Transdiagnostic Prediction of Affective, Cognitive, and Social Function Through Brain Reward Anticipation in Schizophrenia, Bipolar Disorder, Major Depression, and Autism Spectrum Diagnoses.
The relationship between transdiagnostic, dimensional, and categorical approaches to psychiatric nosology is under intense debate. To inform this discussion, we studied neural systems linked to reward anticipation across a range of disorders and behavioral dimensions. We assessed brain responses to reward expectancy in a large sample of 221 participants, including patients with schizophrenia (SZ; n = 27), bipolar disorder (BP; n = 28), major depressive disorder (MD; n = 31), autism spectrum disorder (ASD; n = 25), and healthy controls (n = 110). We also characterized all subjects with an extensive test battery from which a cognitive, affective, and social functioning factor was constructed. These factors were subsequently related to functional responses in the ventral striatum (vST) and neural networks linked to it. We found that blunted vST responses were present in SZ, BP, and ASD but not in MD. Activation within the vST predicted individual differences in affective, cognitive, and social functioning across diagnostic boundaries. Network alterations extended beyond the reward network to include regions implicated in executive control. We further confirmed the robustness of our results in various control analyses. Our findings suggest that altered brain responses during reward anticipation show transdiagnostic alterations that can be mapped onto dimensional measures of functioning. They also highlight the role of executive control of reward and salience signaling in the disorders we study and show the power of systems-level neuroscience to account for clinically relevant behaviors.


Portable Gait Lab: Estimating 3D GRF Using a Pelvis IMU in a Foot IMU Defined Frame.
Ground Reaction Forces (GRF) during gait are measured using expensive laboratory setups such as in-floor or treadmill force plates. Ambulatory measurement of GRF using wearables enables remote monitoring of gait and balance. Here, we propose using an Inertial Measurement Unit (IMU) mounted on the pelvis to estimate the GRF during gait in daily life. Calibration procedures and an Error State Extended Kalman filter (EEKF) were used to transform the accelerations at the center of mass (CoM) to the 3D GRF. The instantaneous 3D GRF was estimated for different overground walking patterns and compared with the 3D GRF measured using the reference ForceShoe™ system. Furthermore, we introduce a changing reference frame called the current step frame that followed the direction of each step made. The frame was defined using movement of the feet, and the estimated GRF were expressed in this new frame. This allowed direct comparison and validation with the reference. The mean and standard deviation of error between the estimated instantaneous 3D GRF and the reference, normalized against the range of the reference, was 12.1 ± 3.3% across all walking tasks, in the horizontal plane. The error margins show that a single pelvis IMU could be a minimal and ambulatory sensing alternative for estimating the instantaneous 3D components of GRF during overground gait.


Study Design Characteristics and Pharmacological Mechanisms in International Clinical Trials Registry Platform: Registered Clinical Trials on Antiviral Drugs for COVID-19.
This study aimed to evaluate the pharmacological mechanisms of antiviral drugs against the novel coronavirus disease (COVID-19) and the study designs in clinical trials registered with the International Clinical Trials Registry Platform (ICTRP). Clinical trials involving antiviral drugs for treating COVID-19 were retrieved from the ICTRP database. For each trial, the study design, number of participants, primary endpoints, source register, antiviral mechanism, and results were evaluated. On June 10, 2020, 145 eligible clinical trials were retrieved from the ICTRP, of which 99 (68.3%) were randomized trials, 109 (75.2%) were parallel assignment trials, 38 (26.2%) were double or single blinded, 130 (89.7%) involved two groups, and 75 (51.6%) included more than 100 participants; and clinical improvement or recovery and virus-negative conversion were the two most common endpoints, accounting for 40.7% and 18.6%, respectively. The drugs were divided according to the antiviral mechanism into HIV reverse transcriptase inhibitors, RNA-dependent RNA polymerase inhibitors, HIV protease inhibitors (PIs), hepatitis C virus NS3 PIs, and anti-influenza drugs. The design characteristics of clinical trials of antiviral drugs for treating COVID-19 as well as the mechanism of action and antiviral efficacy of the drugs were evaluated in this study. The results of these trials could constitute a reference for future clinical trials to be executed on COVID-19 treatment and prevention.


Keeping it short: a comparison of methods for brief picture presentation.
Research has shown that backward masking is a powerful tool for studying unconscious mental processes. Whereas studies have traditionally presented stimuli using cathode-ray tube (CRT) monitors or mechanical shutters together with slide projectors, recent studies (mainly in functional magnetic resonance imaging, fMRI) have begun to use methods based on liquid crystal displays (LCDs) and thin-film transistor (TFT) technology. However, because of differences in technology, all methods may not be equally suited for masking. When methods were compared for their accuracy in presenting pictures at short durations, LCD and TFT presentations had poor accuracy, but shutter and CRT presentations had better accuracy. Because CRTs interfere with the imaging process in fMRI, we recommend the use of mechanical shutters. However, our results may not generally apply to all displays, so we advise researchers to validate the presentation parameters of their displays. The procedure described here may be useful for that purpose.


Liquefied after cataract and its surgical treatment.
To describe liquefied after cataract (LAC) and its surgical management following an uneventful phacoemulsification with posterior chamber in-the-bag intraocular lens (IOL) implantation and continuous curvilinear capsulorrhexis (CCC). Interventional case series. Eleven patients with LAC, following uneventful phacoemulsification with CCC and in-the-bag IOL implantation were enrolled. After the basic slit lamp examination, each case was investigated with Scheimpflug photography and ultrasound biomicroscopy (UBM). Each case was treated with capsular lavage. Biochemical composition of the milky fluid was evaluated and ring of anterior capsular opacity (ACO) was examined under electron microscope. All 11 cases presented with blurring of vision after 6-8 years of cataract surgery with IOL implantation. All cases had IOL microvacuoles, 360° anterior capsule, and anterior IOL surface touch along with ACO, ring of Soemmering, and posterior capsule distension filled with opalescent milky fluid with whitish floppy or crystalline deposits. Biochemically, the milky fluid contained protein (800 mg/dl), albumin (100 mg/dl), sugar (105 mg/dl), and calcium (0.13%) and was bacteriologically sterile. Histologically, the dissected ACO showed fibrous tissue. All cases were successfully treated with capsular lavage with good visual recovery and with no complication. There was no recurrence of LAC during 2 years postoperative follow-up in any of the cases. LAC is a late complication of standard cataract surgery. It may be a spectrum of capsular bag distension syndrome (CBDS) without shallow anterior chamber and secondary glaucoma. Capsular bag lavage is a simple and effective treatment for LAC and a safe alternative to neodymium-doped yttrium aluminum garnet (Nd-YAG) capsulotomy.


Efficient and ultraviolet durable planar perovskite solar cells via a ferrocenecarboxylic acid modified nickel oxide hole transport layer.
Planar perovskite solar cells (PSCs) that use nickel oxide (NiOx) as a hole transport layer have recently attracted tremendous attention because of their excellent photovoltaic efficiencies and simple fabrication. However, the electrical conductivity of NiOx and the interface contact properties of the NiOx/perovskite layer are always limited for the NiOx layer fabricated at a relatively low annealing temperature. Ferrocenedicarboxylic acid (FDA) was firstly introduced to modify a p-type NiOx hole transport layer in PSCs, which obviously improves the crystallization of the perovskite layer and hole transport and collection abilities and reduces carrier recombination. PSCs with a FDA modified NiOx layer reached a PCE of 18.20%, which is much higher than the PCE (15.13%) of reference PSCs. Furthermore, PSCs with a FDA interfacial modification layer show better UV durability and a hysteresis-free effect and still maintain the original PCE value of 49.8%after being exposed to UV for 24 h. The enhanced performance of the PSCs is attributed to better crystallization of the perovskite layer, the passivation effect of FDA, superior interface contact at the NiOx/perovskite layers and enhancement of the electrical conductivity of the FDA modified NiOx layer. In addition, PSCs with FDA inserted at the interface of the perovskite/PCBM layers can also improve the PCE to 16.62%, indicating that FDA have dual functions to modify p-type and n-type carrier transporting layers.


Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669.
A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described (Countaway, J. L., Northwood, I. C., and Davis, R. J. (1989) J. Biol. Chem. 264, 10828-10835). Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase. However, the second peak of activity was found to be a distinct enzyme. We present here the purification of this enzyme from human tumor KB cells by sequential ion-exchange chromatography. The isolated protein kinase was identified as a 46-kDa protein by polyacrylamide gel electrophoresis and silver staining. Gel filtration chromatography demonstrated that the enzyme was functional in a monomeric state. A kinetic analysis of the purified enzyme was performed at 22 degrees C using a synthetic peptide substrate based on the primary sequence of the EGF receptor (KREL VEPLT669PSGEAPNQALLR). The Km(app) for ATP was 40 +/- 5 microM (mean +/- S.D., n = 3). GTP was not found to be a substrate for the purified enzyme. The Km(app) for the synthetic peptide substrate was 260 +/- 40 microM (mean +/- S.D., n = 3). The Vmax(app) for the isolated protein kinase was determined to be 400-900 nmol/mg/min. The purified enzyme was designated EGF receptor Thr669 (ERT) kinase. It is likely that the MAP2 and ERT kinases account for the phosphorylation of the EGF receptor at Thr669 observed in cultured cells. The marked stimulation of protein kinase activity caused by growth factors indicates that these enzymes may have an important function during signal transduction.


