[The epidemiological transition of chronic and degenerative diseases in Mexico].
Mexico during the last decades has achieve an important development, therefore the frequency of most of the transmissible diseases dropped and an increase in frequency has been noticed in regard the chronic non-transmissible diseases of multifactorial etiology. Diagnosis and management in those cases require a great effort in fields such as internal medicine and surgery, as well as a substantial portion of resources assigned to biomedical research. Chronic and degenerative diseases have a sound impact on health economy, need medical decisions with population impact and justify an epidemiological approach in the national health service. Life expectancy reached 69 years by 1990, there is a proportional increase in adults and older person in our population, increasing urbanization and a epidemiological transition which results in a different picture of mortality in Mexico, now heart diseases, malignant neoplasia and diabetes mellitus are 3 of the 5 leading causes of death. Morbidity is not as easy to define because lack of consistent data, however, there is no doubt in regard the important role played by chronic and degenerative diseases in it. General education and health promotion as well as a changing behaviour at issues such as nutrition, physical exercise and avoiding unhealthy habits should be encouraged because its obvious value as preventive measures. After long years of heavy work we are facing a changing mexico in terms of demography and epidemiology, which requires the concern of all health professionals in order to achieve a different epidemiological picture through health education, promotion and behaviour in the whole population, it is necessary not only to live longer, we must have a superior quality of life.


Cost effectiveness of enzyme immunoassay and immunoblot testing for the diagnosis of syphilis.
The burden of disease and associated health-care costs of syphilis are significant despite widespread screening and treatment. Our objective was to conduct an economic evaluation using a simulation model when comparing enzyme immunoassay (EIA) initial testing and Inno-Lia (IL) confirmatory testing (EIA + IL) with rapid plasma reagin (RPR) initial testing and Treponema pallidum particle agglutination assay (TPPA) and fluorescent treponemal antibody absorption assay (FTA-ABS) confirmatory testing (RPR + TPPA/FTA). Estimates of prevalence, test costs and utilization of services for 2006 were derived from Alberta databases. Estimates of test characteristics were derived from the available literature. The incremental cost-effectiveness ratio was Canadian $461 per additional correct diagnosis (less costly and more effective). EIA + IL is cost-effective when compared with RPR + TPPA/FTA for screening and diagnosis of syphilis.


Relative cerebral perfusion by rapid sequence tomography.
Rapid Sequence Tomography is shown to be a valid instrument to study the local distribution of more or less vascularized brain structures. Functional states as hypo- or hyperperfusion become clearly visible. RSCT permits a clear differentiation between intra- and extravascular contrast enhancement and offers an excellent insight into the angioarchitecture and quality of cerebral lesions.


Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer During Follow-Up and Prognosis.
The prognostic relevance of circulating tumor cells (CTCs) at the time of primary diagnosis has been well established. However, little information is available regarding their prognostic relevance to follow-up care. The multicenter, open-label, phase III SUCCESS A trial compared two adjuvant chemotherapy regimens followed by 2 vs 5 years of zoledronate for early-stage, high-risk breast cancer patients. The presence of CTCs was assessed before and 2 years after chemotherapy using the FDA-approved CellSearch System. Overall survival (OS) and disease-free survival (DFS) were analyzed using univariate log-rank tests and multivariable Cox regressions. OS and DFS were measured starting from an assessment of CTCs 2 years after the completion of chemotherapy. All statistical tests were two-sided. The sample included 1087 patients who participated in the translational research program of the SUCCESS A trial and for whom sufficient translational data were available regarding CTC status at baseline and at the 2-year follow-up visit. Two years after chemotherapy, 198 (18.2%) patients were CTC-positive. The median follow-up after this timepoint was 37 months. Cox regressions that included CTC status at baseline revealed that CTC status 2 years after chemotherapy had statistically significant and independent prognostic relevance for OS (hazard ratio [HR] = 3.91, 95% confidence interval [CI] = 2.04 to 7.52, P < .001) and DFS (HR = 2.31, 95% CI = 1.50 to 3.55, P < .001). The presence of CTCs 2 years after chemotherapy was associated with decreased OS and DFS. Based on these results, active individualized surveillance strategies for breast cancer survivors based on biomarkers should be reconsidered.


Physical and chemical processes in baled waste fuel, with emphasis on gaseous emissions.
Over a period of seven months, the temperature and the emissions from six cylindrical and two rectangular stored bales containing waste for later use as fuel were measured. The bales were kept at two different ranges of temperatures: 30-35 degrees C and 20-25 degrees C respectively. It was found that only the rectangular bales showed significant production of CO2. The increase of emission for one of the rectangular bales kept at 30-35 degrees C, was 0.246% vol. CO2 per day for a 2-week period, after which there was a decrease of CO2 concentrations at a rate of 0.0224% vol. during a 32-week period. The other rectangular bale kept at 20-25 degrees C, exhibited a similar trend. However, the increase of CO2 concentrations was less at a rate of 0.0259% vol. per day during a 8-week period, after which the CO2 emission decreased at a rate of 0.0224% vol. per day during a 25-week period. All the bales exhibited aerobic decomposition in the sampling point. However on measuring the leachate concentrations, it was evident that the bales were actually in the equivalent acid-generating phase of a young landfill. The temperature inside the bales did not increase higher than the ambient air temperature.


[Comparative assessment of the parameters of visual fixation in amblyopia of different origin].
Examination of visual fixation parameters is an important diagnostic method in patients with amblyopia of different origin. To study the visual fixation parameters for various types of amblyopia. The study included 108 patients (213 eyes) aged 5-11 years with moderate and high amblyopia: 27 patients (54 eyes) with strabismic amblyopia, 45 patients (87 eyes) with refractive and anisometropic amblyopia, and 36 patients (72 eyes) with relative amblyopia caused by deprivation nystagmus. All examinations were performed on the NIDEK MP-1 Microperimeter. Fixation density within 2° and 4°, the amplitude of the horizontal and vertical fixation point displacement, the averaged value of the fixation point displacement and the average velocity of displacement were evaluated. There was a positive correlation between visual acuity and fixation density for all types of amblyopia, the higher the visual acuity, the higher the fixation density in the area of 2° and 4°. The maximum values of the displacement point amplitude were registered in patients with nystagmus. In patients with strabismic amblyopia, hyperopia and myopia values of displacement point amplitude were lower. The highest average displacement and rate of displacement of the fixation point were found in the group of patients with nystagmus. The differences were much less significant in other groups. A comparative objective study of visual fixation parameters for various types of amblyopia was performed using the NIDEK MP-1 Microperimeter. There was a positive correlation between fixation density decrease, the increase of amplitude and average displacement of the fixation point, and visual acuity decrease for all types of amblyopia. There was no significant correlation between average rate of displacement and visual acuity. The maximum disturbance of fixation parameters, including the average rate of the fixation point displacement, was registered in nystagmus.


Source, optical and detector requirements for X-ray diffraction and scattering.
The standard curves used to describe the properties of synchrotron radiation sources usually consist of a plot of the flux or brightness from the source as a function of wavelength. These curves are useful for the case where a high flux or brightness is required. Many experiments do not fall into this category. An alternative description of the source requirements is to provide the maximum flux into the phase space volume defined by the specimen. A diagrammatic way of illustrating how this can be achieved is derived. This illustrates how the source, optics and detectors can be matched to the requirements of a particular experiment. This approach is illustrated using, as examples, a beamline on the SRS and two beamlines planned for DIAMOND, the proposed new UK third-generation source.


Detection of Lipid Mediators of Inflammation in the Human Tear Film.
Lipid mediators of inflammation are a group of signaling molecules produced by various cells under physiological conditions and modulate the inflammatory process during various pathologic conditions. Although eicosanoids and F2-isoprostanes are recognized lipid mediators of inflammation, there is no consensus yet on the extraction and mass spectrometry (MS) method for their analysis in individual human tear samples. Thus, the aim of this study was to develop an optimal method for extraction of lipid mediators of inflammation in the tear film and evaluate MS techniques for their analysis. Basal tears were collected from each eye of 19 subjects using glass microcapillaries. Lipid extraction was performed using either varying concentrations of acidified methanol, a modified Folch method, or solid-phase extraction. Initially, an untargeted analysis of the extracts was performed using SCIEX TripleTOF 5600 mass spectrometer to identify any lipid mediators of inflammation (eicosanoids) and later a targeted analysis was performed using the SCIEX 6500 Qtrap to identify and quantify prostaglandins and isoprostanes. Mass spectra and chromatograms were analyzed using Peakview, XCMS, and Multiquant software. Prostaglandins and isoprostanes were observed and quantified using the Qtrap mass spectrometer under multiple reaction monitoring (MRM) mode after solid-phase extraction. Extraction with acidified methanol along with the Folch method produced cleaner spectra during MS with the Triple time of flight (TOF) mass spectrometer. Lipid mediators of inflammation were not observed in any of the tear samples using the Triple TOF mass spectrometer. Solid-phase extraction may be the method of choice for extraction of prostaglandins and isoprostanes in low volumes of tears. The SCIEX Qtrap 6500 in MRM mode may be suitable to identify and quantify similar lipid mediators of inflammation.


