The contribution of malglycemia to mortality among allogeneic hematopoietic cell transplant recipients.
Allogeneic hematopoietic cell transplantation (HCT) continues to be associated with substantial rates of nonrelapse mortality (NRM). Numerous factors influence glucose metabolism among HCT recipients. We hypothesized that "malglycemia," defined as hyperglycemia, hypoglycemia or increased glycemic variability, is associated with increased mortality in HCT patients. In a retrospective cohort study Cox regression was used to assess the association of malglycemia after transplant with day 200 NRM. A total of 66,062 blood glucose (BG) measurements from 1175 adult allogeneic HCT recipients between 2000 and 2005 at the Fred Hutchinson Cancer Research Center were evaluated (median 0.55 values per patient-day, range: 0.09-3.62). Overall, there were 215 cases of NRM by day 200 post-HCT and 601 deaths from any cause throughout observation. After adjustment for previously identified factors associated with NRM, all 3 components of malglycemia were associated with increased NRM when individually modeled as time-dependent covariates. Specifically, the hazard ratio for death was 1.93 for BG >200 mg/dL (P = .0009) and 2.78 for BG >300 (P = .0004) compared with BG 101-150 mg/dL. A minimum BG </=89 was associated with a risk of day 200 NRM 2.17 times that of a minimum BG >89 (P < .0001). The upper quartile of glucose variability was associated with a 14.57-fold increase in risk of NRM by day 200 relative to the first quartile (P < .0001). These retrospective data indicate that malglycemia is associated with mortality following HCT. The applicability of these findings to other situations and whether correcting malglycemia in HCT can lead to reductions in mortality remain to be determined.


Interfacial strength of novel PMMA/HA/nanoclay bone cement.
In the present study, nanoclay was introduced to PMMA bone cement to obtain a new formulation of bioactive PMMA cement (PMMA/HA/nanoclay). To evaluate the interfacial property of the new bioactive cement for use as a fixation agent, Brazilian disk specimens were used to study the interfacial strength of synthetic bone-cement interface. The results show that, for tensile loading, the addition of 17.5 wt% HA into PMMA cement produced a notable decrease in the fracture load, while a further addition of 0.5 wt% nanoclay slightly counteracted the decrease due to the addition of HA. The addition of 1.0 wt% nanoclay brought the fracture load back to the same level as that of pure PMMA cement, although with the further increase of nanoclay (1.5 wt% nanoclay and 2.0 wt% nanoclay), the fracture loads decreased again. The same trend in the calculated strain energy release rates was also observed. For shear loading, however, the same trend was not observed due to the premature fracture and collapsing of the foam. This finding may be useful in the development of novel bioactive bone cements to improve the fixation of joint arthroplasty.


High-Throughput and Site-Specific N-Glycosylation Analysis of Human Alpha-1-Acid Glycoprotein Offers a Great Potential for New Biomarker Discovery.
Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases, and some changes appear to be disease-specific; thus, it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers, and enable better understanding of AGP's role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96-well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography-based solid-phase extraction and analyzed by reversed-phase-liquid chromatography-electrospray ionization-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in three time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP's second glycosylation site and lower sialylation of N-glycans on AGP's third and AGP1's fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.


Search for natural products related to regeneration of the neuronal network.
The reconstruction of neuronal networks in the damaged brain is necessary for the therapeutic treatment of neurodegenerative diseases. We have screened the neurite outgrowth activity of herbal drugs, and identified several active constituents. In each compound, neurite outgrowth activity was investigated under amyloid-beta-induced neuritic atrophy. Most of the compounds with neurite regenerative activity also demonstrated memory improvement activity in Alzheimer's disease-model mice. Protopanaxadiol-type saponins in Ginseng drugs and their metabolite, M1 (20-O-beta-D-glucopyranosyl-(20S)-protopanaxadiol), showed potent regeneration activity for axons and synapses, and amelioration of memory impairment. Withanolide derivatives (withanolide A, withanoside IV, and withanoside VI) isolated from the Indian herbal drug Ashwagandha, also showed neurite extension in normal and damaged cortical neurons. Trigonelline, a constituent of coffee beans, demonstrated the regeneration of dendrites and axons, in addition to memory improvement.


Assessing the burden of cancer in Texas using vital statistics data.
Vital statistics data were used to describe the burden of cancer in Texas. Average annual age-adjusted mortality data in Texas (1986 to 1990) for 17 cancer types were compared with the US data for whites and blacks and with California data for Hispanics. Trends were examined from 1980 to 1990 for the entire state and from 1976 to 1989 for 24 geographic regions within the state. Mortality excesses were detected for lung and liver cancer, and deficits for colorectal, breast, and prostate cancers. Rates were generally stable from 1980 to 1990 with several exceptions (lung, liver, colon). Six areas of Texas, including four areas along the Gulf Coast, had relatively more excesses of various cancers, without a discernible pattern by cancer type. Overall, Texas has fared favorably in cancer mortality when compared with the United States. Enhanced evaluation of the frequency of cancer, as well as the conduct of etiologic research, must await the availability of statewide long-term cancer incidence data.


Development and the fragmented self: longitudinal study of dissociative symptomatology in a nonclinical sample.
Dissociative behaviors and their relation to both the self and self-organization were examined using the developmental psychopathology perspective in a prospective longitudinal study of high-risk children. Participants were 168 young adults (n = 79 females, n = 89 males, age = 18-19 years) considered high-risk for poor developmental outcomes at birth due to poverty. The present study investigated whether trauma, sense of self, quality of early mother-child relationship, temperament, and intelligence were related to dissociative symptomatology measured at four times across 19 years. Findings were (a) age of onset, chronicity and severity of trauma were highly correlated and predicted level of dissociation; (b) both the avoidant and disorganized patterns of attachment were strong predictors of dissociation; (c) dissociation in childhood may be a more normative response to disruption and stress, while dissociation in adolescence and young adulthood may be more indicative of psychopathology; (d) preliminary support was found for a model proposed by G. Liotti that links disorganized attachment, later trauma, and dissociation in adulthood; and (e) strong support was found for N. Waller, F. W. Putnam, and E. B. Carlson's contention that psychopathological dissociation should not be viewed as the top end of a continuum of dissociative symptomatology, but as a separate taxon that represents an extreme deviation from normal development.


Motivation to change and pathological gambling: analysis of the relationship with clinical and psychopathological variables.
OBJECTIVES. The present study analyses the internal factor structure of the University of Rhode Island Change Assessment (URICA) Scale in pathological gambling (PG). The scale's association with the clinical profile of patients is also evaluated. METHOD. The factor analysis was based on a sample of 531 men with a DSM-IV diagnosis of pathological gambling. The statistical analysis included confirmatory factor analysis and linear correlation. RESULTS. The analyses confirmed the internal structure obtained for the URICA. The internal consistency was satisfactory (Cronbach's alpha between .74 and .85). The association between URICA scores and the socio-demographic and clinical profile of patients ranged between moderate and weak (R coefficients below .30). Lower motivation was present in 28.4% of cases and it was associated with shorter duration of the disorder, lower severity of the PG symptoms, and high psychopathology. Conclusions. The results support the validity and reliability of the URICA in a Spanish clinical population of pathological gamblers.


Metabolomics in Ecology and Bioactive Natural Products Discovery: Challenges and Prospects for a Comprehensive Study of the Specialised Metabolome.
Metabolomics is playing an increasingly prominent role in chemical ecology and in the discovery of bioactive natural products (NPs). The identification of metabolites is a common/central objective in both research fields. NPs have significant biological properties and play roles in multiple chemical-ecological interactions. Classically, in pharmacognosy, their chemical structure is determined after a complex process of isolating and interpreting spectroscopic data. With the advent of powerful analytical techniques such as liquid chromatography-mass spectrometry (LC-MS) the annotation process of the specialised metabolome of plants and microorganisms has improved considerably. In this article, we summarise the possibilities opened by these advances and illustrate how we harnessed them in our own research to automate annotations of NPs and target the isolation of key compounds. In addition, we are also discussing the analytical and computational challenges associated with these emerging approaches and their perspective.


Photon-Mediated Stroboscopic Quantum Simulation of a Z_{2} Lattice Gauge Theory.
Quantum simulation of lattice gauge theories, aiming at tackling nonperturbative particle and condensed matter physics, has recently received a lot of interest and attention, resulting in many theoretical proposals as well as several experimental implementations. One of the current challenges is to go beyond 1+1 dimensions, where four-body (plaquette) interactions, not contained naturally in quantum simulating devices, appear. In this Letter, we propose a method to obtain them based on a combination of stroboscopic optical atomic control and the nonlocal photon-mediated interactions appearing in nanophotonic or cavity QED setups. We illustrate the method for a Z_{2} lattice gauge theory. We also show how to prepare the ground state and measure Wilson loops using state-of-the-art techniques in atomic physics.


Using a laptop computer to improve clinical performance.
Computer-generated notes (CGNs) created on a laptop computer can both improve your clinical skills in the examining room and enhance patient care. Myriad gains can be realized from the use of CGNs, from the elimination of illegible and ambiguous handwritten records to improved follow-up and patient management. This article guides the reader through the hardware and software requirements for setting up CGNs, as well as basic instructions for creating your own CGN files.


