiolus" childressi, the gastropod Bathynerita naticoidea, the siboglinid polychaete tube worm Lamellibrachia luymesi, and the asteroid Sclerasterias tanneri. Non-seep species included the echinoids Cidaris blakei and Stylocidaris lineata from sedimented slopes in the Bahamas and the wood-dwelling sipunculan Phascolosoma turnerae, found in Barbados, the Bahamas, and the Gulf of Mexico. Durations of the planktonic larval stages ranged from 3 weeks in lecithotrophic tubeworms to more than 2 years in planktotrophic starfish. Planktotrophic sipunculan larvae from the northern Gulf of Mexico were capable of reaching the mid-Atlantic off Newfoundland, a distance of more than 3000 km, during a 7- to 14-month drifting period, but the proportion retained in the Gulf of Mexico varied significantly among years. Larvae drifting in the upper water column often had longer median dispersal distances than larvae drifting for the same amount of time below the permanent thermocline, although the shapes of the distance-frequency curves varied with depth only in the species with the longest larval trajectories. Even species drifting for >2 years did not cross the ocean in the North Atlantic Drift.


Leisure time physical exercise during pregnancy and the risk of miscarriage: a study within the Danish National Birth Cohort.
To examine the association between leisure time physical exercise during pregnancy and the risk of miscarriage. Prospective study with elements of retrospective data collection. Denmark 1996-2002. A total of 92,671 pregnant women enrolled in the Danish National Birth Cohort and interviewed subsequently. Data on exercise during pregnancy and potential confounders were obtained through computer-assisted telephone interviews either during pregnancy or after an early miscarriage. Outcome of pregnancy was identified by register linkage. Using Cox regression analysis, we estimated the hazard ratio (HR) of miscarriage according to weekly amount of exercise and the type of exercise. The HR was estimated for <11, 11-14, 15-18, and 19-22 weeks of gestation, respectively. Miscarriage, defined as fetal loss before 22 completed weeks of gestation. A stepwise increasing relation was found between amount of exercise and risk of miscarriage, where risk of miscarriage increased by amount of exercise up to HR = 3.7 (95% CI 2.9-4.7) for women who exercised more than 7 hours per week compared with nonexercisers. Particularly 'high-impact exercise' was associated with an increased risk of miscarriage. No association was seen between exercise and risk of miscarriage after 18 weeks of gestation. This study suggests that exercise early in pregnancy is associated with an increased risk of miscarriage. The results should, however, be interpreted cautiously as potential bias arising from retrospective data collection may explain part of the association.


Lichen sclerosus of the oral mucosa: a case report.
Lichen sclerosus or lichen sclerosus et atrophicus is a chronic inflammatory disease predominantly affecting the genital mucosa and skin. Clinically, it is characterized by white atrophic plaques in the anogenital region. The lesions are generally asymptomatic, but may cause discomfort with itching and pain. Extragenital mucosal involvement is very unusual, and lesions limited to the oral mucosa are even less frequent. Knowledge of such lesions is important in order to establish a differential diagnosis with other white oral lesions, and histological confirmation is required. We present the case of a 31-year-old woman with a well delimited, pearly white lesion located in the upper gingival mucosa, lip mucosa and adjacent skin. The lesion had led to loss of periodontal attachment of the affected tooth, causing pain in response to tooth brushing. The biopsy confirmed lichen sclerosus, and treatment was provided in the form of intralesional corticoid injections, followed by improvement of the mucosal lesion, though without recovery of the periodontal loss.


Stacked LSTM based deep recurrent neural network with kalman smoothing for blood glucose prediction.
Blood glucose (BG) management is crucial for type-1 diabetes patients resulting in the necessity of reliable artificial pancreas or insulin infusion systems. In recent years, deep learning techniques have been utilized for a more accurate BG level prediction system. However, continuous glucose monitoring (CGM) readings are susceptible to sensor errors. As a result, inaccurate CGM readings would affect BG prediction and make it unreliable, even if the most optimal machine learning model is used. In this work, we propose a novel approach to predicting blood glucose level with a stacked Long short-term memory (LSTM) based deep recurrent neural network (RNN) model considering sensor fault. We use the Kalman smoothing technique for the correction of the inaccurate CGM readings due to sensor error. For the OhioT1DM (2018) dataset, containing eight weeks' data from six different patients, we achieve an average RMSE of 6.45 and 17.24 mg/dl for 30 min and 60 min of prediction horizon (PH), respectively. To the best of our knowledge, this is the leading average prediction accuracy for the ohioT1DM dataset. Different physiological information, e.g., Kalman smoothed CGM data, carbohydrates from the meal, bolus insulin, and cumulative step counts in a fixed time interval, are crafted to represent meaningful features used as input to the model. The goal of our approach is to lower the difference between the predicted CGM values and the fingerstick blood glucose readings-the ground truth. Our results indicate that the proposed approach is feasible for more reliable BG forecasting that might improve the performance of the artificial pancreas and insulin infusion system for T1D diabetes management.


Challenges in undertaking nonlinear Mendelian randomization.
Mendelian randomization (MR) is a widely used method that exploits the unique properties of germline genetic variation to strengthen causal inference in relationships between exposures and outcomes. Nonlinear MR allows estimation of the shape of these relationships. In a previous paper, the authors applied linear and nonlinear MR to estimate the effect of BMI on mortality in UK Biobank, providing evidence for a J-shaped association. However, it is now clear that there are problems with widely used nonlinear MR methods, which draws attention to the likely erroneous nature of the conclusions regarding the shapes of several explored relationships. Here, the authors explore the utility and likely biases of these nonlinear MR methods with the use of a negative control design. Although there remains good evidence for a causal effect of higher BMI increasing the risk of mortality, the pattern of this association across different levels of BMI requires further characterization.


Ponticulus posticus is a frequent radiographic finding on lateral cephalograms in nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).
Nevoid basal cell carcinoma syndrome (NBCCS) is a predisposition to a rare tumor type with a variable phenotype. Besides tumors, skeletal alterations, such as bifid ribs or frontal bossing constitute the phenotype. Recently, a variant of the first cervical vertebra, the ponticulus posticus, was reported to occur in 50% of patients with NBCCS as revealed by analysis of lateral cephalograms. Lateral cephalograms of eight patients with NBCCS were studied for the presence of ponticulus posticus. The ponticulus posticus was present in all patients. In one case, a series of cephalograms performed during a period of 20 years allowed the slow and continuous recording of a ponticulus posticus formation. Besides the predisposition to developing neoplasms, NBCCS also affects bone development. Some diagnostic criteria for NBCCS rely on certain osseous transformations either in hard tissues, e.g. keratocystic odontogenic tumor in jaws, or in soft tissues, e.g. calcification of the falx cerebri. Furthermore, the physiognomy can be affected by skeletal alterations, e.g. frontal bossing or hypertelorism. Given this wide spectrum of osseous involvement in NBCCS, the high prevalence rate of ponticulus posticus should be added to the relevant diagnostic findings of the skull and vertebral column. However, the onset of ponticulus posticus formation in the life of such patients is unclear and thus the relevance of this finding in early diagnosis of NBCCS remains to be elucidated.


Postpartum depression and anxiety: a community-based study on risk factors before, during and after pregnancy.
Depression and anxiety occur frequently postpartum, calling for early detection and treatment. Evidence on risk factors may support early detection, but is inconclusive. Our aim was to identify risk factors for postpartum depression and anxiety, before, during and after pregnancy. We used data from 1406 mothers of the intervention arm of the Post-Up study. Risk factors were collected at 3 weeks and 12 months postpartum. Depression and anxiety symptoms were measured in the first month postpartum by the Edinburgh Postnatal Depression Scale (EPDS) and 6-item State-Trait Anxiety Inventory (STAI-6), respectively. We used stepwise logistic regression to identify relevant risk factors. Of the mothers, 8.0% had EPDS-scores ≥9 and 14.7% STAI-6-scores ≥42. Factors associated with higher risk of depression were: foreign language spoken at home, history of depression, low maternal self-efficacy and poor current health of the mother. No initiation of breastfeeding was associated with lower risk of depression, no breastfeeding at 3 weeks postpartum increased the risk. Factors associated with higher risk of anxiety were: higher educational level, history of depression, preterm birth, negative experience of delivery and first week postpartum, excessive infant crying, low maternal self-efficacy, low partner support and poor current maternal health. Use of a self-report instrument, potential bias by postpartum mood status, and no inclusion of emerging depression cases after one month postpartum. The shared and separate risk factors for postpartum depression and anxiety may help professionals in identifying mothers at increased risk and provide opportunities for preventive interventions and treatment.


Conservation and restoration of a keystone species: Understanding the settlement preferences of the European oyster (Ostrea edulis).
The European oyster Ostrea edulis is a keystone species that is internationally recognised as 'threatened and declining' in the NE Atlantic by OSPAR and several nations have consequently adopted strategies for its conservation and restoration. Understanding the settlement behaviour of O. edulis larvae is crucial to inform these strategies. We compared the efficiency of several treatments in triggering settlement. The most effective settlement occurred with the presence of conspecifics: 100% settled in <23 h. Marine stones with habitat-associated biofilms induced 81% settlement that started after a 45 h delay. Sterile shells and terrestrial stones did not induce more settlement than control treatments. These results indicate that O. edulis larvae are gregarious and finely-tuned to settle in response to cues which are indicative of their adult habitat requirements. The role of chemical cues in mediating settlement, and the importance of this to restoration, are discussed.


Reaction products of styrene oxide with guanosine in aqueous media.
Styrene oxide was reacted with guanosine in fully aqueous conditions, and the products were purified by cation exchange chromatography and h.p.l.c. The products were characterized by u.v. and mass spectra, loss of tritium from the C-8 position and dissociation properties. About 90% of the total product was identified, of which 57, 28 and 15% were assigned to N-7, N2 and O6 adducts. The two diastereomers of beta-substitution accounted for 53% of the N-7 adducts, while the two alpha-substitutions accounted for the remaining 47%. Two species of N2 and O6 products were also isolated but their substitution pattern was not established.