Specific plasma oxylipins increase the odds of cardiovascular and cerebrovascular events in patients with peripheral artery disease.
Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina, and acute coronary syndrome was n = 16, 10, 16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events. Plasma fatty acids and oxylipins were analyzed with gas chromatography and HPLC-MS/MS, respectively. None of 24 fatty acids quantified were associated with events. In contrast, 39 plasma oxylipins were quantified, and 8 were significantly associated with events. These 8 oxylipins are known regulators of vascular tone. For example, every 1 unit increase in Thromboxane B2/Prostaglandin F1α and every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid, thromboxane B2, or 11,12-dihydroxyeicosatrienoic acid (DiHETrE) increased the odds of having had ≥2 events versus no event (p < 0.05). The greatest predictor was plasma 8,9-DiHETrE, which increased the odds of acute coronary syndrome by 92-fold. In conclusion, specific oxylipins were highly associated with clinical events and may represent specific biomarkers and (or) therapeutic targets of cardiovascular disease.


Aberrant membranes and double-membrane structures accumulate in the axons of Atg5-null Purkinje cells before neuronal death.
Autophagy (macroautophagy) is an evolutionally conserved process by which cytoplasmic proteins and organelles are surrounded by unique double membranes and are subsequently degraded upon fusion with lysosomes. Many autophagy-related genes (Atg) have been identified in yeast; a ubiquitin-like Atg12-Atg5 system is also essential for the elongation of the isolation membrane in mammalian cells. Nevertheless, the regulation of autophagy in neurons remains largely unknown. In this study, we crossed conditional knockout mice Atg5(flox/flox) with pcp2-Cre transgenic mice, which express Cre recombinase through a Purkinje cell-specific promoter, pcp2. In Atg5(flox/flox); pcp2-Cre mice, the Atg5 gene was excised as early as postnatal day 6; Purkinje cells started to degenerate after approximately 8 weeks, and the animals showed an ataxic gait from around 10 months. Initially, however, the Purkinje cells showed axonal swelling around its terminals from as early as 4 weeks after birth. An electron microscopic analysis revealed the accumulation of autophagosome-like double-membrane structures in the swollen regions, together with numerous membranous organelles, such as tubular or sheet-like smooth endoplasmic reticulum and vesicles. These results suggest that Atg5 plays important roles in the maintenance of axon morphology and membrane structures, and its loss of function leads to the swelling of axons, followed by progressive neurodegeneration in mammalian neurons.


De novo endo-functionalized organic cages as cooperative multi-hydrogen-bond-donating catalysts.
Two endo-functionalized organic cages as oxyanion hole mimics were achieved via dynamic covalent chemistry, which exhibit good size selectivity, catalytic activity and broad substrate scopes for Friedel-Crafts reactions. The modular character of the synthesis provides an easy way to modify the size, shape and inner function of the molecular cavity.


Coronary Artery Disease in Persons With Human Immunodeficiency Virus Without Detectable Viral Replication.
We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 6, IL-1β, and high-sensitivity C-reactive protein (hsCRP), were associated with CAD. From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as >0% stenosis, and obstructive CAD as ≥50% stenosis. Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels >2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1β was not associated with CAD. In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD.


Acute respiratory compromise on inpatient wards in the United States: Incidence, outcomes, and factors associated with in-hospital mortality.
To estimate the United States' incidence and in-hospital mortality of acute respiratory events on inpatient wards and to identify factors associated with mortality. This is an analysis of prospectively collected data from the Get With the Guidelines(®) - Resuscitation registry. We included adult patients with index acute respiratory events on inpatient wards from January 2005 to December 2013. A negative binomial regression model was used to estimate the 2012 United States incidence and a multivariable logistic regression model was used to examine time trends and characteristics associated with in-hospital mortality. There were 13,086 index events from 320 hospitals included in the analysis. Using 2012 data, the estimated number of events in the United States was 44,551 (95%CI: 25,170-95,371). The in-hospital mortality for the entire cohort was 39.4% (95%CI: 38.5, 40.2) and rose to 82.6% (95%CI: 79.9, 85.2) for events leading to cardiac arrest. There was a decrease in in-hospital mortality over time (48.3% in 2005 to 34.5% in 2013, p<0.001). Characteristics associated with mortality included agonal breathing, hypotension and septicemia. Acute respiratory events on inpatient wards in the US is common with an associated in-hospital mortality of approximately 40% that has been decreasing over the past decade. Multiple factors were associated with in-hospital mortality.


Effect of piriformis versus trochanteric starting point on fixation stability of short intramedullary reconstruction nails.
Recently, a new, shorter IM nail using two 6 mm reconstruction screws for proximal fixation was introduced in two versions for femoral insertion: piriformis fossa (FAN) and greater trochanter (TAN). These nails were compared experimentally for their fixation stability, proximal load transmission, and failure strength in an unstable intertrochanteric fracture model in cadaveric femurs. Vertical and axial loads were first applied to the intact femurs. Fractures were created, subsequent fixation applied, and the femurs underwent a series of both vertical and axial loading tests. There was no significant difference in strain readings between the nails for either axial loading or cyclical loading. There was no statistically significant difference between the loads to failure for the trochanteric nails and the standard antegrade nails. The average ultimate loadfor the FAN and TAN nails were 3010 N and 2830 N respectively. These two nails performed very similarly throughout our testing.


Laboratory testing of the Pressio intracranial pressure monitor.
The Sophysa Pressio (Sophysa Ltd., Orsay, France) is a new intracranial pressure monitoring system. This study aimed to evaluate its accuracy and compare it with the popular Codman intracranial pressure transducer (Codman/Johnson & Johnson, Raynham, MA) in vitro. A computerized rig was used to test the Pressio and Codman transducers simultaneously. Properties that were tested included drift over 7 days, the effect of temperature on drift, frequency response, the accuracy of measurement of static and pulsatile pressures, and connectivity of the system. Long-term (7 d) relative zero drift was less than 0.05 mmHg. The temperature drift was low (0.3 mmHg/207C). Absolute static accuracy was better than 0.5 mmHg over the range of 0 to 100 mmHg. Pulse waveform accuracy, relative to the Codman transducer, was better than 0.2 mmHg over the range of 1 to 20 mmHg. The frequency bandwidth of the Pressio transducer was 22 Hz. The Pressio monitor can transmit data directly to an external computer without the use of a pressure bridge amplifier. The new Pressio transducer proved to be accurate for measuring static and dynamic pressure during in vitro evaluation.


Trifluoroethylamines as amide isosteres in inhibitors of cathepsin K.
The P2-P3 amide of dipeptide cathepsin K inhibitors can be replaced by the metabolically stable trifluoroethylamine group. The non-basic nature of the nitrogen allows the important hydrogen bond to Gly66 to be made. The resulting compounds are 10- to 20-fold more potent than the corresponding amide derivatives. Compound 8 is a 5 pM inhibitor of human cathepsin K with >10,000-fold selectivity over other cathepsins.


Lumbar root stimulation for restoring leg function: results in paraplegia.
We have implanted an intradural array of 12 tripolar electrodes on the anterior roots L2-S2, left and right, at cauda equina level, in a 33-year-old woman with a complete T9 cord lesion of 3 years' duration. They are driven by an implanted multiplexed stimulator system using radio frequency (RF) power and control signals. All channels generate movements, in patterns that might be predicted from the known anatomy of the cauda equina. In particular, stimulation of L2 and L3 gives hip adduction; L3, L4, and L5 gives quadriceps femoris movements; L5, S1, and S2 gives hamstrings movement; and S1 and S2 give plantar flexion. Stimulation of L5 gives mixed movements at the ankle. Surprisingly, stimulation of the L2 roots has not given strong hip flexion. Responses have been stable. Some thresholds have varied, probably as a result of tissue encapsulation. The moment generated within each degree of freedom of the legs has been measured for each root, using a specially designed multimoment measurement apparatus. For several roots, a movement of lower threshold may be accompanied by a second movement of higher electrical threshold, suggesting that different muscles may have fiber populations that differ in their diameter or their location in the root. The use of stimulus forms that enable selective anodal block may, in the future, enable separation of two distinct movements from a single motor root.


Nanoassemblies constructed from bimodal mesoporous silica nanoparticles and surface-coated multilayer pH-responsive polymer for controlled delivery of ibuprofen.
The pH-sensitive poly(D-A) grafted amine-functionalized bimodal mesoporous silica (D-A/BMMs) was prepared by a facile method used as a drug delivery vehicle. They exhibited superior properties such as good dispersion in aqueous medium, high drug loading efficiency, improved stability and high drug release rates. Meanwhile, its structural features and performances in a controlled delivery of ibuprofen (IBU) were systematically investigated by using XRD, N2 adsorption and desorption, SEM, TEM, FT-IR, elemental analysis and TG techniques. The results demonstrated that the obtained nanocomposite presented a flexible control over drug release by controlling the grafting amount of D-A onto the mesopores surface of aminated BMMs. The cumulative percent release of IBU from D-A/BMMs was found to be much higher at pH 7.4 than at pH 2.0. The release rate was very slow in an acidic medium but became faster in a neutral medium, owing to hydrogen bonding in an acidic medium and electrostatic repulsion between negatively charged carboxyl groups in an alkaline medium.


Chemotherapy drug handling in first opinion small animal veterinary practices in the United Kingdom: results of a questionnaire survey.
To investigate how first opinion small animal veterinary surgeons in the UK handled chemotherapeutic agents, a questionnaire was distributed at the 2014 British Small Animal Veterinary Association congress and by internet. Chemotherapy was regularly offered by 70.4 per cent of the respondents. Gold standards defined according to available guidelines for safe handling of antineoplastic drugs were poorly followed by general practitioners with only 2 per cent of respondents complying with all of them. Dedicated facilities for preparation and administration of cytotoxic drugs were variably available among participants. The level of training of staff indirectly involved in handling chemotherapy was appropriate in less than 50 per cent of practices. No association was found between demographic characteristics of the sampled population and the decision to perform chemotherapy. The results of this study raise concerns about the safety of the veterinary staff in first opinion practices involved in handling chemotherapy.