Evaluation of the Possibility to Detect Circulating Tumor DNA From Pituitary Adenoma.
Objective: Circulating free DNA (cfDNA) in general and circulating tumor DNA (ctDNA) in particular is becoming an increasingly used form of liquid biopsy biomarkers. In this study, we are investigating the ability to detect ctDNA from the plasma of pituitary adenoma (PA) patients. Design: Tumor tissue samples were obtained from planed PA resections, before which blood plasma samples were taken. Somatic variants found in PA tissue samples were evaluated in related cfDNA, isolated from plasma samples. Methods: Sanger sequencing, as well as previously obtained whole-exome sequencing data, were used to evaluate somatic variants composition in tumor tissue samples. cfDNA was isolated from the same PA patients and competitive allele-specific TaqMan PCR and amplicon-based next-generation sequencing (NGS) approach were used for targeted detection of variants found in corresponding tumor tissue samples. Results: Using NGS-based analysis, we detected five out of 17 somatic variants in 40 to 60% of total reads, three variants in 0.50-5.00% of total read count, including GNAS c.601C>T, which was detected using ultra-deep NGS (1.78 million X) in 0.77% of amplicons reads. Nine variants were not detected. We also detected We were not able to detect variant found in PA tissue in cfDNA using cast-PCR, indicating that the portion of variant-containing ctDNA in total isolated cfDNA is too small to be detected with this method. Conclusions: For the first time, we demonstrate the possibility to detect somatic variants of PA in cfDNA isolated from patients' blood plasma. Whether the source of variant detected in cfDNA is PA should be further tested.


Mental health stigma among university health care students in Nigeria: a cross-sectional observational study.
stigma is a key barrier to access and utilization of mental health services, particularly in low- and middle- income countries. The authors explore the specific content of mental health stigma among Nigerian university health care students at a national teaching hospital. These students are key stakeholders and represent a vital demographic to engage in stigma reduction initiatives. We evaluated the extent to which demographic characteristics, mood symptoms and utilization of resources are associated with stigma. the authors examined data obtained from surveys completed by university health care students (N = 82) at Lagos University teaching hospital. Surveys assessed demographic background, mood symptoms and use of mental health services. Simple linear regression was used to model the unadjusted association between each component variable and overall stigma score. All analyses were conducted using R (version 3.5.3, 2019, The R Foundation) and assumed a two-sided, 5% level of significance. being a member of the minority ethnic group within our study population was associated with increased stigma. Individuals having greater need for mental health services (due to mood symptoms) were associated with increased stigma. Willingness to use medical services and community support from family and friends was associated with lower stigma. Religious themes were prominent among the majority of respondents. consideration of the content details of stigma among university health care students in Nigeria is essential to inform interventions and strategies to reduce stigma within this subgroup. Those students who have symptoms of depression or anxiety may have lower utilization of mental health services.


The novel use of waste animal bone from New Zealand agricultural sources as a feedstock for forming plasma sprayed hydroxyapatite coatings on biomedical implant materials.
This study presents the feasibility of using animal bone-derived hydroxyapatite (HAP) as feedstock powders for plasma spraying. Bovine, cervine and ovine bone from abattoirs was boiled in a pressure cooker to remove blood, fat and adhering meat tissue. The bone was then placed in a muffler furnace, pyrolyzed at approximately 1000 degrees C to remove collagen and resid-ual organics, cooled and subsequently ground to a powder then digested in nitric acid. Sodium hydroxide was added to the digest to reprecipitate the HAP. Ageing of the precipitate followed by filtration, extensive washing and drying produced the white powder used as the feedstock. X-ray diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR) confirmed the powder to be poorly crystalline HAP with low-level carbonate. Out of several batches of the sieved powders, one batch was plasma sprayed to produce adherent HAP coatings; therefore, demonstrating that animal bone-derived HAP powders can be seri-ously considered as a feedstock powder, subject to the powder being processed for the correct rheological characteristics for easy flowing within the plasma spray flow lines. The phase composition of the successful plasma sprayed HAP coatings on both stainless steel and titanium were found by XRD to be mainly HAP with minor contributions from á -tricalcium phosphate, tetra-calcium phosphate and CaO; therefore, demonstrating that feedstock decomposition on its passage through the plasma spray torch was insignificant under the conditions employed. Scanning electron microscopy (SEM) micrographs of the coatings indicated that their morphology featured the classical heterogeneous and splat-like appearance expected of plasma sprayed coatings. Young's modulus and Vicker's microhardness tests conducted on the coatings revealed values in the range, respectively, 22-87 GPa and 166-287 (HV200 ) indicating high strength plasma spray HAP coatings had been produced from the feedstock powder.


Anti-nerve growth factor therapy attenuates cutaneous hypersensitivity and musculoskeletal discomfort in mice with osteoporosis.
The prevalence of osteoporosis is increasing with the aging population and is associated with increased risk of fracture and chronic pain. Osteoporosis is currently treated with bisphosphonate therapy to attenuate bone loss. We previously reported that improvement in bone mineral density is not sufficient to reduce osteoporosis-related pain in an ovariectomy (OVX)-induced mouse model of osteoporosis, highlighting the need for new treatments. Targeting of nerve growth factor (NGF) with sequestering antibodies is a promising new direction for the treatment of musculoskeletal pain including back pain and arthritis. Its efficacy is currently unknown for osteoporotic pain. To investigate the efficacy of anti-NGF antibody therapy on osteoporotic pain in an OVX-induced mouse model. Ovariectomy- and sham-operated mice were injected with an anti-NGF antibody (10 mg/kg, intraperitoneally, administered 2×, 14 days apart), and the effect on behavioural indices of osteoporosis-related pain and on sensory neuron plasticity was evaluated. Treatment with anti-NGF antibodies attenuated OVX-induced hypersensitivity to mechanical, cold, and heat stimuli on the plantar surface of the hind paw. The OVX-induced impairment in grip force strength, used here as a measure of axial discomfort, was partially reversed by anti-NGF therapy. No changes were observed in the rotarod or open-field tests for overall motor function and activity. Finally, anti-NGF treatment attenuated the increase in calcitonin gene-related peptide-immunoreactive dorsal root ganglia neurons observed in OVX mice. Taken together, these data suggest that anti-NGF antibodies may be useful in the treatment of prefracture hypersensitivity that is reported in 10% of patients with osteoporosis.


The rkpU gene of Sinorhizobium fredii HH103 is required for bacterial K-antigen polysaccharide production and for efficient nodulation with soybean but not with cowpea.
In this work, the role of the rkpU and rkpJ genes in the production of the K-antigen polysaccharides (KPS) and in the symbiotic capacity of Sinorhizobium fredii HH103, a broad host-range rhizobial strain able to nodulate soybean and many other legumes, was studied. The rkpJ- and rkpU-encoded products are orthologous to Escherichia coli proteins involved in capsule export. S. fredii HH103 mutant derivatives were contructed in both genes. To our knowledge, this is the first time that the role of rkpU in KPS production has been studied in rhizobia. Both rkpJ and rkpU mutants were unable to produce KPS. The rkpU derivative also showed alterations in its lipopolysaccharide (LPS). Neither KPS production nor rkpJ and rkpU expression was affected by the presence of the flavonoid genistein. Soybean (Glycine max) plants inoculated with the S. fredii HH103 rkpU and rkpJ mutants showed reduced nodulation and clear symptoms of nitrogen starvation. However, neither the rkpJ nor the rkpU mutants were significantly impaired in their symbiotic interaction with cowpea (Vigna unguiculata). Thus, we demonstrate for the first time to our knowledge the involvement of the rkpU gene in rhizobial KPS production and also show that the symbiotic relevance of the S. fredii HH103 KPS depends on the specific bacterium-legume interaction.


Understanding the driving mechanisms of site contamination in China through a data-driven approach.
China currently faces significant environmental risks stemming from contaminated sites. The driving mechanism of site contamination, influenced by various drivers, remain obscured due to a dearth of quantitative methodologies and comprehensive data. Here, we used a data-driven causality inference approach to construct an interpretable random forest (RF) model. Results show that: (1) the trained RF model demonstrated remarkable predictive accuracy for identifying contaminated sites, with an accuracy rate of 0.89. In contrast to conventional correlation analysis, the RF model excels in discerning the key drivers through non-linear and genuine causal relationships between these drivers and site contamination. (2) Among the 25 potential drivers, we identified 18 key drivers of site contamination. These drivers encompass a broad spectrum of factors, including production and operational data, pollutant control level, site protection capability, pollutant characteristics, and physical-geographical conditions. (3) Each key driver exerts varying impacts on site pollution, with diverse directions, intensities, and underlying patterns. The partial dependence plots (PDPs) illuminate the role of each key driver, its critical value contributing to site pollution, and the interplay between these drivers. The key drivers facilitate the realization of three primary contamination processes: uncontrolled release, effective migration, and persistent accumulation. In light of our findings, environmental managers can proactively prevent site contamination by regulating single, dual, and multiple key drivers to disrupt critical pollution processes. This research offers valuable insights for devising targeted strategies and interventions aimed at mitigating environmental risks associated with contaminated sites in China.


Activated carbon modified with copper for adsorption of propanethiol.
Activated carbons were characterized texturally and chemically before and after treatment, using surface area determination in the BET model, Boehm titration, TPR, DRX and immersion calorimetry. The adsorption capacity and the kinetics of sulphur compound removal were determined by gas chromatography. It was established that the propanethiol retention capacity is dependent on the number of oxygenated groups generated on the activated carbon surface and that activated carbon modified with CuO at 0.25 M shows the highest retention of propanethiol. Additionally is proposed a mechanism of decomposition of propenothiol with carbon-copper system.


Rituximab in idiopathic membranous nephropathy.
Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria <0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h, each also having >50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m(2) among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.


