Reactivity of first-row transition metal monocations (Sc+, Ti+, V+, Zn+) with methyl fluoride: a computational study.
The gas-phase reactivity of methyl fluoride with selected first-row transition metal monocations (Sc(+), Ti(+), V(+), and Zn(+)) has been theoretically investigated. Our thermochemical and kinetics study shows that early transition-metal cations exhibit a much more active chemistry than the latest transition metal monocation Zn(+). The strong C-F bond in methyl fluorine can be activated by scandium, titanium, and vanadium monocations yielding the metal fluorine cation, MF(+). However, the rate efficiencies vary dramatically along the period 0.73 (Sc), 0.91 (Ti), and 0.028 (V) in agreement with the experimental observation. The kinetics results show the relative importance of the entrance and exit channels, apart from the "inner" bottleneck, to control the global rate constant of these reactions. At the mPW1K/QZVPP level our computed kglobal (at 295 K), 1.99 × 10(-9) cm(3) molecule(-1) s(-1) (Sc(+)), 1.29 × 10(-9) cm(3) molecule(-1) s(-1) (Ti(+)), and 3.46 × 10(-10) cm(3) molecule(-1) s(-1) (V(+)) are in good agreement with the experimental data at the same temperature. For the reaction of Zn(+) and CH3F our predicted value for kouter, at 295 K, 3.79 × 10(-9) cm(3) molecule(-1) s(-1), is in accordance with the capture rate constant. Our study suggests that consideration of the lowest excited states for Ti(+) and V(+) is mandatory to reach agreement between calculations and experimental measurements.


DNA genome size affects the stability of the adenovirus virion.
Replication-defective adenovirus (Ad) vectors can vary considerably in genome length, but whether this affects virion stability has not been investigated. Helper-dependent Ad vectors with a genome size of approximately 30 kb were 100-fold more sensitive to heat inactivation than their parental helper virus (>36 kb), and increasing the genome size of the vector significantly improved heat stability. A similar relationship between genome size and stability existed for Ad with early region 1 deleted. Loss of infectivity was due to release of vertex proteins, followed by disintegration of the capsid. Thus, not only does the viral DNA encode all of the heritable information essential for virus replication, it also plays a critical role in maintaining capsid strength and integrity.


Indications for flexible versus rigid bronchoscopy in children with suspected foreign-body aspiration.
Diagnostic indications for flexible bronchoscopy in the initial investigation of children with suspected foreign-body (FB) aspiration have not been evaluated prospectively. We prospectively collected history, clinical, and radiologic findings at prebronchoscopic examination of all children referred for suspected FB aspiration between February 1993 and September 1995. Children with asphyxiating FB aspiration, requiring immediate rigid bronchoscopy, were excluded. If there was clear evidence of FB aspiration from the physical and radiographic findings, rigid bronchoscopy was directly performed. If the evidence was not convincing, children underwent diagnostic flexible bronchoscopy under local anesthesia. If an FB was found, rigid bronchoscopy was always performed for extraction. Eighty-three consecutive children (median age: 24 mo) were included. Among 28 who underwent rigid bronchoscopy first, 23 had an FB. Among the 55 children who underwent flexible bronchoscopy first, 17 had an FB. Predictive signs of a bronchial FB were a radiopaque FB, and associated unilaterally decreased breath sounds and obstructive emphysema (positive predictive value = 0.94). We propose the following management algorithm: Rigid bronchoscopy is performed first in case of asphyxia, a radiopaque FB, or association of unilaterally decreased breath sounds and obstructive emphysema. In any other case, flexible bronchoscopy is performed first for diagnostic purposes. If applied retrospectively to the 83 children in our study, this algorithm would have decreased the negative first rigid bronchoscopy rate to 4%. Flexible bronchoscopy is a safe and cost-saving diagnostic procedure in children with suspected FB aspiration.


Strain-engineered thermophysical properties ranging from band-insulating to topological insulating phases in β-antimonene.
The use of strain in semiconductors allows extensive modification of their properties. Due to their robust mechanical strength and flexibility, atomically thin 2D materials are very well suited for strain engineering to extract exotic electronic and thermophysical properties. We investigated the structural, electronic, thermal, and vibrational characteristics along with the phonon and carrier dynamics of β-Sb elemental monolayers for achieving the band-insulating phase at no strain and topological insulating phase at ∼15% biaxial strain. A reduction in stiffness was noticed due to the weakening of the π and σ bonds with strain, leading to anharmonicity in the system. This was further reflected by the drop in lattice thermal conductivity (κl) from 4.5 to 3.1 W m-1 K-1 at 15% strain, i.e., in the topological phase. The appearance of helical edge states at 15% strain and meeting the Z2 invariant criterion confirm the non-trivial topological state. The significant contribution of the out-of-plane A1g vibrational mode was noticed in the topological phase compared with the band-insulating phase. Further, the observed larger reduction in hole lifetime could be attributed to strong scattering near the valence band edge. Importantly, the dominance of the out-of-plane optical modes contributes significantly along the band edges to the topological phase, which is primarily due to the reduced buckling height under strain. Thus, this work emphasizes the microscopic origin of the onset of the topological phase in strained β-Sb monolayers and provides strain-engineered structure-property correlations for better insights.


The Sensitivity of Bipolar Electromyograms to Muscle Excitation Scales With the Inter-Electrode Distance.
The value of surface electromyograms (EMGs) lies in their potential to non-invasively probe the neuromuscular system. Whether muscle excitation may be accurately inferred from bipolar EMGs depends on how much the detected signal is both sensitive and specific to the excitation of the target muscle. While both are known to be a function of the inter-electrode distance (IED), specificity has been of long concern in the physiological literature. In contrast, sensitivity, at best, has been implicitly assumed. Here we provide evidence that the IED imposes a biophysical constraint on the sensitivity of surface EMG. From 20 healthy subjects, we tested the hypothesis that excessively reducing the IED limits EMGs' physiological content. We detected bipolar EMGs with IEDs varying from 5 mm to 50 mm from two skeletal muscles with distinct architectures, gastrocnemius and biceps brachii. Non-parametric statistics and Bayesian hierarchical modelling were used to evaluate the dependence of the onset of muscle excitation and signal-to-noise ratio (SNR) on the IED. Experimental results revealed that IED critically affects the sensitivity of bipolar EMGs for both muscles-indeliberately reducing the IED yields EMGs that are not representative of the whole muscle, hampering validity. Simulation results substantiate the generalization of experimental results to small and large electrodes. Based on current and previous findings, we discuss a potentially valid procedure for defining the most appropriate IED for a single bipolar, surface recording-i.e., the distance from the electrode to the target muscle boundary may heuristically serve as a lower bound when choosing an IED.


The psychological effects of cyber terrorism.
When ordinary citizens think of cyber threats, most are probably worried about their passwords and banking details, not a terrorist attack. The thought of a shooting in a mall or a bombing at an airport is probably more frightening than a cyber breach. Yet terrorists aim for mental as well as physical destruction, and our research has found that, depending on who the attackers and the victims are, the psychological effects of cyber threats can rival those of traditional terrorism.


Choline kinase active site provides features for designing versatile inhibitors.
Choline kinase (CK) is a homodimeric enzyme that catalyses the transfer of the ATP γ-phosphate to choline, generating phosphocholine and ADP in the presence of magnesium. Several isoforms of CK are present in humans but only the HsCKα has been associated with cancer and validated as a drug target to treat this disease. As a consequence a large number of compounds based on Hemicholinium (HC-3) have been described. Two compounds, previously reported to inhibit the human enzyme, have recently been shown to inhibit P. falciparum CK (PfCK) and therefore their potential applications might be anticipated to other pathogens. Herein, using molecular dynamic simulations, we have firstly observed that the ATP and the choline binding site of different CK in pathogens and human are conserved, suggesting that previous compounds inhibiting the human enzyme may also interact with CKs from different pathogens. We have substantiated such observation with experimental assays showing that HsCKα1, PfCK and CpCK bind to two compounds with distinct structural features in the low μM range. Collectively, these results uncover similarities among the choline kinase binding site from different pathogenic species and the human enzyme, highlighting the feasibility of designing novel inhibitors based on the choline binding pocket.


Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage.
Hydrogen sulfide (H2S), mainly produced by cystathionine γ-lyase (CSE) in vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be involved in atherosclerosis pathogenesis. However, the underlying mechanisms are poorly understood. The present study showed that the levels of CSE mRNA and protein expression, as well as H2S production were decreased in ox-LDL-treated macrophage. CSE overexpression reduced the ox-LDL-stimulated tumor necrosis factor-α (TNF-α) generation in Raw264.7 and primary macrophage while CSE knockdown enhanced it. Exogenous supplementation of H2S with NaHS and Na2S also decreased the production of TNF-α and intercellular adhesion molecule-1 (ICAM-1) in ox-LDL-stimulated macrophage, and alleviated the adhesion of macrophage to endothelial monolayer. Cysteine, a CSE preferential substrate for H2S biosynthesis, produced similar effects on the pro-inflammatory cytokine generation, which were reversed by CSE inhibitors PAG and BCA, respectively. Moreover, NaHS and Na2S attenuated the phosphorylation and degradation of IκBα and p65 nuclear translocation, as well as JNK activation caused by ox-LDL. The JNK inhibitor suppressed the NF-κB transcription activity in ox-LDL-treated cells. Furthermore, inhibitors of NF-κB (PDTC), ERK (U0126 and PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down-regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL-stimulated macrophage by suppressing JNK/NF-κB signaling. The study reveals new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S pathway.