Blood lipids: the relationship with alcohol intake, smoking, and body weight.
The aim was to assess the interrelationship between alcohol intake, cigarette smoking, body weight, and blood lipid concentrations. This was the cross sectional (screening) phase of a prospective study. The main outcome measure was the blood lipids (serum total cholesterol, HDL cholesterol, and triglycerides). General practices in 24 towns (The British Regional Heart Study). Subjects were 7735 men aged 40-59 years, selected at random from the age-sex registers of one group practice in each of the 24 towns. Univariate analysis showed little association between alcohol intake and total cholesterol, a strong positive relation with HDL cholesterol, and a significant increase in triglycerides in heavy drinkers. A strong positive association between alcohol intake and body weight was present in non-smokers but not in moderate/heavy smokers. With the exception of HDL cholesterol, the relationships between alcohol intake and serum lipids were significantly different in smokers and non-smokers, apparently due to the opposing effect of smoking on blood lipids and body weight. Total cholesterol and triglycerides were significantly and positively associated with alcohol intake in non-smokers, the cholesterol association being largely mediated by the influence of alcohol on body weight. In smokers, no such association was seen: current smokers who were heavy drinkers or non-drinkers had the lowest mean cholesterol levels. The association between alcohol intake and body weight and alcohol intake and blood lipids are strongly conditioned by cigarette smoking. Simple standardisation for smoking in multivariate analyses may obscure the independent relationship with alcohol. These findings are of importance in studies seeking to relate alcohol intake, body weight, or cigarette smoking to blood lipid concentrations, or blood lipid concentration to morbidity or mortality.


Generation of femtoliter reactor arrays within a microfluidic channel for biochemical analysis.
We present a simple microfluidic method to generate high-density femotoliter-sized microreactor arrays within microfluidic channels. In general, we designed a main channel with many small chambers built into its walls. After sequentially infusing aqueous solution and organic solvent from a single tube into the device, aqueous droplets are confined in the chambers by the solvent flow. The generated reactors are small and stable enough for carrying out ultrasensitive biochemical assays at single molecule levels. As a demonstration, in this paper, we optically observed hydrolysis activity of β-galactosidase enzymatic molecules in the reactor arrays at single molecule levels. Further, this method has the following advantages: (1) the droplets are observable immediately after formation and (2) its simple procedure is sufficiently robust such that even handy infusion of the preloaded solutions is reproducible. We believe our method provides a platform attractive to a variety of single molecule studies and sensing applications such as clinical diagnostics.


Chemoprevention of cancer of the upper respiratory tract of the Syrian golden hamster by aerosol administration of difluoromethylornithine and 5-fluorouracil.
Research aimed at identifying effective chemopreventive compounds active against carcinogenesis of the upper respiratory tract (URT) has been largely unsuccessful. We are addressing this problem by efforts at agent identification and by using aerosol delivery. Two compounds, difluoromethylornithine (DFMO) and 5-fluorouracil (5-FU) were investigated. DFMO is an irreversible inhibitor of ornithine decarboxylase, an enzyme important in cell proliferation. It has been used widely by oral administration for chemoprevention. 5-FU is a pyrimidine analog used extensively as a chemotherapeutic agent. It is generally administered i.v. and can cause considerable toxicity. However, aerosol administration for therapy of lung cancer in humans has been reported to be without adverse effects (Tatsumura et al., Br J Cancer 1993;68:1146-9). The experimental model used herein entailed six intratracheal administrations of methylnitrosourea (MNU) to hamsters. Each of the test agents was started about 1 week after MNU and was continued for 29 weeks with DFMO. Infiltrating squamous cell carcinomas of the URT occurred in 92% of the controls and were reduced by 50% in animals receiving DFMO (P = 0.0001). The experiment with 5-FU was of shorter duration being terminated 20 weeks after MNU. Thirty percent of the controls had infiltrating carcinomas and were reduced by 60% in animals receiving 5-FU (P = 0.0274). Both compounds resulted in a significant increase in the percent of cancer-free animals. These two agents may have selected use in subjects at high risk of cancer of the URT.


[Features of thalamocortical relations in the phantom pain syndrome (electrophysiologic studies during stereotaxic surgery)].
Corticographic effects are analysed in 14 patients with severe phantom-pain syndrome from data obtained in electric stimulation of specific sensory and nonspecific nuclear structures of the thalamus. The findings of EEG, ECoG and VP analysis reflect reorganization of the thalamo-cortical relationships in the phantom-pain syndrome in the direction of disorganization of the regulating mechanisms. Evidence of this are an increased excitability level in the thalamic nuclei and the central cortex, disorder of the regional differences of the weakly modulated alpha-rhythm, and marked changes in the amplitude and configuration of VP of the parietal and central cortical areas. Various frequencies of stimulating current were used to differentiate the specific sensory and nonspecific thalamic nuclei. It was found that for the identification of the relay sensory nucleus, stimulation with a frequency range of 1-20 Hz is most effective, in which there is local synchronization of the cortical rhythm corresponding with the duration of the stimulation. Electric stimulation with a frequency of 50 Hz and more induces reactions characteristic of nonspecific nuclei: general desynchronization of the cortical rhythm during stimulation with the development of characteristic "spindles" in the after-action.


A microscope perfusion respirometer for continuous respiration measurement of cultured cells during microscopic observation.
The construction of a microscope perfusion respirometer (MPR) for simultaneous recording of cellular respiration and microscopic morphology is described. All light microscope techniques for living cells (e.g. phase contrast, differential interference contrast (DIC), fluorimetry) can be applied to the monolayer cells grown on a coverslip. The main constituents of the MPR are a) a precision operating perfusion pump (constant volume output), b) a modified Dvorak-Stotler perfusion chamber, c) a special holder for the Clark-type oxygen probe, d) gas-tight connections of stainless steel tubing with dead volume-free fittings, and e) a temperature control unit. The cell material, established XTH (Xenopus laevis tadpole heart) cell is characterized. Examples of operation are presented, concerning a) normal respiration, b) respiration during uncoupling of oxidative phosphorylation by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), and c) lactate production under anoxia. The corresponding mitochondrial in situ-morphology is demonstrated on photomicrographs. Details of construction and application are discussed. This new technique is supposed to extend the use of cell cultures instead of animal experiments in pharmaceutical routine tests.


[Heterogeneity of streptococcus group A cell wall protein components].
Cell wall surface proteins of group A streptococcus (M 29) were isolated by mild chemical extraction with 1 M hydroxylamine pH 6.0 (37 degrees C). The proteins were purified by ammonium sulfate fractionation, gel filtration on Sephadex G-150 and ion-exchange chromatography on DEAE-Trisacryl M. Using two independent methods (disc electrophoresis in 7.5% PAAG pH 8.9 and high pressure gel filtration), it was shown that after chromatography on Sephadex G-150 the original protein fraction contains up to 8 protein components, while SDS-PAAG electrophoresis performed according to Laemmli revealed up to 25 protein components in the same fraction. During SDS-PAAG electrophoresis six protein fractions performed after ion-exchange chromatography were resolved into 40 protein components whose molecular masses vary from 13 to 80 kDa. Possible reasons for the heterogeneity of surface proteins of group A streptococcus cell wall are discussed.


siRNA Silencing of FpVtg Induces Ovarian Cell Apoptosis in Redtail Prawn, Fenneropenaeus penicillatus.
Inadequate gonadal maturation and poor spawning performance increasingly threaten the sustainability of shrimp aquaculture. Unraveling the mechanisms regulating ovarian development and maturation hence is critical to address industry challenges. Vitellogenin (Vtg), a precursor of yolk protein found in the hepatopancreas and ovary of shrimp, plays a key role in facilitating shrimp's oocyte maturation and embryonic development after oviposition. This study found that FpVtg was specifically expressed in F. penicillatus hepatopancreas and ovary. FpVtg was localized predominantly in the oocyte cytoplasm and distributed uniformly in the hepatopancreas tissue. Silencing FpVtg led to apoptosis in both hepatopancreas and ovary tissues. Furthermore, FpVtg depletion upregulated the expression of ovarian peritrophin 1, ovarian peritrophin 2, serine proteinase inhibitor 6, and juvenile hormone esterase-like carboxylesterase 1, while downregulated that of vitellogenin, delta-9 desaturase, and insulin-like receptor. KEGG pathway analysis implicated such as PI3K-AKT signaling, RNA transport, ECM-receptor interaction, hippo signaling, oocyte meiosis, and apoptosis were enriched and involved in ovarian development. These findings have provided insights into the FpVtg's reproductive role and the associated regulatory genes and pathways in F. penicillatus. This knowledge can contribute to establishing strategies to improve the breeding and aquaculture production of F. penicillatus by elucidating its vitellogenesis regulation in redtail prawn and other penaeid species. Further characterization of the implicated pathways and genes will clarify the intricacies underlying ovarian maturation.


Tumor targeting of MMP-2/9 activatable cell-penetrating imaging probes is caused by tumor-independent activation.
Activatable cell-penetrating peptides (ACPPs) are a new class of promising molecular imaging probes for the visualization of enzymes in vivo. The cell-penetrating function of a polycationic peptide is efficiently blocked by intramolecular electrostatic interactions with a polyanionic peptide. Proteolysis of a cleavable linker present between the polycationic cell-penetrating peptide and polyanionic peptide affords dissociation of both domains and enables the activated cell-penetrating peptide to enter cells. Here, we aimed to develop an ACPP sensitive to matrix metalloproteinase-2 and -9 (MMP-2/9) for nuclear imaging purposes. MMP-2/9 ACPPs and nonactivatable cell-penetrating peptides (non-ACPP) were prepared by 9-fluorenylmethyloxycarbonyl solid-phase peptide synthesis and labeled with (177)Lu or (177)Lu/(125)I for dual-isotope studies. The in vivo biodistribution of these probes was assessed in MMP-2/9-positive tumor-bearing mice (n = 6) and healthy mice (n = 4) using γ-counting. Furthermore, a radiolabeled cell-penetrating peptide serving as a positive control was evaluated in tumor-bearing mice (n = 6). Biodistribution studies showed a 5-fold-higher retention of ACPP in tumor than in muscle (P < 0.01) and a 6-fold-higher tumor retention relative to non-ACPP (P < 0.01), supporting earlier studies on fluorescently labeled ACPPs proposing activation by tumor-associated MMP-2/9. Surprisingly, however, the uptake of ACPP was significantly higher than that of non-ACPP in almost all tissues (P < 0.01). To unravel the activation process of ACPP in vivo, we developed dual-isotope ACPP analogs (dACPPs) that allowed us to discriminate between uncleaved dACPP and activated dACPP. In vivo biodistribution of dACPP indicated that the tissue-associated counts originated from activated dACPP. Interestingly, dACPP administration to healthy mice, compared with MMP-2/9-positive tumor-bearing mice, resulted in a similar dACPP biodistribution. Furthermore, a radiolabeled cell-penetrating peptide showed tumor-to-tissue ratios equal to those found for ACPP (P > 0.05). This study demonstrates that the tumor targeting of radiolabeled MMP-2/9 ACPPs is most likely caused by the activation in the vascular compartment rather than tumor-specific activation, as suggested earlier. The results in the present paper indicate that different and more tissue-specific enzyme-ACPP combinations are needed to unleash the full potential of the elegant ACPP concept in living animals.