A zeolite ion exchange membrane for redox flow batteries.
The zeolite-T membrane was discovered to have high proton permselectivity against vanadium ions and exhibit low electrical resistance in acidic electrolyte solutions because of its enormous proton concentration and small thickness. The zeolite membrane was demonstrated to be an efficient ion exchange membrane in vanadium redox flow batteries.


Cloning and expression in Escherichia coli of the gene encoding the structural subunit of Bacteroides nodosus fimbriae.
Bacteroides nodosus is the primary causative agent of ovine foot rot. Virulent isolates of this bacterium contain fimbriae which appear to play a major role in both infectivity and protective immunity. This paper presents the cloning and expression in Escherichia coli of the gene encoding the structural subunit of the fimbriae of B. nodosus. Total DNA was isolated from B. nodosus VCS 1001 (serogroup A), digested with HindIII, and inserted into the positive-selection vector pTR262. Recombinant E. coli clones were screened directly with anti-fimbrial antiserum by using a colony immunoassay. Several positive colonies were identified, each of which contained the same 5.5-kilobase HindIII insert. The prototype has been designated pBA101. Some clones also contained additional flanking sequences from the B. nodosus genome. Western transfer analyses verified that the positive clones were producing the B. nodosus fimbrial structural subunit, molecular weight ca. 17,500. The level of expression of the antigen in E. coli was comparable to that in B. nodosus itself and was unaffected by the insertion site or orientation of the cloned fragment, indicating that synthesis was being directed from an internal promoter. Restriction mapping and deletion analyses localized the fimbrial subunit gene to the vicinity of a PvuII site near the central region of the original HindIII insert. The expressed antigen was located in the membrane-cell wall fraction and may be exposed on the surface of the recombinant E. coli cells.


Outcomes of Middle Eastern Patients Undergoing Percutaneous Coronary Intervention: The Primary Analysis of the First Jordanian PCI Registry.
This is a prospective multicenter registry designed to evaluate the incidence of adverse cardiovascular events in Middle Eastern patients undergoing percutaneous coronary interventions (PCI). The registry was also designed to determine the predictors of poor outcomes in such patients. We enrolled 2426 consecutive patients who underwent PCI at 12 tertiary care centers in Jordan between January 2013 and February 2014. A case report form was used to record data prospectively at hospital admission, discharge, and 12 months of follow-up. Mean age was 56 ± 11 years, females comprised 21% of the study patients, 62% had hypertension, 53% were diabetics, and 57% were cigarette smokers. Most patients (77%) underwent PCI for acute coronary syndrome. In-hospital and 1-year mortality rates were 0.78% and 1.94%, respectively. Definite or probable stent thrombosis occurred in 9 patients (0.37%) during hospitalization and in 47 (1.94%) at 1 year. Rates of target vessel repeat PCI and coronary artery bypass graft surgery at 1 year were 3.4% and 0.6%, respectively. The multivariate analysis revealed that cardiogenic shock, congestive heart failure, ST-segment deviation, diabetes, and major bleeding were significantly associated with higher risk of 1-year mortality. In this first large Jordanian registry of Middle Eastern patients undergoing PCI, patients treated were relatively young age population with low in-hospital and 1-year adverse cardiovascular events. Certain clinical features were associated with worse outcomes and may warrant aggressive therapeutic strategies.


Pediatric and adult dilated cardiomyopathy are distinguished by distinct biomarker profiles.
Emerging evidence suggests that pediatric and adult dilated cardiomyopathy (DCM) represent distinct diseases. Few diagnostic tools exist for pediatric cardiologists to assess clinical status and prognosis. We hypothesized that pediatric DCM would have a unique biomarker profile compared to adult DCM and controls. We utilized a DNA aptamer array (SOMAScan) to compare biomarker profiles between pediatric and adult DCM. We simultaneously measured 1310 plasma proteins and peptides from 39 healthy children (mean age 3 years, interquartile range (IQR) 1-14), 39 ambulatory subjects with pediatric DCM (mean age 2.7 years, IQR 1-13), and 40 ambulatory adults with DCM (mean age 53 years, IQR 46-63). Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics. We identified 20 plasma peptides and proteins that were increased in pediatric DCM compared to age- and sex-matched controls. Unbiased multidimensionality reduction analysis suggested previously unrecognized heterogeneity among pediatric DCM subjects. Biomarker profile analysis identified four subgroups of pediatric DCM with distinguishing clinical characteristics. These findings support the emerging concept that pediatric and adult DCM are distinct disease entities, signify the need to develop pediatric-specific biomarkers for disease prognostication, and challenge the paradigm that pediatric DCM should be viewed as a single disease. Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics and outcomes. Our findings suggest that pediatric DCM may be a heterogeneous disease with various sub-phenotypes, including differing biomarker profiles and clinical findings. These data provide prerequisite information for future prospective studies that validate the identified pediatric DCM biomarkers, address their diagnostic accuracy and prognostic significance, and explore the full extent of heterogeneity amongst pediatric DCM patients.


Flow cytometric measurement of benzo[a]pyrene-diol-epoxide-DNA adducts in normal human peripheral lymphocytes and cultured human lung cancer cells.
DNA adducts are mainly detected by 32P-postlabeling and enzyme-linked immunosorbent assays. We have established a method for detection of benzo[a]pyrene-diol-epoxide (BPDE)-DNA adducts by flow cytometry, and have clarified the effects of the DNA adducts on cell-cycle progression and the relationship between cell-cycle phases and DNA adduct formation, using human peripheral lymphocytes and three human lung cancer cell lines. We measured the BPDE-DNA adduct levels in both lymphocytes and cancer cells by isolating nuclei, using a nuclear isolation buffer containing Triton X-100 and staining with a BPDE-DNA-specific monoclonal antibody and biotin-streptavidin fluorescein conjugates. BPDE did not affect cell-cycle progression in human peripheral lymphocytes. However, in human lung cancer cells exposed to > 1 microg/ml BPDE, accumulation of cells in the S phase was seen. Cells with DNA content greater than G2M (aneuploid cells) or cells with less than G1 DNA content (apoptotic cells) increased gradually with exposure to increasing BPDE concentrations, suggesting that BPDE may affect cell-cycle progression through binding to DNA. Thus, the measurement of DNA adducts by flow cytometry may provide new insights into carcinogenesis.


Specific nuclear protein binding to a negative regulatory element on the human CYP1A1 gene.
Employing reporter gene/CYP1A1 chimeric plasmids, we previously identified a 275-base pair (bp) cis-element (-833 to -558; NRE275) that down-regulated the CYP1A1 promoter. In the present study, this negative regulatory activity was further localized to two subfragments of 105 bp (-833 to -728; NRE105) and 170 bp (-728 to -558; NRE170), each of which exhibited activity with a heterologous promoter/enhancer. Co-transfection studies demonstrated a dependence on cellular trans-acting factors present at limiting concentrations. Electrophoretic mobility shift assays revealed the presence of protein(s) that specifically bound to NRE275, NRE105, and NRE170. Based upon competition studies, the protein(s) that bound to NRE105 appeared to recognize sites similar to those recognized by the NRE170-binding proteins. DNase I footprint analysis of NRE105 demonstrated nuclear protein binding to a 21-bp palindrome (-794 to -774). Protection was also observed along conserved guanine/cytosine-rich sequences that flank the palindrome, but in a strand-specific manner. Guanine residues involved in protein binding were identified by methylation interference experiments. Based on transient expression assays with each of the three NRE105 components, all three appear to be necessary for complete negative regulatory activity. However, it is clear the palindrome is the most important sequence with the guanine/cytosine-rich elements playing an ancillary role.


Effects of feeding extruded flaxseed on layer performance, total tract nutrient digestibility, and fatty acid concentrations of egg yolk, plasma and liver.
A study was conducted to determine the effects of graded levels of extruded flaxseed (EF) on laying hen performance, apparent total tract nutrient retention (ATTNR) and fatty acid concentrations of egg yolk, blood plasma and liver. Seventy-two White Leghorn layers (58 weeks old; three per cage) were randomly assigned to one of four dietary treatments: 0 (control), 3, 6 and 9% of EF-supplemented diets for 8 weeks. Results showed that feed intake, egg production, feed conversion ratio and egg weight were not affected by treatments. The ATTNR of dry matter (p = .001) and gross energy (p = .014) was lower for layers fed 9% EF than those fed the control diet, while ATTNR of organic matter (p = .001) and nitrogen-corrected apparent metabolizable energy (p = .003) were lower for birds fed 6% and 9% EF compared with those fed the control diet. Relative to the control diet, feeding EF increased (p < .001) egg yolk, plasma and liver n-3 polyunsaturated fatty acid (PUFA) concentrations. Birds fed 6% EF produced eggs > 300 mg of n-3 PUFA after two weeks of feeding, while the highest of n-3 PUFA concentrations were achieved for birds fed 9% EF. It was concluded that feeding EF up to 9% of the diet had no adverse effects on layer performance and increased n-3 PUFA concentrations in blood plasma, liver and egg yolk. However, moderate to high levels of EF (i.e., 6% and 9% of the diet) reduced nutrient ATTNR and nitrogen-corrected apparent metabolizable energy. Omega-3-enriched eggs can be achieved by feeding layers EF at 6% of the diet.


