Phytochemical and antinociceptive properties of Matayba elaeagnoides Radlk. barks.
A mixture of triterpenes named lupeol (1), alpha-amyrin (2), beta-amyrin (3), and beta-sitosterol (4) has been isolated from the hexane fraction of Matayba elaeagnoides. In addition, scopoletin (5), umbelliferone (6), 3beta-O-D-glycopyranosyl-sitosterol (7) and betulin (8) were isolated from the chloroform fraction. All the structures were identified by spectroscopic techniques in accordance with literature data. The extracts (hydroalcoholic and methanolic) and some fractions (hexane, chloroform, ethyl acetate and butanol) exerted promising antinociceptive effects in mice. In addition, we have tested the pure compound betulin (8). When analyzed against induced pain using the writhing test (3-10 mg kg(-1), i.p.), betulin showed a dose-dependent effect with a calculated ID50 value of 7.74 (6.53-9.17) mg kg(-1) [17.5 (14.7-20.7) micromol kg(-1)] and a maximal inhibition (MI) of 58.3% in relation to the control group. When evaluated in the formalin test (3-10 mg kg(-1), i.p.), this compound inhibited both phases of pain (neurogenic and inflammatory pain), with calculated ID50 values of 18.3 (17.7-18.9) and 8.3 (7.7-8.9) mg kg(-1) [41.5 (38.4-42.7) and 18.8 (17.6-19.9) micromol kg(-1)] and maximal inhibition of 40.8 and 64.39% for the first and second phases, respectively. Using the same models, this compound was several times more active than two clinically used drugs, namely aspirin and paracetamol, suggesting that its main active principle is related to the antinociceptive effect found for the chloroform fraction of M. elaeagnoids barks.


HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates.
Induction and maintenance of antibody and T cell responses will be critical for developing a successful vaccine against HIV. A rational approach for generating such responses is to design vaccines or adjuvants that have the capacity to activate specific antigen-presenting cells. In this regard, dendritic cells (DCs) are the most potent antigen-presenting cells for generating primary T cell responses. Here, we report that Toll-like receptor (TLR) agonists and ligands that activate DCs in vitro influence the magnitude and quality of the cellular immune response in nonhuman primates (NHPs) when administered with HIV Gag protein. NHPs immunized with HIV Gag protein and a TLR7/8 agonist or a TLR9 ligand [CpG oligodeoxynucleotides (CpG ODN)] had significantly increased Gag-specific T helper 1 and antibody responses, compared with animals immunized with HIV Gag protein alone. Importantly, conjugating the HIV Gag protein to the TLR7/8 agonist (Gag-TLR7/8 conjugate) dramatically enhanced the magnitude and altered the quality of the T helper 1 response, compared with animals immunized with HIV Gag protein and the TLR7/8 agonist or CpG ODN. Furthermore, immunization with the Gag-TLR7/8 conjugate vaccine elicited Gag-specific CD8+ T responses. Collectively, our results show that conjugating HIV Gag protein to a TLR7/8 agonist is an effective way to elicit broad-based adaptive immunity in NHPs. This type of vaccine formulation should have utility in preventive or therapeutic vaccines in which humoral and cellular immunity is required.


Depressive symptoms and comorbid problems in pregnancy - results from a population based study.
To estimate the prevalence of antenatal depressive symptoms, identify relevant risk factors, and assess comorbid mental health problems, among pregnant women enrolled in a population based study. This was a secondary analysis of data collected from 1916 pregnant women who participated in the TRansgenerational Assessment of Children's Environmental Risk (TRACER) study in Kuwait, and had answered the Baseline Questionnaire and completed the Edinburgh Depression Scale (EDS). Logistic regression models were used to examine the association of depressive symptoms with baseline socio-demographic characteristics and psychosocial indicators. The prevalence of antenatal depressive symptoms, using a cut-off of EDS score ≥ 10, was 20.1%. Depressive symptoms were reported more by women of lower family income and had self-reported history of depression prior to pregnancy, with women in the third trimester having higher odds of antenatal depressive symptoms compared to those in the second trimester. Pregnancy-related anxiety, higher perceived stress levels, and post-traumatic stress disorder symptoms were comorbid with the presence of depressive symptoms. The findings showed that one in five pregnant women in Kuwait experiences antenatal depressive symptoms and that these symptoms are comorbid with other mental health problems. Screening for antenatal depression and providing support to pregnant women should be considered.