Recurrence and Risk Factors for Relapse in Patients with Non-Small Cell Lung Cancer Treated by Surgery with Curative Intent.
Surgery remains the potentially curative treatment for early-stage non-small cell lung cancer (NSCLC). Despite this, tumor recurrence is the most common cause of treatment failure after surgery. Data were collected retrospectively from clinical files of patients who underwent lung surgery for NSCLC from January 2008 to December 2012 in a University Hospital. Demographic data, tumor characteristics, type of surgery and recurrence were recorded. A comparison of the distribution of variables using adjustment tests was made. The study included 102 patients, 68.6% were male with a mean age of 63.7 ± 9.3 years old. The majority of tumors had a peripheral location (72.5%) and consisted of adenocarcinomas (61.8%). The most frequently performed surgery was lobectomy. Recurrence was noted in 43.1% of cases. Mean disease-free survival was 57.9 ± 3.8 months. Multifactorial analyses showed that stage IIIA, tumor located in other lobes than the right lower lobe and pleural invasion were independent predictors of recurrence. Our recurrence rate was similar to those in the international literature. As in other studies, we found a positive relation between the lymphatic permeation and pleural invasion and the risk of lung cancer recurrence. We consider that some characteristics of the tumor should be assessed to define alternative modalities of treatment and follow-up in order to predict and rapidly recognize the recurrence.


The atopic thigh: a "starting-school' symptom?
In a retrospective survey of 1112 patients with atopic dermatitis we found that the age of onset of lesions localized to the lower gluteal and posterior femoral regions reached its peak at the age of 7 to 8 years. We speculated that this is due to sweat retention caused by prolonged sitting when these predisposed individuals start school.


Membrane Disruption and Enhanced Inhibition of Cell-Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin-Resistant Bacteria.
Resistance to glycopeptide antibiotics, the drugs of choice for life-threatening bacterial infections, is on the rise. In order to counter the threat of glycopeptide-resistant bacteria, we report development of a new class of semi-synthetic glycopeptide antibiotics, which not only target the bacterial membrane but also display enhanced inhibition of cell-wall biosynthesis through increased binding affinity to their target peptides. The combined effect of these two mechanisms resulted in improved in vitro activity of two to three orders of magnitude over vancomycin and no propensity to trigger drug resistance in bacteria. In murine model of kidney infection, the optimized compound was able to bring bacterial burden down by about 6 logs at 12 mg kg(-1) with no observed toxicity. The results furnished in this report emphasize the potential of this class of compounds as future antibiotics for drug-resistant Gram-positive infections.


The absence of Mth1 inactivation and DNA polymerase kappa overexpression in rat mammary carcinomas with frequent A:T to C:G transversions.
Single nucleotide instability (SNI), an increase in spontaneous point mutation rates (MRs) without involvement of microsatellite instability, is present in rat mammary carcinoma cell lines and human breast cancer cell lines. A:T to C:G transversions, which are generally rare, were frequently observed in two rat mammary carcinoma cell lines and in their primary carcinomas, and were considered to be related to the molecular mechanism of SNI. In this study, two known molecular mechanisms that cause increases of A:T to C:G transversions, inactivation of the MutT mammalian homologue (Mth1) gene and overexpression of the DNA polymerase k (Pol k) gene, were analyzed in two rat mammary carcinoma cell lines and 11 rat primary carcinomas. PCR-SSCP analysis revealed no mutations in the entire Mth1 coding region. Quantitative real-time RT-PCR analysis showed that Mth1 mRNA expression was slightly, but significantly, increased in the primary carcinomas (P = 0.001 using GAPDH for normalization, and P = 0.002 using histone H4, t-test), contrary to our expectation, and was decreased to 1 / 2 in the cell lines. The expression of Pol k, which is known to be error-prone with frequent A:T to C:G transversions, was rather decreased in the cell lines and primary carcinomas. Inactivation of Mth1 and overexpression of Pol k were unlikely to have caused SNI in the two rat mammary carcinoma cell lines with a high frequency of A:T to C:G transversions, and searching for other unknown molecular mechanisms is important.


Challenges and opportunities for medications development in alcoholism: an international perspective on collaborations between academia and industry.
This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on September 30, 2004. The organizers and cochairs were Bankole A. Johnson, DSc, MD, PhD, and Karl Mann, MD. The presentations included the following: (1) A Perspective from Academia, by Bankole A. Johnson, DSc, MD, PhD; (2) A Perspective from NIAAA, by Mark L. Willenbring, MD; (3) A Perspective from US Clinical Practice, by Robert M. Swift, MD, PhD; (4) A European Perspective on Medications Development, by Otto M. Lesch, MD, PhD, and (5) A Scandinavian Perspective on Evidence-Based Addiction Treatment, by Mats Berglund, MD.


Intragenic suppression of Gal3C interaction with Gal80 in the Saccharomyces cerevisiae GAL gene switch.
Gal4-mediated activation of GAL gene transcription in Saccharomyces cerevisiae requires the interaction of Gal3 with Gal80, the Gal4 inhibitor protein. While it is known that galactose and ATP activates Gal3 interaction with Gal80, neither the mechanism of activation nor the surface that binds to Gal80 is known. We addressed this through intragenic suppression of GAL3C alleles that cause galactose-independent Gal3-Gal80 interaction. We created a new allele, GAL3SOC, and showed that it suppressed a new GAL3C allele. We tested the effect of GAL3SOC on several newly isolated and existing GAL3C alleles that map throughout the gene. All except one GAL3C allele, D368V, were suppressible by GAL3SOC. GAL3SOC and all GAL3C alleles were localized on a Gal3 homology model that is based on the structure of the highly related Gal1 protein. These results provide evidence for allosterism in the galactose- and ATP-activation of Gal3 binding to Gal80. In addition, because D368V and residues corresponding to Gal80-nonbinder mutations colocalized to a domain that is absent in homologous proteins that do not bind to Gal80, we suggest that D368 is a part of the Gal80-binding surface.


Dietary surveys indicate vitamin intakes below recommendations are common in representative Western countries.
Vitamins play a crucial role in health, but modern lifestyles may lead to suboptimal intakes even in affluent countries. The aim of the present study is to review vitamin intakes in Germany, the UK, The Netherlands and the USA and to compare them with respective national recommendations. Data on adults from the most recently published national dietary intake surveys for the first three countries and data for adults from the US National Health and Nutrition Examination Survey from 2003 to 2008 for the USA were used as a basis for the analysis. The proportions of the populations with intakes below recommendations were categorised as < 5, 5-25, >25-50, >50-75 and >75 % for each vitamin. The data generated are presented in a 'traffic light display', using colours from green to red to indicate degrees of sufficiency. The trends found were compared with the results from the European Nutrition and Health Report 2009, even though in that report, only information on mean intakes in the different countries was available. We showed that, although inter-country differences exist, intakes of several vitamins are below recommendations in a significant part of the population in all these countries. The most critical vitamin appears to be vitamin D and the least critical niacin. The variation between the countries is most probably due to differences in recommendations, levels of fortification and local dietary habits. We show that a gap exists between vitamin intakes and requirements for a significant proportion of the population, even though diverse foods are available. Ways to correct this gap need to be investigated.


Evaluation of Shear Bond Strength of Methacrylate- and Silorane-based Composite Resin Bonded to Resin-Modified Glass-ionomer Containing Micro- and Nano-hydroxyapatite.
The adhesion of resin-modified glass-ionomer (RMGI) to composite resin has a very important role in the durability of sandwich restorations. Hydroxyapatite is an excellent candidate as a filler material for improving the mechanical properties of glass ionomer cement. The aim of this study was to assess the effect of adding micro- and nano-hydroxyapatite (HA) powder to RMGI on the shear bond strength (SBS) of nanofilled and silorane-based composite resins bonded to RMGI containing micro- and nano-HA. Sixty cylindrical acrylic blocks containing a hole of 5.5×2.5 mm (diameter × height) were prepared and randomly divided into 6 groups as Group 1 with RMGI (Fuji II LC) plus Adper Single Bond/Z350 composite resin (5.5×3.5 mm diameter × height); Group 2 with RMGI containing 25 wt% of micro-HA plus Adper Single Bond/Z350 composite resin; Group3 with RMGI containing 25 wt% of nano-HA plus Adper Single Bond/Z350 composite resin; Group 4 with RMGI plus P90 System Adhesive/P90 Filtek composite resin (5.5×3.5 mm diameter × height); Group 5 with RMGI containing 25 wt% of micro-HA plus P90 System Adhesive/P90Filtek composite resin; and Group 6 with RMGI containing 25 wt% of nano-HA plus P90 System Adhesive/P90 Filtek composite resin. The specimens were stored in water (37° C, 1 week) and subjected to 1000 thermal cycles (5°C/55°C). SBS test was performed by using a universal testing machine at a crosshead speed of 1 mm/min. Data were analyzed by two-way ANOVA and Tukey test (p< 0.05). There were significant differences between groups 1 and 4 (RMGI groups, p= 0.025), and groups 3 and 6 (RMGI+ nano-HA groups, p= 0.012). However, among Z350 and P90 specimens, no statistically significant difference was detected in the SBS values (p= 0.19, p= 0.083, respectively). RMGI containing HA can improve the bond strength to methacrylate-based in comparison to silorane-based composite resins. Meanwhile, RMGI without HA has the best bond strength to silorane-based composite resins.


Healthy Families America effectiveness: a comprehensive review of outcomes.
This paper reviews 33 evaluations of Healthy Families America sites, with emphasis on 15 studies that include a control or comparison group. Outcome domains include child health and development, maternal life course, parenting, and child maltreatment. Parenting outcomes (e.g., parenting attitudes) show the most consistent positive impacts. Mixed results in other domains indicate the need for in-depth research to identify factors associated with better outcomes. Several factors that may contribute to differences in outcomes are discussed, including site implementation and quality, differences in family risk levels, and recent augmentations to program design. The paper also highlights two large-scale evaluations, one community-wide (Hampton, Virginia) and one statewide (Indiana), to illustrate exemplary evaluation approaches found in HFA research. Overall, HFA's continuing evolution has been positively impacted by researcher-practitioner partnerships.