The potential role of PD0332991 (Palbociclib) in the treatment of multiple myeloma.
Multiple myeloma (MM) remains an incurable malignancy indicating a need for continued investigation of novel therapies. Recent studies have highlighted the role of cyclin-dependent kinases (CDK) in the pathogenesis of MM. PD0332991 (Palbociclib) is an orally bioavailable, highly selective inhibitor of the CDK4/6-cyclin complex and downstream retinoblastoma protein (Rb) activation pathway that induces cell cycle arrest in the G1 phase. In this review, the authors summarize the role of the CDK4/6 signaling pathway in MM. They also summarize the development of PD0332991 as a specific inhibitor of CDK4/6, and the reported preclinical and clinical data supporting the potential role of PD0332991 in MM. While PD0332991 is essentially cytostatic, inducing prolonged G1 arrest, it enhances the cytotoxic effect of other agents effective in MM, including bortezomib and lenalidomide, as confirmed in early phase clinical trials. However, with a plethora of other drugs of different classes being tested in MM, further development of PD0332991 will depend on defining the most efficacious combination with least toxicity. An unexplored opportunity remains the potential protective effect of PD0332991 against lytic bone lesions of MM. The next few years are likely to better define the place of PD0332991 in the treatment of MM.


Streptococcus mutans levels and caries prevalence in low-income schoolchildren.
Previous studies have shown that persons having high Streptococcus mutans levels in the saliva are "at risk" for dental caries. Most investigators agree, that if high levels of S. mutans were identified early in the life of at-risk children, dental decay could be reduced or eliminated through intervention. The purpose of this study is to show an association between S. mutans levels and caries prevalence in a sample of elementary school children. The study group consisted of 242 school children, ages 5-13 years. The subjects were divided into two age groups, 5-8 years and 9-13 years. Approximately 59 percent were African Americans. The sample of 242 children were equally females and males, 50 percent in each group. The Dentocult SM Test was used to make S. mutans determinations. The df-t index was used to determine the number of decayed and filled teeth of children ages 5-8 years; the DMF-T Index estimated the number of decayed, missing or filled teeth of children ages 9-13 years. Dental caries were found in 58 percent of the children (mean = 2.67, and range of 1-11). Approximately 47 percent of the children with caries had high S. mutans levels (100K-1M). Females had higher S. mutans levels than males in the 9-13 age group, p < .05. Analysis of Variance Test indicated that S. mutans levels for older females (ages 9-13) were significantly higher than those observed in males the same age (p < .01). This trend was not observed in younger children, ages 5-8 years. In addition, no significant difference or interaction was noted by sex for S. mutans levels and decayed or filled teeth (df-t) for younger children. We conclude that high levels of Streptococcus mutans are related to increased number of decayed teeth and conversely, low Streptococcus mutans levels are related to fewer dental caries. This study was supported in part by Colgate-Palmolive Company and the National Dental Association Foundation, Inc.


A meta-analysis on the relationship between exposure to ELF-EMFs and the risk of female breast cancer.
To comprehensively analyze the relationship between exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and the development of female breast cancer. Reports of case-control studies published from 1990 to 2010 were analyzed. The quality effect model was chosen to calculate total odds ratio (OR) depending on the data in studies and quality scores. Subgroup analyses were also performed by the situation of menopause, estrogenic receptor and exposure assessment respectively. For all 23 studies the OR was 1.07, 95% CI=1.02-1.13, for estrogen receptor positive subgroup,OR=1.11, 95% CI=1.03-1.20; for premenopausal subgroup, OR=1.11, 95% CI=1.00-1.23. The results of other subgroups showed no significant association between ELF-EMF and female breast cancer. ELF-EMFs might be related to an increased risk for female breast cancer, especially for premenopausal and ER+ females. However, it's necessary to undertake better epidemiologic researches to verify the association between ELF-EMF and female breast cancer due to the limits of current study, especially the one on exposure assessment.


Which procedures are performed by general internists practicing primary care in Germany? - a cross-sectional study.
Due to differences of residency training programs' emphases - inpatient vs office-based - internal medicine and family medicine residents consistently reported differences in preparedness to care for common adult conditions. Study's aim was to add knowledge about procedures that a) are performed by general internists working in primary care and b) should be learned during residency in general internists' appraisal. A cross-sectional postal survey was carried out by using a questionnaire that comprised 90 procedures relevant in primary care. Each procedure implied the two questions "Do you perform this procedure in your own practice?" and "How important do you think it is to learn this procedure during residency?" The final questionnaire was sent to 1002 general internists working in primary care in Germany in May 2015. Data analysis was performed using SPSS Version 24.0 (SPSS inc., IBM). Next to descriptive statistics subgroup analyses were performed using cross tabulation and Chi-square tests for evaluation of differences in the performance of most frequently performed procedures in urban or rural areas as well as by male or female physicians. Twenty-eight percent of sent questionnaires (276/1002) could be included in analysis. Mean age of participants was 52 years with 13 years of practice experience; 40% were female. Twenty-nine (32%) of 90 given procedures were performed by at least half of the participants, foremost technical diagnostics, punctures, procedures of the integument and resuscitation. After Bonferroni correction, five of those procedures were performed by more male than female physicians and two procedures by more physicians working in a rural practice than physicians practicing in an urban location. Moreover, 46 (51%) procedures were assessed as important to learn during residency by at least 50% of participants. General internists working in German primary care perform a narrow scope of procedures offered by primary care physicians. In order to provide best ambulatory care for patients, residency training programs must ensure training in procedures that are necessary for providing high quality care. Therefore, a consensus aligned with patients' and health-systems' needs on procedures required for working as a general internist in primary care is necessary.


Anthropogenic Chloroform Emissions from China Drive Changes in Global Emissions.
Emissions of chloroform (CHCl3), a short-lived halogenated substance not currently controlled under the Montreal Protocol on Substances that Deplete the Ozone Layer, are offsetting some of the achievements of the Montreal Protocol. In this study, emissions of CHCl3 from China were derived by atmospheric measurement-based "top-down" inverse modeling and a sector-based "bottom-up" inventory method. Top-down CHCl3 emissions grew from 78 (72-83) Gg yr-1 in 2011 to a maximum of 193 (178-204) Gg yr-1 in 2017, followed by a decrease to 147 (138-154) Gg yr-1 in 2018, after which emissions remained relatively constant through 2020. The changes in emissions from China could explain all of the global changes during the study period. The CHCl3 emissions in China were dominated by anthropogenic sources, such as byproduct emissions during disinfection and leakage from chloromethane industries. Had emissions continued to grow at the rate observed up to 2017, a delay of several years in Antarctic ozone layer recovery could have occurred. However, this delay will be largely avoided if global CHCl3 emissions remain relatively constant in the future, as they have between 2018 and 2020.


1-Naphthylpiperazine derivatives as potential atypical antipsychotic agents.
The design and synthesis of a series of potential atypical antipsychotic agents based on the structure of 1-naphthylpiperazine are described. The incorporation of dopamine antagonist activity into the parent structure was achieved with heterocyclic surrogates for the catechol moiety of dopamine. Compound 4b from this series showed a biochemical profile that translated to behavioral activity in the rat predictive of an antipsychotic agent with a low propensity to cause extrapyramidal side effects in man.


Longitudinal analysis on the effect of insertion torque on delayed single implants: A 3-year randomized clinical study.
Implant stability is commonly related to insertion torque. Recently, it has been suggested that higher insertion torque may lead to greater bone resorption. The aim of the present randomized clinical study was to evaluate the role of different insertion torque values in terms of implant success, marginal bone loss, and facial soft tissues recession. Patients requiring a single dental implant were recruited and randomized to receive one of two implants with the same macro-geometry but different cutting designs. First group consists of a 90 degrees cutting groove know as self-tapping implant, and the second group known as Blossom™ cutting groove. (Intra-Lock, Boca Raton, Florida). The insertion torque (IT) was assessed and two groups followed: high-IT (≥50 Ncm) group and regular-IT (<50 Ncm) group. After 3 months, all the implants were restored. At baseline, buccal bone thickness (BBT) was recorded. During the 3-year survey, the following outcomes had been registered: implant failures and success, radiographic marginal bone level around dental implant (MBL) and facial soft tissue level (FSTL). A hundred and sixteen implants were placed in healed sites. The overall survival rate after 3 years was 96.5%. The Cumulative Success Rate was 91.3% for the High IT group and 98.2% for the Regular IT group. The mean marginal bone loss and facial soft tissue recession, at a 3-year evaluation, were significantly greater for the High-IT group and in the mandible than that reached in the Regular-IT group and in the maxilla. Present findings showed that implants placed with higher insertion torque in mandible led to greater bone resorption and mucosal recession than that registered for implants placed with a regular IT. Moreover, sites with a thick buccal bone wall (≥1 mm) showed smaller recession at the facial soft tissue level after 3 years.


The effects of interstimulus interval on sensory gating and on preattentive auditory memory in the oddball paradigm. Can magnitude of the sensory gating affect preattentive auditory comparison process?
P50, and mismatch negativity (MMN) are components of event-related potentials (ERP) reflecting sensory gating and preattentive auditory memory, respectively. Interstimulus interval (ISI) is an important determinant of the amplitudes of these components and N1. In the present study the interrelation between stimulus gating and preattentive auditory sensory memory were investigated as a function of ISI in 1.5, 2.5 and 3.5s in 15 healthy volunteered participants. ISI factor affected the N1 peak amplitude significantly. MMN amplitude in 2.5s ISI was significantly smaller compared to 1.5 and 3.5s ISI. ISI X stimuli interaction on P50 amplitude was statistically significant. P50 amplitudes to deviant stimuli in 2.5s ISI were larger than the P50 amplitudes in other ISIs. P50 difference (P50d) waveform amplitude correlated significantly with MMN amplitude. The results suggest that: (i) auditory sensory gating could affect preattentive auditory sensory memory by supplying input to the comparator mechanism; (ii) 2.5s ISI is important in displaying the sensory gating and preattentive auditory sensory memory relation.


[Arterial hypertension in Ilha do Governador, Rio de Janeiro, Brazil: I. Methodology].
The aim of this paper (first of a series of two) is to present the main methodological aspects used in a cross-sectional study whose proposals were to establish the prevalence of arterial hypertension in adults in Ilha do Governador (a district of the city of Rio de Janeiro, Brazil), and to examine its relationship to other risk factors, including those for cardiovascular diseases, so as to establish its control status. Sampling design (of clusters in strata, according to mean household income) is described in detail, in addition to measurement methods, and training of observers. Indicators of performance in field work and quality control are also presented as results of the application of the metodology of study.


Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels.
An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous-level tagged proteins. Isolations of triple-FLAG and GFP-tagged fusion proteins involved in RNA metabolism are presented.


Systematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease.
Whether N-acetylcysteine (NAC) therapy can promote the improvement of clinical symptoms and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has not been verified by large-scale randomized controlled trials, only a few small sample studies. English databases were searched using a combination of the following terms: "chronic obstructive pulmonary disease", "acute exacerbation of chronic obstructive pulmonary disease", and "N-acetylcysteine". Studies examining NAC in the treatment of AECOPD were screened, so as to be a reference for the experimental group. Meta-analysis was performed using RevMan 5.3 software (Cochrane, Northern Europe), with a total of 15 included literatures. The heterogeneity test of improvement rate showed Chi2=1.89, df=7, I2=0% <50%, and P=0.97 (>0.01); the risk rate was 1.09, the 95% confidence interval (CI) was (1.04-1.14), Z=3.93, and P<0.0001. The heterogeneity test of forced expiratory volume in the first second (FEV1) showed that Tau2=63.39, Chi2=118.66, df=9, I2=92% >50%, and P=0.88 (<0.0001); the mean difference was 30.63 (95% CI: 25.48-35.78), Z=11.65, and P<0.0001. The results of the heterogeneity test of forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) showed that Tau2=60.03, Chi2=74.09, df=5, I2=93% >50%, and P<0.0001; the mean difference was 30.42 (95% CI: 24.00-36.85), Z=9.28, and P<0.0001. The heterogeneity test for glutathione sulfur transferase (GSH-ST) activity showed that Tau2=4.12, Chi2=58.12, df=5, I2=91% >50%, and P<0.0001; the mean difference was 3.10 (95% CI: 1.38-4.82), Z=3.63, and P=0.0004. Our meta-analysis confirmed that NAC could promote the symptom improvement rate of patients with AECOPD, improve lung function in FEV1 and FEV1/FVC, and enhance the body's antioxidant capacity.


3'-Daidzein sulfonate sodium provides neuroprotection by promoting the expression of the α7 nicotinic acetylcholine receptor and suppressing inflammatory responses in a rat model of focal cerebral ischemia.
In a previous study using a rat model of focal cerebral ischemia/reperfusion (I/R) injury, we found that 3'-Daidzein sulfonate sodium (DSS), a derivative of daidzein, exerts neuroprotective effects by alleviating brain edema and reducing levels of interleukin (IL)-6. The present study was designed to further examine the potential mechanisms of the neuroprotective properties of DSS in a rat model of cerebral I/R injury. We found that treatment with DSS ameliorated neurological deficit, infarct size, and cerebral water content in rats with cerebral I/R injury. Moreover, treatment with DSS significantly reduced the levels of IL-1β, IL-6, and tumor necrosis factor (TNF)-α in serum and in the ischemic penumbra. Additionally, DSS treatment increased the expression of nicotinic acetylcholine receptor alpha 7 (α7nAChR), and inhibited the expression of glial fibrillary acidic protein, phosphorylated p65 nuclear factor κB, and phosphorylated inhibitor of NF-κBα, suggesting that DSS provides neuroprotection by suppressing inflammatory responses after focal cerebral I/R injury. Notably, α-bungarotoxin, an antagonist of α7nAChR, reversed the neuroprotective effects of DSS after cerebral I/R injury, suggesting that inhibition of α7nAChR expression is sufficient for reversal of the neuroprotective effects of DSS. In conclusion, we found that DSS treatment provides neuroprotection by promoting α7nAChR expression in a rat model of focal cerebral ischemia, thus establishing α7nAChR as a potential therapeutic target in cerebral I/R injury.


Limit dilution analysis of peripheral blood T lymphocytes specific to periodontopathic bacteria.
Limit dilution analysis (LDA) was used to determine the presence and frequency of periodontopathic-bacteria-specific T cells in the peripheral blood of patients with chronic inflammatory periodontal disease. Twelve adult periodontitis (AP), 13 marginal gingivitis (MG) and 12 healthy control subjects took part in the study. Bacteroides gingivalis and Actinomyces viscosus were used as test organisms, while tetanus toxoid was used as the control antigen. The median PTL-p frequencies to B. gingivalis were 46.33 x 10(-6), 45.33 x 10(-6) and 58.83 x 10(-6) in the control, gingivitis and AP groups respectively, while the median PTL-p frequencies to A. viscosus were 13.8 x 10(-6), 17.33 x 10(-6) and 11.5 x 10(-6), again in the control, gingivitis and AP groups. There were no statistically significant differences between the groups. All subjects displayed 'single-hit' kinetics with the control tetanus toxoid antigen and, with three exceptions, 'single-hit' kinetics was also found with the two test organisms. One control subject displayed a 'saw-tooth' curve with A. viscosus and a 'suppressor' curve with B. gingivalis, while two MG subjects had a 'saw-tooth' curve with B. gingivalis. These complex curves suggest that, in some subjects, more than one limiting cell type may exist in the cultures. Nevertheless, the results of the present study illustrate that lymphocytes specific to periodontopathic bacteria exist in the peripheral blood of both diseased and non-diseased subjects.


The effect of delactosed whey permeate on phytochemical content of canned tomatoes.
The effect of delactosed whey permeate (DWP) treatment on antioxidant and phyto-chemical components of canned Irish plum tomatoes were investigated. Tomatoes were sterilised for 5 min (F(0)) at 120 °C and stored for 6 months. The DWP treatment retained significantly (p<0.05) higher levels of ascorbic acid and lycopene of tomatoes. The antioxidant activity of DWP treated tomatoes was higher (7%) than the control at the end of storage. The firmness in DWP-treated fruits was around 40% higher than that in control. All the parameters decreased significantly (p<0.05) during storage except lycopene and total phenols. Lycopene content showed no significant change and total phenols increased during storage. The changes in ascorbic acid, antioxidant activity and texture were fitted well to Weibull kinetic models with high coefficients of determination (R(2)) and low RMSE (root mean sum of squared error). The results clearly indicate that DWP enhanced the retention of antioxidant compounds in tomatoes during storage.


Isolation and characterization of a generalized transducing bacteriophage for Acinetobacter.
A series of bacteriophages which grow in various strains of Acinetobacter have been isolated. One of these, phage P78, which forms turbid plaques on Acinetobacter strain 78 is specific for this particular host and fails to attack 389 other independently isolated strains of Acinetobacter. Phage P78 appears to be a temperate phage which lysogenizes its host. Various agents such as N-methyl-N'-nitro-N-nitrosoguanidine, diethyl sulfate, mitomycin C, and ultraviolet light are effective inducers of the lysogen. Phage lysates of wild-type cells are capable of transducing auxotrophs of strain 78 to prototrophy at frequencies ranging from 0.3 x 10(-7) to 34 x 10(-7) per plaque-forming unit adsorbed. To date, no linkage has been detected between any of the markers studied in two-factor crosses. Donor phage grown in one particular mutant, strain 78 (arg-1), has been shown to give rise to significantly higher transduction frequencies than when phage is grown on wild-type or other auxotrophic strains. Phage P78 is rapidly adsorbed to its bacterial host and has a latent period of 25 min, and infection results in a burst size of approximately 50. Some of the physical properties of phage P78 and its DNA are described.


Radiographic hand osteoarthritis in two ethnic groups living in the same geographic area.
The aim of the study was to compare the prevalence of radiographic hand osteoarthritis (OA) and its association with age, sex, body mass index in two ethnic groups, Russian and Buryats who reside in the same geographic area. It was a cross-sectional observational study. The study population comprised ethnic Russians (N = 572) and Buryats (N = 327) from the Barguzinsky District of the Buryat Republic, Russian Federation. OA was evaluated in 14 joints of the left hand according to Kellgren and Lawrence's grading system. A diagnosis of OA was determined by the number of affected joints and by the presence of at least one affected joint. Statistical analyses included prevalence estimation, linear and logistic regressions, and chi(2) tests. Our major finding was that individuals of different ethnic groups, residing in the same location, have similar prevalence and severity of radiographic hand OA. Considering the results of our previous study, where we found significant differences in the prevalence and severity of hand OA between the Russian samples (same ethnicity) with diverse places of residence, we conclude that environmental factors play an important role in the development of hand OA.


In vitro-in vivo correlation and translation to the clinical outcome for CJ-13,610, a novel inhibitor of 5-lipoxygenase.
The metabolism of the 5-lipoxygenase inhibitor, 4-(3-(4-(2-methyl-1H-imidazol-1-yl)phenylthio)phenyl)-tetrahydro-2H-pyran-4-carboxamide (CJ-13,610), was investigated in liver microsomes from human and preclinical species in an effort to compare metabolite profiles and evaluate the in vitro-in vivo correlation for metabolic clearance. Overall, the metabolite profile of CJ-13,610 was comparable across the species tested with multiple oxidative metabolites observed, including sulfoxidation. The sulfoxidation kinetics characterized in rat, dog, and human liver microsomes (HLM) indicated a low apparent Michaelis-Menten constant (K(m, app)) of 4 to 5 microM. Results from cDNA-expressed cytochrome P450 (P450) studies indicated that the metabolism in HLM was primarily mediated by CYP3A4 and 3A5. A subsequent in vitro study using ketoconazole as an inhibitor of CJ-13,610 sulfoxidation corroborated the CYP3A4/5-mediated pathway (IC(50) = 7 nM). Assessment of multiple methods for predicting the human pharmacokinetic profile observed with CJ-13,610 after a 30-mg single oral dose indicated that clearance scaled from human liver microsomes yielded a better prediction when coupled with a Vd(ss) term that was scaled from dog [area under the concentration-time curve (AUC) and half-life within 1.3-fold of actual] versus a Vd(ss) term obtained from rat. Single-species allometric scaling of clearance and Vd(ss) from dog pharmacokinetic studies was equally predictive, whereas scaling from rat resulted in underpredictions of both AUC and maximal concentration (C(max)). Results from these studies support the strategy of predicting human pharmacokinetics using human liver microsomal intrinsic clearance data. More importantly, results from the present investigation enabled the selection of alternative drug candidates from the chemical series via in vitro screening, while subsequently eliminating costly routine preclinical in vivo studies.