Bicarbonate transport in sheep parotid secretory cells.
1. Intracellular pH (pH1) was measured by microfluorimetry in secretory endpieces isolated from sheep parotid glands and loaded with the pH-sensitive fluoroprobe 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). 2. Stimulation with 1 microM acetylcholine (ACh) caused a large, transient decrease in pH1 of 0.37 +/- 0.02 pH units followed by a slower recovery. The transient, which was reduced by 60% in the absence of HCO3-, could be attributed mainly to HCO3- efflux. During sustained stimulation, pH1 increased to a value that exceeded the resting value by 0.083 +/- 0.023 pH units after 20 min. 3. The anion channel blocker NPPB (0.1 mM) reduced the transient acidification in response to ACh by 48% and raised pH1 during sustained stimulation. Simultaneous application of NPPB and ACh accelerated the re-alkalinization following the initial acidification, indicating that NPPB inhibits HCO3- efflux. 4. The stilbene derivative H2DIDS (0.5 mM) reduced the transient acidification in response to ACh by 76% but caused a marked decrease in pH1 during sustained stimulation. Simultaneous application of H2DIDS and ACh slowed the re-alkalinization following the initial acidification, indicating that the main effect of H2DIDS was to inhibit HCO3- accumulation. 5. In the absence of HCO3-, the recovery from an acid load was unaffected by ACh stimulation. Acid extrusion, although dependent on Na+, was not inhibited by amiloride (1 mM), clonidine (1 mM) or H2DIDS (0.5 mM) and was therefore provisionally attributed to a Na(+)-H+ exchanger isoform other than NHE1 or NHE2. 6. In the presence of HCO3-, the rate of recovery from an acid load was reduced during ACh stimulation, probably as a result of the increased efflux of HCO3-. Acid extrusion was dependent on Na+ and was significantly inhibited by H2DIDS. 7. We conclude that ACh-evoked HCO3- secretion in the sheep parotid gland differs from that in many other salivary glands by being driven predominantly by basolateral Na(+)-HCO3- cotransport rather than by Na(+)-H+ exchange.


[Levels and distribution of short chain chlorinated paraffins in seafood from Dalian, China].
Seafood samples were collected from Dalian, China to study the accumulation and distribution characteristics of short chain chlorinated paraffins (SCCPs) by GC/ECNI-LRMS. Sum of SCCPs (dry weight) were in the range of 77-8 250 ng.g-1, with the lowest value in Scapharca subcrenata and highest concentration in Neptunea cumingi. The concentrations of sum of SCCPs (dry weight) in fish, shrimp/crab and shellfish were in the ranges of 100-3 510, 394-5 440, and 77-8 250 ng.g-1 , respectively. Overall, the C10 and C11 homologues were the most predominant carbon groups of SCCPs in seafood from this area,and a relatively higher proportion of C12-13 was observed in seafood with higher concentrations of sum of SCCPs . With regard to chlorine content, Cl1,, CI8 and CI6 were the major groups. Significant correlations were found among concentrations of different SCCP homologues (except C1, vs. Cl10 ) , which indicated that they might share the same sources and/or have similar accumulation, migration and transformation processes.


Chondroprotective effects of a polycarbonate-urethane meniscal implant: histopathological results in a sheep model.
injury or loss of the meniscus generally leads to degenerative osteoarthritic changes in the knee joint. However, few surgical options exist for meniscal replacement. The goal of this study was to examine the ability of a non-degradable, anatomically shaped artificial meniscal implant, composed of Kevlar-reinforced polycarbonate-urethane (PCU), to prevent progressive cartilage degeneration following complete meniscectomy. the artificial meniscus was implanted in the knees of mature female sheep following total medial meniscectomy, and the animals were killed at 3- and 6-months post-surgery. Macroscopic analysis and semi-quantitative histological analysis were performed on the cartilage of the operated knee and unoperated contralateral control joint. the PCU implants remained well secured throughout the experimental period and showed no signs of wear or changes in structural or material properties. Histological analysis showed relatively mild cartilage degeneration that was dominated by loss of proteoglycan content and cartilage structure. However, the total osteoarthritis score did not significantly differ between the control and operated knees, and there were no differences in the severity of degenerative changes between 3 and 6 months post-surgery. current findings provide preliminary evidence for the ability of an artificial PCU meniscal implant to delay or prevent osteoarthritic changes in knee joint following complete medial meniscectomy.


[Effects of praeruptorin C on isolated guinea pig atrium and myocardial compliance in patients].
Praeruptorin C (Pra-C, 2-methyl-,10-(acetyloxy)-9,10- dihydro-8,8-dimethyl-2-oxo-2H, 8H-benzo[1,2-b:3,4-b'] dipyran-9-ol ester of 2-butenoic acid) was first isolated by Chinese researcher. Pra-C 10 mumol/L reduced automatic rhythm and positive chronotropic effects of CaCl2 in right atrium. Its antagonistic effects on isoproterenol-mediated increase in beat rate were non-competitive with a pD'2 of 4.8. Pra-C 5-50 mumol/L shortened functional refractory period with little effects on the excitability and epinephrine-induced ecotopic automaticity. Modification of myocardial compliance during 2 wk oral Pra-C therapy in patients with hypertrophic cardiomyopathy was also investigated.


Clinicopathologic analysis of 370 cases of vulvar intraepithelial neoplasia. Italian Study Group on Vulvar Disease.
To investigate epidemiologic, clinical and pathologic aspects of various grades of vulvar intraepithelial neoplasia (VIN). A retrospective, multicenter study of 370 cases of vulvar intraepithelial neoplasia (VIN) was performed by the Italian Study Group on Vulvar Disease. Of the 370 cases, 148 were VIN 1 (40.0%, 53 were VIN 2 (14.3%), and 169 were VIN 3 (45.7%). The mean age of the patients was 52.6 years. During the study period an increase in the rate of human papillomavirus-associated VIN was observed. In addition, while VIN 1 and 2 were associated mostly with squamous cell hyperplasia, VIN 3 was almost equally associated with lichen sclerosus and squamous cell hyperplasia; the difference was statistically significant. Intraepithelial or invasive squamous neoplasia of the lower genital tract was associated in 22% of the cases (82/370). The results of the investigation, although not allowing firm conclusions due to the retrospective and multicentered nature of the study, demonstrate the extreme heterogeneity of VIN lesions.


Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis.
Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. To date, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of individuals with moderate/severe AD compared to healthy controls. An exploratory case-control study was conducted. AD patients (n = 23) and controls (n = 21) were enrolled at the International Center for Clinical Studies, Santiago, Chile. Complete dermatological and periodontal evaluations (involving the collection of GCF samples) were made. The levels of 35 proteases were analyzed using a human protease antibody array in matching AD patients (n = 6) and controls (n = 6) with healthy periodontium. The GCF levels of zinc-binding ADAM8, ADAM9, MMP8, Neprilysin/CD10, aspartyl-binding Cathepsin E, serin-binding Protein convertase9, and uPA/Urokinase proteases were lower in moderate/severe AD patients compared to controls (p < 0.05). No inter-group differences in the levels of the other 28 proteases were found. MMP8, Cathepsin E, and ADAM9 were the biomarkers with the highest sensitivity and specificity regarding the detection of AD (p < 0.05). The area under receiver operating characteristic (ROC) curve for MMP8 was 0.83 and MMP8 + ADAMP9 was 0.90, with no significant differences (p = 0.132). A combined model of MMP8, Cathepsin E, and ADAM9 was not considered since it did not converge. Then, levels of MMP8 in GCF were determined using a multiplex bead immunoassay in 23 subjects with AD and 21 healthy subjects. Lower levels of MMP8 in the GCF from the AD group versus healthy group (p = 0.029) were found. This difference remained significant after adjustment by periodontitis (p = 0.042). MMP8 revealed the diagnostic potential to identify AD patients versus healthy controls, (ROC area = 0.672, p < 0.05). In conclusion, differences in the protease profile between AD and control patients were associated with MMP8, Cathepsin E, and ADAM9. Based on the multiplex assay results, MMP8 was lower in AD patients than controls, suggesting that MMP8 may be a diagnostic biomarker candidate.


A summary index of infant and child feeding practices is associated with child growth in urban Shanghai.
Recently, an infant and child feeding index (ICFI) constructed on brief recalls of breastfeeding, feeding frequency and food diversification was assumed to provide long-term prediction about child feeding practices. The aim of this study was to investigate the association between the cross-sectional ICFI (CS-ICFI) or longitudinal ICFI (L-ICFI) and child anthropometric indices in downtown Shanghai, China. The prospective cohort study included 180 infants aged 5-7 mo with their main caregivers who were visited 3 times every 6 months over 12 months. A CS-ICFI was constructed for each visit by using data on feeding practices based on 24-h and 7-d recalls. An L-ICFI was constructed with use of the 3 CS-ICFIs. The associations between ICFI and length-for-age z score (LAZ), weight-for-age z score (WAZ), and weight-for-length z score (WLZ) were examined. The stability of the CS-ICFI was assessed by using repeatability coefficient (RC). The L-ICFI was positively associated with LAZ and WAZ at Visit 3(beta = 0.151, P = 0.040 and beta = 0.173, P = 0.024, respectively). Moreover, the CS-ICFI at Visit 1 was positively associated with LAZ, WAZ and WLZ (beta = 0.160, P = 0.029; beta = 0.191, P = 0.009; beta = 0.176, P = 0.020) at Visit 3, and the CS-ICFI at Visit 3 was also positively associated with LAZ (beta = 0.176, P = 0.016). Stability of the CS-ICFI was shown by the value of 0.14 (95% CI: 0.07, 0.31) of the RC, which differed significantly from 0 (P < 0.05). The ICFI constructed on brief recalls based on cross-sectional studies can be used to evaluate the effects of child feeding practice on child growth.


Photopic negative response of focal electoretinograms in glaucomatous eyes.
To determine the clinical importance of the photopic negative response (PhNR) of the focal electoretinogram (fERG) for diagnosing glaucoma. Fifty-nine eyes of 38 patients with open-angle glaucoma (OAG), 12 glaucoma suspects, and 32 eyes of 32 normal controls were studied. The fERGs were elicited by a 15 degrees stimulus spot on the macula region, the supero-temporal, and infero-temporal regions of the macula. The mean of the visual sensitivity was measured by standard automated perimetry (SAP). The optimal cutoff amplitudes of the focal PhNR and ratios of the focal PhNR/b-wave amplitudes that discriminated glaucomatous eyes from normal eyes were obtained from the receiver operating characteristic curves. The amplitudes of the PhNR were significantly smaller in patients with OAG than in normal controls (P < 0.00001). A curvilinear relationship was found between the mean sensitivity (dB, on log scale) and the PhNR amplitude, and between the mean sensitivity and the PhNR/b-wave amplitude ratio. After converting the mean sensitivity from a logarithmic to a linear scale, the amplitude of the PhNR and PhNR/b-wave ratio were linearly correlated with the SAP-determined visual sensitivity in all retinal areas (r = .428-0.544, P < 0.0001). When the optimal cutoff values were used, the sensitivity and specificity of the PhNR/b-wave amplitude ratio were 98.3% and 90.1%, respectively. The reduction of the focal PhNR amplitude was associated with a local decrease in the retinal sensitivity in OAG. The high sensitivity and specificity suggest that the focal PhNR can be used to detect functional loss in OAG.