Plant evolutionary history mainly explains the variance in biomass responses to climate warming at a global scale.
Evolutionary history shapes the interspecific relatedness and intraspecific variation, which has a profound influence on plant functional traits and productivity. However, it is far from clear how the phylogenetic relatedness among species and intraspecific variation could contribute to the observed variance in plant biomass responses to climate warming. We compiled a dataset with 284 species from warming experiments to explore the relative importance of phylogenetic, intraspecific, experimental and ecological factors to warming effects on plant biomass, using phylogenetic eigenvector regression and variance decomposition. Our results showed that phylogenetic relatedness could account for about half the total variance in biomass responses to warming, which were correlated with leaf economic traits at the family level but not at species level. The intraspecific variation contributed to approximately one-third of the variance, whereas the experimental design and ecological characteristics only explained 7-17%. These results suggest that intrinsic factors (evolutionary history) play more important roles than extrinsic factors (experimental treatment and environment) in determining the responses of plant biomass to warming at the global scale. This highlights the urgent need for land surface models to include evolutionary aspects in predicting ecosystem functions under climate change.


[Formation of congenital defects during ocular development. I. Embryogenesis of the eye and developmental birth defects].
Formation of developmental congenital defects of organ of vision finds its direct basis in the course of eye embryogenesis. Author of this work presents on the base of the literature, the crucial stages of embryonal development of eyeball and its individual structures. At every stage of development, the critical moments are shown, when the disturbance of the developmental process may lead to the origination of different groups of congenital eye defects. The knowledge of the potential period of particular congenital eye defects formation, facilitates the identification of eventual teratogenic factors, that have acted during pregnancy. It enables, to state the activity of gradually discovered genes, that regulate the course of embryonal development of the eye.


Expression of stromal cell-derived factor 1 and CXCR7 ligand receptor system in pancreatic adenocarcinoma.
Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Research has demonstrated that SDF-1/CXCR7 interaction could play an important role in cancer progression. In this study, we aimed to investigate the expression of the SDF-1/CXCR7 ligand receptor system and the relationship between this expressions and clinicopathological characteristics in pancreatic adenocarcinoma. Expressions of SDF-1 and CXCR7 in 64 cases of pancreatic adenocarcinoma tissue and 24 cases of normal pancreatic tissue were detected immunohistochemically. Expressions of SDF-1 and CXCR7 were negative in normal pancreatic tissues. Respectively, positive expression rates of SDF-1 and CXCR7 in pancreatic adenocarcinoma were 45.3% and 51.6%. The expression of SDF-1 correlated with histological grades; the expression rate in moderate to low differentiation was higher than in high differentiation (P<0.05). The expression of CXCR7 positively correlated with lymph node metastasis (P<0.05). A log-rank test showed that the expression of SDF-1+/CXCR7+ correlated with poor prognosis (P<0.05). The SDF-1/CXCR7 receptor ligand system may take part in invasive progression and metastasis of pancreatic adenocarcinoma, and might be useful as an index for evaluating invasiveness and prognosis.


A parsimonious mixture of Gaussian trees model for oversampling in imbalanced and multimodal time-series classification.
We propose a novel framework of using a parsimonious statistical model, known as mixture of Gaussian trees, for modeling the possibly multimodal minority class to solve the problem of imbalanced time-series classification. By exploiting the fact that close-by time points are highly correlated due to smoothness of the time-series, our model significantly reduces the number of covariance parameters to be estimated from O(d(2)) to O(Ld), where L is the number of mixture components and d is the dimensionality. Thus, our model is particularly effective for modeling high-dimensional time-series with limited number of instances in the minority positive class. In addition, the computational complexity for learning the model is only of the order O(Ln+d(2)) where n+ is the number of positively labeled samples. We conduct extensive classification experiments based on several well-known time-series data sets (both single- and multimodal) by first randomly generating synthetic instances from our learned mixture model to correct the imbalance. We then compare our results with several state-of-the-art oversampling techniques and the results demonstrate that when our proposed model is used in oversampling, the same support vector machines classifier achieves much better classification accuracy across the range of data sets. In fact, the proposed method achieves the best average performance 30 times out of 36 multimodal data sets according to the F-value metric. Our results are also highly competitive compared with nonoversampling-based classifiers for dealing with imbalanced time-series data sets.