Molecular insights into cardiac development.
Recent discoveries have led to a greater appreciation of the diverse mechanisms that underlie cardiac morphogenesis. Genetic strategies (primarily gene targeting approaches in mice) have significantly broadened research in cardiovascular developmental biology by illuminating new pathways involved in heart development and by allowing the genetic evaluation of pathways that have previously been implicated in these events. Advances have also been made using biochemical and cell- and tissue-based approaches. This review summarizes the author's interpretation of current trends in the effort to understand the molecular basis of cardiac-development, with an emphasis on insights obtained from genetic models.


Single-Bundle Augmentation for a Partial Tear of the Anterior Cruciate Ligament.
Given the prevalence of anterior cruciate ligament (ACL) tears in young athletes, it is essential to elucidate and illustrate surgical interventions that return the most favorable outcomes. Although most ACL injuries are full-thickness tears, occasionally either the anteromedial (AM) or posterolateral (PL) bundle is torn in isolation, allowing consideration of an ACL reconstruction or augmentation. Because the ACL-deficient knee has been shown to exhibit less proprioceptive feedback, the preservation of the intact bundle may offer an inherent component of stability. After arthroscopy has confirmed a partial ACL tear, the decision to augment the intact bundle can be made. The technique is adapted from principles of the double-bundle reconstruction such that the graft follows the path of either the native AM bundle or the native PL bundle, depending on the location of the partial tear. We present our surgical technique for ACL AM bundle augmentation with PL bundle reconstruction using a semitendinosus tendon autograft.


Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha-2b in metastatic melanoma (phase II DeCOG trial).
During a clinical study with combined therapy of sorafenib and pegylated interferon alpha-2b (SoraPeg study) of the German Dermatologic Oncology Group (ADO/DeCOG), multiple and severe cutaneous side effects were observed. This study sought to analyze these cutaneous side effects, particularly because future studies with combinations of interferon alpha and targeted therapies are planned. In a multicenter phase-II-DeCOG study (NCT00623402) in 10 dermato-oncology centers, 55 patients with metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally) and pegylated interferon alpha-2b (3 μg/kg body weight 1 x/week subcutaneously). All cutaneous side effects were documented. Forty-one patients (74.5 %) developed cutaneous side effects, particularly exanthems (51.2 %), hand-foot syndrome (36.5 %), alopecia (36.5 %) and pruritus (24.4 %). Due to the cutaneous side effects, dose reductions were required in 10 patients, interruption of therapy in 10 cases and permanent discontinuation of therapy and in one patient with extensive follicular-cystic lesions. Exanthems were seen more frequently in women (76.2 %) than in men (23.8 %). The occurrence of cutaneous side effects was not correlated with clinical outcome or prognosis. The combination of sorafenib/pegylated interferon alpha-2b caused more cutaneous side effects than have been reported for single agents. Despite intensive dermatologic management of the cutaneous side effects 24 % of patients required a dose modification.


Lung function in wheezing infants.
Recurrent wheeze is a very frequent disease during infancy. In many cases, this condition is a transient one, but some infants who suffer from this illness, have a persistent recurrent wheeze. During the past decades different international cohorts have been designed to answer what are the risk factors to develop recurrent wheeze and to make the conditon persistent even into the adulthood. Infant lung function could explain some aspects of this pathophysiology. The aim of this article is to review the current knowledge on the relationships of recurrent wheeze with an eventual impairment in lung function, the beginning of this impairment early in life, its relationship with asthma later in life and what risk factors are related with low lung function.


Functional connectivity analysis using whole brain and regional network metrics in MS patients.
In the present study we investigated brain network connectivity differences between patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC) as derived from functional resonance magnetic imaging (fMRI) using graph theory. Resting state fMRI data of 18 RRMS patients (12 female, mean age ± SD: 42 ± 12.06 years) and 25 HC (8 female, 29.2 ± 5.38 years) were analyzed. In order to obtain information of differences in entire brain network, we focused on both, local and global network connectivity parameters. And the regional connectivity differences were assessed using regional network parameters. RRMS patients presented a significant increase of modularity in comparison to HC, pointing towards a network structure with densely interconnected nodes within one module, while the number of connections with other modules outside decreases. This higher decomposable network favours cost-efficient local information processing and promotes long-range disconnection. In addition, at the regional anatomical level, the network parameters clustering coefficient and local efficiency were increased in the insula, the superior parietal gyrus and the temporal pole. Our study indicates that modularity as derived from fMRI can be seen as a characteristic connectivity feature that is increased in MS patients compared to HC. Furthermore, specific anatomical regions linked to perception, motor function and cognition were mainly involved in the enhanced local information processing.


Placental transmogrification of the lung: CT findings with pathologic correlation in six patients.
Placental transmogrification of the lung is a very rare benign lung disease with a characteristic finding being alveoli resembling chorionic villi of the placenta. The purpose of this study was to assess the computed tomography (CT) findings of placental transmogrification of the lung in six patients and their relation to the histopathologic findings. Six patients with histopathologically proven placental transmogrification of the lung from 2004 to 2021 were included. Their CT findings were analyzed and their imaging features were compared with pathology specimens. In four of six cases, CT showed variable sized cystic lesions confined to a unilateral lung. One case presented nodule and cystic lesion together. The other case showed solitary pulmonary nodule without cystic lesion. Moreover, nodular interlobular septal thickening and clustered interstitial nodules were observed in all six cases. In four of the six cases, these nodules merged into dense nodular consolidation. Three cases showed dilated pulmonary vasculatures of the involved lung. On CT, placental transmogrification of the lung typically presents as cystic lesion confined to a unilateral lung. Pulmonary nodule with or without associated cystic lesion can also be seen. Nodular interlobular septal thickening and clustered interstitial nodules were observed in all cases. This might be attributable to the proliferation of chorionic villi-like structures in interstitium which are found in histopathologic specimens.


A Reply to Commentaries on "How the Object of Affect Guides Its Impact"
Commentaries focused on the emotional appraisal part of our article. Cunningham and Van Bavel argued for distinguishing core disgust from moral disgust, and we describe how the theory might accommodate their proposal. They also suggested that temporal and other comparisons could account for emotional variety. We concur, but see such comparisons as inherent in the different emotional objects. Winkielman emphasized unconscious affect, but we suggest its power flows from the absence of situational constraints on its meaning. He characterized our appraisal model as coldly cognitive rather than embodied, but the complaint is misdirected, as the model addresses emotional structure, not emotional process. Indeed, embodied accounts will still require structural accounts to determine why one emotion rather than another is elicited.


Whole-Genome Identification of Regulatory Function of CDPK Gene Families in Cold Stress Response for Prunus mume and Prunus mume var. Tortuosa.
Calcium-dependent protein kinases (CDPK) are known to mediate plant growth and development and respond to various environmental changes. Here, we performed whole-genome identification of CDPK families in cultivated and wild mei (Prunus mume). We identified 14 and 17 CDPK genes in P. mume and P. mume var. Tortuosa genomes, respectively. All 270 CPDK proteins were classified into four clade, displaying frequent homologies between these two genomes and those of other Rosaceae species. Exon/intron structure, motif and synteny blocks were conserved between P. mume and P. mume var. Tortuosa. The interaction network revealed all PmCDPK and PmvCDPK proteins is interacted with respiratory burst oxidase homologs (RBOHs) and mitogen-activated protein kinase (MAPK). RNA-seq data analysis of cold experiments show that cis-acting elements in the PmCDPK genes, especially PmCDPK14, are associated with cold hardiness. Our results provide and broad insights into CDPK gene families in mei and their role in modulating cold stress response in plants.


A new apparatus design for high temperature (up to 950°C) quasi-elastic neutron scattering in a controlled gaseous environment.
A design for a sample cell system suitable for high temperature Quasi-Elastic Neutron Scattering (QENS) experiments is presented. The apparatus was developed at the Spallation Neutron Source in Oak Ridge National Lab where it is currently in use. The design provides a special sample cell environment under controlled humid or dry gas flow over a wide range of temperature up to 950 °C. Using such a cell, chemical, dynamical, and physical changes can be studied in situ under various operating conditions. While the cell combined with portable automated gas environment system is especially useful for in situ studies of microscopic dynamics under operational conditions that are similar to those of solid oxide fuel cells, it can additionally be used to study a wide variety of materials, such as high temperature proton conductors. The cell can also be used in many different neutron experiments when a suitable sample holder material is selected. The sample cell system has recently been used to reveal fast dynamic processes in quasi-elastic neutron scattering experiments, which standard probes (such as electrochemical impedance spectroscopy) could not detect. In this work, we outline the design of the sample cell system and present results demonstrating its abilities in high temperature QENS experiments.


Sperm motility, plasma membrane integrity, and binding capacity to homologous zona pellucida of cryopreserved epididymal spermatozoa in the domestic cat.
We examined motility, plasma membrane integrity, and binding capacity to homologous zona pellucidae (ZP) of frozen/thawed epididymal cat sperm as a model species for endangered felines. Epididymal spermatozoa from 20 domestic cats were frozen with freezing egg-yolk extender containing 3.0% glycerol in 0.25-ml straws. Post-thaw motility and plasma membrane integrity of the frozen/thawed spermatozoa were 31.8 +/- 2.4% and 32.2 +/- 4.2%, respectively. The frozen/thawed spermatozoa were co-cultured with frozen/thawed immature homologous oocytes with intact ZP for 3 h to examine their ability to bind to the ZP. Sixteen of the 20 frozen/thawed sperm samples demonstrated the ability to bind to ZP. These results indicated that the freezing system for epididymal sperm used in the present study gives appropriate information for banking the genetic resources of wild felid species.