High growth rate fails to enhance adaptive immune responses of neonatal calves and is associated with reduced lymphocyte viability.
The objective of the study was to evaluate the effects of 3 targeted growth rates on adaptive (i.e., antigen-specific) immune responses of preruminant, milk replacer-fed calves. Calves (9.1 +/- 2.4 d of age) were assigned randomly to one of 3 dietary treatments to achieve 3 targeted daily rates of gain [no growth (maintenance) = 0.0 kg/d, low growth = 0.55 kg/d, or high growth = 1.2 kg/d] over an 8-wk period. The NRC Nutrient Requirements of Dairy Cattle calf model computer program was used to estimate the milk replacer intakes needed to achieve target growth rates. All calves were fed a 30% crude protein, 20% fat, all-milk protein milk replacer reconstituted to 14% dry matter. Diets were formulated to ensure that protein would not be limiting. All calves were vaccinated 3 wk after initiation of dietary treatments with Mycobacterium bovis, strain bacillus Calmette-Guerin and ovalbumin. Growth rates for no-growth (0.11 kg/d), low-growth (0.58 kg/d), and high-growth (1.16 kg/d) calves differed throughout the experimental period. Blood glucose concentrations in high-growth calves increased with time and were higher than in low- and no-growth calves. Mononuclear and polymorphonuclear leukocyte percentages in peripheral blood were unaffected by growth rate but did change with advancing age. Percentages of CD4(+) T cells increased with age in no-growth and low-growth calves, a characteristic of maturation, but failed to increase in high-growth calves. Growth rate did not affect the percentages of CD45RO(+) (memory) CD4(+) and CD8(+) T cells, antigen (i.e., ovalbumin)-specific serum IgG concentrations, or antigen (i.e., purified protein derivative)-induced IFN-gamma and nitric oxide secretion by mononuclear cell cultures. Antigen-elicited cutaneous delayed-type hypersensitivity responses of no-growth calves exceeded responses of low-growth, but not high-growth, calves. In resting- and antigen-stimulated cell cultures, viabilities of CD4(+), CD8(+), and gammadeltaTCR(+) T cells from high-growth calves were lower than those of the same T cell subsets from no-growth and low-growth calves. Alternatively, resting cultures of mononuclear leukocytes from high-growth calves produced more nitric oxide than those from no-growth and low-growth calves. In conclusion, adaptive immune responses were affected minimally by growth rate. The results suggest that protein-energy malnutrition in the absence of weight loss is not detrimental to antigen-specific responses of neonatal vaccinated calves and that a high growth rate does not enhance these responses. The negative effect of a high growth rate on the viability of circulating T cell populations may influence infectious disease resistance of the calf.


E-cadherin in gastric carcinomas: Relations with histological parameters and its prognostic value.
Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors being diagnosed at advanced stage. The need for identification of prognostic and early detection biomarkers is thus compulsory. E-cadherin is one of the emerging biomarkers that is currently evaluated in the literature in the frame of epithelial-mesenchymal transition (EMT). Our aim was to study the expression of E-cadherin in the various histological subtypes of GC and to evaluate its prognostic value. This historical cohort survey was performed on gastric tumors obtained from 66 (46 men and 20 women) patients with documented gastric adenocarcinoma who underwent total or partial gastrectomy and regional lymphadenectomy from 2003 till 2011. Features such as tumor size, depth of invasion, grade and histological subtype, lymphovascular space invasion and regional lymph nodes involvement were also evaluated. Immunohistochemistry (IHC) was used for assessing the expression of E-cadherin with a semi-quantitative model. The correlation of E-cadherin tissue expression with patient overall survival (OS) or disease-free survival (DFS) was not statistically significant, as well as with gender, T stage, N stage, TNM stage, grade, positive lymph nodes ratio or lymphovascular invasion. 73.0% of the evaluated tumors showed abnormal E-cadherin expression in IHC, but the correlation of E-cadherin tissue expression with patient OS or DFS was not statistically significant. Literature stands equivocal about the association between E-cadherin gene mutation, and histopathology and tumor invasiveness. Our results further strengthen the need of larger studies to fully elucidate the predictive role of E-cadherin in the natural history of GC.


Complete cure of experimental visceral leishmaniasis with amphotericin B in stearylamine-bearing cationic liposomes involves down-regulation of IL-10 and favorable T cell responses.
Visceral leishmaniasis caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of liver, spleen, and bone marrow. Most available drugs are toxic. Moreover, relapse after seemingly successful therapy remains a chronic problem. In this study, we evaluated a new therapeutic approach based on combination of a low dose of amphotericin B (AmB) in association with suboptimum dose of stearylamine (SA)-bearing cationic liposomes, itself having leishmanicidal activity. We demonstrate that a single-shot therapy with this formulation caused clearance of parasites from liver and spleen below the level of detection in the selected piece of the organs of BALB/c mice. The combination was superior to free AmB and AmBisome for therapy, as well as for prevention of relapse and reinfection. Besides having better killing activity, AmB in SA liposomes, in contrast to AmBisome, maintained the immunomodulatory effect of free AmB on CD4(+) and CD8(+) T cells for IFN-gamma production, at the same time reducing the toxic effects of the drug, reflected through decline in TNF-alpha. In addition, IL-10 was down-regulated to almost negligible levels, most efficiently through therapy with SA-bearing cationic liposomes-AmB. This IL-10-deficient environment of IFN-gamma-secreting T cells probably up-regulated the enhanced IL-12 and NO production observed in splenic culture supernatants of these mice, correlating with prolonged disease suppression better than free AmB and AmBisome. The ability of the formulation to elicit protective immunity was reconfirmed in a prophylactic model. Our results emphasize the requirement of effective immune stimulation, additionally, by antileishmanials for persistent disease protection, demonstrated by this liposomal AmB formulation.


Knowledge, attitudes, and practices regarding environmental cleaning among environmental service workers in Chinese hospitals.
We conducted a study using a face-to-face survey to assess knowledge, attitudes, and practices of environmental service workers (ESWs) concerning routine cleaning and disinfection at 3 tertiary hospitals in China. There were 115 (89.1%) respondents who agreed that environmental cleaning can contribute to keep patients safe, whereas 63 (48.8%) reported they were very willing to make cleaning practices better. Only 15 (11.6%) ESWs agreed they were in risk of nosocomial infections during daily cleaning. Our findings suggest that the level of ESWs' knowledge regarding cleaning practices was passable, but the awareness of occupational safety and health was weak. There is a need to introduce sustained education and training aimed at ESWs.


Dopamine in schizophrenia: a review and reconceptualization.
The initial hypothesis that schizophrenia is a manifestation of hyperdopaminergia has recently been faulted. However, several new findings suggest that abnormal, although not necessarily excessive, dopamine activity is an important factor in schizophrenia. The authors discuss these findings and their implications. All published studies regarding dopamine and schizophrenia and all studies on the role of dopamine in cognition were reviewed. Attention has focused on post-mortem studies, positron emission tomography, neuroleptic drug actions, plasma levels of the dopamine metabolite homovanillic acid (HVA), and cerebral blood flow. Evidence, particularly from intracellular recording studies in animals and plasma HVA measurements, suggests that neuroleptics act by reducing dopamine activity in mesolimbic dopamine neurons. Post-mortem studies have shown high dopamine and HVA concentrations in various subcortical brain regions and greater than normal dopamine receptor densities in the brains of schizophrenic patients. On the other hand, the negative/deficit symptom complex of schizophrenia may be associated with low dopamine activity in the prefrontal cortex. Recent animal and human studies suggest that prefrontal dopamine neurons inhibit subcortical dopamine activity. The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity (causing deficit symptoms) leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms). The possible co-occurrence of high and low dopamine activity in schizophrenia has implications for the conceptualization of dopamine's role in schizophrenia. It would explain the concurrent presence of negative and positive symptoms. This hypothesis is testable and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.


Enhanced transforming growth factor-beta signaling and fibrogenesis in ovine fetal skeletal muscle of obese dams at late gestation.
Maternal obesity (MO) is increasing at an alarming rate. The objective of this study was to evaluate the effect of MO on fibrogenesis in fetal skeletal muscle during maturation in late gestation. Nonpregnant ewes were assigned to a control diet (Con; fed 100% of NRC nutrient recommendations, n = 6) or obesogenic diet (OB; fed 150% of NRC recommendations, n = 6) from 60 days before conception, and fetal semitendenosus (St) muscle was sampled at 135 days of gestation (term 148 days). Total concentration and area of collagen in cross-sections of muscle increased by 27.0 +/- 6.0 (P < 0.05) and 105.1 +/- 5.9% (P = 0.05) in OB compared with Con fetuses. The expression of precursor TGF-beta was 177.3 +/- 47.6% higher, and concentration of phospho-p38 74.7 +/- 23.6% was higher (P < 0.05) in OB than in CON fetal muscle. Increases of 327.9 +/- 168.0 (P < 0.05) and 188.9 +/- 82.1% (P < 0.05), respectively, were observed for mRNA expression of Smad7 and fibronectin in OB compared with Con muscles. In addition, enzymes involved in collagen synthesis, including lysyl oxidase, lysyl hydroxylase 2b, and prolyl 4-hydroxylase-alpha1, were increased by 350.2 +/- 90.0 (P < 0.05), 236.5 +/- 25.2 (P < 0.05), and 82.0 +/- 36.2% (P = 0.05), respectively, in OB muscle. In conclusion, MO-enhanced fibrogenesis in fetal muscle in late gestation was associated with upregulation of the TGF-beta/p38 signaling pathway. Enhanced fibrogenesis at such an early stage of development is expected to negatively affect the properties of offspring muscle because muscle fibrosis is a hallmark of aging.