Identification of a 14-3-3 binding sequence in the common beta chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors that is serine-phosphorylated by GM-CSF.
The common beta chain (beta(c)) of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors is the major signaling subunit of these receptors coupling ligand binding to multiple biological activities. It is thought that these multiple functions arise as a consequence of the recruitment of specific signaling molecules to tyrosine-phosphorylated residues in the cytoplasmic domain of beta(c). However, the contribution of serine phosphorylation in beta(c) to the recruitment of signaling molecules is not known. We show here the identification of a phosphoserine motif in the cytoplasmic domain of beta(c) that interacts with the adaptor protein 14-3-3zeta. Coimmunoprecipitation and pull-down experiments with a glutathione S-transferase (GST):14-3-3zeta fusion protein showed that 14-3-3 directly associates with beta(c) but not the GM-CSF receptor alpha chain. C-terminal truncation mutants of beta(c) further showed that a region between amino acids 544 and 626 in beta(c) was required for its association with 14-3-3zeta. This region contains the sequence (582)HSRSLP(587), which closely resembles the RSXSXP (where S is phosphorylated) consensus 14-3-3 binding site identified in a number of signaling molecules, including Raf-1. Significantly, substitution of (582)HSRSLP(587) for EFAAAA completely abolished interaction of beta(c) with GST-14-3-3zeta. Furthermore, the interaction of beta(c) with GST-14-3-3 was greatly reduced in the presence of a peptide containing the 14-3-3 binding site, but only when (585)Ser was phosphorylated. Direct binding experiments showed that the peptide containing phosphorylated (585)Ser bound 14-3-3zeta with an affinity of 150 nmol/L. To study the regulation of (585)S phosphorylation in vivo, we raised antibodies that specifically recognized (585)Ser-phosphorylated beta(c). Using these antibodies, we showed that GM-CSF stimulation strongly upregulated (585)Ser phosphorylation in M1 myeloid leukemic cells. The proximity of the SHC-binding site ((577)Tyr) to the 14-3-3-binding site ((582)HSRSLP(587)) and their conservation between mouse, rat, and human beta(c) but not in other cytokine receptors suggest that they form a distinct motif that may subserve specialized functions associated with the GM-CSF, IL-3, and IL-5 receptors.


Multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) in the evaluation of the mandibular invasion by squamous cell carcinomas (SCC) of the oral cavity. Correlation with pathological data.
To retrospectively compare the diagnostic accuracy of magnetic resonance imaging (MRI) and multidetector-row computed tomography (MDCT) in the assessment of the mandibular invasion by squamous cell carcinoma (SCC) having histopathological exams as standard of reference. Institutional review board approval with a waiver of informed patient consent was obtained. Of the 147 patients selected from our database who underwent surgical excision of a tumour arising into the oral cavity, thirty-six patients (26 men, 10 women; mean age, 56 years; range, 30-75 years) with hystologically proven SCC who performed both a preoperative MRI and MDCT, composed our final study population.Images were qualitatively analyzed in consensus by two expert radiologist in head and neck imaging. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were assessed for both MRI and MDCT.Differences in sensitivity, specificity, positive and negative predictive values were calculated at a statistical significance of p < .05. The sensitivity, the specificity and the accuracy of MRI and MDCT in the detection of the mandibular involvement were respectively 93%, 82%, 86% and 79%, 82%, 81%, while the positive predictive value (PPV) and negative predictive value (NPV) were respectively 76%, 95% and 73%, 86%. There wasn't any statistically significant difference in overall diagnostic accuracy between MRI and MDCT in the evaluation of mandibular tumour invasion (p > .05). MRI showed to have a higher sensitivity compare to MDCT in the assessment of mandibular involvement from SCC arising in the oral cavity although none statistically significant differences were noted.


Effect of dosing volume on intramuscular absorption rate of aminoglycosides.
The Loo-Riegelman method was applied to serum amikacin level data after intravenous and intramuscular administration. Intramuscular amikacin absorption can be described by first-order kinetics, but the absorption rate constant decreased from 1.95 hr-1 at a 125-mg dose to 1.00 hr-1 at a 750-mg dose. This rate change apparently is a physical phenomenon due to differing dosing volumes at different doses and attendant changes in the surface area to volume ratio at the injection site. Amikacin absorption rates on intramuscular injection can be maximized by giving several smaller injections rather than a single larger injection. This phenomenon should be generally observed with aminoglycoside antibiotics and could be partly responsible for reported variations in the absorption rate and the poor predictability of serum concentrations.


Predicting early sexual activity with behavior problems exhibited at school entry and in early adolescence.
Youth who initiate sexual intercourse in early adolescence (age 11-14) experience multiple risks, including concurrent adjustment problems and unsafe sexual practices. The current study tested two models describing the links between childhood precursors, early adolescent risk factors, and adolescent sexual activity: a cumulative model and a meditational model. A longitudinal sample of 694 boys and girls from four geographical locations was utilized, with data collected from kindergarten through high school. Structural equation models revealed that, irrespective of gender or race, high rates of aggressive disruptive behaviors and attention problems at school entry increased risk for a constellation of problem behaviors in middle school (school maladjustment, antisocial activity, and substance use) which, in turn, promoted the early initiation of sexual activity. Implications are discussed for developmental models of early sexual activity and for prevention programming.


Pleomorphic Liposarcoma of the Parapharyngeal Space: A Rare Case Report.
Pleomorphic liposarcomas (PLS) are the rarest subtype of liposarcomas, representing only 5-10% of liposarcomas. Pleomorphic liposarcomas are extremely aggressive and have a poor prognosis. Here, we present the case of a 66-year-old female who presented with difficulty swallowing, talking, and hearing. An extensive investigation revealed the presence of an aggressively growing parapharyngeal space mass. The patient underwent a left parapharyngeal space exploration and left deep lobe parotidectomy by the cervicoparotid approach. Histopathological evaluation of the surgical specimen further confirms the presence of pleomorphic subtype of liposarcoma. The patient received adjuvant radiotherapy following the procedure. At 6 months postop, the patient is in good health and shows no evidence of recurrence. In addition to this treatment, we discuss the radiologic and histologic findings of this current case.


Neural tube defects among neonates delivered in Al-Ramadi Maternity and Children's Hospital, western Iraq.
To study the incidence, types, and sites of neural tube defects (NTDs) and its associated maternal and environmental variables. All preterm and full term live and stillborn babies delivered at Al-Ramadi Maternity and Children's Hospital, Al-Anbar Governorate, Iraq, from the 1st of November 2007 to the 1st of November 2008 were examined for gender, gestational age, NTDs, and associated congenital malformations. Mother's data included age, parity, consanguinity, education, antenatal care, previous medical illnesses, other NTDs history, folic acid supplementation, and diagnostic ultrasound. Incidence was calculated per 1000 births. During the study, 33 infants were delivered with NTDs, giving an incidence of 3.3/1000 births. Most were of myelomeningocele and anencephaly types, and thoracolumbar and lumbosacral sites. Two-thirds of the cases found were from consanguineous marriage, 12 NTD's mothers took folic acid during their pregnancy, while none of them received the drug during the periconceptional period. Three mothers had another NTD affected babies before, and mothers 25-34 years old produced most of the NTD deliveries than any other age groups. The NTDs incidence is still high compared with developed, and some developing countries. High consanguinity marriage and 100% lack of periconceptional folic acid intake needs further study considerations to reduce such morbid and mortal anomalies.


The location of the repressor binding sites in the lac operon.
The affinity of various mutant lac DNAs for the lac repressor was examined by means of a competition binding assay. The results indicate that there exist at least two binding sites for the lac repressor. The primary binding site is coincidental with the operator, as defined by genetic studies. Mutations of the promoter or the Z gene have little or no effect on the repressor binding properties of this primary binding site, thereby confirming that the operator is distinct from lacP and Z. The secondary binding site(s), which has a 25- to 31-fold lower affinity for the repressor, is located within the operator proximal third of the Z gene.


Effect of apigenin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in RAW-264.7 macrophages.
Polyphenols such as apigenin, kaempferol or resveratrol are typically found in plants, including fruits, vegetables, herbs and spices, which have a wide range of biological functions such as antioxidative, anti-inflammatory, vasodilative, anticoagulative and proapoptotic. Discovering such multifunctional compounds in widely consumed plant-based products - ones that both inhibit the release of TNF-α from tissue macrophages and at the same time enhance the secretion of IL-10 - would be an important signpost in the quest for effective pharmacological treatment of numerous diseases that have an inflammatory etiology. The aim of the study is to investigate the impact of biologically active polyphenols such as apigenin, resveratrol and kaempferol on gene expression and protein secretion of IL-10 and TNF-α in line RAW-264.7. Cells were cultured under standard conditions. IL-10 and TNF-α genes expression were examined using QRT-PCR and to assess cytokines concentration ELISA have been used. Apigenin, kaempferol and resveratrol at a dose 30μM significantly decrease the TNF-α expression and secretion. Apigenin decrease the IL-10 expression and secretion. Furthermore, increase in IL-10 secretion after administration of kaempferol and resveratrol were observed. In the process of administration of tested compounds before LPS, which activate macrophages, decrease of TNF-α secretion after apigenin and kaempferol and increase of IL-10 secretion after resveratrol were observed. The results of present work indicate that 1) apigenin, resveratrol and kaempferol may reduce the intensity of inflammatory processes by inhibiting the secretion of proinflammatory cytokine TNF-α, and resveratrol and kaempferol additionally by increasing the secretion of anti-inflammatory cytokine IL-10 2) the studies indicate the potentially beneficial - anti-inflammatory - impact of diet rich in products including apigenin, resveratrol and kaempferol.