Blood Biochemical Profile in Fertile and Repeat Breeder Ongole Cross Breed Cows.
Repeat breeding is a major problem in beef cows. The objective of the present study was to determine the blood biochemical levels in repeat breeder and fertile Ongole cross breed cows. This study compared the blood biochemical profiles from 30 repeat breeders and 30 fertile Ongole cross breed cows. Plasma glucose, total cholesterol, total protein and urea nitrogen concentrations were examined in repeat breeder cows and compared with those of fertile cows. Blood samples were collected from the caudal vein into anticoagulant-coated tubes. Cells were removed from plasma by centrifugation and blood glucose, total cholesterol and urea nitrogen concentrations were measured using commercially available kits; a non-commercial kit was used to determine total protein content. Significantly different blood profiles between repeat breeder and fertile cows were reported. Specifically, repeat breeder cows had lower levels of glucose, total cholesterol and total protein, but higher levels of urea nitrogen than fertile cows. Finally, a low level of total protein, total cholesterol and glucose, accompanied by a high level of urea nitrogen, may cause reproductive problems in repeat breeders. Additionally, present findings indicated that biochemical blood profiling could be used as a diagnostic tool for repeat breeding.


[Intraventricular transplantation of human neural stem cells into embryonic rats].
To explore the migration and distribution of human neural stem cells (NSCs) after they were transplanted into lateral cerebroventricles of embryonic rats. This study was conducted with the proxy consent and the permission from the Hospitals Ethical Review Committee. The cells from the embryonic human cortices were mechanically dissociated. N2 medium was used to culture and expand the cells. And the cells were identified by immunocytochemistry; then after being labelled with BrdU or adenovirus carrying LacZ gene, they were implanted into the lateral cerebroventricles of embryonic rats. The rats were sacrificed after they were born and the brain sections were examined by immunocytochemistry at different time points. NSCs from embryonic humans were successfully cultured; they formed typical neurospheres in suspension, and the majorities of the cells expressed nestin, which was the marker for neural progenitor cells, and the cells could differentiate into neurons, astrocytes and oligodendrocytes. NSCs could steadily expressed exogenous gene in vivo and in vitro; after transplantation into embryonic rat brains, the fetal human NSCs incorporated individually into all major compartments of the brains, generating widespread CNS chimerism and having a wide distribution in the host fore-, mid-, and hindbrain. NSCs could express foreign gene steadily and were the ideal cell sources for cell and gene therapy. These cells could incorporate into developing brains and generate widespread chimerism. These chimeras provide a unique model for studying human neural cell migration and differentiation in a functional nervous system.


Adult Spinal Deformity: A Comprehensive Review of Current Advances and Future Directions.
Owing to rapidly changing global demographics, adult spinal deformity (ASD) now accounts for a significant proportion of the Global Burden of Disease. Sagittal imbalance caused by age-related degenerative changes leads to back pain, neurological deficits, and deformity, which negatively affect the health-related quality of life (HRQoL) of patients. Along with the recognized regional, global, and sagittal spinopelvic parameters, poor paraspinal muscle quality has recently been acknowledged as a key determinant of the clinical outcomes of ASD. Although the Scoliosis Research Society-Schwab ASD classification system incorporates the radiological factors related to HRQoL, it cannot accurately predict the mechanical complications. With the rapid advances in surgical techniques, many surgical options for ASD have been developed, ranging from minimally invasive surgery to osteotomies. Therefore, structured patient-specific management is important in surgical decision-making, selecting the proper surgical technique, and to prevent serious complications in patients with ASD. Moreover, utilizing the latest technologies such as robotic-assisted surgery and machine learning, should help in minimizing the surgical risks and complications in the future.


Immunoassay Detects Salivary Anti-SSA/Ro-52 Autoantibodies in Seronegative Patients with Primary Sjögren's Syndrome.
The diagnostic work-up for Sjögren's syndrome is challenging and complex, including testing for serum autoantibodies to SSA/Ro and a labial salivary gland biopsy. Furthermore, the diagnosis is often delayed. In this study, we tested the hypothesis that anti-SSA/Ro autoantibodies are detectable in the saliva of patients with primary Sjögren's syndrome (pSS) because the disease affects the salivary glands, and these autoantibodies display greater discriminatory performance in saliva than in serum. SSA/Ro-52 Ags were used to develop what is, to our knowledge, a novel quantitative electrochemical-based immunoassay: the electric field-induced release and measurement (EFIRM) platform. The clinical utility was determined by measuring salivary anti-SSA/Ro-52 autoantibodies in patients with pSS and sicca (n = 34), patients without pSS with sicca (n = 35), and healthy subjects (n = 41). The statistical analysis of discrimination included the area under the receiver operating characteristic curve. Salivary anti-SSA/Ro-52 autoantibodies were measured in 94% (32 of 34) of patients with pSS with 85% (29 of 34) seropositivity. Four of the five seronegative patients with pSS had EFIRM-measurable anti-SSA/Ro-52 autoantibodies in saliva. Additionally, 60% (21 of 35) of the seronegative patients without pSS who had sicca had EFIRM-detectable SSA/Ro-52 autoantibodies in saliva, indicating the onset of autoimmune disease. Two of the 41 healthy control subjects had EFIRM-detectable SSA/Ro-52 autoantibodies in their saliva. Salivary SSA/Ro-52 autoantibodies significantly discriminated patients with pSS or patients with the initial stage of autoimmune disease from healthy subjects with an area under the receiver operating characteristic curve of 0.91. Our findings suggest that the proposed saliva SSA/Ro-52 immunoassay improves early and accurate diagnosis of seronegative patients with pSS and patients with early-onset autoimmune disease.


Down-regulation of oxytocin receptors and secretion of prostaglandin F2alpha after chronic treatment of ewes with estradiol-17beta.
Experiments were conducted to investigate the mechanisms through which chronic treatment with estradiol-17beta (E2) prolongs the estrous cycle in the ewe. To determine whether treatment with estradiol maintained the corpus luteum (CL), mature ewes were assigned randomly to two groups receiving s.c. injections of either 500 microg E2 in corn oil or vehicle alone for 20 days beginning on Day 4 of the cycle (n = 5 per group). Laparotomy of E2-treated ewes on Day 24 revealed the presence of CL previously marked with India ink on Day 7 of the cycle. Treatment increased the mean interestrous interval for 4 of 5 animals compared with that of controls (p < 0.001). Therefore, to determine whether the increase in the interestrous interval was due to an effect on the function and/or concentration of uterine oxytocin receptors (OTr), ewes (n = 5 per group) were injected with 500 microg E2 or vehicle as described above from Days 4 to 14 of the cycle. On Day 15, a jugular blood sample was collected for progesterone (P4) analysis, after which ewes were given an i.v. injection of oxytocin (OT; 20 IU USP) or saline, and blood samples were collected at frequent intervals for 60 min to determine plasma concentrations of 13,14-dihydro-15-ketoprostaglandin F2alpha (PGFM). Laparotomies were performed after blood collection to remove uterine endometrium for OTr analysis. Mean serum concentrations of P4 were greater in treated than in control ewes on Day 15 (p < 0.05). Treatment of ewes with E2 prolonged luteal function and resulted in reduced uterine concentration of OTr compared with that of controls (p = 0.002). Treatment with E2 reduced OT-induced plasma concentrations of PGFM compared with controls (p < 0.01). Collectively, these data suggest that chronic treatment of ewes with estradiol during the cycle can prolong the interestrous interval by reducing uterine concentration of OTr and hence OT-induced secretion of prostaglandin.


Assessing readiness to work in primary health care: the content validity of a self-check tool for physiotherapists and other health professionals.
The New Zealand Primary Health Care Strategy has emphasised the importance of well-coordinated service teams in managing complex chronic conditions. There is international evidence that physiotherapists can contribute effectively to the prevention and management of these conditions. However, there are few examples of physiotherapists in New Zealand (NZ) engaging in primary health care (PHC). It has been recognised that professional development is necessary to optimise physiotherapists' participation in PHC. The aim of this study was to both design a self-check tool that physiotherapists could use as an initial step in preparing to work in PHC and to assess the content validity of the tool. A literature review informed the development of the self-check tool. The tool was reviewed by members of the Physiotherapy New Zealand PHC working party to establish content validity. The tool was found to have excellent content validity with an overall score of 0.937, exceeding the acceptable index of 0.8. Item validity was excellent or acceptable for all except two items, which were subsequently modified in the final tool. This investigation provides initial support for the tool's potential use by physiotherapists as a means of determining their readiness to work in PHC. It could have application beyond individual professional development to the wider context of team and organisational development. Additionally, with minor modifications the tool could have broader application to other professional groups.


The effects of melatonin on bovine uniparental embryos development in vitro and the hormone secretion of COCs.
Melatonin is a unique multifunctional molecule that mediates reproductive functions in animals. In this study, we investigated the effects of melatonin on bovine parthenogenetic and androgenetic embryonic development, oocyte maturation, the reactive oxygen species (ROS) levels in parthenogenetic and androgenetic embryos and cumulus-oocyte complexes (COCs) hormone secretion with melatonin supplementation at four concentrations (0, 10, 20, and 30 pmol/mL), respectively. The results showed that melatonin significantly promoted the rates of bovine parthenogenetic and androgenetic embryonic cleavage and morula and blastocysts development (P < 0.05). The rate of cleavage was higher in the androgenetic embryo than that in the parthenogenetic embryo. Compared with the parthenogenetic embryos, the androgenetic embryos had a poor developmental competence from morula to blastocyst stage. Moreover, the levels of ROS were significantly lower in the parthenogenetic and androgenetic embryoes with melatonin-treated group than that of the control group (P < 0.05). Melatonin supplemented significantly increased the maturation rate of oocyte in vitro (P < 0.05). More importantly, melatonin significantly promoted the secretion of progesterone and estradiol by COCs (P < 0.05). To reveal the regulatory mechanism of melatonin on steroids synthesis, we found that steroidogenic genes (CYP11A1, CYP19A1 and StAR) were upregulated, suggesting that melatonin regulated estradiol and progesterone secretion through mediating the expression of steroidogenic genes (CYP11A1, CYP19A1 and StAR). In addition, MT1 and MT2 were identified in bovine early parthenogenetic and androgenetic embryos using western blot. It could be concluded that melatonin had beneficial effects on bovine oocyte in vitro maturation, COC hormone secretion, early development of subsequent parthenogenetic and androgenetic embryos. It is inferred that melatonin could be used to enhance the efficiency of in vitro developed embryos.