Use of the clavicle in anterior cervical discectomy/corpectomy fusion procedures: cadaveric feasibility study.
Graft sources for cervical fusion procedures include synthetic materials, donor grafts, and autologous bones such as the iliac crest. Considering the data that autologous bone grafts seem to generate the best results for fusion, the next logical step is to seek alternative donor sites so as to attempt to reduce the morbidity associated with these procedures. To our knowledge, autologous clavicle has not been explored as a potential source for cervical fusion. Therefore, the following study was performed to verify the utility of this bone for these procedures. Seven adult cadavers were used for this study. In the supine position, a standard surgical approach and dissection to the anterior cervical spine were performed. Specimens underwent a standard discectomy or corpectomy with placement of harvested ipsilateral clavicle previously dissected. An anterior cervical plating system was next placed over these sites using standard techniques. Measurements of the harvested clavicle were made. The results of our morphometric analysis were as follows: An average of 5 cm of bone was easily removed from the middle one third of the clavicle. No gross injury was found to vicinal neurovascular structures. The middle one third of the clavicle offered sufficient bone for the one to two segments fused in our study with remaining bone for at least two additional segments. The mean diameter of this part of the clavicle was 1.2 cm. Based on our cadaveric study, such a bony substitute as autologous clavicle might be a reasonable alternative to the iliac crest for use in anterior cervical fusion procedures.


Operative management of trigeminal schwannomas: based on a modified classification in a study of 93 cases.
Advances in microscopic and endoscopic surgical techniques have outpaced traditional classification and transcranial surgical strategies, especially with reference to the treatment of trigeminal schwannomas (TSs). A modified TS classification is proposed and appropriate surgical strategies are discussed. The cases of 93 patients who underwent surgical treatment in Beijing Tiantan Hospital in the previous 6 years were analyzed retrospectively, and a literature review was conducted. Classification is based on surgical direction. Tumors were classified as follows: type A, backward orientation, located in the orbit or orbit and middle cranial fossa (8 cases, 8.6%); type B, upward orientation, located in the pterygopalatine fossa, infratemporal fossa or pterygopalatine fossa, infratemporal fossa, and middle cranial fossa (23 cases, 24.7%); type C, forward and backward orientations, located in the middle cranial fossa, posterior cranial fossa or both (58 cases, 62.4%); and type D, located in multiple regions (4 cases, 4.3%). 91.40% of patients underwent gross total resection (GTR) with 29 cases receiving endoscopic resection of whom 93.10% (27/29) experienced GTR. The 93 cases were satisfactorily divided into four types, according to tumor location and surgical orientation, enabling safe and effective removal by appropriate surgery.


Biomechanical evaluation of implant placement in the reconstructed mandible.
Following resection of malignant tumors from the mandible, immediate reconstruction of the discontinuous jaw is commonly performed. The present study aims to define the risks associated with dynamic loading of the reconstructed mandible. Computer-aided design simulations of eight mandibles were produced and termed normal models. The normal models were then modified by removing part of the right body and restoring the defects with bone from the rib or fibula. These modified models were termed reconstructed models. Thereafter, an implant was embedded in the first molar region of the left side for all models. Using finite element analysis, the stresses occurring at the implant-bone interface with simulated mastication were calculated. The Wilcoxon signed rank test was applied to compare the magnitudes of stresses in both models. In terms of the stress exerted at the implant-bone interface during mastication, the normal models and the reconstructed models showed no significant differences (P > .05). Placement of an implant on the nonreconstructed side following partial resection and mandibular reconstruction presents no significant risk.


The role of dental hygienists in state public health programs.
The role and personnel status of dental hygienists in state public health programs have not been documented. In October 1987, a 13-page questionnaire was mailed to the 55 state and territorial dental directors around the country, requesting information on dental hygienists who are employed by the state in public health positions. The questionnaire was divided into three categories: educational services; clinical services; and hygienists who divide their time between clinical and oral health educational services. Questions in each category requested information on job title, educational requirements, salary, benefits, and programmatic areas of responsibility. The purpose of this survey was to document the role and extent of participation by dental hygienists in state public health programs. Forty-eight states responded to the questionnaire, with 37 states employing dental hygienists in state public health programs. Twelve percent of the educational services and seven percent of the clinical services employing hygienists are in supervisory or management-level positions, with advanced degree requirements not necessarily a factor. Only 61% have dental hygienists involved with water fluoridation educational programs which, considering the known benefits of community water fluoridation, is surprisingly low. The survey results may be used to assist administrators in developing appropriate programs utilizing dental hygienists.


CONSIDERATION OF THE PECULIARITIES OF A PERSON WITH POST-TRAUMATIC STRESS DISORDER IN MEDIATOR`S PROFESSIONAL ACTIVITY.
Aim: To study and take into account the behavioral characteristics of a person with post-traumatic stress disorder (PTSD) during the mediation procedure and to experimentally test the peculiarities of PTSD in young adults and to study the causal relationship between PTSD and personality resilience. Materials and Methods: The diagnosis was carried out using the methods of diagnosing resilience (S. Muddy in the adaptation of D. Leontiev) and the Mississippi Scale for Combat-Related PTSD. Statistical analysis was performed using the statistical software package STATISTICA 10. The analysis of the study results included the distribution of the results of the arithmetic mean and the identification of correlations using Pearson's correlation coefficient. The obtained empirical data were processed qualitatively and quantitatively. Results: In the course of the study we found that mediation is the best alternative way to resolve legal disputes with a person with PTSD, as the mediator creates a safe space, an atmosphere of trust, helps to cope with emotions, and, through questioning and other techniques, forms a conscious attitude towards their own needs and interests. Such interaction is empathetic and non-traumatic for a person with PTSD who is a party to mediation. It has been established that the level of PTSD manifestation in young adults affects their level of resilience. Conclusions: mediator's work with a person with PTSD requires more activity on the part of the mediator, empathic communication, and possession of skills in dealing with psychotrauma. All decisions made as a result of mediation will be aimed at satisfying the basic need for safety of such a person.


Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma.
Obesity is a risk factor for the development of colon carcinoma. The influence of body mass index (BMI) on long-term outcomes and treatment-related toxicity in patients with colon carcinoma has not been well characterized. This cohort study was conducted within a large, randomized adjuvant chemotherapy trial of 3759 men and women with high-risk, Stage II and Stage III colon carcinoma who were treated between 1988 and 1992 throughout the United States. With a median follow-up of 9.4 years, the authors examined the influence of BMI on disease recurrence, overall survival, and treatment-related toxicity. Compared with women of normal weight (BMI, 21.0-24.9 kg/m(2)), obese women with colon carcinoma (BMI > or = 30.0 kg/m(2)) experienced significantly worse overall mortality (hazard ratio [HR], 1.34; 95% confidence interval [95% CI], 1.07-1.67) and a nonsignificant increase in the risk of disease recurrence (HR, 1.24; 95% CI, 0.98-1.59). The influence of BMI among women was not related to any differences in chemotherapy dose-intensity across categories of BMI. In contrast, BMI was not related significantly to long-term outcomes among male patients in this cohort. Among all study participants, obese patients had significantly lower rates of Grade 3-4 leukopenia and lower rates of any Grade > or = 3 toxicity compared with patients of normal weight. Among women with Stage II-III colon carcinoma, obesity was associated with a significant increase in overall mortality as well as a borderline significant increase in disease recurrence. Nonetheless, obesity was not associated with any increase in chemotherapy-related toxicity.


Wild-derived inbred mice have a novel basis of susceptibility to polyomavirus-induced tumors.
Polyomavirus induces a broad array of tumors when introduced into newborn mice of certain standard inbred strains, notably those bearing the H-2(k) haplotype. Susceptibility in these mice is conferred by an endogenous mouse mammary tumor virus superantigen (Mtv-7 sag) that acts to delete T cells required for polyomavirus-induced tumor immunosurveillance. In the present study we show that mice of two wild-derived inbred strains, PERA/Ei (PE) and CZECH II/Ei (CZ), are highly susceptible to polyomavirus but carry no detectable Mtv sag-related sequences and show no evidence of Vbeta deletion. C57BR/cdJ (BR) mice, which are H-2(k) but lack the endogenous Mtv-7, are highly resistant based on an effective anti-polyomavirus tumor immune response. When crossed with BR, both PE and CZ mice transmit their susceptibility in a dominant fashion, indicating a mechanism(s) that overrides the immune response of BR. Susceptibility in PE and CZ mice is not based on interference with antigen processing or presentation since cytotoxic T cells from BR can efficiently kill F(1)-derived tumor cells in vitro. The expected precursors of polyomavirus-specific cytotoxic T cells are present in both the wild inbred animals and their F(1) progeny. These findings indicate a novel basis of susceptibility that operates independently of endogenous superantigen and prevents the development of tumor immunity.