Estrogen receptor α and G-protein coupled estrogen receptor 1 are localized to GABAergic neurons in the dorsal striatum.
Estrogens affect dopamine transmission in the striatum, increasing dopamine availability, maintaining D2 receptor density, and reducing the availability of the dopamine transporter. Some of these effects of estrogens are rapid, suggesting that they are mediated by membrane associated receptors. Recently our group demonstrated that there is extra-nuclear labeling for ERα, ERβ, and GPER1 in the striatum, but that ERα and GPER1 are not localized to dopaminergic neurons in this region. GABAergic neurons are the most common type of neuron in the striatum, and changes in GABA transmission affect dopamine transmission. Thus, to determine whether ERα or GPER1 are localized to GABAergic neurons, we double labeled the striatum with antibodies for ERα or GPER1 and GABA and examined them using electron microscopy. Ultrastructural analysis revealed that ERα and GPER1 are localized exclusively to extranuclear sites in the striatum, and ∼35% of the dendrites and axon terminals labeled for these receptors contain GABA immunoreactivity. Binding at membrane-associated ERα and GPER1 could account for rapid estrogen-induced decreases in GABA transmission in the striatum, which, in turn, could affect dopamine transmission in this region.


A case report: longitudinal stress fracture of the patella-a cause of peripatellar pain in a runner.
A 25-year-old national class distance runner came to our clinic complaining of inferior subpatellar pain. After initial diagnostic studies proved inconclusive, the patient was treated conservatively for patellofemoral arthralgia. After allowing him to return to participation following rest and rehabilitation, the patient continued to complain of pain. Further diagnostic studies (bone scan) revealed the presence of a longitudinal stress fracture of the patella. The patient was treated with nonweightbearing exercise and rest. After 8 weeks, he resumed training, and after 20 weeks he was competing on a national class level. This study implicates a patellar stress fracture as a possible etiology in a runner complaining of intractable patellofemoral pain that does not respond to conservative management. J Orthop Sports Phys Ther 1987 9(5):194-197.


A new method for the accurate determination of the isotopic state of single amide hydrogens within peptides using Fourier transform ion cyclotron resonance mass spectrometry.
A new method is presented to accurately determine the probability of having a deuterium or hydrogen atom on a specific amide position within a peptide after deuterium/hydrogen (D/H) exchange in solution. Amide hydrogen exchange has been proven to be a sensitive probe for studying protein structures and structural dynamics. At the same time, mass spectrometry in combination with physical fragmentation methods is commonly used to sequence proteins based on an amino acid residue specific mass analysis. In the present study it is demonstrated that the isotopic patterns of a series of peptide fragment ions obtained with capillary-skimmer dissociation, as observed with a 9.4 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer, can be used to calculate the isotopic state of specific amide hydrogens. This calculation is based on the experimentally observed isotopic patterns of two consecutive fragments and on the isotopic binomial distributions of the atoms in the residue constituting the difference between these two consecutive fragments. The applicability of the method is demonstrated by following the sequence-specific D/H exchange rate in solution of single amide hydrogens within some peptides.


Stability and change in alcohol habits of different socio-demographic subgroups--a cohort study.
Stability in alcohol habits varies over time and in subgroups, but there are few longitudinal studies assessing stability in alcohol habits by socio-demographic subgroups and potential predictors of stability and change. The aim was to study stability and change in alcohol habits by sex, age, and socio-economic position (SEP). Data derived from two longitudinal population based studies in Sweden; the PART study comprising 19 457 individuals aged 20-64 years in 1998-2000, and the Stockholm Public Health Cohort (SPHC) with 50 067 individuals aged 18-84 years in 2002. Both cohorts were followed-up twice; PART 2000-2003 and 2010, and SPHC 2007 and 2010. Alcohol habits were measured with the Alcohol Use Disorders Identification Test (AUDIT), and with normal weekly alcohol consumption (NWAC). Stability in alcohol habits was measured with intraclass correlation. Odds ratios were estimated in multinomial logistic regression analysis to predict stability in alcohol habits. For the two drinking measures there were no consistent patterns of stability in alcohol habits by sex or educational level. The stability was higher for older age groups and self-employed women. To be a man aged 30-39 at baseline predicted both increase and decrease in alcohol habits. The findings illustrate higher stability in alcohol habits with increasing age and among self-employed women with risky alcohol habits. To be a man and the age 30-39 predicted change in alcohol habits. No conclusive pattern of socio-economic position as predictor of change in alcohol habits was found and other studies of potential predictors seem warranted.


Temperature-dependent resetting of the molecular circadian oscillator in Drosophila.
Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster: the transcripts and proteins for the clock genes period (per) and timeless (tim). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clock-independent temperature-driven transcription of per. The cold-induced expression of Drosophila per contrasts with the previously reported heat-induced regulation of mammalian Period 2. An altered and more readily re-entrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the 'Tim 4' genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting.


Assessing the Network of Agencies in Local Communities that Promote Healthy Eating and Lifestyles among Populations with Limited Resources.
We assessed the network of agencies in local communities that promote healthy eating and lifestyles among populations with limited resources. Network surveys were administered among 159 Illinois agencies identified as serving limited-resource audiences categorized into 8 types: K-12 schools, early childhood centers, emergency food providers, health-related agencies, social resource centers, low-income/subsidized housing complexes, continuing education organizations, and others. Network analysis was conducted to examine 4 network structures - communications, funding, cooperation, and collaboration networks between agencies within each county/county cluster. Agencies in a network were found to be loosely connected, indicated by low network density. Reporting accuracy might be of concern, indicated by low reciprocity. Agencies in a network are decentralized rather than centralized around a few influential agencies, indicated by low betweenness centrality. There is suggestive evidence regarding homophily in a network, indicated by some significant correlations within agencies of the same type. Agencies connected in one network are significantly more likely to be connected in all the other networks as well. Promoting healthy eating and lifestyles among populations with limited resources warrants strong partnership across agencies in communities. Network analysis serves as a useful tool to evaluate community partnerships and facilitate coalition building..


Slow glycinergic transmission mediated by transmitter pooling.
Most fast-acting neurotransmitters are rapidly cleared from synaptic regions. This feature isolates synaptic sites, rendering the time course of synaptic responses independent of the number of active synapses. We found an exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus. Here the duration of inhibitory postsynaptic currents (IPSCs) was dependent on the number of presynaptic axons that were stimulated and on the number of vesicles that were released from each axon. Increasing the stimulus number or frequency, or blocking glycine uptake, slowed synaptic decays, whereas a low-affinity competitive antagonist of glycine receptors (GlyRs) accelerated IPSC decay. These effects could be explained by unique features of GlyRs that are activated by pooling of glycine across synapses. Functionally, increasing the number of IPSPs markedly lengthened the period of spike inhibition following the cessation of presynaptic stimulation. Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.


Cholinergic reactivity of cerebral arteries in the developing fetal and newborn lamb.
Cerebral arteries of newborn pigs and baboons constrict to acetylcholine, suggesting that endothelium-dependent dilator mechanisms may be lacking in immature cerebral arteries. The present study tested this possibility in the immature sheep by examining the response of cerebral arterioles in fetal and newborn sheep to endothelium-dependent dilator, acetylcholine. Pial arteriolar diameter was measured in 9 anaesthetized foetuses in utero (4 preterm, 90-111 days gestation and 5 term, 128-143 days gestation) and in 5 anaesthetized, newborn lambs (14 days) using a closed cranial window with intravital microscopy. Application of acetylcholine to the pial surface induced dose-dependent increase in pial arteriolar diameter in all age groups; EC50 for acetylcholine was 0.10 +/- 0.03, 0.28 +/- 0.08 and 0.26 +/- 0.17 microM for preterm fetal, term fetal, and newborn lambs, respectively. The data demonstrate a sensitive dilator response to acetylcholine in immature fetuses as well as newborn lambs suggesting that cholinergic-mediated release of endothelium-dependent relaxing factor is functional early in gestation. The contractile response to acetylcholine observed in newborn pigs and premature baboons may reflect a species difference rather than maturational lack of endothelium-dependent dilator mechanisms.


Auditory traits of "own voice".
People perceive their recorded voice differently from their actively spoken voice. The uncanny valley theory proposes that as an object approaches humanlike characteristics, there is an increase in the sense of familiarity; however, eventually a point is reached where the object becomes strangely similar and makes us feel uneasy. The feeling of discomfort experienced when people hear their recorded voice may correspond to the floor of the proposed uncanny valley. To overcome the feeling of eeriness of own-voice recordings, previous studies have suggested equalization of the recorded voice with various types of filters, such as step, bandpass, and low-pass, yet the effectiveness of these filters has not been evaluated. To address this, the aim of experiment 1 was to identify what type of voice recording was the most representative of one's own voice. The voice recordings were presented in five different conditions: unadjusted recorded voice, step filtered voice, bandpass filtered voice, low-pass filtered voice, and a voice for which the participants freely adjusted the parameters. We found large individual differences in the most representative own-voice filter. In order to consider roles of sense of agency, experiment 2 investigated if lip-synching would influence the rating of own voice. The result suggested lip-synching did not affect own voice ratings. In experiment 3, based on the assumption that the voices used in previous experiments corresponded to continuous representations of non-own voice to own voice, the existence of an uncanny valley was examined. Familiarity, eeriness, and the sense of own voice were rated. The result did not support the existence of an uncanny valley. Taken together, the experiments led us to the following conclusions: there is no general filter that can represent own voice for everyone, sense of agency has no effect on own voice rating, and the uncanny valley does not exist for own voice, specifically.