Cardiac resynchronisation therapy in chronic atrial fibrillation: impact on left atrial size and reversal to sinus rhythm.
To evaluate the impact of long term cardiac resynchronisation therapy (CRT) on left atrial and left ventricular (LV) reverse remodelling and reversal to sinus rhythm (SR) in patients with heart failure with atrial fibrillation (AF). 74 consecutive patients (age 68 (8) years; 67 men) with advanced heart failure and AF (20 persistent and 54 permanent) were implanted with a CRT device. Patients were evaluated clinically (New York Heart Association (NYHA) class, quality of life, six minute walk test) and echocardiographically (LV ejection fraction, LV diameters, and left atrial diameters) before and after six months of CRT. Additionally, restoration of SR was evaluated after six months of CRT. NYHA class, quality of life score, six minute walk test, and LV ejection fraction had improved significantly after six months of CRT. In addition, left atrial and LV end diastolic and end systolic diameters had decreased from 59 (9) to 55 (9) mm, from 72 (10) to 67 (10) mm, and from 61 (11) to 56 (11) mm, respectively (all p < 0.01). During implantation 18 of 20 (90%) patients with persistent AF were cardioverted to SR. At follow up 13 of 18 (72%) patients had returned to AF and none had spontaneously reverted to SR; thus, only 5 of 74 (7%) were in SR. Six months of CRT resulted in significant clinical benefit with significant left atrial and LV reverse remodelling. Despite these beneficial effects, 93% of patients had not reverted to SR.


Absorption of bacampicillin and ampicillin and penetration into body fluids (skin blister fluid, saliva, tears) in healthy volunteers.
Equimolar doses of bacampicillin, which is rapidly converted to ampicillin in the body by hydrolysis, and ampicillin were administered orally, in the case of ampicillin also by intravenous injection, to 10 healthy subjects (cross-over study). Comparison of the areas under the serum concentrations curves after intravenous and oral administration showed that bacampillin was absorbed to 95% and orally given ampicillin to 35%. The mean peak serum levels (Cmax) after 0.8 g of oral bacampicillin were higher (15.9 microgram/ml) and appeared earlier (tmax 60 min) than after 0.556 g of oral ampicillin (3.2 microgram/ml, tmax 150 min). One and three hours after oral administration skin blister fluid contained four times more ampicillin after doses of bacampicillin than after oral ampicillin. One hour after intravenous injection of ampicillin the skin blister concentrations were 20 times higher than after oral administration of this antibiotic and three to four times higher than after oral administration of bacampicillin. The levels in saliva and tears were also determined and showed similar relationships. Since higher peaks serum levels resulted in higher and longer lasting concentrations in the extravascular space, bacampicillin is to be preferred for oral therapy.


[Varicella--mild or dangerous disease].
The aim was an analysis of causes of varicella complications in children hospitalized in the Department if Infectious Diseases In Childhood of Medical University in Warsaw. 105 children from 15 day to 15 years of age was observed. 58.1% were male. The median age was 5,8 years. Bacterial skin infections and neurological complications were the most frequent complications. Sepsis was diagnosed in 3 children. Vaccination program against varicella can reduce the risk of very severe complications.