Obinutuzumab: what is there to learn from clinical trials?
Obinutuzumab (OBZ) is a recombinant type II anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody (mAb), recently approved in chronic lymphocytic leukemia (CLL; B-cell CLL) and follicular lymphoma (FL). Rituximab (RTX) is frequently considered as its "ancestor" and OBZ clinical development was justified by the importance of FcγRIIIA-mediated mechanisms in RTX clinical activity. However, RTX differs from OBZ in 2 critical independent properties: being a type I anti-CD20 mAb and not being Fc-optimized. Moreover, the use of a different dosing regimen for RTX and OBZ further complicates any interpretation of clinical results. The results obtained for OBZ in CLL provide new arguments for FcγRIIIA-mediated mechanisms when the target antigen is expressed at a low density. Results of OBZ in FL confirm the interest for FcγRIIIA-mediated mechanisms, with some limitations, some of them being possibly due to lack of OBZ-induced complement activation. The situation in diffuse large B-cell lymphoma is deceiving, as the possible gains of activity of OBZ appear to be annihilated by the lack of complement activation. Although RTX was by chance an anti-CD20 mAb with equilibrated pharmacodynamic properties, the reinforcement of some of these properties, which has been done at the expense of complement activation, has conferred an advantage in some B-cell disorders while restricting OBZ indications. The OBZ story nicely demonstrates that the future of naked mAbs is to design agents with optimized and tailored properties, and that this must be done step by step, with a full clinical validation.


In vivo imaging of lymphocyte trafficking.
Over the past decades, intravital microscopy (IVM), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues.


Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease.
It is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system. Patients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis. A total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827-0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816-0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720-0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness. The CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages.


Association of CD2 with fibrinogen in human plasma: depletion of the soluble E-receptor in blood clotting.
The soluble E-receptor (SER) of lymphocytes that is related to CD2 was detected in human plasma and serum using immunoelectrophoresis with sheep antiserum. All plasma samples (n=18) demonstrated reactivity with antiserum, whereas the reactivity of the corresponding sera remained low or undetectable. The depletion of SER in clotting is associated with fibrinogen, as shown by crossed-affinity immunoelectrophoresis with antisera to plasma proteins. The SER-associated fibrinogen was purified and analysed by the SDS-polyacrylamide gel electrophoresis and immunoblotting. A band close to 66 kDa was detected with monoclonal antibodies to CD2. The association of CD2 and other soluble receptors with fibrinogen via domains is suggested. It is recommended that the fresh plasma, not serum, should be used to study circulating receptors because coagulation may appreciably diminish their physiological level in blood samples.


Sphingosine-1-Phosphate Receptors in the Central Nervous and Immune Systems.
Sphingosine-1-phosphate receptor (S1PR) modulators have entered clinical practice as immune-modulators for the treatment of multiple sclerosis (MS). Pharmacologic modulation of S1PR expression on lymphocytes inhibits these cells capacity to respond to the S1P gradient within regional lymph nodes (LNs) (and thymus) that promotes their exit into peripheral circulation. The resultant peripheral blood restricted lymphopenia is considered to underlie the capacity of S1PR modulators to reduce new inflammatory lesion formation in MS in the absence of global immune suppression. These modulators also regulate entry of selective lymphocyte populations and dendritic cells (DCs) into LNs and modulate sphingosine-1-phosphate (S1P) cell signaling networks that govern the generation of specific cell subsets within LNs. S1PR modulators that access the CNS can also have functional effects within this compartment since S1PRs are expressed by cells comprising the blood brain barrier (BBB) and by those within the parenchyma, including neurons, astrocytes, oligodendrocytes and microglia. Absence of S1P1 receptor (S1PR1) on astrocytes reduces disease severity in experimental autoimmune encephalomyelitis (EAE). Even under conditions that inhibit cell responses to the natural ligand, S1PR modulators can continue to induce active signaling responses; such responses may be relevant for promoting neuroprotection and augmenting tissue repair within the CNS.


Comparative anatomy of the larynx in man and the chimpanzee: implications for language in Neanderthal.
Using the larynges of the newborn human and chimpanzee as models, Lieberman and Crelin ('71) and Lieberman, Crelin and Klatt ('72) have reconstructed the larynx of the "classic" Neanderthal La Chapelle aux Saints. The authors used their reconstructed vocal tract to generate linguistic functions which led them to conclude that Neanderthal lacked the ability to produce fully articulate human speech. In this paper, it is shown that their reconstruction of the larynx of Neanderthal is based on a placement of the hyoid bone of La Chapelle which is too high. The reconstructed hyoid bone of La Chalpelle which is too high. The reconstructed hyoid bone has been placed in a position unlike that occupied by hyoid bones of newborn humans, adult humans, stillborn chimpanzees or adult chimpanzees. In any laryngeal reconstruction, the function of swallowing must be taken into account. The ability of the reconstructed Neanderthal to swallow is discussed in light of a comparative analysis of swallowing in man and the chimpanzee. It is concluded that the statement that Neanderthal was less than fully articulate remains unsubstantiated because it rests on a questionable reconstruction of the larynx.


Use of the BCR probe to demonstrate extramedullary recurrence of CGL with a T cell lymphoid phenotype following bone marrow transplantation.
A case of Philadelphia chromosome (Ph1) positive chronic granulocytic leukemia (CGL) is described in which the patient underwent successful treatment with supralethal chemoradiotherapy and allogeneic bone marrow transplantation (BMT) after transformation to blast crisis. Supraclavicular adenopathy developed 5 months after BMT and biopsy revealed a hematopoietic lymphoid neoplasm with an early T cell phenotype. A concurrent bone marrow was microscopically and cytogenetically normal. A metaphase chromosome preparation could not be obtained from nodal tissue. Lymph node DNA, however, was easily extracted and a rearrangement of BCR identical to that in the bone marrow prior to BMT was demonstrated indicating recurrent CGL rather than a de novo lymphoproliferative process. Appropriate therapy for lymphoid blast crisis resulted in a marked regression of measurable disease. The BCR probe may prove to be a useful tool for the diagnosis of CGL when standard cytogenetic techniques cannot be applied.


Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria.
A chronic infection with the parasite Toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. Here we have shown that a chronic T. gondii infection can prevent Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. Treatment with soluble T. gondii antigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of P. berghei-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-P. berghei infection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-γ). By 5 days after P. berghei infection, STAg-treated mice had reduced IFN-γ levels compared to those of mock-treated mice, suggesting that reductions in IFN-γ at the time of ECM onset protected against lethality. Using IL-10- and IL-12βR-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of P. berghei-infected mice with recombinant IL-12 significantly decreased parasitemia and mortality. These data suggest that IL-12, either induced by STAg or injected as a recombinant protein, mediates protection from ECM-associated pathology potentially through early induction of IFN-γ and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM.


[Decomposition and phosphorus dynamics of the litters in standing and litterbag of the Hangzhou Bay coastal wetland ].
Wetlands litter decomposition affects wetlands nutrient cycling. The decomposition progress of standing litter was monitored and the litterbag simulation experiment was carried out in order to analyze dynamics of litter decomposition and phosphorus release in Phragmites australis (PA), Spartina alterniflora (SA) and Scirpus mariqueter (SM) marshes of Hangzhou Bay coastal wetland. Results show that the dry mass of standing litter and P concentration decrease gradually and the litter drops to the sediment surface after 180 d. There are distinctive stages of the plant litter decomposition in litterbag simulation experiments. The loss rate is faster during 0- 15 d than that of later days. The loss rate in root decomposition of three plants are SM > PA > SA, while the trend is opposite for that of aboveground tissues. The time needed for 95% of dry mass decomposition in the plant tissues is between 1. 2- 8. 3 a. The P concentration in litters decreases rapidly in the initial stage and then increases slowly while the net P pools decreases all the time. Pearson's correlation coefficient shows that there is no significant correlation between the litter decomposition rate and C/N ratio. However, the litter C/P ratio affects greatly on plant decomposition rate. Environmental factors in the atmospheric temperature also have an impact on the decomposition rate of leaves. The different decomposition progresses between standing litter and litterbag are caused by environmental factors.


Decreased microRNA-155 expression in ocular Behcet's disease but not in Vogt Koyanagi Harada syndrome.
MicroRNAs (miRNAs) have emerged as a class of gene expression regulators involved in immune regulation. In the present study, we investigated the role of miRNA in two uveitis entities: Behcet's disease (BD) and Vogt Koyanagi Harada syndrome (VKH). The expression of five miRNAs was studied in PBMCs, DCs, and CD4(+) T cells from BD patients with active and inactive uveitis, VKH patients with active uveitis, and healthy controls using real-time PCR. MiR-155 mimics and inhibitor were transfected to DCs to evaluate the effect on DC maturation and cytokine production by these cells and CD4(+) T cells. Luciferase reporter assays and Western blotting were performed to identify the target gene of miR-155. Only miR-155 expression was significantly decreased in PBMCs and DCs from BD patients with active uveitis and no differences were observed in the miRNA expression in cells from patients with VKH as compared with controls. Overexpression of miR-155 in DCs was shown to inhibit the production of IL-6 and IL-1β, and to promote the expression of IL-10 by these cells. MiR-155 transfected DCs significantly inhibited intracellular IL-17 expression in allogeneic CD4(+) T cells; however, it did not influence the expression of cell surface markers CD80, CD40, CD83, CD86, and HLA-DR. Luciferase reporter assays revealed that TAB2 was a target gene of miR-155, which was confirmed by Western blotting. The present results suggest that miR-155 expression is decreased in active BD but not in VKH patients. Downregulated miR-155 may be involved in BD pathogenesis by targeting TAB2.