Granulocyte colony-stimulating factor-producing undifferentiated sarcoma occurring in previously fractured femur. A case report and review of the literature.
We examined the case of a 52-year-old man presenting with a sarcoma accompanied by severe leukocytosis, which developed many years after a femoral fracture. Histologic, histochemical, immunohistochemical, and ultrastructural analysis of the tumor revealed that the sarcoma could not be classified by any of the bone or soft tissue tumor classifications currently in use. The tumor cells were isolated from surgical specimens and subcultured in vitro. The concentration of granulocyte colony-stimulating factor in the culture medium was constantly elevated to considerably high levels during 20 cell passages. A genomic study using reverse transcription-polymerase chain reaction showed that the cells retained messenger RNA expression of granulocyte colony-stimulating factor. The aberrant overexpression of granulocyte colony-stimulating factor clearly represented a paraneoplastic phenomenon of the neoplastic cells.


High temperature and eutrophication alter biomass allocation of black mangrove (Avicennia germinans L.) seedlings.
Mangrove restoration is underway along tropical coastlines to combat their rapid worldwide decline. However, restoration success is limited due to local drivers such as eutrophication, and global drivers such as climate change, yet their interactions remain unclear. We conducted a mesocosm experiment to assess the impact of increased nutrients and temperature on the photosynthetic efficiency and development of black mangrove seedlings. Seedlings exposed to high temperature and eutrophication showed reduced root growth and disproportionally long stems, with lower net assimilation rates. This architectonical imbalance between root and stem growth may increase susceptibility to physical disturbances and dislodgement. Notably, none of the experimental seedlings displayed signs of photophysiological stress, and those exposed to increased nutrients and temperature exhibited robust photosynthetic performance. The disbalance in biomass allocation highlights the importance of considering local nutrient status and hydrodynamic conditions in restoration projects, ensuring the effective anchorage of mangrove seedlings and restoration success under a warming climate.


Choice of Differentiation Media Significantly Impacts Cell Lineage and Response to CFTR Modulators in Fully Differentiated Primary Cultures of Cystic Fibrosis Human Airway Epithelial Cells.
In vitro cultures of primary human airway epithelial cells (hAECs) grown at air-liquid interface have become a valuable tool to study airway biology under normal and pathologic conditions, and for drug discovery in lung diseases such as cystic fibrosis (CF). An increasing number of different differentiation media, are now available, making comparison of data between studies difficult. Here, we investigated the impact of two common differentiation media on phenotypic, transcriptomic, and physiological features of CF and non-CF epithelia. Cellular architecture and density were strongly impacted by the choice of medium. RNA-sequencing revealed a shift in airway cell lineage; one medium promoting differentiation into club and goblet cells whilst the other enriched the growth of ionocytes and multiciliated cells. Pathway analysis identified differential expression of genes involved in ion and fluid transport. Physiological assays (intracellular/extracellular pH, Ussing chamber) specifically showed that ATP12A and CFTR function were altered, impacting pH and transepithelial ion transport in CF hAECs. Importantly, the two media differentially affected functional responses to CFTR modulators. We argue that the effect of growth conditions should be appropriately determined depending on the scientific question and that our study can act as a guide for choosing the optimal growth medium for specific applications.


Disagreement in Satisfaction Between Patients and Providers in the Use of Videoconferences by Depressed Adults.
Aim: To evaluate whether there was a difference in satisfaction scores between providers and patients in the use of videoconferences (VCs) by depressed adults. Method: This study was a subanalysis of the joint European project, MasterMind, and participants were recruited from 15 pilot studies in 11 different countries. The Client Satisfaction Questionnaire (CSQ)-3 was used as assessment tool, and scores were summed to give total scores. The questionnaire consists of three items evaluating general satisfaction, fulfillment of needs in treatment, and usability. Results: A total of 362 respondents, 201 patients and 161 providers, completed the questionnaire. Providers had a mean total CSQ-3 score of 9.17 (95% confidence interval [CI] = 8.90-9.45), whereas patients had a mean of 9.70 (95% CI = 9.44-9.98). Mean scores for item 1 (the extent to which VCs had met the needs of the participants): patients 3.19, providers 2.93 (p = 0.00048); for item 2 (general satisfaction): patients 3.22, providers 3.08 (p = 0.083); and item 3 (whether participants wanted to use VCs again): patients 3.28 providers 3.16 (p = 0.045).Conclusion: The results showed that total satisfaction scores were higher in patients than in providers. The differences between patients and providers were significant for items 1 and 3 (p < 0.05), but we did not find a significant difference regarding item 2.


[Ambulatory nursing care for patients with aortic valve disease].
This study aimed at characterizing the profile of outpatients with aortic valve dysfunction, identifying their knowledge about the disease, their major limitations during everyday activities and their means of coping with their predicament. The data obtained by semi-structured interviews with 12 patients and analyzed by quantitative and qualitative methods enabled to identify how the patients perceive the illness and the treatment as well as the implications to their everyday activities, that is, they allowed to capture reality from the subject's perspective, which is the knowledge for the elaboration of an educational proposal.


Large genetic differentiation and low variation in vector competence for dengue and yellow fever viruses of Aedes albopictus from Brazil, the United States, and the Cayman Islands.
We conducted a population genetic analysis of Aedes albopictus collected from 20 sites in Brazil, the United States (Florida, Georgia, and Illinois), and the Cayman Islands. Using isoenzyme analysis, we examined genetic diversity and patterns of gene flow. High genetic differentiation was found among Brazilian samples, and between them and North American samples. Regression analysis of genetic differentiation according to geographic distances indicated that Ae. albopictus samples from Florida were genetically isolated by distance. Infection rates with dengue and yellow fever viruses showed greater differences between two Brazilian samples than between the two North American samples or between a Brazilian sample and a North American sample. Introductions and establishments of new Ae. albopictus populations in the Americas are still in progress, shaping population genetic composition and potentially modifying both dengue and yellow fever transmission patterns.


A multidrug resistance transporter from human MCF-7 breast cancer cells.
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.


Management of subcutaneous emphysema, pneumomediastinum, and pneumothorax during respirator therapy.
Pulmonary barotrauma developed in 18/430 patients receiving respirator support for longer than 12 hours. Pneumothorax occurred in 15 of these patients and was treated with tube thoracostomy and 15-20 cm H2O pleural suction. Full reexpansion of the lungs were achieved in all but three patients, two of whom had bronchopleural fistulae. Major complications occurred in 8/15 patients developing pneumothorax. We recommend extreme conservatism in clamping or removing tube thoracostomy. There should be no air leak and full lung expansion for 48 hours, followed by a trial of underwater seal drainage without recurrence of pneumothorax. Removal should be preceded by an additional trial of tube clamping.


CD40 ligand-induced apoptosis is Fas-independent in human multiple myeloma cells.
We and others previously demonstrated that human multiple myeloma (MM) cells express CD40 and have an active CD40-growth regulatory pathway. This study characterizes the growth outcome of soluble (gp39) or membrane-bound recombinant human CD40-ligand (rCD40L) and its relationship with Fas-dependent apoptosis. Contrary to the moderate growth-stimulatory effect of the CD40-MAb G28.5, gp39 inhibited 3H-thymidine uptake of the plasma dyscrasia lines ARH-77, U266, and HS-Sultan in a dose-dependent fashion by up to 82%. By comparison, RPMI 8226 cells were resistant to CD40L-growth modulation, which may be attributable to a single base substitution (TCA-->TTA, serine-->leucine) at the 3rd cysteine-rich extramembrane region of CD40. Gp39 similarly reduced myeloma clonogenic colony (MCC) formation in patient primary bone marrow cultures by 50% (40-76%; n=6). Studies using transfectant L cells that constitutively expressed CD40L showed that membrane-bound CD40L inhibited the growth of ARH-77, U266, and HS-Sultan cells (66%, 63%, and 32%, respectively), whereas untransfected L cells did not. Growth inhibition by gp39 or CD40L+ L cells was neutralized by coincubation with the CD40L antibodies 5c8 or LL48. CD40L-treatment increased apoptotic activity of MM cells, as defined by oligonucleosomal DNA fragmentation and an increased binding to annexin V (16-28%). All three untreated CD40-responsive MM lines expressed the Fas/Apo-1/CD95 antigen (65-92% CD95+). However, only ARH-77 cells responded to the growth inhibitory effect of the CD95-agonistic antibody CH-11. CD95 expression was not affected significantly by gp39 treatment, and growth inhibition by CH-11 was additive to gp39 (from 42% to 64% decrease in 3H-thmidine uptake). Conversely, the CD95 antagonist antibody ZB4 reversed the Fas-dependent growth inhibitory process but did not significantly alter gp39-mediated growth outcome. Gp39 treatment lowered the expression of TNFR-associated factors TRAF4 and TRAF6 by 38% and 32%, respectively, whereas detectable levels of TRAF1,2,3, and 5 levels remained unchanged. Our observations indicate that the CD40L-binding inhibits human MM cell growth and increases its apoptotic activity. This growth inhibitory effect corresponds to lower levels of cytoplasmic TRAF signaling elements, and appears independent of the Fas-signaling pathway. CD40 receptor mutation may lead to unresponsiveness to CD40 growth modulation in multiple myeloma cells.


Sex differences in translocator protein 18 kDa (TSPO) in the heart: implications for imaging myocardial inflammation.
Myocarditis is more severe in men than in women and difficult to diagnose due to a lack of imaging modalities that directly detect myocardial inflammation. Translocator protein 18 kDa (TSPO) is used extensively to image brain inflammation due to its presence in CD11b(+) brain microglia. In this study, we examined expression of TSPO and CD11b in mice with coxsackievirus B3 (CVB3) myocarditis and biopsy sections from myocarditis patients in order to determine if it could be used to image myocarditis. We found that male mice with CVB3 myocarditis upregulated more genes associated with TSPO activation than female mice. TSPO expression was increased in the heart of male mice and men with myocarditis compared with female subjects due to testosterone, where it was expressed predominantly in CD11b(+) immune cells. We show that TSPO ligands detect myocardial inflammation using microSPECT, with increased uptake of [(125)I]-IodoDPA-713 in male mice with CVB3 myocarditis compared with undiseased controls.