Addressing Health Equity and Social Determinants of Health Through Healthy People 2030.
The evolution of Healthy People reflects growing awareness of health inequities over the life course. Each decade, the initiative has gained understanding of how the nation can achieve health and well-being. To inform Healthy People 2030's visionary goal of achieving health equity in the coming decade, the Secretary's Advisory Committee on National Health Promotion and Disease Prevention Objectives for 2030 (Secretary's Advisory Committee) provided the US Department of Health and Human Services with guidance on key terms, frameworks, and measurement for health equity. Conditions in the environments in which people are born, live, learn, work, play, worship, and age influence health and well-being outcomes, functioning, and quality-of-life outcomes and risks and are mostly responsible for health inequities. No single individual, organization, community, or sector has sole ownership, accountability, or capacity to sustain the health and well-being of an entire population. The COVID-19 pandemic in the United States highlights underlying inequities and disparities in health and health care across segments of the population. Contributing factors that were known prior to the pandemic have led to major discrepancies in rates of infection and death. To reduce health disparities and advance health equity, systems approaches-designed to shift interconnected aspects of public health problems-are needed.


Changes in Muscle Mass and Strength During Follow-Up After One-Year Resistance Training Interventions in Older Adults.
Mertz, KH, Reitelseder, S, Rasmussen, MA, Bülow, J, Højfeldt, G, Jensen, M, Hjulmand, M, Lindberg, J, Kramer, MU, Bechshøft, R, and Holm, L. Changes in muscle mass and strength during follow-up after one-year resistance training interventions in older adults. J Strength Cond Res 37(10): 2064-2070, 2023-The aim of this study was to investigate if home-based resistance training compared with center-based resistance training was associated with better preservation of muscle mass and strength in older individuals, 6 months after the interventions ended. One hundred four healthy older individuals (>65 years) who had completed 1 year of either home-based light-intensity training with daily whey protein supplementation (LITW), center-based heavy resistance training with whey protein supplementation (HRTW), or daily whey protein supplementation alone (WHEY) returned for follow-up measurement 6 months after the interventions. Measures of muscle mass, strength, and power were assessed at the end of intervention as well as at follow-up. Furthermore, we compared changes in these parameters between subjects who continued resistance training (≥1 weekly training session) during follow-up (CONT) with those who stopped (STOP). Resistance training continuation during follow-up did not differ between HRTW and LITW (41 vs. 41%, P = 1.0) but was higher for both groups compared with WHEY (18%, P = 0.04-0.05). However, no between-group differences were observed between LITW/HRTW/WHEY in changes in muscle mass, strength, or power during follow-up. STOP was associated with a poorer preservation of quadriceps cross-sectional area compared with CONT (-1.7 cm 2 [-0.4 to -3.0], P = 0.01, effect size: 0.79). No effect of training continuation was observed on changes in muscle strength and power. In conclusion, maintenance of muscle mass and strength is not superior after home-based resistance training compared with center-based training. However, training continuation seems crucial for the maintenance of muscle mass, irrespective of the training intervention.


[Percutaneous treatment of pulmonary artery stenoses].
Pulmonary artery stenoses are a common problem in pediatric cardiology. They may interfere with the growth and development of the lung and cause pressure overload on the right heart and by increasing pulmonary arterial valvular insufficiency, also volume overload on the right ventricle. This may predispose the patient to cardiac failure, limitation of exercise tolerance and arrhythmias. Percutaneous treatment of pulmonary artery stenoses has undergone significant development over the last 20 years. Above all, the development of high pressure balloon catheters and stents has made treatment results better.


Impact of substance use disorder on ADHD and its treatment.
Attention deficit/hyperactivity disorder (ADHD) is associated with a high rate of psychiatric comorbidity. Substance use disorder (SUD) is common, affecting 1 in 5 adults with ADHD. Adolescents with ADHD are twice as likely to become cigarette smokers as those without ADHD, and cigarette smoking is a significant risk factor for the development of subsequent SUD in adulthood. Patients with SUD and ADHD have been shown to have lower retention in SUD treatment programs, lower rates of SUD remission, and longer courses of SUD. SUD also complicates the diagnosis of adult ADHD. Fortunately, pharmacologic treatment of ADHD does not appear to increase the risk for development of SUD in ADHD patients.


Relationship between uric acid and vascular structure and function in hypertensive patients and sex-related differences.
We sought to analyze the relationship between uric acid (UA) and vascular structure and function based on the carotid intima-media thickness, the pulse-wave velocity (PWV), the central arterial pressure, and the augmentation index in hypertensive patients and to evaluate the sex-related differences. A cross-sectional study was performed with 366 hypertensive individuals aged 34-75 years (men = 61.74%). The vascular structure was assessed based on the carotid intima-media thickness, the arterial stiffness was assessed by PWV, and the vascular function was assessed using hemodynamic parameters such as the central and peripheral augmentation index and the ambulatory arterial stiffness index (AASI). In the bivariable analysis, the PWV (r = 0.28; P < 0.01) and AASI (r = 0.25; P < 0.01) were positively correlated with UA in women. The central augmentation index (r = -0.16; P < 0.05) and peripheral augmentation index (r = -0.18; P < 0.05) were negatively correlated with UA, whereas the maximum carotid intima-media thickness (r = 0.11; P < 0.05) was positively correlated with UA in the global analysis. In the multiple linear regression analysis, a positive association between PWV and UA was observed after adjusting for classical risk factors (β = 0.27; P = 0.01) in women only. In turn, a negative association was observed between the AASI and UA after adjusting for confounders in men (β = -0.06; P = 0.04), with a positive association in women (β = 0.11; P = 0.03). Serum UA showed a positive correlation with the mean maximum intima-media thickness and PWV, and this parameter showed a negative correlation with the central and peripheral augmentation indices, although this relationship was lost after adjusting for confounding factors. AASI showed a positive association in women and a negative association in men after adjusting for confounding factors. Clinical Trials.gov Identifier: NCT01325064.


Hypomagnesemia and cause-specific mortality in hemodialysis patients: 5-year follow-up analysis.
The aim of this prospective study was to evaluate the association between serum magnesium (Mg) and mortality, in particular the cause-specific mortality of Mg and other risk factors in hemodialysis (HD) patients. We studied a cohort of 185 HD patients receiving thrice-weekly HD treatment, on a dialysate Mg concentration of 0.5 mmol/L. We stratified 3 patient groups according to the level of Mg: lower (<1.1 mmol/L), intermediate-reference (1.1 to <1.3 mmol/L), and higher (Mg >1.3 mm/L). During the 5-year follow-up, 60 patients died, with cardiovascular (CV) disease as the predominant cause (73.3%). Hazard ratio (HR) for all-cause and CV mortality were 2.55 and 2.67 in the lower versus intermediate Mg group, but there was no significant association between the higher and intermediate Mg group. Univariate Cox regression analysis showed that Mg <1.1 versus 1.1-1.30 mml/L with HR 2.34, was a significant univariate predictor for increased mortality in addition to the Hb <110 g/L, Alb <40 g/L, C-reactive protein (CRP) ≥10 mg/L and brain natriuretic peptide >1,200 pg/mL. However, in the multivariate analysis only CRP ≥10 mg/L with HR 3.89 was a significant predictor of mortality. Subgroup analyses showed that among patients with CRP >10 mg/L, HR for all-cause and CV mortality of the lower versus intermediate Mg group were 1.96 and 2.39, respectively, not reaching significance for the higher versus intermediate Mg group. Conversely, there was no association between Mg level and all-cause and CV mortality within these 3 groups among patients with CRP <10 mg/L. Lower serum Mg level was significantly associated with an increased all-cause and cardiovascular mortality in HD patients, especially in inflamed patients.


Detection of milk fat adulteration by linear discriminant analysis of fatty acid data.
Analysis of the fatty acid (FA) profile of milk fat (MF) by gas-liquid chromatography is widely used to detect adulteration with foreign fats. On the basis of the FA spectra of 352 genuine Austrian MF samples collected over a 4-year period, the effectiveness of concentration ranges of the major FA of MF and of certain FA ratios to identify non-MF/MF mixtures was tested. FA ratios proved useful for the detection of coconut fat in MF and admixture of vegetable oils rich in linoleic acid down to a level of 2%. This approach failed to identify non-MF/MF blends containing beef tallow, lard, olive oil, or palm oil at a level less than 10% commingling. Linear discriminant analysis applied to FA data was successful in distinguishing pure MF from adulterated MF. Computer-simulated data were used to derive the discriminant functions. Saturated and unsaturated FA with 18 C atoms were the most useful discriminating variables selected by a stepwise variable selection procedure. More than 95% of a data set composed of pure MF, and non-MF/MF blends containing 3% of either tallow, lard, olive oil, or palm oil were correctly classified. The validity of the classification rule was also tested by 206 gravimetrically prepared fat mixtures. Mixtures containing > 3% foreign fat were detected in all cases.


Distinctive expression of T cell guiding molecules in human autoimmune lymph node stromal cells upon TLR3 triggering.
Infections are implicated in autoimmunity. Autoantibodies are produced in lymphoid tissue where lymph node stromal cells (LNSCs) regulate lymphocyte function. Infections can alter the interaction between LNSCs and lymphocytes resulting in defective immune responses. In rheumatoid arthritis (RA) autoantibody production precedes clinical disease allowing identification of at risk individuals. We investigated the ability of human LNSCs derived from RA, RA-risk and healthy individuals to sense and respond to pathogens. Human LNSCs cultured directly from freshly collected lymph node biopsies expressed TLR1-9 with exception of TLR7. In all donors TLR3 triggering induced expression of ISGs, IL-6 and adhesion molecules like VCAM-1 and ICAM-1. Strikingly, T cell guiding chemokines CCL19 and IL-8 as well as the antiviral gene MxA were less induced upon TLR3 triggering in autoimmune LNSCs. This observed decrease, found already in LNSCs of RA-risk individuals, may lead to incorrect positioning of lymphocytes and aberrant immune responses during viral infections.