Alterations in nociception and morphine antinociception in mice fed a high-fat diet.
Currently, more than 78.6 million adults in the United States are obese. A majority of the patient population receiving treatment for pain symptoms is derived from this subpopulation. Environmental factors, including the increased availability of food high in fat and sugar, contribute to the continued rise in the rates of obesity. The focus of this study was to investigate whether long-term exposure to a high-fat, energy-dense diet enhances baseline thermal and inflammatory nociception while reducing sensitivity to morphine-induced antinociception. Antinociceptive and hypothermic responses to morphine were determined in male and female C57BL/6N mice fed either a "western-style" diet high in fat and sucrose (HED) or a standard low-fat chow diet for 15 weeks. Antinociception was assessed using both the hot plate and tail flick tests of acute thermal pain and the formalin test of inflammatory pain. Acute administration of morphine dose-dependently increased antinociception in the hot plate and tail flick assays for mice of both sexes fed chow and HED. However, female mice displayed lower antinociceptive response to morphine compared to males in the tail-flick test. Hypothermic responses to acute morphine were also assessed in mice fed chow or HED. Male and female mice fed chow, and female mice fed HED displayed similar hypothermic responses to morphine. However, males fed HED did not exhibit morphine-induced hypothermia. Tolerance to the antinociceptive and hypothermic effects of morphine was assessed after ten days of repeated daily administration (10mg/kg morphine). Male mice fed chow or HED developed tolerance to morphine in the hot plate test. However, females fed HED did not. In the tail flick assay, only mice fed HED developed tolerance to morphine. All groups showed tolerance to morphine-induced hypothermia. In the formalin test, we found that both male and female mice fed HED had reduced sensitivity to the antinociceptive effects of morphine (6mg/kg). Collectively, these data suggest that sensitivity and tolerance to the antinociceptive effects of morphine may be dependent on diet and sex in the hot plate and tail flick thermal pain models, and that the acute antinociceptive effects of morphine in the formalin inflammatory pain model may also be dependent on these two factors. In addition, diet and sex can influence morphine-induced hypothermia. Exposure to an HED may lead to changes in neuronal signaling pathways that alter nociceptive responses to noxious stimuli in a sex-specific manner. Thus, dietary modifications might be a useful way to impact pain therapy.


Colpotomy drainage of pelvic abscess.
Sixty-five patients who had a pelvic abscess drained by colpotomy or rectal incision were studied. The minority of the patients (28) developed the abscess after a hospital-acquired infection (Group I) while the other 37 patients developed the abscess after a community-acquired infection (Group II). Except for those patients who developed an abscess after hysterectomy, about one-third of the patients in both groups required a subsequent major operative procedure because of residual infection or symptoms. Of the 40 patients in whom there was a possibility of conceiving following the drainage procedure, 4 (10%) conceived at a later date.


UV irradiation impairs in vivo encapsidation of bacteriophage T4 DNA.
T4 DNA structural requirements for encapsidation in vivo were investigated, using thin-section electron microscopy to quantitate the kinetics and yields of head intermediates after synchronous DNA packaging into accumulated processed proheads. UV irradiation (254 nm) of T4-infected bacteria just before initiation of encapsidation resulted in a reduction in the rate of DNA packaged measured by electron microscopy and in the yield of viable phage progeny. In UV-irradiated infections with excision-deficient mutants (denV-), the extent of packaging decline was proportional to the UV dose and phage yields were lower than expected based on the packaging levels observed by microscopy. Rescue analysis of progeny from such infections revealed elevated levels of nonviable virions. Pyrimidine dimers were encapsidated in denV- infections, but in excision-competent infections (denV+) dimers were not packaged. A UV-independent, 15 to 20% packaging arrest was also observed when denV endonuclease was inactive during encapsidation, indicating a denV requirement to achieve normal T4 packaging levels. Pyrimidine dimers apparently represent or induce transient blockage of DNA encapsidation or both, causing a decline in the rate. This is in contrast to other DNA structural blocks to packaging induced by mutations in T4 genes 30 and 49, which appear to arrest the process.


[Advances in fish antifreeze protein research].
Antifreeze proteins (AFPs) can highly effectively protect cells and embryos from damages in freezing process by lowering the freezing points of their cytoplasmic matrix and body fluids in a noncolligative manner. Based on their origins and properties, AFPs have been classified into four types, i.e. type I, II, III and IV. Each of them possesses rather distinct characteristics both in structure and composition, although all of them have ability of lowering freezing points of fluids. AFPs' genes have been characterized as members of a multigene family and the levels of their mRNA synthesis vary significantly with seasons. Adsorption-inhibition operating at the ice surface is nowadays a hypothesis widely used to interpret the molecular mechanisms of noncolligative lowering of the freezing point, but the details of the mechanism on how the different types of AFP are adsorbed onto ice remain uncertain. Progresses in research on structures, amino acid compositions, genes, antifreeze mechanisms of the 4 distinct types of AFPs, and the application of the AFPs in cryopreservation of cells and embryos are reviewed here.


Long-term beneficial effect of tacrolimus conversion on renal transplant recipients.
Acute rejection, chronic allograft nephropathy, and cyclosporine (CsA) toxicity remain serious problems for renal transplant recipients and may lead to graft loss. We retrospectively analyzed 34 patients whose biopsies revealed acute and/or chronic allograft rejection, or CsA nephrotoxicity, and who converted from CsA to tacrolimus. From July 1996 through September 2003, CsA was converted to tacrolimus in 34 renal transplant recipients (26 male, 8 female) with renal biopsy at our hospital. Blood pressure and serum creatinine levels were checked monthly and serum cholesterol, triglyceride, and glutamic-pyruvic transaminase (GPT) levels were checked every three months. A consistently stable and better function after conversion was obtained in a significant portion (24, 71%) of patients. A statistically significant decline in serum creatinine and an improvement in the glomerular filtration rate were found at 3 m, 6 m, 12 m, 36 m, and 72 m after tacrolimus conversion. In 85.7% (12/14) of patients with acute rejection and in 35.7% (5/14) of patients with chronic allograft nephropathy (concomitant with acute rejection in 5), improved or stabilized graft function was noted. In addition, the systolic blood pressure and diastolic BP dropped significantly (P<0.05), while there was no significant change in cholesterol, triglyceride, and GPT levels. The beneficial effect of tacrolimus conversion on patients with acute rejection, chronic allograft nephropathy, or CsA nephrotoxicity was demonstrated in long-term follow up. The improvement in both renal function and blood pressure may be of paramount importance in reducing long-term cardiovascular morbidity and mortality.


Human plasma extrinsic pathway inhibitor activity: II. Plasma levels in disseminated intravascular coagulation and hepatocellular disease.
Plasma or serum extrinsic pathway inhibitor (EPI) activity was measured in 24 patients with disseminated intravascular coagulation (DIC) and in 23 patients with severe hepatocellular disease. EPI was measured as activity in a test sample that inhibited factor VIIa/tissue factor (TF)-catalyzed activation of 3H-factor IX (activation peptide release) in the presence of factor X. Of the 24 patients with DIC, 13 had sepsis and five had metastatic carcinoma, disorders in which tissue factor is believed to initiate DIC. EPI activity ranged from 68% to 300% (mean 134% +/- 50%). Serial measurements in nine patients failed to show depletion of EPI activity coincident with worsening DIC. DIC induced by tissue factor or other activating materials may progress despite normal EPI levels. In the patients with liver disease, of whom 15 had decompensated chronic hepatocellular disease (two fatal cases) and eight had acute fulminant liver failure (seven fatal cases), plasma or serum EPI activity varied from less than 20% to 194%. Values were distributed in a bimodal fashion. EPI activity could not be correlated with either the etiology of the liver disease or the degree of prolongation of the prothrombin time. Patients with chronic hepatocellular disease who survived had normal or elevated EPI activity. Patients with fatal hepatic dysfunction had low, normal, or high values for EPI activity. This must mean that secretion of EPI from cells other than hepatocytes can maintain normal plasma EPI levels.


Effects of Elevated CO₂and Temperature on Pathogenicity Determinants and Virulence of Potato virus X/Potyvirus-Associated Synergism.
Infections of plants by multiple viruses are common in nature and may result in synergisms in pathologies. Several environmental factors influence plant-virus interactions and act on virulence and host defense responses. Mixed viral infections may be more frequent under environmental conditions associated with global warming. Here, we address how changes in the two main parameters behind global warming, carbon dioxide concentrations ([CO₂]) and temperature, may affect virulence of Potato virus X (PVX)/potyvirus-associated synergism compared with single infections in Nicotiana benthamiana. Elevated [CO₂] resulted in attenuated virulence of single infection by PVX, which correlated with a lower accumulation of virus. In contrast, virulence of PVX/potyvirus-associated synergism was maintained at elevated [CO₂]. On the other hand, elevated temperature decreased markedly both virulence and virus titers in the synergistic infection. We also show that the HR-like response elicited by transient coexpression of PVX P25 together with the potyviral helper component-proteinase protein was significantly enhanced by elevated temperature, whereas it was reduced by elevated [CO₂]. Both proteins are main pathogenicity determinants in PVX-associated synergisms. These findings indicate that, under environmental conditions associated with global warming, virulence of PVX/potyvirus-associated synergisms is expected to vary relative to single infections and, thus, may have pathological consequences in the future.


[A case of unresectable gastric cancer in a patient who maintained a good quality of life with multidisciplinary treatment].
Herein, we report the case of 57-year-old woman who visited our hospital for abdominal distention, difficulty in walking, and edema of the legs in January 2012. She underwent gastroendoscopy, resulting in a diagnosis of advanced gastric cancer of the pyloric antrum. A diagnosis of unresectable advanced gastric cancer was made because computed tomography (CT) showed the presence of ascites (suspected to indicate peritoneal dissemination), para-aortic lymph node metastases, and brain metastases. Stenting was performed for pyloric stenosis and cell-free and concentrated ascites reinfusion therapy (CART) was administered to facilitate oral intake. We administered two courses of chemotherapy with weekly paclitaxel. However, CT showed the presence of ascites and growth of the main tumor in the first month after the initiation of chemotherapy. We performed CART, and treatment was changed to S-1/paclitaxe(l 5 courses). Ascites decreased markedly and activities of daily living improved. However, 11 months after the initiation of therapy, the patient died.