Biomagnification of higher brominated PBDE congeners in an urban terrestrial food web in north China based on field observation of prey deliveries.
As an important group of brominated flame retardants, polybrominated diphenyl ethers (PBDEs) persist in the wildlife food webs. However, the biomagnification of PBDEs has not been adequately studied in the terrestrial food webs. In this study, a terrestrial food web composed of common kestrels, sparrows, rats, grasshoppers, and dragonflies in the urban environment from northern China was obtained. A field prey delivery study, reinforced by δ¹³C and δ¹⁵N analyses, indicates that sparrows are the primary prey items of common kestrels. Concentrations of PBDEs were in the following order: common kestrel > sparrow > rat > grasshopper and dragonfly with BDE-209 as the dominant congener. Biomagnification factors (BMFs) were calculated as the ratio between the lipid normalized concentrations in the predator and prey. The highest BMF (6.9) was determined for BDE-153 in sparrow/common kestrel food chain. Other higher brominated congeners, such as BDE-202, -203, -154, -183, -197, and -209, were also biomagnified in this terrestrial food chain with BMF of 1.3-4.7. BDE-47, -99, and -100 were found to be biodiluted from sparrow to common kestrel (BMFs < 1). Measured BMF values for BDE-153, -47, -99, and -100 were consistent with predicted values from a nonsteady-state model in American kestrels from another study. Retention factors and metabolism of BDE congeners may be confounding factors influencing the measured BMFs in this current study.


Theoretical basis validation and oxidative stress markers for cancer prevention clinical trials of aspirin.
Aspirin, a nonsteroidal anti-inflammatory drug, has been proven effective in a clinical trial of carcinogenesis blockade. However, various modes of action have been reported for these effects. Thus, in this study, we aimed to present reasonable mode of actions as a proof of concept for human trials, especially trials for patients with familial adenomatous polyposis (FAP). Aspirin treatment at 1000 ppm inhibited intestinal tumorigenesis in FAP model Min mice. As a mode of action, aspirin regulated β-catenin signaling, inflammation, and oxidative stress both in vivo and in vitro. Furthermore, we examined novel markers predictive of aspirin treatment based on liquid biopsy. Here, we demonstrated that aspirin reduced the levels of reactive carbonyl species in the serum of Min mice. These data are expected to be of use for proof of concept of aspirin human trials and implied for the prediction of aspirin efficacy.


Evaluation of Photosynthetic Behaviors by Simultaneous Measurements of Leaf Reflectance and Chlorophyll Fluorescence Analyses.
Chlorophyll a fluorescence analysis is widely used to measure photosynthetic behaviors in intact plants, and has resulted in the development of many parameters that efficiently measure photosynthesis. Leaf reflectance analysis provides several vegetation indices in ecology and agriculture, including the photochemical reflectance index (PRI), which can be used as an indicator of thermal energy dissipation during photosynthesis because it correlates with non-photochemical quenching (NPQ). However, since NPQ is a composite parameter, its validation is required to understand the nature of the PRI parameter. To obtain physiological evidence for evaluation of the PRI parameter, we simultaneously measured chlorophyll fluorescence and leaf reflectance in xanthophyll cycle defective mutant (npq1) and wild-type Arabidopsis plants. Additionally, the qZ parameter, which likely reflects the xanthophyll cycle, was extracted from the results of chlorophyll fluorescence analysis by monitoring relaxation kinetics of NPQ after switching the light off. These simultaneous measurements were carried out using a pulse-amplitude modulation (PAM) chlorophyll fluorometer and a spectral radiometer. The fiber probes from both instruments were positioned close to each other to detect signals from the same leaf position. An external light source was used to activate photosynthesis, and the measuring lights and saturated light were provided from the PAM instrument. This experimental system enabled us to monitor light-dependent PRI in the intact plant and revealed that light-dependent changes in PRI differ significantly between the wild type and npq1 mutant. Furthermore, PRI was strongly correlated with qZ, meaning that qZ reflects the xanthophyll cycle. Together, these measurements demonstrated that simultaneous measurement of leaf reflectance and chlorophyll fluorescence is a valid approach for parameter evaluation.


Grading of renal cell carcinoma.
Grading of renal cell carcinoma (RCC) has been recognised as a prognostic factor for almost 100 years. Numerous grading systems have been proposed, initially focusing upon a constellation of cytological features and more recently on nuclear morphology. It has been recommended that grading of RCC should be based upon nucleolar prominence/eosinophilia for grades 1-3, while grade 4 requires nuclear anaplasia (including tumour giant cells, sarcomatoid differentiation and/or rhabdoid morphology). The grading system was adopted formally by the International Society of Urological Pathology (ISUP) and subsequently by the World Health Organisation (WHO), being designated the WHO/ISUP grading classification in the fourth edition of the WHO classification tumours of the urinary system and male genital organs (2016). This grading system has been validated for both clear cell and papillary RCC. Validation studies for chromophobe RCC failed to demonstrate a correlation between grade and outcome for both the superseded Fuhrman grading system and the WHO/ISUP grading classification, and it has been recommended that these tumours not be graded. The WHO/ISUP system has been incorporated into the structured reports of the International Cancer Collaboration on Cancer Reporting for both clear cell and papillary RCC. It is also noted that other types of RCC may be graded, but it must be emphasised in the report that this is for descriptive and diagnostic purposes, and not outcome prediction. More recent studies have shown the incorporation of the presence of tumour necrosis into RCC grading to improve outcome prediction, and this has been validated in several studies.


Improved Virus Isoelectric Point Estimation by Exclusion of Known and Predicted Genome-Binding Regions.
Knowledge of the isoelectric points (pIs) of viruses is beneficial for predicting virus behavior in environmental transport and physical/chemical treatment applications. However, the empirically measured pIs of many viruses have thus far defied simple explanation, let alone prediction, based on the ionizable amino acid composition of the virus capsid. Here, we suggest an approach for predicting the pI of nonenveloped viruses by excluding capsid regions that stabilize the virus polynucleotide via electrostatic interactions. This method was applied first to viruses with known polynucleotide-binding regions (PBRs) and/or three-dimensional (3D) structures. Then, PBRs were predicted in a group of 32 unique viral capsid proteome sequences via conserved structures and sequence motifs. Removing predicted PBRs resulted in a significantly better fit to empirical pI values. After modification, mean differences between theoretical and empirical pI values were reduced from 2.1 ± 2.4 to 0.1 ± 1.7 pH units.IMPORTANCE This model fits predicted pIs to empirical values for a diverse set of viruses. The results suggest that many previously reported discrepancies between theoretical and empirical virus pIs can be explained by coulombic neutralization of PBRs of the inner capsid. Given the diversity of virus capsid structures, this nonarbitrary, heuristic approach to predicting virus pI offers an effective alternative to a simplistic, one-size-fits-all charge model of the virion. The accurate, structure-based prediction of PBRs of the virus capsid employed here may also be of general interest to structural virologists.


Effects of Cylindrospermopsis raciborskii strains (Woloszynska, 1912) Senayya & Subba Raju on the mobility of Daphnia laevis (Cladocera, Daphniidae).
Cylindrospermopsis raciborskii is a cyanobacterium distributed worldwide that is known to produce cyanotoxins. Some of the Brazilian strains can produce saxitoxins (STXs), which are classified as neurotoxins and can paralyze cladocerans .Daphnia laevis is a cladoceran with a wide distribution in the Americas and has been studied as a possible test-organism in toxicity bioassays. The present work tested the acute effect on D laevis mobility when fed a saxitoxin-producing (STX and neoSTX) C. raciborskii strain, CYRF-01, and compared the results with the effects of a non-toxic strain (NPCS-1). Neonates (6-24 hours after birth) were exposed to concentrations of C. raciborskii varying from 102 to 106 cells·mL-1 of each strain for up to three hours. The cladocerans were then transferred to a medium without toxic filaments for 24 hours. Only the organisms exposed to the STX-producing strain showed signs of the immobilization of swimming movements, confirming the effects of the toxins. There was a linear correlation between the time required to induce stopping the swimming movement, with a shorter time to needed to induce immobilization at a higher the concentration; this correlation was inverse to the time required to recover the swimming movements (longer at higher concentrations, p < 0.1). D. laevis is a tropical and subtropical species with great potential for use in toxicity tests for the detection of STXs, despite being native to and found in a great array of freshwater bodies. This is the first assay testing STX-producing and non-producing C. raciborskii strains on D. laevis, species that are both found in Brazilian ecosystems.


Crystal polymorphism in chemical process development.
Polymorphism in molecular crystals is a prevalent phenomenon and is of great interest to the pharmaceutical community. The solid-state form is a key quality attribute of a crystalline product. Inconsistencies in the solid phase produced during the manufacturing and storage of drug substances and drug products may have severe consequences. It is essential to understand the solid-state behavior of the drug and to judiciously select the optimal solid form for development. This review highlights the pervasiveness and relevance of polymorphism and describes solid form screening and selection processes. Moreover, case studies on controlling polymorphs from a chemical development perspective are provided.


Background noise removal in x-ray ptychography.
Ptychography is a diffraction-based x-ray microscopy method that removes the resolution limit imposed by image-forming optical elements. However, background noise in the recorded diffraction patterns will degrade the reconstructed images and may cause reconstruction failure. Removal of the background noise from a ptychography dataset is an important but rather ambiguous prereconstruction data processing step because high-spatial-frequency diffraction signals are inevitably partly wiped out along with the noise. In this paper, several newly designed techniques for removing background noise from experimental ptychographic datasets are provided. Meanwhile, effects of residual background noise and high-frequency signal loss on reconstructed image quality are discussed in detail. The image quality is assessed quantitatively by the power spectral density analysis method and spatial resolution calculation. Both the simulated and experimental results indicate that the positive effect of noise removal by these methods clearly exceeds the negative effect of the accompanied high-spatial-frequency signal loss because part of the lost signals can be recovered by the improved consistencies between neighboring diffraction patterns by the noise removal.