Finite Element Formulation of Multiphasic Shell Elements for Cell Mechanics Analyses in FEBio.
With the recent implementation of multiphasic materials in the open-source finite element (FE) software FEBio (febio.org), 3D models of cells embedded within the tissue may now be analyzed, accounting for porous solid matrix deformation, transport of interstitial fluid and solutes, membrane potential, and reactions. The cell membrane is a critical component in cell models, which selectively regulates the transport of fluid and solutes in the presence of large concentration and electric potential gradients, while also facilitating the transport of various proteins. The cell membrane is much thinner than the cell; therefore, in an FE environment, shell elements formulated as 2D surfaces in 3D space would be preferred for modeling the cell membrane, for the convenience of mesh generation from image-based data, especially for convoluted membranes. However, multiphasic shell elements are yet to be developed in the FE literature and commercial FE software. This study presents a novel formulation of multiphasic shell elements and its implementation in FEBio. The shell model includes front- and back-face nodal degrees of freedom for the solid displacement, effective fluid pressure and effective solute concentrations, and a linear interpolation of these variables across the shell thickness. This formulation was verified against classical models of cell physiology and validated against reported experimental measurements in chondrocytes. This implementation of passive transport of fluid and solutes across multiphasic membranes makes it possible to model the biomechanics of isolated cells or cells embedded in their extracellular matrix, accounting for solvent and solute transport.


Production of chick germline chimeras from fluorescence-activated cell-sorted gonocytes.
Modification of the chicken germline has been difficult, because it has been challenging to fractionate sufficient numbers of primordial germ cells for manipulation and implantation into developing embryos. A technique to enrich cell suspensions for primordial germ cells, using fluorescence-activated cell sorting (FACS), has recently been developed. The objective of the current study was to demonstrate that the FACS-enriched early embryonic gonocytes could fully participate in development of the germline. Therefore, cells were disassociated from stage 27 gonads, incubated with mouse anti-stage-specific embryonic antigen-1, which was detected with goat-antimouse IgM-fluorescein isothiocyanate, and the fluorescently labeled cells were sorted from the unlabeled cells using FACS. The isolated gonocyte population was injected into the blastoderm of unincubated stage X embryos, the germinal crescent of 3-d embryos, and into the circulation of stage 17 embryos that were pretreated with busulfan. Barred Plymouth Rock gonocytes were implanted exclusively into recipient White Leghorn embryos, and White Leghorn gonocytes were implanted exclusively into Barred Plymouth Rock recipient embryos. Embryos were cultured until hatch, and male putative chimeras were reared to sexual maturity. Germline chimerism was evaluated by observing feather color of the progeny. All injection methods resulted in germline chimeras demonstrating that FACS-sorted gonocytes can fully participate in development. Moreover, it was demonstrated that gonocytes isolated from stage 27 embryonic gonads can be introduced into embryos at an earlier stage of development, and the introduced gonocytes can fully participate in germline development.


Wood-Derived Carbon with Selectively Introduced C═O Groups toward Stable and High Capacity Anodes for Sodium Storage.
Biomass-derived carbon is a promising sustainable anode material for sodium-ion batteries (SIBs). Although the electrochemical performance can be improved by introducing functional groups, the selective introduction of single functional groups into biomass carbon remains difficult. Here, we overcome this challenge by developing a wood-derived carbon with selectively introduced C═O groups by combining tetramethoxysilane (TMOS) with wood cellulose pulps. The integration of TMOS introduces abundant C═O groups into the carbon during the polycondensation and pyrolysis process. The C═O groups play a dominant role in anode surface-controlled processes, and this leads to improvements in pseudo-capacity and fast electrode process kinetics. Besides, the introduction of C═O groups generates oxygen functional active sites that promote Na+ adsorption and creates a sufficiently large graphene interlayer distance. The as-obtained carbon shows a high capacity of 330 mAh g-1 at 40 mA g-1 and excellent cycling stability. Moreover, our strategy is simple and uses wood cellulose pulps as precursors. It therefore enables low-cost and large-scale synthesis of carbon anode materials for SIBs.


[Treatment progress of Duchenne Muscular Dystrophy (DMD)].
Duchenne muscular dystrophy (DMD) is a common lethal disease for which no effective treatment is currently available. There exists a mouse model of the disease in which the usefulness of gene therapy was established. However, no progress towards human application was made due to the lack of a proper method for gene delivery. During the past several years, researchers acquired data which led them to believe that bone marrow stem cells are capable of generating not only blood cells, but also liver, heart, skin, muscle, and other tissue. Although the term "stem cell plasticity" became very popular, other studies have suggested that bone marrow might contain different types of stem cells that can produce non-hematopoietic cells. For example, mesenchymal stem cell (MSC) in bone marrow give rise to osteocytes, chondrocytes, adipocytes, and skeletal muscle. Recently, researchers have been able to show that transplanted bone marrow cells can contribute to muscle cells in a human patient who was diagnosed with two genetic diseases: severe combined immunodeficiency (SCID) and Duchenne muscular dystrophy. The odds of this happening is estimated at one in seven million. The results of studying this patient's medical history were reported by collaborating researchers at Children's Hospital, Los Angeles and Children's Hospital, Boston in an article titled "Long-term persistence of donor nuclei in a Duchenne muscular dystrophy (DMD) patient receiving bone marrow transplantation" published in the September 2002 issue of the Journal of Clinical Investigation. This patient was transplanted 15 years ago at Children's Hospital Los Angeles with paternal HLA-haploidentical T cell-depleted bone marrow. He engrafted and became a hematopoietic chimera having T and NK lymphocytes of donor origin. Studies performed on the muscle biopsy from the patient 13 years after transplantation demonstrated that the muscle showed evidence of donor derived nuclei. In addition, analysis of his bone marrow showed that small numbers of MSC were also derived from the transplanted bone marrow. Unfortunately, there was no evidence that the number of new muscle cells from the donor was able to decrease the progression of his muscular dystrophy. The revelation of finding the donor's cells in the muscle of the patient provides new hope for patients with the same disease. In the future it may be possible for mesenchymal cells to be isolated, ex vivo expanded and transplanted into patients with muscle diseases.


Eating habits of children with autism.
Autism is a developmental disorder characterized by severe deficits in social interaction and communication, as well as by stereotyped and repetitive behaviors. Children with autism frequently have significant eating difficulties with highly restricted range of food choices. Eating habits and patterns are often unusual and have an impact on family life. The purpose of this article was to review pertinent information regarding this complex developmental disorder and describe a recent study based on a parent survey of feeding patterns in children with autism to give a new perspective for both parents and professionals.


Modeling and in vivo experimental validation of 1,064 nm laser interstitial thermal therapy on brain tissue.
Laser interstitial thermal therapy (LITT) at 1064 nm is widely used to treat epilepsy and brain tumors; however, no numerical model exists that can predict the ablation region with careful in vivo validation. In this study, we proposed a model with a system of finite element methods simulating heat transfer inside the brain tissue, radiative transfer from the applicator into the brain tissue, and a model for tissue damage. To speed up the computation for practical applications, we also validated P1-approximation as an efficient and fast method for calculating radiative transfer by comparing it with Monte Carlo simulation. Finally, we validated the proposed numerical model in vivo on six healthy canines and eight human patients with epilepsy and found strong agreement between the predicted temperature profile and ablation area and the magnetic resonance imaging-measured results. Our results demonstrate the feasibility and reliability of the model in predicting the ablation area of 1,064 nm LITT, which is important for presurgical planning when using LITT.


The role of length and defects on optical quantum efficiency and exciton decay dynamics in single-walled carbon nanotubes.
We perform Monte Carlo simulations of the time-resolved, spatially resolved, and integrated photoluminescence from a nanotube to investigate the role of the nanotube length L and defects using an exciton random-walk and defect-induced quenching model. When nonradiative decay is due solely to diffusion quenching, the quantum efficiency is approximately proportional to L2 at low quantum efficiency. With defects present, the quantum efficiency depends only weakly on the number defects but is instead tied to Leff2 where Leff is the root-mean-square separation between defects. The time-resolved photoluminescence decay of nanotubes is multiexponential for both pristine nanotubes and nanotubes with defects. The dominant time scale for a pristine nanotube is proportional to L2/D, where D is the diffusion constant. The presence of defects on the nanotube introduces additional time scales.


Depressant effects of volatile anesthetics upon rat and amphibian ventricular myocardium: insights into anesthetic mechanisms of action.
To clarify the mechanisms by which volatile anesthetics may depress myocardial contractility, the depressant effects of equivalent concentrations of isoflurane, enflurane and halothane were compared in rat and frog ventricular myocardium, preparations which differ markedly in excitation-contraction coupling. In Tyrode solution, right ventricular papillary muscles from rat exhibited very large, rapidly developing contractions after rest, with a subsequent negative force-frequency relation as the stimulation rate was increased to 0.1, 0.25, 0.5, 1, 2, and 3 Hz. The large contractions after rest and at 0.1 Hz were depressed by 0.75% halothane and 1.7% enflurane to about 60% of control, but less so by 1.3% isoflurane (approximately 0.8 MAC). Halothane at 1.5% was more depressant than 2.5% isoflurane at all stimulation rates, while 3.5% enflurane caused intermediate depression (approximately 1.6 MAC). Contractions in frog ventricular strips were studied in Ringer solution following rest and at stimulation rates of 0.1, 0.25, 0.5, and 1 Hz, in the absence and presence of equivalent anesthetic concentrations. At 0.1 to 1 Hz, isoflurane was less depressant than equivalent concentrations of halothane. Enflurane (1.7%) was less depressant than 0.75% halothane at 0.1 and 0.25 Hz; 3.5% enflurane was more depressant than 2.5% isoflurane at 1 Hz. Anesthetic effects on sustained contractures were also studied in frog ventricular strips that were superfused for 4-5 min with 40, 60, 80, and 100 mM K Ringer solution. Contractures induced by 80 and 100 mM K solution were depressed more by halothane (to 60% of control) than by isoflurane or enflurane (approximately 85% of control). However, only enflurane depressed the contractions at 1 Hz more than the sustained contractures in 100 mM K Ringer. The Ca2+ for activating contractions in rat ventricle is derived largely from the sarcoplasmic reticulum, the intracellular Ca2+ accumulation and release organelle. In contrast, Ca2+ for activating contractions in the frog ventricle originates primarily from the external medium. These results suggest that halothane is more potent than isoflurane in reducing the amount of Ca2+ rapidly released from the sarcoplasmic reticulum (as observed in rat), as well as in depressing entry of extracellular Ca2+ to activate myofibrils (as in frog). Enflurane appears to have intermediate potency with actions distinct from halothane and isoflurane. The greater potency of halothane may also be due in part to greater direct depression of actin-myosin ATPase.