Rehabilitative ultrasound imaging of the abdominal muscles.
Rehabilitative ultrasound imaging (RUSI) of the abdominal muscles is increasingly being used in the management of conditions involving musculoskeletal dysfunctions associated with the abdominal muscles, including certain types of low back and pelvic pain. This commentary provides an overview of current concepts and evidence related to RUSI of the abdominal musculature, including issues addressing the potential role of ultrasound imaging in the assessment and training of these muscles. Both quantitative and qualitative aspects associated with clinical and research applications are considered, as are the possible limitations related to the interpretation of measurements made with RUSI. Research to date has utilized a range of methodological approaches, including different transducer placements and imaging techniques. The pros and cons of the various methods are discussed, and guidelines for future investigations are presented. Potential implications and opportunities for clinical use of RUSI to enhance evidence-based practice are outlined, as are suggestions for future research to further clarify the possible role of RUSI in the evaluation and treatment of abdominal muscular morphology and function.


Cutaneous leukemic infiltration following varicella - a case of Wolf's isotopic response.
Wolf's isotopic response designates the appearance of two subsequent unrelated dermatoses in the same anatomic location. We report the case of a 51-year-old man with a medical history of chronic lymphocytic leukemia without known extra-hematopoietic involvement. The patient developed a disseminated papulo-vesiculous eruption, diagnosed as varicella. Few days after recovering, an erythematous and violaceous papular dermatosis with histopathological examination compatible with leukemic infiltration appeared on the scars of previous herpetic lesions. Complete remission was obtained under systemic corticotherapy, without cutaneous recurrence or blastic transformation. Wolf's isotopic response is attributed to a localized immunologic imbalance following a certain stimulus. In this patient, herpetic infection acted as a local spur for inaugural cutaneous leukemic infiltration, with no impact on the prognosis for the underlying disease.


Blazar Constraints on Neutrino-Dark Matter Scattering.
Neutrino emission in coincidence with gamma rays has been observed from the blazar TXS 0506+056 by the IceCube telescope. Neutrinos from the blazar had to pass through a dense spike of dark matter (DM) surrounding the central black hole. The observation of such a neutrino implies new upper bounds on the neutrino-DM scattering cross section as a function of DM mass. The constraint is stronger than existing ones for a range of DM masses, if the cross section rises linearly with energy. For constant cross sections, competitive bounds are also possible, depending on details of the DM spike.


Integration of the Forced-Choice Questionnaire and the Likert Scale: A Simulation Study.
The Thurstonian item response theory (IRT) model allows estimating the latent trait scores of respondents directly through their responses in forced-choice questionnaires. It solves a part of problems brought by the traditional scoring methods of this kind of questionnaires. However, the forced-choice designs may still have their own limitations: The model may encounter underidentification and non-convergence and the test may show low test reliability in simple test designs (e.g., test designs with only a small number of traits measured or short length). To overcome these weaknesses, the present study applied the Thurstonian IRT model and the Graded Response Model to a different test format that comprises both forced-choice blocks and Likert-type items. And the Likert items should have low social desirability. A Monte Carlo simulation study is used to investigate how the mixed response format performs under various conditions. Four factors are considered: the number of traits, test length, the percentage of Likert items, and the proportion of pairs composed of items keyed in opposite directions. Results reveal that the mixed response format can be superior to the forced-choice format, especially in simple designs where the latter performs poorly. Besides the number of Likert items needed is small. One point to note is that researchers need to choose Likert items cautiously as Likert items may bring other response biases to the test. Discussion and suggestions are given to construct personality tests that can resist faking as much as possible and have acceptable reliability.


Imaging fibrosis in inflammatory diseases: targeting the exposed extracellular matrix.
In a variety of diseases, from benign to life-threatening ones, inflammation plays a major role. Monitoring the intensity and extent of a multifaceted inflammatory process has become a cornerstone in diagnostics and therapy monitoring. However, the current tools lack the ability to provide insight into one of its most crucial aspects, namely, the alteration of the extracellular matrix (ECM). Using a radiolabeled platelet glycoprotein VI-based ECM-targeting fusion protein (GPVI-Fc), we investigated how binding of GPVI-Fc on fibrous tissue could uncover the progression of several inflammatory disease models at different stages (rheumatoid arthritis, cutaneous delayed-type hypersensitivity, lung inflammation and experimental autoimmune encephalomyelitis). Methods: The fusion protein GPVI-Fc was covalently linked to 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and subsequently labeled with 64Cu. We analyzed noninvasively in vivo64Cu-GPVI-Fc accumulation in murine cutaneous delayed-type hypersensitivity, anti-glucose-6-phosphate isomerase serum-induced rheumatoid arthritis, lipopolysaccharide-induced lung inflammation and an experimental autoimmune encephalomyelitis model. Static and dynamic Positron Emission Tomography (PET) of the radiotracer distribution was performed in vivo, with ex vivo autoradiography confirmation, yielding quantitative accumulation and a distribution map of 64Cu-GPVI-Fc. Ex vivo tissue histological staining was performed on harvested samples to highlight the fusion protein binding to collagen I, II and III, fibronectin and fibrinogen as well as the morphology of excised tissue. Results:64Cu-GPVI-Fc showed a several-fold increased uptake in inflamed tissue compared to control tissue, particularly in the RA model, with a peak 24 h after radiotracer injection of up to half the injected dose. Blocking and isotype control experiments indicated a target-driven accumulation of the radiotracer in the case of chronic inflammation. Histological analysis confirmed a prolonged accumulation at the inflammation site, with a pronounced colocalization with the different components of the ECM (collagen III and fibronectin notably). Binding of the fusion protein appeared to be specific to the ECM but unspecific to particular components. Conclusion: Imaging of 64Cu-GPVI-Fc accumulation in the ECM matrix appears to be a promising candidate for monitoring chronic inflammation. By binding to exposed fibrous tissue (collagen, fibronectin, etc.) after extravasation, a new insight is provided into the fibrotic events resulting from a prolonged inflammatory state.


Computer-assisted Diagnosis of Breast Cancer by Cell Network Matrix Extraction and Multilayer Perceptron Analysis.
Diagnosis of breast cancer is based on identification of various morphologic features by histopathologic examination of the specimen. Ancillary immunohistochemical and molecular analyses provide additional information that is prognostic and guides therapy. Because of subjectivity in this approach, we sought to develop a computer model which could assist in differentiating normal or benign tissue from malignant breast carcinoma. Cases of benign sclerosing adenosis (20) and high-grade invasive ductal carcinomas (20) of breast were retrieved and re-examined. Five images of the diagnostic areas from each case were captured (400x). Each image was divided into quadrants and saved as 1-megapixel each. These 800 images were then binarized and segmented using the watershed method. The cell graphs were extracted to identify the matrix of adjacent cells and the network properties were determined for each image. The local network features were fed into a PAM model and global network features were fed into a multilayer perceptrons (MLP) to distinguish between benign and malignant samples. These characteristics were evaluated by training the models on 40% (320) of the randomly assigned images followed by real-time testing of the remaining 60% (480) images. In addition, normal breast tissue from five cases was retrieved and forty (40) images were captured to further test the model. Both local and global network feature models had high area under the curve (AUC) (0.63 and 0.99 respectively), with their adjusted Rand indices (ARI) being 0.61 and 0.87, respectively. Pooling the pseudoprobabilities of the two neural networks greatly increased the accuracy of the model with predictions of the combined model at image level being 100% accurate with AUC of 1. This study shows that using a combination of cell-graph extraction and a deep learning algorithm computers can accurately distinguish between benign and malignant breast lesions.


GPER Mediates Functional Endothelial Aging in Renal Arteries.
Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function.


Laboratory and field performance of consumer bait products for German cockroach (Dictyoptera: Blattellidae) control.
Bait formulations containing boric acid, chlorpyrifos, or hydramethylnon were evaluated in field and laboratory experiments against the German cockroach, Blattella germanica (L.). In continuous exposure tests, chlorpyrifos formulations produced 100% mortality in less than 24 h, boric acid formulations had LT50's of approximately 5.5 d, and hydramethylnon had an LT50 of 0.86 d. LT50's estimated in Ebeling choice boxes were 1.6 to 10.8 times greater than those from continuous exposure tests for chlorpyrifos formulations and 2.5 times greater for the hydramethylnon formulation. The same LT50's were produced by choice box and continuous exposure tests for boric acid formulations. Relative repellency, measured as the mean percentage of live cockroaches in the light side of the choice box, was greatest for chlorpyrifos formulations, followed by boric acid formulations, then hydramethylnon. A performance index (PI) that combined choice box repellency and mortality data indicated that hydramethylnon (Combat) had the greatest potential for field effectiveness. Only hydramethylnon significantly reduced German cockroach populations in the field. Apartments treated with the IT WORKS formulation of boric acid bait had significantly greater cockroach trap catches. The PI is an accurate predictor of the field performance of toxic baits for German cockroach control.


The paradoxical role of social class background in the educational and labour market outcomes of the children of immigrants in the UK.
Despite predominantly lower social class origins, the second generation of established immigrant groups in the UK are now attaining high levels of education. However, they continue to experience poorer labour market outcomes than the majority population. These worse outcomes are often attributed in part to their disadvantaged origins, which do not, by contrast, appear to constrain their educational success. This paper engages with this paradox. We discuss potential mechanisms for second-generation educational success and how far we might expect these to be replicated in labour market outcomes. We substantiate our discussion with new empirical analysis. Drawing on a unique longitudinal study of England and Wales spanning 40 years and encompassing one per cent of the population, we present evidence on the educational and labour market outcomes of the second generation of four groups of immigrants and the white British majority, controlling for multiple measures of social origins. We demonstrate that second-generation men and women's educational advantage is only partially reflected in the labour market. We reflect on the implications of our findings for future research.