The Family and Medical Leave Act of 1993: what does it mean for your organization?
The Family and Medical Leave Act (FMLA) requires that employers with 50 or more employees located within a 75-mile radius of a worksite be granted 12 weeks of unpaid leave. This article summarizes the arguments for and against mandated leave, describes the main tenets of FMLA and suggests how employers can implement FMLA leave in a manner favorable to both the employer and the employees.


Hypertrophic neuritis causing tetraparesis in a cat.
An 8-year-old castrated male cat presented with acute ataxia and paresis in all four limbs. The cat also exhibited signs of autonomic nervous system impairment. Magnetic resonance imaging revealed swelling of the brachial plexuses bilaterally. Despite treatment, the cat died after 10 days of treatment. A postmortem examination revealed swollen radial nerves and cervical nerve roots in which infiltration of inflammatory cells was histologically confirmed. Additionally, lymphocytic infiltration was found around the blood vessels of the sciatic nerve bundle and the vagus nerve. Histological features were comparable to previously reported brachial plexus hypertrophic neuritis in a cat. Our case was unique in that the autonomic nerves were also involved in addition to the somatic nerves in all four limbs.


JAK2 as a surface marker for enrichment of human pluripotent stem cells-derived ventricular cardiomyocytes.
Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for cardiac disease modelling, drug discovery and regenerative medicine. Despite the advancement in various differentiation protocols, the heterogeneity of the generated population composed of diverse cardiac subtypes poses a significant challenge to their practical applications. Mixed populations of cardiac subtypes can compromise disease modelling and drug discovery, while transplanting them may lead to undesired arrhythmias as they may not integrate and synchronize with the host tissue's contractility. It is therefore crucial to identify cell surface markers that could enable high purity of ventricular CMs for subsequent applications. By exploiting the fact that immature CMs expressing myosin light chain 2A (MLC2A) will gradually express myosin light chain 2 V (MLC2V) protein as they mature towards ventricular fate, we isolated signal regulatory protein alpha (SIRPA)-positive CMs expressing intracellular MLC2A or MLC2V using MARIS (method for analysing RNA following intracellular sorting). Subsequently, RNA sequencing analysis was performed to examine the gene expression profile of MLC2A + and MLC2V + sorted CMs. We identified genes that were significantly up-regulated in MLC2V + samples to be potential surface marker candidates for ventricular specification. To validate these surface markers, we performed immunostaining and western blot analysis to measure MLC2A and MLC2V protein expressions in SIRPA + CMs that were either positive or negative for the putative surface markers, JAK2 (Janus kinase 2) or CD200. We then characterized the electrophysiological properties of surface marker-sorted CMs, using fluo-4 AM, a green-fluorescent calcium indicator, to measure the cellular calcium transient at the single cell level. For functional validation, we investigated the response of the surface marker-sorted CMs to vernakalant, an atrial-selective anti-arrhythmic agent. In this study, while JAK2 and CD200 were identified as potential surface markers for the purification of ventricular-like CMs, the SIRPA+/JAK2+ population showed a higher percentage of MLC2V-expressing cells (~ 90%) compared to SIRPA+/CD200+ population (~ 75%). SIRPA+/JAK2+ sorted CMs exhibited ventricular-like electrophysiological properties, including slower beating rate, slower calcium depolarization and longer calcium repolarization duration. Importantly, vernakalant had limited to no significant effect on the calcium repolarization duration of SIRPA+/JAK2+ population, indicating their enrichment for ventricular-like CMs. Our study lays the groundwork for the identification of cardiac subtype surface markers that allow purification of cardiomyocyte sub-populations. Our findings suggest that JAK2 can be employed as a cell surface marker for enrichment of hPSC-derived ventricular-like CMs.


Death with dignity in the Japanese culture.
In Japanese culture, the concept of death with dignity focuses on enhancing the relationship with significant others (especially with family members) and is expected to continue even after death, unlike the autonomous decision making in Western cultures. Deaths in such relationships are self-worthy, majestic and wished for. The author depicts these traits by describing the worship of sudden death aspiration in a special temple, the death ceremonies repeated even after death which involve even distantly related people, a suicide allusively asking for something, and a joint suicide.


A comparison of the emotional and behavioral problems of children of patients with cancer or a mental disorder and their association with parental quality of life.
To compare the emotional and behavioral problems of children of patients suffering from cancer or a mental disorder and their association with parental quality of life. A total of 223 children from 136 families and their 160 parents were investigated from multiple perspectives in a cross-sectional study. The consistency of different adjustment reports between family members was examined. Through mixed models, the differences between parental HRQoL and the children's symptomatology were studied with regard to the type of parental illness. The prediction of children's adjustment through parental HRQoL was further examined. Additionally, gender and age of the children were considered. Half of the children exhibited psychosocial problems. Gender and age differences were independent of the type of parental disease. In families with parental cancer, the reports of children's adjustment were more consistent between family members than in families where a parental mental disorder was present. We found differences in HRQoL between families with mentally ill parents and those with parental cancer patients. Specifically, the healthy partners of mentally ill parents showed worse HRQoL compared with healthy partners of cancer patients. Healthy parents' reduced HRQoL was associated with worse adjustment in their children, regardless of the type of parental illness, but this result was not found for ill parents. Family members confronted with parental cancer or mental disorders are more burdened compared with those from the "normal" population, independently of the type of disease. Our results indicate that the type of a parental disease has no direct effect on children's adjustment. However, there are disease-specific effects on parental HRQoL, which are associated with children's adjustment.


Comparison of Long and Short High-Intensity Interval Exercise Bouts on Running Performance, Physiological and Perceptual Responses.
This study compared the effects of long (4×4 min) and short intervals (4×8×20 s) of high-intensity interval exercise bouts (HIIT) on running performance, physiological and perceptual responses, and excess postexercise oxygen consumption (EPOC). Twelve healthy college students (8 men, 4 women; mean age=22±2 years) performed long (90-95% of peak heart rate) and short intervals (maximal intensity) of high-intensity training (running on a non-motorized treadmill) with the same total duration on separate days. The total volume of consumed oxygen during recovery was the same in both cases ( P =0.21), whereas the short intervals of high-intensity training were performed at a faster mean running velocity (3.5±0.18 vs. 2.95±0.07 m/s) and at a lower RPE breath compared with the long intervals of high-intensity training. The blood lactate concentration also tended to be lower during the short intervals of high-intensity training, indicating that short-interval training was perceived to be easier than long-interval training, even though the cardiovascular and metabolic responses are similar. Furthermore, EPOC lasted significantly longer (83.4±3.2 vs. 61.3±27.9 min, P =0.016) and tended to be higher (8.02±4.22=vs. 5.70±3.75 L O 2 , P =0.053) after short intervals than after long intervals of training.


Public Health Laboratory Service enzyme linked immunosorbent assay for detecting Toxoplasma specific IgM antibody.
An enzyme linked immunosorbent assay (ELISA) based on the antibody class capture method for the detection of specific IgM against Toxoplasma gondii, using the microtitre plate format, was developed. Antigen binding was detected using a monoclonal antibody, CIE3, conjugated to horseradish peroxidase. Prior mixing of the conjugate and antigen improved the stability of these reagents as well as removing an incubation stage from the assay. The incubation time of less than four hours permits a rapid throughput of specimens. Using the assay, a total of 163 sera were examined in a three centre study and good agreement was found. Results were expressed as arbitrary enzyme immunoassay units (EIUs) against a freeze dried standard. Throughout the study the standard serum showed a coefficient of variation less than 10% across the microtitre plate. By measuring IgM titres in patients having toxoplasmic lymphadenopathy with a known date of onset, IgM class antibodies were shown to peak at two months, persisting for about six months. In addition, a case of laboratory acquired toxoplasmosis was monitored. Sera shown to contain rheumatoid factor and antinuclear factor did not give false positive results. This rapid, robust, and simplified assay is used by the Public Health Laboratory Service Toxoplasma Reference Units and will provide a standard with which other assays can be compared.


Exploring the Folding Landscape of Leptin: Insights into Threading Pathways.
The discovery of new protein topologies with entanglements and loop-crossings have shown the impact of local amino acid arrangement and global three-dimensional structures. This phenomenon plays a crucial role in understanding how protein structure relates to folding and function, affecting the global stability, and biological activity. Protein entanglements encompassing knots and non-trivial topologies add complexity to their folding free energy landscapes. However, the initial native contacts driving the threading event for entangled proteins remains elusive. The Pierced Lasso Topology (PLT) represents an entangled topology where a covalent linker creates a loop in which the polypeptide backbone is threaded through. Compared to true knotted topologies, PLTs are simpler topologies where the covalent-loop persists in all conformations. In this work, the PLT protein leptin, is used to visualize and differentiate the preference for slipknotting over plugging transition pathways along the folding route. We utilize the Energy Landscape Visualization Method (ELViM), a multidimensional projection technique, to visualize and distinguish early threaded conformations that cannot be observed in an in vitro experiment. Critical contacts for the leptin threading mechanisms were identified where the competing pathways are determined by the formation of a hairpin loop in the unfolded basin. Thus, prohibiting the dominant slipknotting pathway. Furthermore, ELViM offers insights into distinct folding pathways associated with slipknotting and plugging providing a novel tool for de novo design and in vitro experiments with residue specific information of threading events in silico.


[Pediatrics. Conjugate anti-pneumoccoccal vaccine: what are the results four years after introduction?].
Considerable morbidity and mortality are related to pneumococcal disease predominantly in high risk populations: infants and young children, the elderly and the immunocompromised. A recent heptavalent conjugate anti-pneumococcal vaccine, introduced in the routine immunization program in the United States in 2001, has been shown to be spectacularly effective in the prevention of invasive disease in the very young in contrast to the pre-existing polysaccharide vaccine. As a consequence, horizontal transmission throughout the community is decreased with a reduction in disease rates in non-vaccinated adults. Finally the conjugate vaccine also provides an effective tool for reduction of drug-resistant pneumococcal strains. A review of the existing anti-pneumococcal vaccines, their direct and indirect effects and their recommended use in Switzerland.