Tea brewed in traditional metallic teapots as a significant source of lead, nickel and other chemical elements.
An environmental inquiry conducted by the Brussels Inter-communal Laboratory of Chemistry and Bacteriology (BILCB) has revealed that in 2000a traditional metallic teapot caused in Brussels lead intoxication among a family of Morocco origin. Following this case study of lead poisoning and subsequent preliminary results carried out by the BILCB, which confirmed the dangerousness of this kind of item, samples of traditional metallic teapots were collected from North African groceries in Brussels by the Institute of Public Health (IPH) in collaboration with the BILCB and the Federal Agency for the Safety of the Food Chain (FASFC). Aluminium, copper, iron, nickel, lead and zinc were analysed to identify metals with a potential to migrate into tea solutions. Simulants (natural tea, tea acidified with citric acid and citric acid) were brewed in those teapots in order to identify the leaching potential of migration at boiling point temperature for different contact periods. Multi-elementary analysis was carried out by inductively coupled plasma-atomic emission spectrometry (ICP-AES). It was concluded that the concentrations of those leached metals depend on the nature of the migration liquids, the type of teapots and the contact periods. Most teapots showed a high level of toxic metals in leachates for lead and to a less extent for nickel, which can contribute significantly to the risk of serious poisoning. A comparison of the results with the toxicological reference values was done. The teapots were withdrawn from the market by the FASFC.


A new Oxyma derivative for nonracemizable amide-forming reactions in water.
An Oxyma derivative, (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-2-(hydroxyimino)acetate (2), displayed remarkable physicochemical properties as a peptide-coupling additive for peptide-forming reactions in water. Short peptides to oligopeptides could be synthesized by using 2, EDCI, and NaHCO(3) in water without measurable racemization. Significantly, a simple basic and acidic aqueous workup procedure can remove all reagents utilized in the reactions to afford only coupling products in consistently excellent yields.


Early evolution of photosynthesis: clues from nitrogenase and chlorophyll iron proteins.
Chlorophyll (Chl) is often viewed as having preceded bacteriochlorophyll (BChl) as the primary photoreceptor pigment in early photosynthetic systems because synthesis of Chl requires one fewer enzymatic reduction than does synthesis of BChl. We have conducted statistical DNA sequence analyses of the two reductases involved in Chl and BChl synthesis, protochlorophyllide reductase and chlorin reductase. Both are three-subunit enzymes in which each subunit from one reductase shares significant amino acid identity with a subunit of the other, indicating that the two enzymes are derived from a common three-subunit ancestral reductase. The "chlorophyll iron protein" subunits, encoded by the bchL and bchX genes in the purple bacterium Rhodobacter capsulatus, also share amino acid sequence identity with the nitrogenase iron protein, encoded by nifH. When nitrogenase iron proteins are used as outgroups, the chlorophyll iron protein tree is rooted on the chlorine reductase lineage. This rooting suggests that the last common ancestor of all extant photosynthetic eubacteria contained BChl, not Chl, in its reaction center, and implies that Chl-containing reaction centers were a late invention unique to the cyanobacteria/chloroplast lineage.


Dimethyl selenoxide.
The title molecule, C2H6OSe, has a trigonal-pyramidal structure analogous to that of its sulfur analog, dimethyl sulfoxide (DMSO). The Se-O distance in dimethyl selenoxide (DMSeO) is 1.6756 (16) A [versus S-O of 1.531 (5) A in DMSO], consistent with a highly polar bond. In the solid state, the molecules of DMSeO are linked into centrosymmetric dimers formed by two C-H...O hydrogen bonds. These dimers further aggregate into a ladder-like supramolecular network via two additional intermolecular C-H...O interactions. As a result, each O atom of DMSeO acts as an acceptor of three hydrogen bonds.


Transforming Schools Through Minority Males' Participation: Overcoming Cultural Stereotypes and Preventing Violence.
Violent and racist behaviors are transforming schools into highly controversial sites. A key factor in this phenomenon, though not the only one, is the continued dominance of hegemonic masculinity. While researchers have considered a myriad of strategies to prevent violence, including community involvement, few have focused on the value of having male community members engage in the schools, especially males from minority backgrounds. Drawing from two longitudinal case studies conducted in elementary schools, this article explores the effects of such participation. The authors report on two major benefits: a reduction in the prevalence of cultural stereotypes related to males, and the development of spaces where bullying and other violence can be prevented.


Study protocol for a randomised controlled trial evaluating an evidence-based, stepped and coordinated care service model for mental disorders (RECOVER).
Healthcare systems around the world are looking for solutions to the growing problem of mental disorders. RECOVER is the synonym for an evidence-based, stepped and cross-sectoral coordinated care service model for mental disorders. RECOVER implements a cross-sectoral network with managed care, comprehensive psychological, somatic and social diagnostics, crisis resolution and a general structure of four severity levels, each with assigned evidence-based therapy models (eg, assertive community treatment) and therapies (eg, psychotherapy). The study rationale is the investigation of the effectiveness and efficiency of stepped and integrated care in comparison to standard care. The trial is conducted in accordance to the Standard Protocol Items: Recommendations for Interventional Trials Statement. The study aims to compare the RECOVER model with treatment as usual (TAU). The following questions are examined: Does RECOVER reduce healthcare costs compared with TAU? Does RECOVER improve patient-relevant outcomes? Is RECOVER cost-effective compared with TAU? A total sample of 890 patients with mental disorders will be assessed at baseline and individually randomised into RECOVER or TAU. Follow-up assessments are conducted after 6 and 12 months. As primary outcomes, cost reduction, improvement in symptoms, daily functioning and quality of life as well as cost-effectiveness ratios will be measured. In addition, several secondary outcomes will be assessed. Primary and secondary outcomes are evaluated according to the intention-to-treat principle. Mixed linear or logistic regression models are used with the direct maximum likelihood estimation procedure which results in unbiassed estimators under the missing-at-random assumption. Costs due to healthcare utilisation and productivity losses are evaluated using difference-in-difference regressions. Ethical approval from the ethics committee of the Hamburg Medical Association has been obtained (PV5672). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications. ClinicalTrials.gov (NCT03459664), RECOVER PROTOCOL VERSION: 19 March 2020 (V.3.0).


Scientific Advances in Thoracic Oncology 2016.
Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas, including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for NSCLC, SCLC, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review.


Population Numbers and Reproductive Health.
A recent study published in The Lancet predicts a remarkable drop in population numbers following a peak that will be reached by 2064. A unique feature of the upcoming population drop is that it will be almost exclusively caused by decreased reproduction, rather than factors that increase rates of mortality. The reasons for decreased reproduction are also unique, as, unlike previous centuries, limited reproduction today is hardly due to a shortage in resources. In other words, the predicted population drop is almost exclusively due to changes in reproductive behavior and reproductive physiology. Today, global changes in reproductive behavior are mostly explained by social sciences in a framework of demographic transition hypotheses, while changes in reproductive physiology are usually attributed to effects of endocrine-disrupting pollutants. This review outlines a complementary/alternative hypothesis, which connects reproductive trends with population densities. Numerous wildlife and experimental studies of a broad range of animal species have demonstrated that reproductive behavior and reproductive physiology are negatively controlled via endocrine and neural signaling in response to increasing population densities. The causal chain of this control system, although not fully understood, includes suppression of every level of hypothalamic-pituitary-gonadal cascade by hypothalamic-pituitary-adrenal axis, activated in response to increasing stress of social interactions. This paper discusses evidence in support of a hypothesis that current trends in reproductive physiology and behavior may be partly explained by increasing population densities. Better understanding of the causal chain involved in reproduction suppression by population density-related factors may help in developing interventions to treat infertility and other reproductive conditions.


Impact of sequence variation in the UL128 locus on production of human cytomegalovirus in fibroblast and epithelial cells.
The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism.


A case of vitamin D hydroxylation-deficient rickets type 1A caused by 2 novel pathogenic variants in CYP27B1 gene.
Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)2D3 level (11.2 pg/mL), and normal 25(OH)D3 level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both <3rd percentile). The Bayley Scales of Infant and Toddler Development II indicated significantly delayed development (mental development index <50, psychomotor development index <50). The patient was a compound heterozygous for two novel pathogenic variants in the CYP27B1 gene: c.57_69del (p.Glu20Profs*2) and c.171dupG (p.Leu58Alafs*275), inherited from his mother and father, respectively. The patient showed remarkable improvement after treatment with calcitriol and calcium carbonate.


Mimicking/extracting structure and functions of natural products: synthetic approaches that address unexplored needs in chemical biology.
Natural products are often attractive and challenging targets for synthetic chemists, and many have interesting biological activities. However, synthetic chemists need to be more than simply suppliers of compounds to biologists. Therefore, we have been seeking ways to actively apply organic synthetic methods to chemical biology studies of natural products and their activities. In this personal review, I would like to introduce our work on the development of new biologically active compounds inspired by, or extracted from, the structures of natural products, focusing on enhancement of functional activity and specificity and overcoming various drawbacks of the parent natural products.