Acyclovir therapy of neonatal herpes simplex virus type 2 infections in rabbits.
New Zealand white rabbits less than 30 h old were inoculated subcutaneously with 10(3) 50% tissue culture infectious doses of type 2 herpes simplex virus. The animals were randomly assigned to a treatment schedule of daily intraperitoneal injections of acyclovir, beginning on the day of virus inoculation for 6 or 12 days, on post-inoculation day 1 for 6 days, or on post-inoculation day 2 for 6 days. The acyclovir was given in doses of 50 mg/kg of body weight per day. Similarly infected animals receiving daily intraperitoneal injection of Eagle minimum essential medium served as controls. All of the control animals died on day 4 or 5 after inoculation. At death they exhibited severe skin lesions, viremia, and dissemination of virus in various visceral organs and spinal as well as trigeminal ganglia. In contrast, animals treated with acyclovir failed to develop significant skin lesions, and death did not occur while treatment continued. Termination of treatment after 6 days resulted in late-onset fatal disease and virus isolation from the brain in many rabbits regardless of the treatment schedule. No such late fatality was observed and no virus could be detected from the brain when treatment was initiated on the day of virus inoculation and continued for 12 consecutive days. With respect to all of the variables studied, treatment for 12 days beginning on the day of virus inoculation was most effective.


[WHO Framework Convention on Tobacco Control (FCTC) Article 11: packaging and labelling of tobacco products].
The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) requires member countries to implement measures aimed at reducing the demand for tobacco products. FCTC article 11 describes the important forms of health communication and packaging regulations. And this article recommends on large pictorial health warnings and encourages more effective forms of disclosure on constituents and emissions. Furthermore, article 11 recognizes the importance of the package as a promotional vehicle for tobacco companies and requires the removal of potentially misleading packaging information, including the terms "light" and "mild." The Conference of the Parties (COP) adopted guidelines for implementation of article 11 on "Packaging and labelling of Tobacco Products". Some countries, such as Canada, the U.S.A., Australia, EU countries etc. positively promoted tobacco control by implementing countermeasures such as the graphic health warning labels and plain packages. These countermeasures showed the significant effects of decreasing smoking rate and preventing smoking initiation in young people. Furthermore, these warning labels were effective for the literally challenged. However, the Japanese government has not implemented these countermeasures, and only limited texts are shown on Japanese tobacco packaging. Therefore, Japan should emulate approaches taken by other countries, and promote the tobacco control policy in accordance with FCTC.


[Significance of an angiogenic factor (in omental lipid) for the vascularization of the cornea].
The existence of an angiogenic factor in the omental lipid was verified by injecting four different test materials in dosages of 50 microliters into the corneas of New Zealand rabbits. The test substances were: 1) phosphate-buffered saline solution; 2) chloroform-methanol solution; 3) phosphate-buffered saline homogenate of the chloroform-methanol extract of the lipid cake from the rabbit omentum. The experimental results show that the modes of neovascularization after injection of lipid and nonlipid materials into rabbit corneas are very similar. For angiogenesis to be stimulated, the noxious substances must be retained in the cornea for several days. One day after injection the phosphate-buffered saline solution is totally resorbed. The other test substances (2-4), are retained within the cornea for days or weeks. Test substance 1 does not induce any corneal vascularization. The injection of test substances 2-4 causes similar corneal neovascularization: the proliferation of vessels always starts from that segment of the limbus closest to the stimulation. Since the extent of vascularization after injection of chloroform-methanol solution alone is similar to that which occurs after injection of an omental lipid extract, the hypothesis of a specific angiogenic factor is not supported. Fluorescein angiography reveals a large outflow of fluid (leakage) out of the neovascularization.


Conserved CDR 3 region of T cell receptor BV gene in lymphocytes from bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is an inflammatory lung disease characterized by the accumulation of inflammatory cells and deposition of collagen, resulting in lung remodelling. High numbers of T cells are present in bronchoalveolar lavage fluid (BALF) of IPF patients, although the characteristics of these cells are yet to be determined. To elucidate the pathogenic mechanisms of IPF, we analysed the T cell receptor (TCR) of BALF lymphocytes in three patients with IPF and three healthy subjects as control. TCR repertoire of BALF lymphocytes and T cell clonality were examined by family PCR and Southern blot analysis, and single-strand conformation polymorphism (SSCP), respectively. We observed that the TCR repertoire in the lung was heterogeneous, both in the control subjects and three patients with IPF. SSCP analysis demonstrated an increase in the number of accumulated T cell clones in BALF of two of the three patients, but not in the healthy subject. Furthermore, junctional sequence analysis showed the presence of conserved amino acid motifs (ETGRSG, LAxG, QGQ, GxQP, GRxG, VAR, PGT, GTI, GGT, TGR, LxLxQ, SGQ) in the TCR-CDR 3 region of BAL lymphocytes in patients with IPF, whereas only two amino acid motifs (VTTG, GGE) were found in the control. Our findings suggest that T cells in BALF of patients with IPF expand oligoclonally in the lung, suggesting antigen stimulation of these cells.


Genome-Wide Analysis Provides Evidence on the Genetic Relatedness of the Emergent Xylella fastidiosa Genotype in Italy to Isolates from Central America.
Xylella fastidiosa is a plant-pathogenic bacterium recently introduced in Europe that is causing decline in olive trees in the South of Italy. Genetic studies have consistently shown that the bacterial genotype recovered from infected olive trees belongs to the sequence type ST53 within subspecies pauca. This genotype, ST53, has also been reported to occur in Costa Rica. The ancestry of ST53 was recently clarified, showing it contains alleles that are monophyletic with those of subsp. pauca in South America. To more robustly determine the phylogenetic placement of ST53 within X. fastidiosa, we performed a comparative analysis based on single nucleotide polymorphisms (SNPs) and the study of the pan-genome of the 27 currently public available whole genome sequences of X. fastidiosa. The resulting maximum-parsimony and maximum likelihood trees constructed using the SNPs and the pan-genome analysis are consistent with previously described X. fastidiosa taxonomy, distinguishing the subsp. fastidiosa, multiplex, pauca, sandyi, and morus. Within the subsp. pauca, the Italian and three Costa Rican isolates, all belonging to ST53, formed a compact phylotype in a clade divergent from the South American pauca isolates, also distinct from the recently described coffee isolate CFBP8072 imported into Europe from Ecuador. These findings were also supported by the gene characterization of a conjugative plasmid shared by all the four ST53 isolates. Furthermore, isolates of the ST53 clade possess an exclusive locus encoding a putative ATP-binding protein belonging to the family of histidine kinase-like ATPase gene, which is not present in isolates from the subspecies multiplex, sandyi, and pauca, but was detected in ST21 isolates of the subspecies fastidiosa from Costa Rica. The clustering and distinctiveness of the ST53 isolates supports the hypothesis of their common origin, and the limited genetic diversity among these isolates suggests this is an emerging clade within subsp. pauca.


Acute effects of exercise on appetite, ad libitum energy intake and appetite-regulatory hormones in lean and overweight/obese men and women.
Acute exercise does not elicit compensatory changes in appetite parameters in lean individuals; however, less is known about responses in overweight individuals. This study compared the acute effects of moderate-intensity exercise on appetite, energy intake and appetite-regulatory hormones in lean and overweight/obese individuals. Forty-seven healthy lean (n=22, 11 females; mean (s.d.) 37.5 (15.2) years; 22.4 (1.5) kg m-2) and overweight/obese (n=25, 11 females; 45.0 (12.4) years, 29.2 (2.9) kg m-2) individuals completed two, 8 h trials (exercise and control). In the exercise trial, participants completed 60 min treadmill exercise (59 (4)% peak oxygen uptake) at 0-1 h and rested thereafter while participants rested throughout the control trial. Appetite ratings and concentrations of acylated ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured at predetermined intervals. Standardised meals were consumed at 1.5 and 4 h and an ad libitum buffet meal was provided at 7 h. Exercise suppressed appetite (95% confidence interval (CI) -3.1 to -0.5 mm, P=0.01), and elevated delta PYY (95% CI 10 to 17 pg ml-1, P<0.001) and GLP-1 (95% CI 7 to 10 pmol l-1, P<0.001) concentrations. Delta acylated ghrelin concentrations (95% CI -5 to 3 pg ml-1, P=0.76) and ad libitum energy intake (95% CI -391 to 346 kJ, P=0.90) were similar between trials. Subjective and hormonal appetite parameters and ad libitum energy intake were similar between lean and overweight/obese individuals (P⩾0.27). The exercise-induced elevation in delta GLP-1 was greater in overweight/obese individuals (trial-by-group interaction P=0.01), whereas lean individuals exhibited a greater exercise-induced increase in delta PYY (trial-by-group interaction P<0.001). Acute moderate-intensity exercise transiently suppressed appetite and increased PYY and GLP-1 in the hours after exercise without stimulating compensatory changes in appetite in lean or overweight/obese individuals. These findings underscore the ability of exercise to induce a short-term energy deficit without any compensatory effects on appetite regardless of weight status.


Congenital malformation associated with intrauterine contraceptive device.
Two infants with fibular aplasia and related limb-reduction defects were born to mothers who were using copper-containing intrauterine contraceptive devices. The possibility of a casual association is consistent with the known hazards of intrauterine devices and cannot be excluded on the available experimental evidence. More information is urgently needed, and searches, including radiography of placenta and pelvis, should be made for such devices in mothers who have used them in the past and who give birth to malformed infants.