The bed nucleus of the stria terminalis in drug-associated behavior and affect: A circuit-based perspective.
The bed nucleus of the stria terminalis was first described nearly a century ago and has since emerged as a region central to motivated behavior and affective states. The last several decades have firmly established a role for the BNST in drug-associated behavior and implicated this region in addiction-related processes. Whereas past approaches used to characterize the BNST have focused on a more general role of this region and its subnuclei in behavior, more recent work has begun to reveal its elaborate circuitry and cellular components. Such recent developments are largely owed to methodological advances, which have made possible efforts previously deemed intractable, such as tracing of long-range cell-type specific projections and identifying functional efferent and afferent connections. In this review, we integrate earlier foundational work with more recent and advanced studies to construct a broad overview of the molecular neurocircuitry of the BNST in drug-associated behavior and affect. This article is part of the Special Issue entitled "Alcoholism".


Human T cells constitutively express IL-15 that promotes ex vivo T cell homeostatic proliferation through autocrine/juxtacrine loops.
Homeostatic proliferation of T cells in vivo is responsible for the maintainance of the T cell pool, and IL-15 is a pivotal cytokine implicated in this process. Known cell sources providing physiologically active IL-15 are monocytes/macrophages, dendritic cells, and stromal cells. T lymphocyte expression of functionally active IL-15 and its possible role in T cell biology have not been investigated. In this study, we demonstrate that human T cells constitutively express IL-15 that acts through autocrine/juxtacrine loops to promote ex vivo homeostatic T cell proliferation.


Percutaneous biliary decompression: internal and external drainage in 50 patients.
A review of percutaneous biliary decompression performed at the Mayo Clinic was initiated to study indications, technique, technical problems, and short- and long-term complications. Data were collected on the initial 50 patients in whom biliary decompression had been performed. More than 80% of patients presented with lesions or a record of previous surgery near the ductal bifurcation that resulted in increased difficulty in obtaining internal drainage. Follow-up data were available in 40 patients and allowed careful evaluation of immediate and long-term complications. Significant complications were limited to intraabdominal bleeding, which occurred in four patients and resulted in death in one. Four patients experienced sepsis immediately after the procedure, and episodes of cholangitis occurred in seven patients who had long-term drainage catheters in place.


Contribution of wood combustion to indoor air pollution as measured by mutagenicity in Salmonella and polycyclic aromatic hydrocarbon concentration.
Samples of airborne particles have been collected in the same room when the room was heated by electricity and when heating was done by woodburning. These samples were compared with respect to mutagenic activity and concentration of polycyclic aromatic hydrocarbons (PAH). The effects of the various heating conditions were examined in the presence and absence of tobacco smoking. Whereas wood heating in an "airtight" stove was found to cause only minor changes in the concentration of PAH and no measurable increase of mutagenic activity of the indoor air, both these parameters increased considerably when wood was burned in an open fireplace, yielding PAH concentrations comparable to those of ambient urban air. Relatively high concentrations of moderately polar polycyclic aromatic hydrocarbon derivatives were also found in the indoor air when wood was burned in an open fireplace. Woodburning in the closed stove did, however, result in increased concentrations of mutagenic compounds and PAH on particles sampled in the vicinity of the house. The effects of wood burning in an open fireplace on the mutagenic activity of indoor air could still be considered moderate when compared to those resulting from tobacco smoking in the room. The extracts of particles collected when moderate smoking occurred were several times more mutagenic than samples from urban air collected close to streets with heavy traffic when measured in the Salmonella assay with strain TA98 with metabolic activation.


Risk of Malignancy in Thyroid Nodules Using the American College of Radiology Thyroid Imaging Reporting and Data System in the NIFTP Era.
Recently, the American College of Radiology (ACR) proposed a Thyroid Imaging Reporting and Data System (TI-RADS) for thyroid nodules based on ultrasonographic features. It is important to validate this classification in different centres. The present study evaluated the risk of malignancy in solid nodules>1 cm using ACR TI-RADS. The risk of malignancy was defined including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and after its exclusion from malignant tumours. For the present study, the original images were revised, and each nodule was assigned to one of the TI-RADS levels proposed for solid nodules: TR3, TR4, or TR5. This risk of malignancy was significantly different for the three levels: 1.7%, 11.2%, and 60.6% for TR3, TR4, and TR5, respectively, when NIFTP was included, and 0.6%, 7.9%, and 60.2% for TR3, TR4, and TR5, respectively, when NIFTP was excluded from malignant tumours. The nodules corresponding to NIFTP were classified according to ACR as TR3 in 28.5% of cases, TR4 in 67.8%, and TR5 in only 3.5%. The nodules corresponding to cancer were classified according to ACR as TR3 in only 2.3% of cases, TR4 in 27%, and TR5 in 70.5%. In conclusion, this study shows the validity of the ACR TI-RADS for solid thyroid nodules, even after the exclusion of NIFTP from malignant tumours.


Endurance training induces muscle-specific changes in mitochondrial function in skinned muscle fibers.
The present study was conducted to investigate the potential role of changes in the apparent K(m) for ADP and in the functional coupling of the creatine (Cr) kinase (CK) system (CK efficiency) in explaining the tighter integration of ATP supply and demand after exercise training. Mitochondrial function was assessed in saponin-skinned fibers from the soleus and the deep red portion of the medial gastrocnemius isolated from trained (T; treadmill running, 5 days/wk, 4 wk) and control (C) female Sprague-Dawley rats. In the soleus, V(max) in the presence of 1 mM ADP was increased by 21% after training (5.9 +/- 0.2 vs. 4.7 +/- 0.4 nmol O(2). min(-1). mg dry wt(-1), P < 0.05). This was accompanied by no change in the K(m) for ADP measured in the absence of Cr (146 +/- 9 vs. 149 +/- 13 microM in T and C, respectively) and in its presence (50 +/- 4 vs. 48 +/- 6 microM in T and C, respectively) and in CK efficiency [K(m) (+Cr)/K(m) (-Cr)]. In contrast, in the red gastrocnemius, training decreased, by 35%, the apparent K(m) for ADP in the absence (83 +/- 5 vs. 129 +/- 9 microM, P < 0.01) of Cr, without affecting V(max) (6.2 +/- 0.4 vs. 6.7 +/- 0.3 nmol O(2). min(-1). mg dry wt(-1) in T and C, respectively) and CK efficiency. These results thus suggest that training induces muscle-specific adaptations of mitochondrial function and that a change in the intrinsic sensitivity of mitochondria to ADP could at least partly explain the tighter integration of ATP and demand commonly observed after training.


Correlation of N-terminal-pro-brain natriuretic peptide with postoperative outcomes of older patients undergoing transcatheter aortic valve replacement.
Patients undergoing transcatheter aortic valve replacement surgery (TAVR) are typically older adults with multiple chronic diseases and therefore have a high surgical risk. The N-terminal of brain natriuretic peptide (BNP) and pro-BNP, referred to as NT-pro-BNP, is an easily measurable biomarker of heart failure. Studies on correlation between higher NT-pro-BNP levels and adverse prognoses after TAVR have yielded inconsistent results. Here, we investigated whether preoperative NT-pro-BNP levels are correlated with outcomes among older adults undergoing TAVR. This retrospective study included older adults with severe aortic stenosis (AS) who received TAVR from a medical center between January 2013 and June 2017. The patients' demographics, preoperative laboratory data, postoperative complications, and 1-year mortality were recorded. They were divided into two groups based on their preoperative NT-pro-BNP levels. The post-TAVR outcomes in the two groups were analyzed using a multivariate logistic regression analysis of the binary results. Of the 132 patients included (mean age: 81.5 ± 8.1 years; 47% men), 96 (72.7%) had preoperative NT-pro-BNP levels ≤ 4853 ng/L, and 36 (27.3%) had preoperative NT-pro-BNP levels > 4853 ng/L. The postoperative outcomes were significantly better in the NT-pro-BNP≤4853 group than in the NT-pro-BNP>4853 group: postoperative extracorporeal membrane oxygenation fittings (4.2% vs 16.7%, p = 0.025), number of days in hospital (17.5 ± 21.0 vs 27 ± 17.0, p = 0.009), in-hospital mortality (4.2% vs 16.7%, p = 0.025), and 1-year mortality (11.5% vs 38.9%, p = 0.001); the significant differences persisted after controlling for other variables. For older patients undergoing TAVR with NT-pro-BNP levels > 4853 ng/L, their postoperative outcomes and 1-year mortality were correlated. Thus, NT-pro-BNP is useful for the risk assessment of patients undergoing TAVR and should be regarded as a biomarker in future risk assessments.


MUTUAL POTENTIATION OF AMPHETAMINE AND AMYLOBARBITONE MEASURED BY ACTIVITY IN RATS.
Dose/response relations have been analysed for the actions of amphetamine-barbiturate mixtures on exploratory activity and ataxia in rats. Amphetamine sulphate and amylobarbitone sodium were studied separately and together (in a constant ratio of 1:20) in doses which ranged from those producing no effect to those which incapacitated the animals. Dexamphetamine and amylobarbitone were similarly studied in a ratio of 1:6.5; this corresponds to the ratio of a commercial preparation, Drinamyl. The results showed that mixtures could stimulate exploratory activity and their maximal effects were much greater than the effects produced by any dose of the separate drugs. The maximal effect with the first dose-ratio included conspicuous ataxia, but the maximal effect with the second ratio did not. Further experiments in which the dose of one drug was held constant and that of the other was varied showed that maximal effects on activity could be obtained with mixtures of dexamphetamine and amylobarbitone. Equivalent effects could be obtained both with relatively small and with relatively large amounts of the two drugs, in varying ratios; some constituent doses of the individual drugs were found to be optimal; whether the mixture effect was accompanied by ataxia depended largely on the constituent amount of barbiturate. For practical purposes mixtures producing maximal effects on activity with the smallest amounts of both drugs and not accompanied by ataxia might be most desirable, and these can be approximately read off from an isobol plotted from the results. It was concluded that the marked stimulant effects of the amphetamine-barbiturate mixtures on activity of rats could be regarded as due to true potentiation.