Evaluation of TDP-43 proteinopathy and hippocampal sclerosis in relation to APOE ε4 haplotype status: a community-based cohort study.
Transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy in older adults frequently coexists with Alzheimer's disease pathology and hippocampal sclerosis. It is unclear whether there is a link between APOE ε4 and TDP-43 proteinopathy, and the role of APOE ε4 in the association of TDP-43 proteinopathy with hippocampal sclerosis remains to be examined. We investigated the relationships of TDP-43 proteinopathy and hippocampal sclerosis with APOE ε4. We used data from two community-based cohort studies of ageing and dementia: the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). A battery of cognitive tests examining multiple cognitive domains is given to ROS-MAP participants each year, and a measure of annual global cognitive function for each participant is derived by averaging Z scores of these tests. The final clinical diagnosis is assigned after death by a neurologist using all available clinical data without access to post-mortem pathology. Amyloid-β, paired helical filament tau, Lewy bodies, TDP-43, and hippocampal sclerosis were microscopically evaluated in the midbrain, medial temporal, and neocortical regions that capture the progression of each neuropathology. TDP-43 proteinopathy topographic stage was recorded as an ordinal variable, and TDP-43 burden was defined by averaging a semi-quantitative six-point scale across six brain regions. The relationships among APOE ε4, TDP-43 proteinopathy, and hippocampal sclerosis were tested with regression models controlled for sex and age at death, and they were further explored with a mediation analysis using the quasi-Bayesian Monte Carlo method. ROS began data collection in 1994, and MAP began data collection in 1997. The data included in this study were analysed from Jan 16, 2017, to July 12, 2017. When analysis began in January, 2017, a total of 1059 ROS-MAP participants who were deceased had APOE genotype and complete pathological measures for amyloid-β, paired helical filament tau, and TDP-43 proteinopathy stage. After excluding 15 participants with other pathological diagnoses, 1044 participants, 1042 of whom also had measures of Lewy body pathology, were included in this study (470 from ROS and 574 from MAP). APOE ε4 count was associated with higher TDP-43 proteinopathy stage (odds ratio [OR] 2·0, 95% CI 1·6-2·6; p=1·9 × 10-9) and TDP-43 burden (0·40, 0·28-0·52; p=1·2 × 10-10). Amyloid-β, paired helical filament tau, or Lewy body pathology did not fully explain this association. APOE ε4 increased the odds of hippocampal sclerosis (OR 2·1, 95% CI 1·4-3·0; p=1·7 × 10-4); this effect was largely mediated by TDP-43 burden (mediated effect p<1·0 × 10-4) but not directly by APOE ε4 (direct effect p=0·40). APOE ε4 was associated with worse global cognition proximate to death even after adjusting for amyloid-β and paired helical filament tau (estimated effect -0·18, 95% CI -0·31 to -0·04; p=0·010), but this association was attenuated by additionally adjusting for TDP-43 burden (-0·09, -0·22 to 0·04; p=0·18). APOE ε4 seems to increase TDP-43 burden, and this effect in turn was associated with higher odds of hippocampal sclerosis, a pathology potentially downstream of TDP-43 proteinopathy. TDP-43 proteinopathy contributes to the detrimental effect of APOE ε4 on late-life cognition through mechanisms independent of Alzheimer's disease pathology, and future research should consider that TDP-43 proteinopathy might be an integral component of APOE-related neurodegeneration. US National Institute on Aging and Alzheimer's Association.


The development of the human type II pneumocyte.
Portions of lung from 25 human foetuses between 12 and 26 wk of gestational age were examined for ultrastructural changes during maturation of the epithelial cells. In 10 cases type I pneumocytes and in five cases type II cells were differentiated. The changes associated with the formation of lamellar inclusion bodies in type II cells are described. It is concluded that this is a synthetic process in which protein and lipid assembly are important. Changes in glycogen and participation of dense bodies are striking.


Predicting preferences for dating partners from past experiences of psychological abuse: identifying the psychological ingredients of situations.
Are women who have been the victim of psychological abuse in the past more likely to prefer an abusive dating partner in the future? Are men who have been the perpetrator of abuse more likely to prefer a dating partner with high attachment anxiety, a characteristic associated with victims of abuse? The present research used a highly repeated, within-subject, multilevel approach to identify the characteristics of potential dating partners that constitute salient psychological ingredients of situations influencing partner preference. Study 1 found that college-age women who reported more instances of receiving psychological abuse, compared to women who did not, showed a stronger preference for male dating partners who possessed characteristics associated with an abusive personality (e.g., possessiveness). Study 2 found that college-age men who reported more instances of inflicting psychological abuse, compared to men who did not, showed a stronger preference for female dating partners characterized by high attachment anxiety.


Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus.
Increasing evidence implicates the microbiota in the regulation of brain and behaviour. Germ-free mice (GF; microbiota deficient from birth) exhibit altered stress hormone signalling and anxiety-like behaviours as well as deficits in social cognition. Although the mechanisms underlying the ability of the gut microbiota to influence stress responsivity and behaviour remain unknown, many lines of evidence point to the amygdala and hippocampus as likely targets. Thus, the aim of this study was to determine if the volume and dendritic morphology of the amygdala and hippocampus differ in GF versus conventionally colonized (CC) mice. Volumetric estimates revealed significant amygdalar and hippocampal expansion in GF compared to CC mice. We also studied the effect of GF status on the level of single neurons in the basolateral amygdala (BLA) and ventral hippocampus. In the BLA, the aspiny interneurons and pyramidal neurons of GF mice exhibited dendritic hypertrophy. The BLA pyramidal neurons of GF mice had more thin, stubby and mushroom spines. In contrast, the ventral hippocampal pyramidal neurons of GF mice were shorter, less branched and had less stubby and mushroom spines. When compared to controls, dentate granule cells of GF mice were less branched but did not differ in spine density. These findings suggest that the microbiota is required for the normal gross morphology and ultrastructure of the amygdala and hippocampus and that this neural remodelling may contribute to the maladaptive stress responsivity and behavioural profile observed in GF mice.


Fire Blight Resistance in Wild Accessions of Malus sieversii.
Fire blight (Erwinia amylovora) is a devastating bacterial disease in apple that results in severe economic losses. Epidemics are becoming more common as susceptible cultivars and rootstocks are being planted, and control is becoming more difficult as antibiotic-resistant strains develop. Resistant germplasm currently being utilized by breeding programs tend to have small fruit size and poor flavor characteristics. Malus sieversii, a progenitor species of domestic apple, is notable for its relatively large, palatable fruit and some accessions have been reported to be resistant to fire blight. In this study, nearly 200 accessions of M. sieversii and appropriate controls were inoculated with E. amylovora in both Washington and West Virginia to identify fire blight resistant accessions. Twelve accessions were identified with resistance comparable to highly resistant and resistant controls. Several accessions exhibited a unique resistance response, not previously reported in domestic apple (M. × domestica), characterized by low incidence of infection but high severity once infection was initiated. Several of these M. sieversii accessions will be used as parents in future crosses in the Washington State University apple breeding program.


Enhancing Side Chain Rotamer Sampling Using Nonequilibrium Candidate Monte Carlo.
Molecular simulations are a valuable tool for studying biomolecular motions and thermodynamics. However, such motions can be slow compared to simulation time scales, yet critical. Specifically, adequate sampling of side chain motions in protein binding pockets is crucial for obtaining accurate estimates of ligand binding free energies from molecular simulations. The time scale of side chain rotamer flips can range from a few ps to several hundred ns or longer, particularly in crowded environments like the interior of proteins. Here, we apply a mixed nonequilibrium candidate Monte Carlo (NCMC)/molecular dynamics (MD) method to enhance sampling of side chain rotamers. The NCMC portion of our method applies a switching protocol wherein the steric and electrostatic interactions between target side chain atoms and the surrounding environment are cycled off and then back on during the course of a move proposal. Between NCMC move proposals, simulation of the system continues via traditional molecular dynamics. Here, we first validate this approach on a simple, solvated valine-alanine dipeptide system and then apply it to a well-studied model ligand binding site in T4 lysozyme L99A. We compute the rate of rotamer transitions for a valine side chain using our approach and compare it to that of traditional molecular dynamics simulations. Here, we show that our NCMC/MD method substantially enhances side chain sampling, especially in systems where the torsional barrier to rotation is high (≥10 kcal/mol). These barriers can be intrinsic torsional barriers or steric barriers imposed by the environment. Overall, this may provide a promising strategy to selectively improve side chain sampling in molecular simulations.


Simple Gd3+-Neu5NAc complexation results in NMR chemical shift asymmetries of structurally equivalent complex-type N-glycan branches.
In the present Communication, we propose a quite simple but previously overlooked approach for conveniently analyzing, assigning, and extracting sialic acid-containing N-glycan structures using high-resolution NMR spectroscopy without pre-installing metal chelators. Paramagnetic metals, such as Gd3+, appear to bind to the carboxyl groups of N-acetylneuraminic acid when introduced at room temperature, leading to the measurement of nonequivalent proton and carbon NMR spectral signals among otherwise "identical" glycan branched structures.


Regulation of Cdc42-mediated morphological effects: a novel function for p53.
The tumour suppressor functions of p53 that are important for its activity depend on its role as a cell cycle arrest mediator and apoptosis inducer. Here we identify a novel function for p53 in regulating cell morphology and movement. We investigated the overall effect of p53 on morphological changes induced by RhoA, Rac1 and Cdc42 GTPases in mouse embryonic fibroblasts (MEFs). Interestingly, p53 exerted a selective effect on Cdc42-mediated cell functions. (i) Both overexpression of wild-type p53 and activation of endogenous p53 counteracted Cdc42-induced filopodia formation. Conversely, p53-deficient MEFs exhibited constitutive membrane filopodia. Mechanistic studies indicate that p53 prevents the initiating steps of filopodia formation downstream of Cdc42. (ii) Over expression of p53 modulates cell spreading of MEFs on fibronectin. (iii) During cell migration, the reorientation of the Golgi apparatus in the direction of movement is abolished by wild-type p53 expression, thus preventing cell polarity. Our data demonstrate a previously uncharacterized role for p53 in regulating Cdc42-dependent cell effects that control actin cytoskeletal dynamics and cell movement. This novel function may contribute to p53 anti-tumour activity.