Molecular signatures database (MSigDB) 3.0.
Well-annotated gene sets representing the universe of the biological processes are critical for meaningful and insightful interpretation of large-scale genomic data. The Molecular Signatures Database (MSigDB) is one of the most widely used repositories of such sets. We report the availability of a new version of the database, MSigDB 3.0, with over 6700 gene sets, a complete revision of the collection of canonical pathways and experimental signatures from publications, enhanced annotations and upgrades to the web site. MSigDB is freely available for non-commercial use at http://www.broadinstitute.org/msigdb.


Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells.
The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia. Leukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels. We demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan. Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3-dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they inhibit naive T-cell proliferation and impair the complete maturation of normal dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells are capable of in vitro suppression of a leukemia-specific T cell-mediated immune response, directed against the leukemia-associated antigen, Wilms' tumor protein. These data identify indoleamine 2,3-dioxygenase-mediated catabolism as a tolerogenic mechanism exerted by leukemic dendritic cells and have clinical implications for the use of these cells for active immunotherapy of leukemia.


Gene transfer of matrix metalloproteinase-9 induces tumor regression of breast cancer in vivo.
Matrix metalloproteinases (MMP) are important regulators of angiogenesis and tumor progression by degradation of extracellular matrix. Clinical trials using MMP inhibitors have failed and recent studies suggest that MMPs may in contrast suppress tumor growth. It is not known, however, if MMPs or their inhibitors, tissue inhibitor of metalloproteinases (TIMP), can be used as therapy of established cancer. Here, adenovirus vectors carrying the human genes for MMP-9, TIMP-1, or empty controls were injected intratumorally in breast cancers established in mice supplemented with estradiol and treated with tamoxifen. Microdialysis was used to quantify MMP activity and sampling of endostatin and vascular endothelial growth factor (VEGF) in situ. We show that AdMMP-9 increased MMP activity in vivo, decreased tumor growth rate, and decreased microvessel area significantly. AdMMP-9 therapy resulted in significantly increased levels of endostatin in vivo, whereas VEGF levels were unaffected. As previously shown, tamoxifen exposure by itself increased MMP activity in all treatment groups. Moreover, the combined therapy with AdMMP-9 and tamoxifen further reduced tumor growth and increased the endostatin levels compared with either treatment alone. Gene transfer of TIMP-1 had no effects on tumor progression and counteracted the therapeutic effect of tamoxifen in our breast cancer model. This is the first report showing that overexpression of MMP-9 results in increased generation of antiangiogenic fragments, decreased angiogenesis, and therapeutic effects of established breast cancer.


Effect of lead design and pacing vector on electrical parameters of quadripolar coronary sinus leads: The RALLY-X4 study.
Various lead designs have been developed to accommodate different coronary sinus anatomies. Our objectives were to compare electrical parameters of straight and spiral left ventricular leads, to evaluate capture thresholds and impedances using different pacing vectors, and to study evolution of thresholds over time. The RALLY-X4 study enrolled patients implanted with a lead from the Acuity X4 family (straight, spiral short, or spiral long). Electrical parameters (including capture thresholds from all 17 vectors) were measured at baseline and follow-up. Data from 795 patients who were successfully implanted were analyzed. Straight and spiral leads had similar proportions of patients with thresholds <2.5 V/0.4 ms using the distal electrode (61-65% of patients) or from at least one of the proximal (E2-E4) electrodes (81-83% of patients). Unipolar vectors had significantly lower thresholds and impedances than bipolar vectors, with similar measurements compared to extended bipolar configurations. Capture thresholds increased with more proximal electrodes for all leads. Over a mean follow-up of 1 year, a slight decrease in capture thresholds was observed. Straight and spiral quadripolar leads allow to obtain clinically acceptable capture thresholds from at least one of the proximal electrodes in >80% of patients. Pacing vectors significantly affect electrical parameters, with higher thresholds in more proximal electrodes and lower thresholds with unipolar and extended bipolar configurations. Capture thresholds slightly decreased over a mean follow-up of 1 year.


Management of Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients.
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life and is perceived by patients as a major adverse effect of the treatment. This review summarizes the safety and efficacy of current antiemetic agents for the prevention of CINV in children. Information on antiemetic prophylaxis for CINV in children was obtained from a literature review of current peer-reviewed articles and recent international guidelines. The literature review and the international antiemetic guidelines provide recommendations for use of specific antiemetics in children based on the emetogenicity of the chemotherapy. 5-Hydroxytryptamine-3 (5-HT3) receptor antagonists have been safe and effective in the prevention of acute emesis with a few patients experiencing mild headache. No adequate studies have been conducted to date for specific recommendations for the prevention of delayed nausea and vomiting in children. The neurokinin (NK)-1 receptor antagonist aprepitant has been approved by the US FDA for use in children of a specific age and weight. No studies for the NK1 receptor antagonists netupitant and rolapitant in children have been conducted. Olanzapine, an antipsychotic, has been shown to be safe and effective in preventing nausea and emesis in adult patients receiving chemotherapy. Its use in children has been limited to children with poor control of CINV; more studies are necessary in this population. In conclusion, practitioners should follow international antiemetic guidelines to provide patients with the specific antiemetics in the recommended dose for the highest possible quality of care.


Multivariate pattern analysis of MEG and EEG: A comparison of representational structure in time and space.
Multivariate pattern analysis of magnetoencephalography (MEG) and electroencephalography (EEG) data can reveal the rapid neural dynamics underlying cognition. However, MEG and EEG have systematic differences in sampling neural activity. This poses the question to which degree such measurement differences consistently bias the results of multivariate analysis applied to MEG and EEG activation patterns. To investigate, we conducted a concurrent MEG/EEG study while participants viewed images of everyday objects. We applied multivariate classification analyses to MEG and EEG data, and compared the resulting time courses to each other, and to fMRI data for an independent evaluation in space. We found that both MEG and EEG revealed the millisecond spatio-temporal dynamics of visual processing with largely equivalent results. Beyond yielding convergent results, we found that MEG and EEG also captured partly unique aspects of visual representations. Those unique components emerged earlier in time for MEG than for EEG. Identifying the sources of those unique components with fMRI, we found the locus for both MEG and EEG in high-level visual cortex, and in addition for MEG in low-level visual cortex. Together, our results show that multivariate analyses of MEG and EEG data offer a convergent and complimentary view on neural processing, and motivate the wider adoption of these methods in both MEG and EEG research.


Harnessing the Electronic Health Record and Computerized Provider Order Entry Data for Resource Management During the COVID-19 Pandemic: Development of a Decision Tree.
The COVID-19 pandemic has resulted in shortages of diagnostic tests, personal protective equipment, hospital beds, and other critical resources. We sought to improve the management of scarce resources by leveraging electronic health record (EHR) functionality, computerized provider order entry, clinical decision support (CDS), and data analytics. Due to the complex eligibility criteria for COVID-19 tests and the EHR implementation-related challenges of ordering these tests, care providers have faced obstacles in selecting the appropriate test modality. As test choice is dependent upon specific patient criteria, we built a decision tree within the EHR to automate the test selection process by using a branching series of questions that linked clinical criteria to the appropriate SARS-CoV-2 test and triggered an EHR flag for patients who met our institutional persons under investigation criteria. The percentage of tests that had to be canceled and reordered due to errors in selecting the correct testing modality was 3.8% (23/608) before CDS implementation and 1% (262/26,643) after CDS implementation (P<.001). Patients for whom multiple tests were ordered during a 24-hour period accounted for 0.8% (5/608) and 0.3% (76/26,643) of pre- and post-CDS implementation orders, respectively (P=.03). Nasopharyngeal molecular assay results were positive in 3.4% (826/24,170) of patients who were classified as asymptomatic and 10.9% (1421/13,074) of symptomatic patients (P<.001). Positive tests were more frequent among asymptomatic patients with a history of exposure to COVID-19 (36/283, 12.7%) than among asymptomatic patients without such a history (790/23,887, 3.3%; P<.001). The leveraging of EHRs and our CDS algorithm resulted in a decreased incidence of order entry errors and the appropriate flagging of persons under investigation. These interventions optimized reagent and personal protective equipment usage. Data regarding symptoms and COVID-19 exposure status that were collected by using the decision tree correlated with the likelihood of positive test results, suggesting that clinicians appropriately used the questions in the decision tree algorithm.


Excessive Wnt/beta-catenin signaling promotes midbrain floor plate neurogenesis, but results in vacillating dopamine progenitors.
The floor plate (FP), a ventral midline structure of the developing neural tube, has differential neurogenic capabilities along the anterior-posterior axis. The midbrain FP, unlike the hindbrain and spinal cord floor plate, is highly neurogenic and produces midbrain dopaminergic (mDA) neurons. Canonical Wnt/beta-catenin signaling, at least in part, is thought to account for the difference in neurogenic capability. Removal of beta-catenin results in mDA progenitor specification defects as well as a profound reduction of neurogenesis. To examine the effects of excessive Wnt/beta-catenin signaling on mDA specification and neurogenesis, we have analyzed a model wherein beta-catenin is conditionally stabilized in the Shh+domain. Here, we show that the Foxa2+/Lmx1a+ domain is extended rostrally in mutant embryos, suggesting that canonical Wnt/beta-catenin signaling can drive FP expansion along the rostrocaudal axis. Although excess canonical Wnt/beta-catenin signaling generally promotes neurogenesis at midbrain levels, less tyrosine hydroxylase (Th)+, mDA neurons are generated, particularly impacting the Substantia Nigra pars compacta. This is likely because of improper progenitor specification. Excess canonical Wnt/beta-catenin signaling causes downregulation of net Lmx1b, Shh and Foxa2 levels in mDA progenitors. Moreover, these progenitors assume a mixed identity to that of Lmx1a+/Lmx1b+/Nkx6-1+/Neurog1+ progenitors. We also show by lineage tracing analysis that normally, Neurog1+ progenitors predominantly give rise to Pou4f1+ neurons, but not Th+ neurons. Accordingly, in the mutant embryos, Neurog1+ progenitors at the midline generate ectopic Pou4f1+ neurons at the expense of Th+ mDA neurons. Our study suggests that an optimal dose of Wnt/beta-catenin signaling is critical for proper establishment of the mDA progenitor character. Our findings will impact embryonic stem cell protocols that utilize Wnt pathway reagents to derive mDA neuron models and therapeutics for Parkinson's disease.