Cystathionine β-Synthase Suppresses NLRP3 Inflammasome Activation via Redox Regulation in Microglia.
Aims: Cystathionine β-synthase (CBS) is essential for homocysteine (Hcy) transsulfuration, yielding cysteine as a common precursor of hydrogen sulfide (H2S), glutathione (GSH), and other sulfur molecules, which produce neuroprotective effects in neurological conditions. We previously reported a disruption of microglial CBS/H2S signaling in a Parkinson's disease (PD) mouse model. Yet, it remains unclear whether CBS affects nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activity and other pathologies in PD. Results: Microglial CBS expression decreased after lipopolysaccharide (LPS) stimulation. Elevated GSSG (the oxidized GSH) content and decreased H2S generation were found in the brains of microglial cbs conditional-knockout (cbscKO) mice, whereas serum and brain Hcy levels remained unaltered. Moreover, microglial cbscKO mice were susceptible to NLRP3 inflammasome activation and dopaminergic neuron losses caused by LPS injection into the substantia nigra, whereas cbs overexpression or activation produced opposite effects. In vitro studies showed that cbs overexpression or activation suppressed microglial NLRP3 inflammasome activation and interleukin (IL)-1β secretion by reducing mitochondrial reactive oxygen species (mitoROS) level. Conversely, ablation of cbs enhanced NLRP3 expression and mitoROS generation and augmented microglial NLRP3 inflammasome activity in response to adenosine triphosphate challenge, which was blocked by the mitoROS scavenger. Innovation and Conclusion: The study demonstrated an elevated GSSG level and reduced H2S generation, which correlated with a susceptible status of microglia in the brain of cbscKO mice. Our findings reveal a critical role of CBS in restraining the microglial NLRP3 inflammasome by controlling redox homeostasis and highlight that activation or upregulation of CBS may become a potential strategy for PD treatment.


The in vitro effect of paclitaxel on a LacZ-transfected malignant transitional cell line.
As bladder cancer is potentially lethal, the development of effective and tolerable therapeutic options is vital. In the present assay, we examined the in vitro effect of paclitaxel (Taxol) on the transitional cell carcinoma (TCC) cell line Hu1703He. Our model has several advantages over other in vitro models. The microenvironment in vivo is mimicked, and the important interaction between benign and malignant cells is consequently preserved in vitro. In addition, the results are not influenced by humoral immune factors. LacZ transfection and exposure to X-gal resulted in blue staining of the tumour cells and made them easy to visualise in sections. Tumour cell aggregates were cultured with continuous paclitaxel exposure to examine the drug's effect on tumour cell migration in monolayer and spheroidal growth in suspension culture. Paclitaxel treatment inhibited both tumour cell migration and spheroidal growth. Invasion was studied by confronting paclitaxel-treated and untreated tumour spheroids with benign bladder fragments in suspension culture. The co-cultures were followed for 4 weeks. Growth of the tumour cells encircling the bladder fragment and cellular infiltration of the bladder stroma were both inhibited by paclitaxel treatment. The expression of MMP-1 in tumour cells was also negatively influenced.


P2X7 Receptor Expression and Signaling on Dendritic Cells and CD4+ T Cells is Not Required but Can Enhance Th17 Differentiation.
The purinergic receptor P2X7 (P2X7R) is important in inflammasome activation and generally considered to favor proinflammatory immune responses. However, there is still a limited understanding of the role of P2X7R signaling in Th cell differentiation, particularly, Th17 differentiation. Herein, the impact of P2X7R signaling on primary Th17 and Th1 cell responses was examined when P2X7R was expressed specifically on dendritic cells (DCs) and CD4+ T cells. Surprisingly, global genetic ablation and pharmacological inhibition of the P2X7R did not affect the generation of Th17 and Th1 development in response to immunization with Complete Freund's Adjuvant and the model antigens, keyhole limpet hemocyanin or OVA. However, in-depth in vitro and in vivo investigations revealed differences in the balance of Th1/Th17 differentiation when P2X7R blockade was restricted to either DCs or CD4+ T cells. In this regard, in vitro DCs treated with a P2X7R agonist released more IL-6 and IL-1β and induced a more robust Th17 response in mixed leukocyte reactions when compared to controls. To test the hypothesis that P2X7R signaling specifically in DCs enhances Th17 responses in vivo, DC-specific P2X7R deficient chimeras were immunized with CFA and OVA. In this model, the P2X7R expression on DCs decreased the Th1 response without impacting Th17 responses. Following an assessment of CD4+ T cell P2X7R signaling, it was determined that in vitro P2X7R sufficient T cells develop an increased Th17 and suppressed Th1 differentiation profile. In vivo, P2X7R expression on CD4+ T cells had no effect on Th17 differentiation but likewise significantly suppressed the Th1 response, thereby skewing the immune balance. Interestingly, it appears that WT OT-II Th1 cells are more sensitive to P2X7R-induced cell death as evidence by a decrease in cell number and an increase in T cell death. Overall, these studies indicate that in vitro P2X7R signaling does enhances Th17 responses, which suggests that compensatory Th17 differentiation mechanisms are utilized in vivo in the absence of P2X7R signaling.


[Joseph Babinski's contribution to neurological symptomatology].
Joseph Babinski (1857-1932) was an excellent clinician. André Breton, a French poet, described Babinski's way of clinical examination in his Manifeste du surréalisme (1924), which vividly revealed Babinski's meticulous character. Babinski is well known by his eponymous Babinski reflex. Although some predecessors had described this phenomenon briefly, its meaning was interpreted by Babinski. His contribution to neurological symptomatology was not restricted to his plantar skin reflex, but also to other wide area. In this article, symptoms described by Babinski, i.e. plantar skin reflex, cerebellar symptoms including cerebellar asynergy, adiadochokinesis, dysmetria, cerebellar catalepsy, and rising sign, platysma sign, anosognosia are explained and are critically discussed.


Blood pressure changes on upright tilting predict falls in older people.
orthostatic hypotension may be an important risk factor for falls, though this has not yet been demonstrated in prospective studies. This may be because conventional methods of measuring blood pressure changes are too imprecise and not optimally timed. to determine whether changes in blood pressure induced by upright tilt are associated with falls in older people, and whether medication use and symptoms of dizziness are associated with blood pressure changes and falls. seventy men and women aged 62-92 years participated. We measured blood pressure with a plethysmograph monitor continuously before and after upright tilt. We recorded medication use and symptoms of dizziness in response to the tilt. Subjects were then followed up for 12 months to determine the incidence of falls. subjects who fell in the follow-up period had significantly greater decreases in systolic blood pressure when tilted than those who did not fall. Furthermore, those who had unstable systolic blood pressure during the 3 minutes after tilting, in addition to large blood pressure drops, had a two-fold increased risk of falling compared with those with neither of these conditions. Symptoms of dizziness on tilting were uncommon and not associated with blood pressure or heart rate changes, medication use, or falls incidence. Antidepressant and antihypertensive medication use were associated with decreases in diastolic rather than systolic blood pressure, but were not associated with falls. these findings indicate that both the decrease in blood pressure and the unstable nature of the blood pressure response following upright tilt are useful predictors of falls in older people.


[Expression of intercellular adhesion molecule-1 and neutrophil infiltration induced by injection of thrombin in rats].
To investigate the role of the thrombin in inducing inflammatory response in brain tissue adjacent to hematoma in the brain. Seventy-two male Wistar rats were randomly divided into two groups: sham-operated control group and thrombin injection group. Immunohistochemical technique and myeloperoxidase (MPO) determination were respectively used to evaluate intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration in adjacent brain tissue of the thrombin injection zone at 6, 12, 24, 48, 72 and 128 hours after thrombin injection. The expression of ICAM-1 in tissues adjacent to thrombin injection started to increase 6 hours after the injection, peaking at 72 hours, and lasting for 120 hours. MPO activity of tissues in the area increased 6 hours, reached a high level at 24 hours, then decreased slightly, and it peaked at 72 hours after thrombin injection, correlating closely with the increase in ICAM-1 expression except the changes at 24 hours. The increased expression of ICAM-1 after thrombin injection is correlated with the degree of the neutrophil infiltration in the brain tissue around the thrombin injection zone, indicating thrombin is important to produce secondary brain damage after cerebral hemorrhage.


Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder.
The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy.


Chronic active hepatitis in mice caused by Helicobacter hepaticus.
Helicobacter infections cause chronic gastroenteritis in humans and several animal species. We recently discovered a new Helicobacter (H. hepaticus) that is the etiological agent of a unique chronic active hepatitis in mice. Natural infection appeared to be acquired early in life in enzootically infected colonies. Liver lesions arose as focal necrosis and focal nonsuppurative inflammation by 1 to 4 months of age in susceptible mouse strains. By 6 to 8 months, extensive liver involvement included hepatocytomegaly, bile ductular (oval cell) hyperplasia, and cholangitis. There was an age-related increase in proliferating cell nuclear antigen hepatocyte nuclear labeling index. The bacteria were usually found within bile canaliculi as determined by ultrastructural evaluation of liver lesions, the Steiner modification of the Warthin-Starry stain and immunohistochemistry with a rabbit antibody to Helicobacter pylori. Naturally infected mice showed an age-related increase in serum IgG antibodies to Helicobacter hepaticus proteins. The disease was experimentally reproduced by intraperitoneal injection of liver suspensions from affected livers or bacteria cultivated in vitro. The earliest lesions of the experimental disease appeared 4 weeks after injection. The course of spontaneous and experimental infection was slow and insidious and resulted in high titers of antibodies to bacterial proteins. This chronic bacterial infection represents a new model of chronic liver disease.


Deficiency of CKIP-1 aggravates high-fat diet-induced fatty liver in mice.
Casein kinase 2 interacting protein-1(CKIP-1) is widely expressed in a variety of tissues and cells, and plays an important role in various critical cellular and physiological processes including cell growth, apoptosis, differentiation, cytoskeleton and bone formation. Here, we found: (1) CKIP-1 deficient mice exhibited increased body weight, liver weight, number and size of lipid droplets, and TG content comparing with WT mice after being exposed to high fat diet (HFD); (2) the levels of serum insulin, liver glycogen, phosphorylated C-Jun-N-terminal kinase-1 (pJNK1) and phosphorylated insulin receptor substrate -1(pIRS1) in CKIP-1-/- mice were higher than those of WT mice; (3) CKIP-1 interacted with JNK1 in vitro. Our results indicate that CKIP-1 deficiency in mice aggravates HFD-induced fatty liver by upregulating JNK1 phosphorylation and further upregulating IRS-1 phosphorylation and RI.