Passivity and Passification of Memristor-Based Recurrent Neural Networks With Additive Time-Varying Delays.
This paper presents a new design scheme for the passivity and passification of a class of memristor-based recurrent neural networks (MRNNs) with additive time-varying delays. The predictable assumptions on the boundedness and Lipschitz continuity of activation functions are formulated. The systems considered here are based on a different time-delay model suggested recently, which includes additive time-varying delay components in the state. The connection between the time-varying delay and its upper bound is considered when estimating the upper bound of the derivative of Lyapunov functional. It is recognized that the passivity condition can be expressed in a linear matrix inequality (LMI) format and by using characteristic function method. For state feedback passification, it is verified that it is apathetic to use immediate or delayed state feedback. By constructing a Lyapunov-Krasovskii functional and employing Jensen's inequality and reciprocal convex combination technique together with a tighter estimation of the upper bound of the cross-product terms derived from the derivatives of the Lyapunov functional, less conventional delay-dependent passivity criteria are established in terms of LMIs. Moreover, second-order reciprocally convex approach is employed for deriving the upper bound for terms with inverses of squared convex parameters. The model based on the memristor with additive time-varying delays widens the application scope for the design of neural networks. Finally, pertinent examples are given to show the advantages of the derived passivity criteria and the significant improvement of the theoretical approaches.


Biomedical practices from a patient perspective. Experiences of Polish female migrants in Barcelona, Berlin and London.
This paper focuses on the diversity in patients' experience of bio-medicine and contrasts it with the normative view characteristic of health professionals. Ethnographic fieldwork among Polish migrant women in London, Barcelona and Berlin included interviews about their experiences with local healthcare and health professionals. Themes drawn from the narratives are differences between the cities in terms of communication between patients and health professionals, respect for patients' choices and dignity, attitudes to pregnancy and birth (different levels of medicalization), and paediatric care. It is argued that patients continuously negotiate among their own views and expectations based on previous experiences and knowledge from personal communication; internet forums and publications; and the offer of medical services in the countries of their settlement. Patients experience pluralism of therapeutic traditions within and outside bio-medicine. In turn, representatives of bio-medicine are rarely aware of other medical practices and beliefs and this leads to various misunderstandings. By highlighting the pluralism of medical practices in European countries and the increasing mobility of patients, this case study has useful implications for medical anthropologists and health professionals in a broader Western context, such as raising sensitivity to different communication strategies and a diversity of curing traditions and expectations.


Restoring low-input high-diversity grasslands as a potential global resource for biofuels.
Reducing meat consumption by humans and shifting to more efficient plant and animal protein sources could potentially free up large areas of pasture and feedcrop agricultural land for restoration or conversion to low-input high-diversity (LIHD) grasslands. LIHD grasslands improve biodiversity, carbon sequestration, erosion control, water storage, while also providing opportunities to produce biofuels. We examined the potential of converting pastures globally, and animal feedstock agricultural lands in the USA and Brazil, to LIHD biomass sources and the capacity of these systems to meet national energy demands via (1) cellulosic ethanol and (2) integrated gasification and combined cycle technology with Fischer-Tropsch hydrocarbon synthesis (IGCC-FT) processing. Our analyses, which we argue are conservative, indicate that large amounts of energy, far in excess of many country's current demands, can potentially be produced from IGCC-FT processing of grassland biomass grown on converted pastures, especially in tropical developing countries. Over 40 countries could meet ≥100% of their domestic demands for electricity, gasoline, and diesel. If energy products were shared between countries, the 95 countries with positive energy production yields could meet 46%, 28%, and 39% of their combined electricity, gasoline, and diesel demands, respectively. While it is clearly unrealistic to propose a 100% conversion of pasture lands to biofuel production, these analyses highlight the potential gains in ecosystem services and energy production that could theoretically be achieved on already-managed lands.


Survey of Ebola Viruses in Frugivorous and Insectivorous Bats in Guinea, Cameroon, and the Democratic Republic of the Congo, 2015-2017.
To clarify the role of bats in the ecology of Ebola viruses, we assessed the prevalence of Ebola virus antibodies in a large-scale sample of bats collected during 2015-2017 from countries in Africa that have had previous Ebola outbreaks (Guinea, the Democratic Republic of the Congo) or are at high risk for outbreaks (Cameroon). We analyzed 4,022 blood samples of bats from >12 frugivorous and 27 insectivorous species; 2-37 (0.05%-0.92%) bats were seropositive for Zaire and 0-30 (0%-0.75%) bats for Sudan Ebola viruses. We observed Ebola virus antibodies in 1 insectivorous bat genus and 6 frugivorous bat species. Certain bat species widespread across Africa had serologic evidence of Zaire and Sudan Ebola viruses. No viral RNA was detected in the subset of samples tested (n = 665). Ongoing surveillance of bats and other potential animal reservoirs are required to predict and prepare for future outbreaks.


New 99m Tc(CO)3 -radiolabeled arylpiperazine pharmacophore as potent 5HT1A serotonin receptor radiotracer: Docking studies, chemical synthesis, radiolabeling, and biological evaluation.
In spite of previous efforts, there is lack of a radiotracer for imaging the 5HT1A receptor density in human brain, which is involved in several neurological brain disorders. The aim of this study was to prepare a new derivative of 1-(2-methoxyphenyl)piperazine (MPP) as a main chemical structure of 5HT1A receptor antagonist with 3-carbon linker and radiolabeled by [99m Tc][Tc(CO)3 (H2 O)3 ]+ precursor. Docking studies before chemical synthesis showed similar fashion of interaction for both WAY100635 (potent 5HT1A receptor antagonist) and new designed ligand, despite of addition of 99m Tc(CO)3 group in the structure of new ligand. MPP-(CH2 )3 -N3 was synthesized via three efficient and reliable chemical synthesis steps (more than 80% yield) then radiolabeled by addition of 2-ethynylpyridine and [99m Tc][Tc(CO)3 (H2 O)3 ]+ precursor in one pot procedure (more than 95% radiochemical efficiency) through click chemistry method. After incubation, radiotracer was found stable in vitro up to 2 hours. Binding assays showed about 33% specific binding of radiotracer to the 5HT1A receptors. Brain biodistribution studies indicated (0.26 ± 0.05)% ID/g hippocampus uptake at 30 minutes post injection, which its specificity was verified through blocking studies. These results suggested that new designed radioligand might serve as a potent SPECT imaging agent to estimate status of 5HT1A receptors.


Roles of the procollagen C-propeptides in health and disease.
The procollagen C-propeptides of the fibrillar collagens play key roles in the intracellular assembly of procollagen molecules from their constituent polypeptides chains, and in the extracellular assembly of collagen molecules into fibrils. Here we review recent advances in understanding the molecular mechanisms controlling C-propeptide trimerization which have revealed the importance of inter-chain disulphide bonding and a small number of charged amino acids in the stability and specificity of different types of chain association. We also show how the crystal structure of the complex between the C-propeptide trimer of procollagen III and the active fragment of procollagen C-proteinase enhancer-1 leads to a detailed model for accelerating release of the C-propeptides from procollagen by bone morphogenetic protein-1 and related proteinases. We then discuss the effects of disease-related missense mutations in the C-propeptides in relation to the sites of these mutations in the three-dimensional structure. While in general there is a good correlation between disease severity and structure-based predictions, there are notable exceptions, suggesting new interactions involving the C-propeptides yet to be characterized. Mutations affecting proteolytic release of the C-propeptides from procollagen are discussed in detail. Finally, the roles of recently discovered interaction partners for the C-propeptides are considered during fibril assembly and cross-linking.


Transfer of a Catabolic Pathway for Chloromethane in Methylobacterium Strains Highlights Different Limitations for Growth with Chloromethane or with Dichloromethane.
Chloromethane (CM) is an ozone-depleting gas, produced predominantly from natural sources, that provides an important carbon source for microbes capable of consuming it. CM catabolism has been difficult to study owing to the challenging genetics of its native microbial hosts. Since the pathways for CM catabolism show evidence of horizontal gene transfer, we reproduced this transfer process in the laboratory to generate new CM-catabolizing strains in tractable hosts. We demonstrate that six putative accessory genes improve CM catabolism, though heterologous expression of only one of the six is strictly necessary for growth on CM. In contrast to growth of Methylobacterium strains with the closely related compound dichloromethane (DCM), we find that chloride export does not limit growth on CM and, in general that the ability of a strain to grow on DCM is uncorrelated with its ability to grow on CM. This heterologous expression system allows us to investigate the components required for effective CM catabolism and the factors that limit effective catabolism after horizontal transfer.


CPB1 of Aedes aegypti interacts with DENV2 E protein and regulates intracellular viral accumulation and release from midgut cells.
Aedes aegypti is a principal vector responsible for the transmission of dengue viruses (DENV). To date, vector control remains the key option for dengue disease management. To develop new vector control strategies, a more comprehensive understanding of the biological interactions between DENV and Ae. aegypti is required. In this study, a cDNA library derived from the midgut of female adult Ae. aegypti was used in yeast two-hybrid (Y2H) screenings against DENV2 envelope (E) protein. Among the many interacting proteins identified, carboxypeptidase B1 (CPB1) was selected, and its biological interaction with E protein in Ae. aegypti primary midgut cells was further validated. Our double immunofluorescent assay showed that CPB1-E interaction occurred in the endoplasmic reticulum (ER) of the Ae. aegypti primary midgut cells. Overexpression of CPB1 in mosquito cells resulted in intracellular DENV2 genomic RNA or virus particle accumulation, with a lower amount of virus release. Therefore, we postulated that in Ae. aegypti midgut cells, CPB1 binds to the E protein deposited on the ER intraluminal membranes and inhibits DENV2 RNA encapsulation, thus inhibiting budding from the ER, and may interfere with immature virus transportation to the trans-Golgi network.