Corticotropin-releasing hormone and proopiomelanocortin gene expression is altered selectively in the male rat fetal thymus by maternal alcohol consumption.
The present study was carried out to investigate how hormonal changes caused by chronic alcohol exposure of rats during the late period of gestation are coordinated with neuroendocrine functions of the fetal thymus, namely thymic expression of CRH and POMC genes. Alcohol consumption by pregnant dams led to a 5-fold elevation of plasma corticosterone (CORT) levels and significantly decreased fetal CORT levels. This generally inverse correlation between maternal and fetal CORT was absent in alcohol-consuming dams and their male fetuses on day 19 of gestation. These day 19 fetuses also had an attenuated plasma testosterone surge that occurred in the male control (pair-fed) fetus on day 19 of embryonic life. Furthermore, fetal alcohol exposure (FAE) resulted in a significant increase in thymic CRH and a decrease in thymic POMC expression in the male fetuses only, specifically on embryonic day 19. Thus, the strong positive correlation between CRH and POMC gene expression in the thymus of pair-fed male and female FAE fetuses was abolished in the FAE males. However, regardless of embryonic age or treatment, a strong positive correlation between thymic POMC gene expression and plasma testosterone levels in the male fetuses was detected. These data suggest that the sexually dimorphic effect of FAE on the fetal thymic POMC and CRH expression in males is driven by testosterone and may be related, therefore, to the presence of alcohol at the time of the prenatal testosterone surge in the male fetuses.


Effectiveness and family experiences of interventions promoting partnerships between families and pediatric and neonatal intensive care units: a mixed methods systematic review protocol.
This mixed methods systematic review examines the effectiveness and family experiences of interventions that promote partnerships between parents and the multidisciplinary health care team in pediatric and neonatal intensive care units. The hospitalization of a child or infant in an intensive care unit can have considerable negative effects on them and their family. Family members can experience increased stress, anxiety or depression and detrimental impacts on quality of life and family functioning. Interventions that promote families as health care partners may improve negative outcomes arising from intensive care hospitalization. The review will include family members of pediatric or neonatal patients hospitalized in an intensive care unit. It will focus on interventions that promote partnership between families and multidisciplinary health care teams in pediatric and neonatal intensive care units and the family's experiences of these interventions. The outcomes of interest are stress, anxiety, depression, quality of life, family functioning, family empowerment or satisfaction with family-centered care. The proposed review will follow the JBI methodology for convergent segregated mixed methods systematic reviews. It will search for published and unpublished studies from eight different sources. Studies will be reviewed by title and abstract and potentially eligible studies will have full text retrieved for further review. Studies meeting the inclusion criteria will be assessed on methodological quality and the data will be extracted. Separate quantitative and qualitative analysis and synthesis will be performed and an overall analysis will be presented. PROSPERO CRD42019137834.


Accuracy of Three Types of Apex Locators versus Digital Periapical Radiography for Working Length Determination in Maxillary Premolars: An In Vitro Study.
This study aimed to compare the accuracy of three types of apex locators versus digital radiography for working length (WL) determination. This experimental study was conducted on 58 extracted maxillary premolars. The teeth were decoronated, the access cavity was prepared, and WL was determined using a #15 K-file to serve as reference. The WL was then measured by Woodpex V, Woodpex III, and Root ZX apex locators in the presence of 0.9% saline, and also on a photostimulable phosphor plate (PSP) digital radiograph taken by the parallel technique. The values were compared with the actual WL using the paired t-test (alpha = 0.05). Digital radiography, Root ZX, Woodpex V, and Woodpex III determined the WL within ±0.5 mm from the actual value in 84.48%, 100%, 89.66%, and 87.93% of the cases, respectively. Woodpex V (p = 0.039), Woodpex III (p = 0.001), and Root ZX (p = 0.001) significantly over-estimated the WL. The WL measured on digital radiographs was not significantly different from the actual WL (p = 0.213). The position of the apical foramen (central/lateral) had no significant effect on the accuracy of WL determination by different techniques (p >0.05). Within the limitations of this in vitro study, all the tested modalities showed acceptable accuracy for WL determination in maxillary premolars.


Multifunctional nanoparticles inhibit tumor and tumor-associated macrophages for triple-negative breast cancer therapy.
Tumor-associated macrophages (TAM) are the mainstay of immunosuppressive cells in the tumor microenvironment, and elimination of M2-type macrophages (M2-TAM) is considered as a potential immunotherapy. However, the interaction of breast cancer cells with macrophages hinders the effectiveness of immunotherapy. In order to improve the efficacy of triple-negative breast cancer (TNBC) therapy, strategies that simultaneously target the elimination of M2-TAM and breast cancer cells may be able to achieve a better therapy. LyP-SA/AgNP@Dox multifunctional nanoparticles were synthesized by electrostatic adsorption. They were characterized by particle size, potential and spectroscopy. And the efficacy of multifunctional nanoparticles was evaluated in 4 T1 cell lines and M2 macrophages, including their cell uptake intracellular reactive oxygen species (ROS) production and the therapeutic effect. Furthermore, based on the orthotopic xenotransplantation model of triple negative breast cancer, the biological distribution, fluorescence imaging, biosafety evaluation and combined efficacy evaluation of the nanoplatform were performed. We have successfully prepared LyP-SA/AgNP@Dox and characterized. Administering the nanosystem to 4 T1 tumor cells or M2 macrophages in culture induced accumulation of reactive oxygen species, destruction of mitochondria and apoptosis, and inhibited replication and transcription. Animal experiments demonstrated the nanoparticle had favorable targeting and antitumor activity. Our nanosystem may be useful for simultaneously inhibiting tumor and tumor-associated macrophages in breast cancer and, potentially, other malignancies.


Can wearable technology be used to approximate cardiopulmonary exercise testing metrics?
Consumer wrist-worn wearable activity monitors are widely available, low cost and are able to provide a direct measurement of several markers of physical activity. Despite this, there is limited data on their use in perioperative risk prediction. We explored whether these wearables could accurately approximate metrics (anaerobic threshold, peak oxygen uptake and peak work) derived using formalised cardiopulmonary exercise testing (CPET) in patients undergoing high-risk surgery. Patients scheduled for major elective intra-abdominal surgery and undergoing CPET were included. Physical activity levels were estimated through direct measures (step count, floors climbed and total distance travelled) obtained through continuous wear of a wrist worn activity monitor (Garmin Vivosmart HR+) for 7 days prior to surgery and self-report through completion of the short International Physical Activity Questionnaire (IPAQ). Correlations and receiver operating characteristic (ROC) curve analysis explored the relationships between parameters provided by CPET and physical activity. Our choice of consumer wearable device was made to maximise feasibility outcomes for this study. The Garmin Vivosmart HR+ had the longest battery life and best waterproof characteristics of the available low-cost devices. Of 55 patients invited to participate, 49 (mean age 65.3 ± 13.6 years; 32 males) were enrolled; 37 provided complete wearable data for analyses and 36 patients provided full IPAQ data. Floors climbed, total steps and total travelled as measured by the wearable device all showed moderate correlation with CPET parameters of peak oxygen uptake (peak VO2) (R = 0.57 (CI 0.29-0.76), R = 0.59 (CI 0.31-0.77) and R = 0.62 (CI 0.35-0.79) respectively), anaerobic threshold (R = 0.37 (CI 0.01-0.64), R = 0.39 (CI 0.04-0.66) and R = 0.42 (CI 0.07-0.68) respectively) and peak work (R = 0.56 (CI 0.27-0.75), R = 0.48 (CI 0.17-0.70) and R = 0.50 (CI 0.2-0.72) respectively). Receiver operator curve (ROC) analysis for direct and self-reported measures of 7-day physical activity could accurately approximate the ventilatory equivalent for carbon dioxide (VE/VCO2) and the anaerobic threshold. The area under these curves was 0.89 for VE/VCO2 and 0.91 for the anaerobic threshold. For peak VO2 and peak work, models fitted using just the wearable data were 0.93 for peak VO2 and 1.00 for peak work. Data recorded by the wearable device was able to consistently approximate CPET results, both with and without the addition of patient reported activity measures via IPAQ scores. This highlights the potential utility of wearable devices in formal assessment of physical functioning and suggests they could play a larger role in pre-operative risk assessment. This study entitled "uSing wearable TEchnology to Predict perioperative high-riSk patient outcomes (STEPS)" gained favourable ethical opinion on 24 January 2017 from the Welsh Research Ethics Committee 3 reference number 17/WA/0006. It was registered on ClinicalTrials.gov with identifier NCT03328039.


Low-voltage self-assembled monolayer field-effect transistors on flexible substrates.
Self-assembled monolayer field-effect transistors (SAMFETs) of BTBT functionalized phosphonic acids are fabricated. The molecular design enables device operation with charge carrier mobilities up to 10(-2) cm(2) V(-1) s(-1) and for the first time SAMFETs which operate on rough, flexible PEN substrates even under mechanical substrate bending.