Functional screening for triclosan resistance in a wastewater metagenome and isolates of Escherichia coli and Enterococcus spp. from a large Canadian healthcare region.
The biocide triclosan is in many consumer products and is a frequent contaminant of wastewater (WW) such that there is concern that triclosan promotes resistance to important antibiotics. This study identified functional mechanisms of triclosan resistance (TCSR) in WW metagenomes, and assessed the frequency of TCSR in WW-derived and clinical isolates of Escherichia coli and Enterococcus spp. Metagenomic DNA extracted from WW was used to profile the microbiome and construct large-insert cosmid libraries, which were screened for TCSR. Resistant cosmids were sequenced and the TCSR determinant identified by transposon mutagenesis. Wastewater Enterococcus spp. (N = 94) and E. coli (N = 99) and clinical Enterococcus spp. (N = 146) and vancomycin-resistant E. faecium (VRE; N = 149) were collected and tested for resistance to triclosan and a comprehensive drug panel. Functional metagenomic screening revealed diverse FabV homologs as major WW TCSR determinants. Resistant clones harboured sequences likely originating from Aeromonas spp., a common WW microbe. The triclosan MIC90s for E. coli, E. faecalis, and E. faecium isolates were 0.125, 32, and 32 mg/L, respectively. For E. coli, there was no correlation between the triclosan MIC and any drug tested. Negative correlations were detected between the triclosan MIC and levofloxacin resistance for E. faecalis, and between triclosan and vancomycin, teicoplanin, and ampicillin resistance for E. faecium. Thus, FabV homologs were the major contributor to the WW triclosan resistome and high-level TCSR was not observed in WW or clinical isolates. Elevated triclosan MICs were not positively correlated with antimicrobial resistance to any drug tested.


Antimicrobial resistance profiles of Streptococcus suis isolated from pigs, wild boars, and humans in France between 1994 and 2020.
Streptococcus suis, an emerging zoonotic pathogen, causes invasive infections and substantial economic losses in the pig industry worldwide. Antimicrobial resistance against 22 antibiotics was studied for 200 S. suis strains collected in different geographical regions of France. Most of the strains (86%) showed resistance to at least one antibiotic with a low rate of resistance to fluoroquinolones, penicillins, pleuromutilin, and diaminopyrimidine-sulfonamides, and a higher rate to macrolides-lincosamides and tetracycline. Multi-resistance patterns were observed in 138 strains; three of them being resistant to six antibiotic families. Statistical analyses highlighted a decrease in the resistance to trimethoprim-sulfamethoxazole, in our collection, between the two periods studied-before 2010 and after 2015-as well as an impact of the geographical origin with a higher rate of resistance to macrolides-lincosamides and penicillin in Brittany than in the other French regions. Furthermore, macrolides-lincosamides and tetracycline resistance patterns were more likely to be found in pig isolates than in human and wild boar isolates. A difference in resistance was also observed between serotypes. Most of the penicillin-resistant strains belong to serotypes 1, 5, 9, 11, 12, 15, 27, and 29. Finally, penicillin and pleuromutilin resistances were mostly found in "non-clinical" isolates. The empirical treatment of human and porcine infections due to S. suis in France can therefore still be carried out with beta-lactams. However, this study emphasizes the need to monitor antimicrobial resistance in this zoonotic pathogen.


Generalized Synthesis to Produce Transparent Thin Films of Ternary Metal Oxide Photoelectrodes.
Developing facile approaches to prepare non-light-scattering ternary oxide thin film photoelectrodes is an important goal for solar water splitting tandem cells. Herein, a novel synthesis route is reported that employs ethylenediaminetetraacetic acid (EDTA) to enable compatible water solubility of diverse metal cations, which affords transparent films by solution processing. By using BiVO4 as a model material, a remarkable improvement in transparency is demonstrated, quantified by the direct transmittance at 600 nm of >80 % versus the <10 % observed with state-of-the-art electrodeposited thin films while maintaining reasonable solar-driven oxidation photocurrents (1.75 mA cm-2 in the presence of a sulfite hole scavenger). Furthermore, it is demonstrated that the synthesis technique can be applied in a general fashion towards the synthesis of diverse n- and p-type metal oxide materials, such as ZnFe2 O4 and CuFeO2 .


Unilateral hydrocephalus from a gangliocytoma-somatotrophinoma: first reported case.
Although pituitary macroadenomas often cause mass effects on surrounding structures, it is extremely rare for pituitary lesions to disturb cerebrospinal fluid circulation. Sellar gangliocytoma-pituitary adenomas (SGPAs) are also extremely rare. Here we report the unique case of a man with the unusual combination of acromegaly from an SGPA, who presented with unilateral hydrocephalus. A 60-year-old man presented with rapid neurological deterioration, bitemporal hemianopia, and acromegalic features. Neuroimaging revealed a large sellar lesion extending superiorly into the left foramen of Monro, causing acute obstructive unilateral hydrocephalus. External ventricular drain placement improved consciousness immediately. Biochemical assessment confirmed acromegaly. Following trans-sphenoidal debulking, histology revealed a mixed gangliocytoma/sparsely-granulated somatotrophinoma. Despite the residual disease, his vision recovered remarkably, low-dose cabergoline controlled residual excess growth hormone (GH) secretion, and the residual tumour has remained extremely stable over 2 years. Hydrocephalus is an extremely rare complication of pituitary lesions, and unilateral hydrocephalus has never been reported previously. GH secretion in SGPAs is more common than for pituitary adenomas in general, raising questions regarding the aetiology and therapeutic approach to this rare combination tumour. Pituitary tumours most commonly present with symptoms related to endocrine disturbance or mass effects upon visual pathways (e.g. optic chiasm, nerves in the lateral cavernous sinus). However, extremely rarely, pituitary masses may disrupt cerebrospinal fluid (CSF) circulation resulting in hydrocephalus. Sellar gangliocytomas are very rare tumours and most of them are hybrid tumours with pituitary adenomas (SGPAs). SGPAs are typically indolent and may be functioning or non-functioning tumours. Growth hormone (GH)-producing SGPAs are less likely to respond to somatostatin agonists than classic somatotrophinomas. Primary surgical debulking via a trans-sphenoidal approach was effective in this individual, leading to the restoration of CSF circulation and improvement in visual disturbance, while also negating the need for permanent CSF diversion despite the residual tumour burden.


Insights From Matched Office and Ambulatory Blood Pressure in Youth: Clinical Relevance.
Information on the relationship between ambulatory blood pressure (ABP) and concurrently office blood pressure (BP) values in youth still suffers from limitations. We provide information on the differences between office BP and ABP, the factors related, and the clinical implications. Three thousand six hundred ninety matched measurements of office BP and ABP on the same day, from 2390 children, aged 5 to 15 years, of both sexes were eligible. Office BP was measured using an oscillometric device (Omron 705 IT) and 24-hour ABP using oscillometric SpaceLabs 90207. Average of office, 24-hour, daytime, nighttime, systolic, and diastolic BP and heart rate was calculated. BP categories according to the European guidelines and phenotype of mismatch office BP versus ABP were defined. Both daytime systolic and diastolic BP were higher than office BP with a progressive reduction of the differences from 5 to 15 years. The office minus daytime BP differences were the largest in normotensive subjects, less at high-normal, and reversed in hypertensive ones, independently of age and weight status. White coat and masked hypertension covered no more than 13.6% at all ages. In youth, it is inaccurate to obtain reference values for ABP by extrapolating from office BP values. The differences between office BP and ABP are minimal in children with office BP values in the range of hypertension, reinforcing the recommendation to use ABP measurement at the time to confirm hypertension.


Anaemia of lung cancer is due to impaired erythroid marrow response to erythropoietin stimulation as well as relative inadequacy of erythropoietin production.
Many studies have been done in order to elucidate the pathogenesis of the anaemia of chronic disorders accompanying cancer, with conflicting results. This is probably due to the heterogeneity of the patient population selected for these studies (many patients treated by chemotherapy). To avoid this pitfall, in this study a very homogenous group of chemotherapy and radiotherapy-naive patients with lung cancer were selected. Serum erythropoietin and soluble transferrin receptor measurements suggested that the anaemia of non-treated lung cancer is mainly due to an impaired erythroid marrow response to erythropoietin stimulation. However, a relative inadequacy of erythropoietin production may also contribute.


Inner Retinal Oxygen Extraction Fraction in Response to Light Flicker Stimulation in Humans.
Light flicker has been shown to stimulate retinal neural activity, increase blood flow, and alter inner retinal oxygen metabolism (MO2) and delivery (DO2). The purpose of the study was to determine the change in MO2 relative to DO2 due to light flicker stimulation in humans, as assessed by the inner retinal oxygen extraction fraction (OEF). An optical imaging system, based on a modified slit lamp biomicroscope, was developed for simultaneous measurements of retinal vascular diameter (D) and oxygen saturation (SO2). Retinal images were acquired in 20 healthy subjects before and during light flicker stimulation. Arterial and venous D (DA and DV) and SO2 (SO2A and SO2V) were quantified within a circumpapillary region. Oxygen extraction fraction was defined as the ratio of MO2 to DO2 and was calculated as (SO2A - SO2V)/SO2A. Reproducibility of measurements was assessed. Coefficients of variation and intraclass correlation coefficients of repeated measurements were <5% and ≥0.83, respectively. During light flicker stimulation, DA, DV , and SO2V significantly increased (P ≤ 0.004). Oxygen extraction fraction was 0.37 ± 0.08 before light flicker and significantly decreased to 0.31 ± 0.07 during light flicker (P = 0.001). Oxygen extraction fraction before and during light flicker stimulation is reported in human subjects for the first time. Oxygen extraction fraction decreased during light flicker stimulation, indicating the change in DO2 exceeded that of MO2. This technology is potentially useful for the detection of changes in OEF response to light flicker in physiological and pathological retinal conditions.