Acoustic tweezer with complex boundary-free trapping and transport channel controlled by shadow waveguides.
Acoustic tweezers use ultrasound for contact-free, bio-compatible, and precise manipulation of particles from millimeter to submicrometer scale. In microfluidics, acoustic tweezers typically use an array of sources to create standing wave patterns that can trap and move objects in ways constrained by the limited complexity of the acoustic wave field. Here, we demonstrate spatially complex particle trapping and manipulation inside a boundary-free chamber using a single pair of sources and an engineered structure outside the chamber that we call a shadow waveguide. The shadow waveguide creates a tightly confined, spatially complex acoustic field inside the chamber without requiring any interior structure that would interfere with net flow or transport. Altering the input signals to the two sources creates trapped particle motion along an arbitrary path defined by the shadow waveguide. Particle trapping, particle manipulation and transport, and Thouless pumping are experimentally demonstrated.


Optimization of One-Time Fertilization Scheme Achieved the Balance of Yield, Quality and Economic Benefits of Direct-Seeded Rice.
There is limited information available to assess the impact of one-time fertilization on the yield, quality, and economic benefits of direct-seeded rice. This study reports the effects of three one-time fertilizer treatments (BBU1, BBU2, and BBU3) on the yield, quality, and economic benefits of direct-seeded rice, where controlled-release nitrogen (N) fertilizer (CRNF) provided 50%, 60%, and 70% of the total N (270 kg N ha-1), and the control treatment (CK) was a split application of conventional urea (CU). The results showed that the yield of direct-seeded rice decreased significantly (p < 0.05) with the increased application ratio of CRNF under one-time fertilization, which was mainly related to N accumulation between the heading time and maturity stages. Compared to CK, the one-time fertilization treatments (BBU1, BBU2, and BBU3) maintained high milling quality, with significantly reduced chalkiness (p < 0.05), which could be related to the slow rate of N release from the CRNF. In addition, the one-time fertilization treatments reduced the protein content and increased the amylose content of the milled rice, which significantly improved the eating quality (p < 0.05). Furthermore, there was no significant difference in yield and economic benefit between BBUI and CK (p > 0.05). Overall, CRNF replacing conventional urea with 50% total N could be helpful to reduce fertilization frequency, achieve high yield and high economic efficiency, and improve rice quality of direct-seeded rice under one-time fertilization.


Analysis of a nuclear accident: fission and activation product releases from the Fukushima Daiichi nuclear facility as remote indicators of source identification, extent of release, and state of damaged spent nuclear fuel.
Researchers evaluated radionuclide measurements of environmental samples taken from the Fukushima Daiichi nuclear facility and reported on the Tokyo Electric Power Co. Website following the 2011 tsunami-initiated catastrophe. This effort identified Units 1 and 3 as the major source of radioactive contamination to the surface soil near the facility. Radionuclide trends identified in the soils suggested that: (1) chemical volatility driven by temperature and reduction potential within the vented reactors' primary containment vessels dictated the extent of release of radiation; (2) all coolant had likely evaporated by the time of venting; and (3) physical migration through the fuel matrix and across the cladding wall were minimally effective at containing volatile species, suggesting damage to fuel bundles was extensive. Plutonium isotopic ratios and their distance from the source indicated that the damaged reactors were the major contributor of plutonium to surface soil at the source, decreasing rapidly with distance from the facility. Two independent evaluations estimated the fraction of the total plutonium inventory released to the environment relative to cesium from venting Units 1 and 3 to be ∼0.002-0.004%. This study suggests significant volatile radionuclides within the spent fuel at the time of venting, but not as yet observed and reported within environmental samples, as potential analytes of concern for future environmental surveys around the site. The majority of the reactor inventories of isotopes of less volatile elements like Pu, Nb, and Sr were likely contained within the damaged reactors during venting.


Estimation of biomass and specific growth rate in a recombinant Escherichia coli batch cultivation process using a chemical multisensor array.
A chemical multisensor array is used in combination with an artificial neural network to estimate the biomass concentration and specific growth rate in a recombination Escherichia coli batch cultivation. It is shown that by providing sufficient information to the artificial neural network, an accuracy comparable to that of an established dry weight method can be achieved. The obtained prediction error (1 sigma) of 0.043 g l-1 for biomass compares well with the error of the dry weight method in this low biomass concentration range (0.1-3 g l-1). The prediction for the specific growth rate is accurate during important parts of the cell growth (1 sigma = 0.025 h-1). The results show that this non-invasive method is potentially useful for estimating biomass and specific growth rate on-line in bioprocesses.