Diet-derived advanced glycation end products are major contributors to the body's AGE pool and induce inflammation in healthy subjects.
Advanced glycation end products (AGEs) are a heterogeneous group of compounds that form continuously in the body. Their rate of endogenous formation is markedly increased in diabetes mellitus, a condition in which AGEs play a major pathological role. It is also known, however, that AGEs form during the cooking of foods, primarily as the result of the application of heat. This review focuses on the generation of AGEs during the cooking of food, the gastrointestinal absorption of these compounds, and their biological effects in vitro and in vivo. We also present preliminary evidence of a direct association between dietary AGE intake and markers of systemic inflammation such as C-reactive protein in a large group of healthy subjects. Together with previous evidence from diabetics and renal failure patients, these data suggest that dietary AGEs may play an important role in the causation of chronic diseases associated with underlying inflammation.


The Time Varying Networks of the Interoceptive Attention and Rest.
Focused attention to spontaneous sensations is a dynamic process that demands interoceptive abilities. Failure to control it has been linked to neuropsychiatric disorders like illness-anxiety disorder. Regulatory strategies, such as focused attention meditation (FAM), may enhance the ability to control focused attention particularly to body sensations, which can be reflected on functional neuroanatomy. The functional connectivity (FC) related to focused attention has been described, however, the dynamic brain organization associated to this process and the differences to the resting state remains to be studied. To quantify the cerebral dynamic counterpart of focused attention to interoception, we examined fifteen experienced meditators while performing a 20-min attentional task to spontaneous sensations. Subjects underwent three scanning sessions obtaining a resting-state scan before and after the task. Sliding window dynamic FC (DFC) and k-means clustering identified five recurrent FC patterns along the dorsal attention network (DAN), default mode network (DMN), and frontoparietal network (FPN). Subjects remained longer in a low connectivity brain pattern during the resting conditions. By contrast, subjects spent a higher proportion of time in complex patterns during the task than rest. Moreover, a carry-over effect in FC was observed following the interoceptive task performance, suggestive of an active role in the learning process linked to cognitive training. Our results suggest that focused attention to interoceptive processes, demands a dynamic brain organization with specific features that distinguishes it from the resting condition. This approach may provide new insights characterizing the neural basis of the focused attention, an essential component for human adaptability.


Palivizumab prophylaxis during nosocomial outbreaks of respiratory syncytial virus in a neonatal intensive care unit: predicting effectiveness with an artificial neural network model.
To identify subgroups of premature infants who may benefit from palivizumab prophylaxis during nosocomial outbreaks of respiratory syncytial virus (RSV) infection. Retrospective analysis using an artificial intelligence model. Level IIIB, 35-bed, neonatal intensive care unit (NICU) at a tertiary care hospital in the United Arab Emirates. One hundred seventy six premature infants, born at a gestational age of 22-34 weeks, and hospitalized during four RSV outbreaks that occurred between April 2005 and July 2007. We collected demographic and clinical data for each patient by using a standardized form. Input data consisted of seven categoric and continuous variables each. We trained, tested, and validated artificial neural networks for three outcomes of interest: mortality, days of supplemental oxygen, and length of NICU stay after the index case was identified. We compared variable impacts and performed reassignments with live predictions to evaluate the effect of palivizumab. Of the 176 infants, 31 (17.6%) received palivizumab during the outbreaks. All neural network configurations converged within 4 seconds in less than 400 training cycles. Infants who received palivizumab required supplemental oxygen for a shorter duration compared with controls (105.2 ± 7.2 days vs 113.2 ± 10.4 days, p=0.003). This benefit was statistically significant in male infants whose birth weight was less than 0.7 kg and who had hemodynamically significant congenital heart disease. Length of NICU stay after identification of the index case and mortality were independent of palivizumab use. Palivizumab may be an effective intervention during nosocomial outbreaks of RSV in a subgroup of extremely low-birth-weight male infants with hemodynamically significant congenital heart disease.


Emotional and behavioral problems in children with epilepsy attending the pediatric neurology clinic at a referral hospital in Kenya.
Epilepsy is a common neurological condition, with a lifetime prevalence of 1% in children. Research has shown a high prevalence of emotional and behavioral problems in children with epilepsy. The aim of this study was to determine the prevalence of emotional and behavioral problems in children with epilepsy attending the pediatric neurology clinic in a referral hospital in Kenya and examine associated sociodemographic and clinical variables. This was a cross-sectional descriptive study. Children with epilepsy aged between 6 and 12 years attending the Kenyatta National Hospital pediatric neurology clinic were recruited. Inclusion criteria for the study were children diagnosed with epilepsy, age between 6 and 12 years, accompanied by a primary caregiver, and the primary caregiver being willing to participate in the study. A sociodemographic questionnaire as well as the Child Behavior Checklist school-age version (CBCL/6-18) was administered to the caregiver accompanying the child. One hundred and seventy-seven children with epilepsy were recruited (66% males) with a mean age of 8.9 (standard deviation (SD): 2) years. The mean age at onset of seizures was 4.5 years; 48% of the children had first seizure while aged less than 2 years, 76% reported generalized tonic-clonic seizures, and 58% were on antiepileptic drugs (AEDs). The overall prevalence of emotional and behavioral problems was 46%, and the four leading symptom clusters were attention problems, aggressive behavior, social problems, and withdrawal/depression. The risk of emotional and behavioral problems was increased in children using more than one AED (odds ratio (OR) = 2.21, 95% confidence interval (CI), 1.18-4.14) and those aged ten years and above (OR = 2.7, 95% CI, 1.3-5.64). The risk of emotional and behavioral problems was reduced in children with infrequent seizures (OR = 0.08, 95% CI, 0.01-0.06) and in children reporting no seizure in the past year (OR = 0.08, 95% CI, 0.01-0.65). Emotional and behavioral problems are common among children with epilepsy in Kenya. This highlights the need to screen for these problems in children on treatment for epilepsy for early identification and subsequent management to improve outcome.


TEL/ETV6 is a signal transducer and activator of transcription 3 (Stat3)-induced repressor of Stat3 activity.
The signal transducer and activator of transcription 3 (Stat3) transcription factor is required for the antiproliferative effects induced by cytokines, such as the interleukin-6 type. In order to investigate the role of Stat3 in inhibition of cell proliferation, we have used an inducible Stat3 construct in A375 melanoma cells. We found that activation of Stat3 to moderate levels was sufficient to repress A375 proliferation, by slowing cell transit through the cell cycle. Enhanced and prolonged Stat3 activity led to cell cycle arrest and apoptosis. Genes whose expression was altered by Stat3 activation were identified by oligonucleotide microarray analysis. We found that TEL (ETV6), a novel Stat3 target identified in this study, is a negative regulator of Stat3 activity. Small interfering RNA-mediated inhibition of TEL expression resulted in increased Stat3-dependent transcriptional activity and stronger Stat3 antiproliferative activity. Confirming these results, overexpression of TEL repressed Stat3 transcriptional activity. Intriguingly, Stat3 repression did not require TEL DNA binding and appeared to proceed via recruitment of TEL to Stat3. Inhibition of Stat3 activity by TEL represents a novel mechanism regulating the Stat3 signaling pathway.


Blood trauma potential of the HeartWare Ventricular Assist Device in pediatric patients.
Mechanical circulatory support has become a standard therapy for adult patients with end-stage heart failure. For pediatric patients, technologic development lags behind with no currently approved implantable rotary blood pump. As an alternative, the HeartWare Ventricular Assist Device (Medtronic, Minneapolis, Minn), originally designed for adults, is increasingly used in pediatric patients. The aim of this multicenter study was to assess in silico, in vitro, and in vivo the blood trauma potential of this pump in pediatric application. Clinical outcome and indicators for in vivo blood trauma were investigated retrospectively in 14 pediatric patients with the HeartWare Ventricular Assist Device (age 11.3 ± 4.8 years). Blood trauma mechanisms of the HeartWare Ventricular Assist Device were examined in silico and in vitro at an adult and pediatric operating point (5 L/min and 2.5 L/min at 2800 rpm and 2200 rpm, respectively). The flow was simulated by computational fluid dynamics and analyzed regarding flow structures, shear stresses, and washout. Hemolysis was assessed with pumps circulating bovine blood in a temperate flow circuit. In the retrospective in vivo analysis, lactate dehydrogenase and D-dimer values were 1.5- and 3-fold elevated, respectively, compared with adult patients with the HeartWare Ventricular Assist Device. Major bleedings were observed in 42.9%, and suspected pump thrombosis and neurologic dysfunction were observed in 14.3% of all patients. In the pediatric conditions, simulations predicted elevated mechanical stress profile below 50 Pa, more stagnant flow field, and longer washout times within the pump. In vitro measurements revealed an increased normalized index of hemolysis (17.5 vs 8.2 mg/100 L; P = .0021). The HeartWare Ventricular Assist Device, operated at lower speeds and flows, induces elevated blood trauma. Further studies are required to assess the clinical implications of these findings.


High-power coherent microwave emission from magnetic tunnel junction nano-oscillators with perpendicular anisotropy.
The excitation of the steady-state precessions of magnetization opens a new way for nanoscale microwave oscillators by exploiting the transfer of spin angular momentum from a spin-polarized current to a ferromagnet, referred to as spin-transfer nano-oscillators (STNOs). For STNOs to be practical, however, their relatively low output power and their relatively large line width must be improved. Here we demonstrate that microwave signals with maximum measured power of 0.28 μW and simultaneously narrow line width of 25 MHz can be generated from CoFeB-MgO-based magnetic tunnel junctions having an in-plane magnetized reference layer and a free layer with strong perpendicular anisotropy. Moreover, the generation efficiency is substantially higher than previously reported STNOs. The results will be of importance for the design of nanoscale alternatives to traditional silicon oscillators used in radio frequency integrated circuits.