Estimation of total CH4 emission from Japanese rice paddies using a new estimation method based on the DNDC-Rice simulation model.
Methane (CH4) is a greenhouse gas, and paddy fields are one of its main anthropogenic sources. In Japan, country-specific emission factors (EFs) have been applied since 2003 to estimate national-scale CH4 emission from paddy field. However, these EFs did not consider the effects of factors that influence CH4 emission (e.g., amount of organic C inputs, field drainage rate, climate) and can therefore produce estimates with high uncertainty. To improve the reliability of national-scale estimates, we revised the EFs based on simulations by the DeNitrification-DeComposition-Rice (DNDC-Rice) model in a previous study. Here, we estimated total CH4 emission from paddy fields in Japan from 1990 to 2010 using these revised EFs and databases on independent variables that influence emission (organic C application rate, paddy area, proportions of paddy area for each drainage rate class and water management regime). CH4 emission ranged from 323 to 455ktCyr-1 (1.1 to 2.2 times the range of 206 to 285ktCyr-1 calculated using previous EFs). Although our method may have overestimated CH4 emissions, most of the abovementioned differences were presumably caused by underestimation by the previous method due to a lack of emission data from slow-drainage fields, lower organic C inputs than recent levels, neglect of regional climatic differences, and underestimation of the area of continuously flooded paddies. Our estimate (406ktC in 2000) was higher than that by the IPCC Tier 1 method (305ktC in 2000), presumably because regional variations in CH4 emission rates are not accounted for by the Tier 1 method.


Design and fabrication of porous biodegradable scaffolds: a strategy for tissue engineering.
Current strategies of tissue engineering are focused on the reconstruction and regeneration of damaged or deformed tissues by grafting of cells with scaffolds and biomolecules. Recently, much interest is given to scaffolds which are based on mimic the extracellular matrix that have induced the formation of new tissues. To return functionality of the organ, the presence of a scaffold is essential as a matrix for cell colonization, migration, growth, differentiation and extracellular matrix deposition, until the tissues are totally restored or regenerated. A wide variety of approaches has been developed either in scaffold materials and production procedures or cell sources and cultivation techniques to regenerate the tissues/organs in tissue engineering applications. This study has been conducted to present an overview of the different scaffold fabrication techniques such as solvent casting and particulate leaching, electrospinning, emulsion freeze-drying, thermally induced phase separation, melt molding and rapid prototyping with their properties, limitations, theoretical principles and their prospective in tailoring appropriate micro-nanostructures for tissue regeneration applications. This review also includes discussion on recent works done in the field of tissue engineering.


Genetic Influence on Intergenerational Educational Attainment.
Using twin (6,105 twin pairs) and genomic (5,825 unrelated individuals taken from the twin sample) analyses, we tested for genetic influences on the parent-offspring correspondence in educational attainment. Genetics accounted for nearly half of the variance in intergenerational educational attainment. A genomewide polygenic score (GPS) for years of education was also associated with intergenerational educational attainment: The highest and lowest GPS means were found for offspring in stably educated families (i.e., who had taken A Levels and had a university-educated parent; M = 0.43, SD = 0.97) and stably uneducated families (i.e., who had not taken A Levels and had no university-educated parent; M = -0.19, SD = 0.97). The average GPSs fell in between for children who were upwardly mobile (i.e., who had taken A Levels but had no university-educated parent; M = 0.05, SD = 0.96) and children who were downwardly mobile (i.e., who had not taken A Levels but had a university-educated parent; M = 0.28, SD = 1.03). Genetic influences on intergenerational educational attainment can be viewed as an index of equality of educational opportunity.


Engineering the nucleotide coenzyme specificity and sulfhydryl redox sensitivity of two stress-responsive aldehyde dehydrogenase isoenzymes of Arabidopsis thaliana.
Lipid peroxidation is one of the consequences of environmental stress in plants and leads to the accumulation of highly toxic, reactive aldehydes. One of the processes to detoxify these aldehydes is their oxidation into carboxylic acids catalyzed by NAD(P)+-dependent ALDHs (aldehyde dehydrogenases). We investigated kinetic parameters of two Arabidopsis thaliana family 3 ALDHs, the cytosolic ALDH3H1 and the chloroplastic isoform ALDH3I1. Both enzymes had similar substrate specificity and oxidized saturated aliphatic aldehydes. Catalytic efficiencies improved with the increase of carbon chain length. Both enzymes were also able to oxidize α,β-unsaturated aldehydes, but not aromatic aldehydes. Activity of ALDH3H1 was NAD+-dependent, whereas ALDH3I1 was able to use NAD+ and NADP+. An unusual isoleucine residue within the coenzyme-binding cleft was responsible for the NAD+-dependence of ALDH3H1. Engineering the coenzyme-binding environment of ALDH3I1 elucidated the influence of the surrounding amino acids. Enzyme activities of both ALDHs were redox-sensitive. Inhibition was correlated with oxidation of both catalytic and non-catalytic cysteine residues in addition to homodimer formation. Dimerization and inactivation could be reversed by reducing agents. Mutant analysis showed that cysteine residues mediating homodimerization are located in the N-terminal region. Modelling of the protein structures revealed that the redox-sensitive cysteine residues are located at the surfaces of the subunits.


3D reconstruction of dynamic behaviors of vacuum arcs under transverse magnetic fields via computer tomography.
The transverse magnetic field (TMF) contacts make the vacuum arcs deviate from the axisymmetric structure, so complete spatiotemporal evolution information of the plasma cannot be obtained by adopting one- or two-dimensional (2D) diagnostic methods. To address the issues, computer tomography was introduced in this paper. First, a multi-angle diagnostic imaging system based on split fiber bundles was proposed, which used a high-speed camera to simultaneously acquire eight angles of the arc image over time. In addition, a tomography algorithm called the maximum likelihood expectation maximum with Split Bregman denoising was proposed to reconstruct the dynamic spatiotemporal characteristics of the arc under complex conditions. Then, the three-dimensional (3D) distribution of Cu i and Cr i particles inside the contact gap was obtained by adopting optical filters. The 3D distribution of the vacuum arc had shown an obvious asymmetrical pattern under the TMF contacts, and there was a ring-like aggregation zone inside the arc, which can cause severe ablation on the anode contacts. According to the reconstructed 3D distribution of Cu i and Cr i, it is found that the metal vapor was mainly concentrated near the electrode surface and showed a clear distribution of non-uniform aggregates, while the concentration of particles in the gap was low. Moreover, on the cathode surface, the cathode spots moved in the form of groups driven by the TMF, while the anode surface was ablated by the electric arc, and the metal vapor existed in the form of bands.


Behaviorally fractionated reaction time to an omitted stimulus: tests with visual, auditory, and tactile stimuli.
Two experiments tested the adequacy of behavioral criteria to fractionate reaction time (RT) into independent premotor (cognitive) and motor components. Healthy participants performed an omitted stimulus reaction time task in which they responded to the termination of a train of lateralized visual, auditory or tactile stimuli. Exp. 1 with 48 participants (24 men) showed premotor RT was independent of motor RT in each sensory modality and did not differ as a function of side of presentation or sex. Repeated tests administered in Exp. 2 (N= 12) also showed no significant association between the behaviorally fractionated measures. These results are comparable to those obtained using muscle potential to fractionate RT and suggest behaviorally fractionated premotor and motor RT could be a reliable, useful tool in the assessment of cognitive and motor processing in different sensory modalities of healthy people or those with brain injury, disease, or drug-induced disturbances.


Plasma lipoproteins in familial dysbetalipoproteinemia associated with apolipoproteins E2(Arg158-->Cys), E3-Leiden, and E2(Lys146-->Gln), and effects of treatment with simvastatin.
Using a density-gradient ultracentrifugation technique, we analyzed in detail the plasma lipoprotein profiles of 18 patients with familial dysbetalipoproteinemia (FD) who had apolipoprotein (apo) E2(Arg158-->Cys) homozygosity (the E2-158 variant, n = 6), apoE3-Leiden heterozygosity (the E3-Leiden variant, n = 6), or apoE2(Lys146-->Gln) heterozygosity (the E2-146 variant, n = 6), with average plasma cholesterol concentrations of 8.99 +/- 1.34 mmol/L, 9.29 +/- 1.55 mmol/L, and 8.46 +/- 1.10 mmol/L, respectively. No significant differences in sex, age, body mass index, dietary habits, and standard laboratory tests between the three groups were observed. The lipoprotein profiles of all FD patients were characterized by higher concentrations of very-low-density lipoprotein (VLDL) 1, VLDL2, and intermediate-density lipoprotein (IDL) and a higher cholesteryl ester content of VLDL1 and VLDL2 than in 6 normolipidemic control subjects with an average plasma cholesterol concentration of 5.90 +/- 0.53 mmol/L. Major differences between the plasma lipoprotein profiles of patients with the E2-158 variant, the E3-Leiden variant, and the E2-146 variant and the normolipidemic control subjects were in IDL cholesterol concentration (1.70 +/- 0.26, 1.50 +/- 0.26, 1.05 +/- 0.36, and 0.47 +/- 0.14 mmol/L, respectively), LDL cholesterol concentration (1.83 +/- 0.50, 3.09 +/- 0.32, 3.79 +/- 0.76, and 3.77 +/- 0.56 mmol/L, respectively), and the molar ratio of IDL cholesterol to LDL cholesterol (0.98 +/- 0.28, 0.48 +/- 0.04, 0.28 +/- 0.09, and 0.12 +/- 0.03, respectively). After 10 weeks of simvastatin treatment the concentrations of plasma cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol in 3 patients with the E2-158 variant fell significantly, by 46%, 56%, 53%, and 48%, respectively; they also fell in 3 patients with the E3-Leiden variant, by 48%, 54%, 57%, and 52%, respectively, and in 3 patients with the E2-146 variant, by 38%, 55%, 46%, and 35%, respectively. Simvastatin therapy lowered plasma activity of cholesteryl ester transfer protein but had no significant effect on plasma activity of lecithin:cholesterol acyltransferase. It is concluded that patients with FD due to various apoE variants have different lipoprotein profiles, mainly with regard to IDL and LDL levels, although they have a number of similar features of dysbetalipoproteinemia. Simvastatin therapy effectively reduced the plasma concentrations of total cholesterol, VLDL2 cholesterol, IDL cholesterol, and LDL cholesterol in the three groups of patients studied. It is proposed that apoE-dependent defects of the conversion of IDL to LDL may be an important mechanism in the pathophysiology of FD.