Application of immunofluorescence to studies on the ecology of Sphaerophorus necrophorus.
Sphaerophorus necrophorus (bovine liver abscess isolates) antiserum was fractionated and labeled with fluorescein isothiocyanate. The fluorescent-antibody (FA) conjugate proved to be species-specific and facilitated the detection of S. necrophorus cells in liver abscesses, viscera, and ruminal contents of cattle. Brightly fluorescing S. necrophorus cells were observed in experimentally inoculated soil incubated anaerobically at 37 and 4 C for 8 and 10 months, respectively. When incubated under moist conditions (80% water holding capacity) at 37 C, the test organism survived in both sterile and unsterile soil for as long as 8 weeks. Results strongly support the feasibility of using FA techniques concurrent with cultural methods for rapid detection of S. necrophorus infections.


Severe asthma in children: An official statement from Saudi Pediatric Pulmonology Association.
In Saudi Arabia, the prevalence of pediatric asthma ranges between 8% and 25%. However, there are no sufficient data regarding severe asthma in childhood in Saudi Arabia. Therefore, a task force has been formed by the Saudi Pediatric Pulmonology Association which is a subsidiary group of the Saudi Thoracic Society and consists of Saudi experts with well-respected academic and clinical backgrounds in the fields of pediatric asthma as well as other respiratory diseases to write a consensus on definitions, phenotypes, and pathophysiology, evaluation, and management. To achieve this, the subject was divided into various sections, each of which was assigned to at least 2 experts. Without a central literature review, the authors searched the literature using their own strategies. To reach an agreement, the entire panel reviewed and voted on proposed findings and recommendations.


Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus.
Recent animal studies have shown that CD4+CD25+ T cells play a crucial role in the suppression of the immune response and that depletion of this subset of T cells might lead to development of autoimmune diseases. The aim of the present study was to investigate the levels of CD4+CD25+ T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE). Ninety-four SLE patients, 52 patients with rheumatoid arthritis (RA) and 50 age- and gender-matched healthy individuals were enrolled in the study. A flowcytometric method was applied in the measurement of CD4+CD25+ T cells. The results showed that patients with SLE had statistically lower levels of CD4+CD25+ T cells than did normal controls, when expressed as either percentages of peripheral blood mononuclear cells (PBMCs) (mean +/- SD, 8.49 +/- 6.36 versus 11.11 +/- 4.58%, P < 0.05) or absolute cell numbers (98.77 +/- 97.52 versus 213.93 +/- 104.52 cells/mm3, P < 0.05). In terms of CD25brightCD4+ T cells, defined as having a fluorescence intensity of CD25 expression exceeding 100, SLE patients still had significantly lower levels than did normal controls expressed as percentages of PBMCs (1.76 +/- 1.32 versus 3.73 +/- 1.30%, P < 0.05). No significant differences could be found between RA patients and normal controls. The overwhelming majority of CD4+CD25+ T cells belonged to CD45RO+ cells and most did not express the CD69 molecule. Although decreased CD4+CD25+ T cells were found in SLE patients, we failed to find a significant correlation between the levels of CD4+CD25+ T cells and disease activities of SLE. To the best of our knowledge, this is the first study to demonstrate that patients with SLE had decreased CD4+CD25+ T cells. However, the exact role of the decreased CD4+CD25+ T cells in the pathogenesis of SLE remains to be elucidated.


Mortality in the United States, 2019.
This report presents final 2019 U.S. mortality data on deaths and death rates by demographic and medical characteristics. These data provide information on mortality patterns among U.S. residents by variables such as sex, age, race and Hispanic origin, and cause of death. Life expectancy estimates, agespecific death rates, 10 leading causes of death, and 10 leading causes of infant death were analyzed by comparing 2019 and 2018 final data (1).


Differential replication efficiencies between Japanese encephalitis virus genotype I and III in avian cultured cells and young domestic ducklings.
Japanese encephalitis virus (JEV) genotype dominance has shifted to genotype I (GI) from genotype III (GIII) in China as demonstrated by molecular epidemiological surveillance. In this study, we performed a serological survey in JEV-non-vaccinated pigs to confirm JEV genotype shift at the sero-epidemiological level. The average ratio of GI/GIII infection was 1.87, suggesting co-circulation of GI and GIII infections with GI infection being more prevalent in pigs in China. To gain an insight into the reasons for this JEV genotype shift, the replication kinetics of seven recently-isolated JEV isolates including three GI strains and four GIII strains were compared in mosquito C6/36 cells, chicken fibroblast cells (DF-1) and porcine iliac artery endothelial cells (PIEC). We observed that GI strains replicated more efficiently than GIII strains in DF-1 and PIEC cells, particularly in DF-1 cells with titers reaching 22.9-225.3 fold higher than GIII strains. This shows an enhanced replication efficiency of GI viruses in avian cells. To examine this enhanced replication efficiency in vivo, young domestic ducklings were used as the animal model and inoculated with GI and GIII strains at day 2 post-hatching. We observed that GI-inoculated ducklings developed higher viremia titers and displayed a comparatively longer viremic duration than GIII-inoculated ducklings. These results conform to the hypothesis of an enhanced replication efficiency for GI viruses in birds. There are 36 amino acid differences between GI and GIII viruses, some of which may be responsible for the enhanced replication efficiency of GI viruses in birds. Based on these findings, we speculated that the enhanced replication of GI viruses in birds would have resulted in higher exposure and therefore infection in mosquitoes, which could result in an increased transmission efficiency of GI viruses in the birds-mosquitoes-birds enzootic transmission cycle, thereby contributing to JEV genotype shift.


The timing of protein synthesis required for the development of the sodium action potential in embryonic spinal neurons.
Embryonic amphibian neurons grown in dissociated cell culture extend neurites and can produce action potentials. The ionic dependence of the inward current of the action potential gradually changes from primarily calcium to primarily sodium. Early exposure of these neurons to protein synthesis inhibitors (cycloheximide, puromycin) blocked the appearance of neurites; later exposure blocked the normal change in the ionic basis of the action potential. These drugs apparently arrested the development of the sodium component of the action potential and, additionally, may have blocked a reduction in the calcium component. Inhibitor applied at still later times did not prevent the normal development of these traits. The development of voltage-sensitive delayed rectification was unaffected by the addition of inhibitor at any of the times tested.


Prediction of CP and starch concentrations in ruminal in situ studies and ruminal degradation of cereal grains using NIRS.
Ruminal in situ incubations are widely used to assess the nutritional value of feedstuffs for ruminants. In in situ methods, feed samples are ruminally incubated in indigestible bags over a predefined timespan and the disappearance of nutrients from the bags is recorded. To describe the degradation of specific nutrients, information on the concentration of feed samples and undegraded feed after in situ incubation ('bag residues') is needed. For cereal and pea grains, CP and starch (ST) analyses are of interest. The numerous analyses of residues following ruminal incubation contribute greatly to the substantial investments in labour and money, and faster methods would be beneficial. Therefore, calibrations were developed to estimate CP and ST concentrations in grains and bag residues following in situ incubations by using their near-infrared spectra recorded from 680 to 2500 nm. The samples comprised rye, triticale, barley, wheat, and maize grains (20 genotypes each), and 15 durum wheat and 13 pea grains. In addition, residues after ruminal incubation were included (at least from four samples per species for various incubation times). To establish CP and ST calibrations, 620 and 610 samples (grains and bag residues after incubation, respectively) were chemically analysed for their CP and ST concentration. Calibrations using wavelengths from 1250 to 2450 nm and the first derivative of the spectra produced the best results (R 2 Validation=0.99 for CP and ST; standard error of prediction=0.47 and 2.10% DM for CP and ST, respectively). Hence, CP and ST concentration in cereal grains and peas and their bag residues could be predicted with high precision by NIRS for use in in situ studies. No differences were found between the effective ruminal degradation calculated from NIRS estimations and those calculated from chemical analyses (P>0.70). Calibrations were also calculated to predict ruminal degradation kinetics of cereal grains from the spectra of ground grains. Estimation of the effective ruminal degradation of CP and ST from the near-infrared spectra of cereal grains showed promising results (R 2>0.90), but the database needs to be extended to obtain more stable calibrations for routine use.


A comparison of emotional eating, social anxiety and parental attitude among adolescents with obesity and healthy: A case-control study.
This case-controlled study was conducted to determine and compare the emotional eating, social anxiety and parental attitude in those adolescents with obesity and healthy counterparts. The sample of the study consist of obese adolescents in 14-18 aged (n = 150) followed up in the pediatric endocrinology outpatient clinic of a tertiary hospital and healthy adolescents in 14-18 aged (n = 150) who were studying in high schools. The data were collected using a questionnaire form, Emotional Eating Scale Adapted to Use in Children and Adolescents (EES-C), Social Anxiety Scale for Children-Revised (SASC-R) and Parenting Style Scale (PSS). The SASC-R and EES-C mean scores of obese adolescents were 39.03 ± 13.09 (p ≤ 0.001) and 76.66 ± 16.30 (p ≤ 0.001), respectively. The mean scores of PSS-AI, PSS-SS and PSS-PA subscales in obese adolescents were 26.80 ± 4.42 (p ≤ 0.001), 28.14 ± 4.06 (p ≤ 0.001) and 22.32 ± 4.63 (p = 0.037), respectively. There was a low-level correlation between the EES-C and SASC-R mean scores of obese adolescents (p < 0.05). The mean scores of PSS-AI, PSS-SS and PSS-PA subscales of PSS with EES-C and SASC-R of obese adolescents were no correlated (p > 0.05). In this study, the mean scores of the emotional eating and social anxiety of obese adolescents were higher than healthy ones. There was a low level of positive correlation between emotional eating and social anxiety mean scores of obese adolescents.


Oculogyric crisis associated with disulfiram-induced pallidonigral lesion.
We report a man who developed oculogyric crisis one month after disulfiram intoxication. Brain MRI showed lesions involving bilateral globus pallidus and left substantia nigra. In our patient, neuronal discharges from pathologically reorganized basal ganglia circuit to the mid-brain ocular motor center might lead to tonic deviation of the eyes.