Aging Impairs Audiovisual Facilitation of Object Motion Within Self-Motion.
The presence of a moving sound has been shown to facilitate the detection of an independently moving visual target embedded among an array of identical moving objects simulating forward self-motion (Calabro et al., Proc. R. Soc. B, 2011). Given that the perception of object motion within self-motion declines with aging, we investigated whether older adults can also benefit from the presence of a congruent dynamic sound when detecting object motion within self-motion. Visual stimuli consisted of nine identical spheres randomly distributed inside a virtual rectangular prism. For 1 s, all the spheres expanded outward simulating forward observer translation at a constant speed. One of the spheres (the target) had independent motion either approaching or moving away from the observer at three different speeds. In the visual condition, stimuli contained no sound. In the audiovisual condition, the visual stimulus was accompanied by a broadband noise sound co-localized with the target, whose loudness increased or decreased congruent with the target's direction. Participants reported which of the spheres had independent motion. Younger participants showed higher target detection accuracy in the audiovisual compared to the visual condition at the slowest speed level. Older participants showed overall poorer target detection accuracy than the younger participants, but the presence of the sound had no effect on older participants' target detection accuracy at either speed level. These results indicate that aging may impair cross-modal integration in some contexts. Potential reasons for the absence of auditory facilitation in older adults are discussed.


Surgical Treatment of a Rare "Reverse" Madelung Deformity in 11 Years Female Patient.
Madelung deformity is an abnormality of the distal part of the forearm due to a growth arrest in the distal radial physis creating an increase of the radial tilt angle associated with a dorsal subluxation of the distal ulna in most cases. It is a rare condition which represents only 1.7% of hand deformities being characterized by the presence of an abnormal structure, Vickers ligament, that tethers the distal radius to the lunate bone. Although it is believed to be a congenital disorder, the symptoms are absent till late childhood. We present a case of a 11 years old girl patient, who came to our clinic for deformity of both forearms, which consisted of an anteriorly curved radius, volar proeminence of the distal ulna, partial limitation of supination and pain in the last 6 months, with and insidious onsed and aggravated lately. The mother of the patient, at the age of 13, was diagnosed with the same deformity which was surgically treated at that time. Furthermore, the patient has an older sister with no deformity of the forearms. X-rays revealed an increased radial tilt and anterior luxation of the distal ulna. Considering the deformity and the presence of pain we decided to excise the Vickers ligament and make an opening and derotation wedge osteotomy of the distal radius.


FB21, a monoclonal antibody that reacts with a sialic-acid-dependent carbohydrate epitope, is a marker for glomerular endothelial cell injury.
FB21 is reactive with glomerular endothelial cells and distal tubules of the human kidney and is bound to a sialic-acid-dependent cell-surface antigen. We evaluated FB21 staining in fetal kidneys and kidneys of children and adults with normal kidneys and glomerulonephritis and investigated whether FB21 can be used as a marker for endothelial cell injury. This study was performed on 6 children, 10 adults, and 12 fetuses with normal kidneys and 113 patients diagnosed with primary and secondary glomerulonephritis. We evaluated renal staining for FB21 in children with normal kidneys and glomerulonephritis and measured serum E-selectin concentrations in patients with hemolytic uremic syndrome (HUS) and Henoch-Schönlein purpura nephritis (HSPN). (1) FB21 was reactive with endothelial cells of normal kidneys and detected on the surface of endothelial cells by immunoelectron microscopy. (2) FB21 was reactive with endothelial cells in kidneys of fetuses older than 32 weeks. (3) Endothelial cell FB21 staining scores in the first renal biopsy specimens of patients with HUS and HSPN were lower than those in normal kidneys of children and correlated negatively with serum E-selectin concentrations. (4) Endothelial cell FB21 staining of crescentic and sclerotic glomerular lesions in patients with immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis was weaker than that in normal kidneys. These results suggest that FB21 can be used as a marker for glomerular endothelial cell injury in various types of glomerulonephritis.


Design-Build-Validate Strategy to 3D Print Bioglass Gradients for Anterior Cruciate Ligament Enthesis Reconstruction.
A rupture of the anterior cruciate ligament (ACL) is one of the most common knee ligament injuries affecting the young and active population. Tissue engineering strategies to reconstruct the damaged ACL have met with significant challenges mainly associated with poor graft integration at the bone-ligament interface (i.e., enthesis). In this study, a "design-build-validate" strategy was employed by combining 3D Raman spectral mapping and 3D printing to develop a tissue engineered scaffold that is compositionally similar to the ACL bone-ligament interface and can provide the essential biochemical cues to promote interface regeneration and facilitate functional graft to bone integration. Results showed that Raman spectroscopy is a highly efficient nondestructive technique to determine the biochemical composition of native ACL enthesis. 3D printing using combinatory inks consisting of different compositions of methacrylated collagen (CMA) and Bioglass (BG) allowed for the fabrication of BG gradient-incorporated collagen matrices (BioGIMs) with a transition region confirmed by Alizarin red S staining. Furthermore, Raman spectroscopy validated replication of ACL enthesis composition in BioGIMs. In addition, human mesenchymal stem cells (hMSCs) cultured on BioGIMs showed morphological differences along the length of the BioGIMs as evidenced by confocal microscopy of cell cytoskeleton-stained images indicating that the cells can sense the underlying differences in matrix composition. Overall, the "design-build-validate" strategy developed in this study has significant potential to generate biomimetic tissue constructs for use at the interface regions of synthetic grafts to promote better host integration and achieve full reconstruction of the ACL. Impact statement Poor graft integration at the bone-ligament interface (i.e., enthesis) is a significant clinical problem in anterior cruciate ligament (ACL) repair and reconstruction. In this study, Raman spectroscopy and 3D printing technologies were used in combination for the first time in a design-build-validate strategy to develop a continuous biomimetic Bioglass gradient-incorporated collagen matrix (BioGIM) that compositionally emulates the native ACL enthesis. These BioGIMs can be fused onto the ends of synthetic ACL grafts and have significant potential to provide the essential biochemical cues to guide tissue-specific cell differentiation, augment functional matrix reorganization, promote better graft integration, and achieve full reconstruction of damaged ACL.


NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization.
Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-GuC)rin) activates disabled naC/ve macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-N2) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.


[Usefulness and limitations of dobutamine stress echocardiography for detection of coronary artery disease].
The value of dobutamine stress echocardiography for detecting coronary artery disease was evaluated in 67 patients with normal left ventricular wall motion at rest who also underwent quantitative angiography. The overall sensitivity and specificity of dobutamine stress echocardiography for detecting coronary artery disease were 83% and 70%, respectively. The sensitivities for detecting multivessel disease and single vessel disease were 92% and 76%, respectively. The sensitivity of dobutamine stress echocardiography was 91% in patients treated without beta-blocker, and 70% in patients treated with beta-blocker (p < 0.001). The relatively low peak heart rate during dobutamine infusion in patients treated with beta-blocker seems to affect the sensitivity of dobutamine stress echocardiography. There were no severe complications during dobutamine infusion. Dobutamine stress echocardiography is a safe and accurate method for detecting coronary artery disease. However, an additional technique to increase peak heart rate in patients treated with beta-blocker such as injection of atropin should be considered.


Isolation of complementary DNAs encoding a cerebellum-enriched nuclear factor I family that activates transcription from the mouse myelin basic protein promoter.
A nuclear factor I (NFI) binding sequence in the myelin basic protein (MBP) promoter is required for brain-specific transcription. In the present study, we isolated multiple cDNAs encoding a family of NFI, NFI-B, from mouse brain cDNA libraries. These clones contain unique nucleotide sequences at their 5', 3', or middle portions, presumably as a result of alternative splicing. The entire sequence of NFI-B suggests that NFI-B is a mouse counterpart of NFI-L, which was previously isolated from rat liver. NFI-B is highly enriched in the cerebellum, in contrast with a ubiquitous NFI, CTF/NF-I. NFI-B proteins translated in vitro could bind to the MBP NFI site. Furthermore, we demonstrated by transfection experiments that NFI-B activated transcription from transfected MBP promoter in neuronal/glial NG108-15 cells.


Time-domain analysis of scrotal thermoregulatory impairment in varicocele.
Varicocele is a common male disease defined as the pathological dilatation of the pampiniform plexus and scrotal veins with venous blood reflux. Varicocele usually impairs the scrotal thermoregulation via a hemodynamic alteration, thus inducing an increase in cutaneous temperature. The investigation of altered scrotal thermoregulation by means of thermal infrared imaging has been proved to be useful in the study of the functional thermal impairment. In this study, we use the Control System Theory to analyze the time-domain dynamics of the scrotal thermoregulation in response to a mild cold challenge. Four standard time-domain dynamic parameters of a prototype second order control system (Delay Time, Rise Time, closed poles locations, steady state error) and the static basal temperatures were directly estimated from thermal recovery curves. Thermal infrared imaging data from 31 healthy controls (HCS) and 95 varicocele patients were processed. True-positive predictions, by comparison with standard echo color Doppler findings, higher than 87% were achieved into the proper classification of the disease stage. The proposed approach could help to understand at which specific level the presence of the disease impacts the scrotal thermoregulation, which is also involved into normal spermatogenesis process.


Quadricuspid aortic valve perforation resulting from bacterial endocarditis--2-D echo- and angiographic diagnosis and its surgical treatment.
A 75-year-old man with quadricuspid aortic valve regurgitation affected by bacterial endocarditis is reported. The aortic valve consisted of 4 equal-sized cusps (type a) and a supernumerary cusp located between the right and noncoronary cusps. A right coronary ostium was close to the accessory commissure, but there was no displacement. A few small fenestrations were found at the 4 commissures and a large perforation resulting from endocarditis was observed in the noncoronary cusp. 2-D echocardiogram and angiogram suggested these findings, and they were confirmed at surgery. Successful aortic valve replacement was achieved.