Characterization and developmental expression pattern of the relaxin receptor rxfp1 gene in zebrafish.
We report the gene characterization, the cDNA cloning and the temporal and spatial expression pattern of the relaxin receptor rxfp1 gene in the zebrafish Danio rerio. The zebrafish rxfp1 gene has the same syntenic genomic organization, and a similar exon-intron structure to the homologue human gene. Furthermore, the deduced Rxfp1 protein sequence shows a high degree of amino acid similarity when compared with the human protein and the conservation of all amino acid identity necessary for the binding with relaxin. Our results show that rxfp1 gene is active either during embryogenesis or in the adult organism, showing a wide expression pattern. Moreover, we provide the first description of rxfp1 spatial expression pattern during embryo development, showing that the transcript is already present at the early developmental stage and is distributed in all of the embryonic cells until somitogenesis. Starting at the pharyngula stage the gene expression becomes mainly restricted in the brain territories. In fact, at the larval stage, the transcript is detectable in the epiphysis, postoptic region, posterior tuberculum, hypothalamus, optic tectum, tegmentum/pons, medulla and also in the structure of a peripheral nervous system, the terminal nerve. The rxfp1 expression pattern in Danio rerio embryos is very similar to that reported in the adult mammalian brain, suggesting a pivotal role of this receptor in the neurophysiology processes already at very early developmental stages.


Atypical carcinoid tumor of the lung, associated with giant-cell transformation in bone metastasis.
A case of neuroendocrine lung tumor located beneath the pleura in a 71-year-old woman is reported. At autopsy, the tumor was found to have metastasized to the bones and liver without involving the hilar lymph nodes. Histologically, the tumor cells at the primary site and in the liver metastasis exhibited a carcinoid-like organoid structure, whereas pleomorphic giant cells were noted in the bone metastasis. The argyrophilic tumor cells were immunoreactive for neuron-specific enolase, chromogranin A, serotonin, calcitonin, calcitonin gene-related peptide, gastrin-releasing peptide, neuropeptide Y, gastrin, pancreatic polypeptide, glicentin, the alpha-subunit of human chorionic gonadotropin, keratin, epithelial membrane antigen, Leu M1 and carcinoembryonic antigen. Electron microscopy revealed abundant neurosecretory granules in the cytoplasm. This was considered to be a rare case of neuroendocrine lung tumor showing carcinoid-like histology at the primary site and large-cell transformation in bone metastasis.


Pneumonectomy: quality of life and long-term results.
Pneumonectomy is the standard surgery for resectable locally advanced lung cancer. Objectives of this study were: 1) to assess the overall survival; 2) to evaluate the pulmonary and cardiac function impairment; 3) to monitor quality of life (QoL) in a consecutive series of patients undergoing pneumonectomy, defining the potential risk factors of a poor prognosis. From January 2003 to March 2010, 71 patients undergoing pneumonectomy for lung cancer or mesothelioma were prospectively enrolled in this study. Twenty-six patients underwent right pneumonectomy (2 of them underwent intrapericardial pneumonectomy), 31 left pneumonectomy (3 of them underwent intrapericardial pneumonectomy), 3 extended pneumonectomy, 3 extrapleural pneumonectomy and 5 patients underwent completion pneumonectomy. Three patients were not included in the study for early postoperative deaths (4.3%). All patients underwent complete preoperative assessment and one year after surgery. QoL was assessed by a questionnaire. One and five-year survival rate was 93% (N.=63) and 20% (N.=14), respectively. Mean values of FEV1 decreased from 2.59±0.75 L to 1.8±0.72 L (P<0.001). One year after surgery all patients showed moderate tricuspid valve insufficiency, PASP significantly higher and right ventricular free wall thickness moderately increased. An increased negative effect was recorded in the QoL scores with P<0.001. Three clinical and surgical parameters were identified as risk or protective factors for the survival outcome. Postoperative mortality (4.3%) and five-year survival (20%) after pneumonectomy seem to be satisfactory. Late cardiopulmonary insufficiency is uncommon and acceptable QoL is still achievable.


[Analysis of rs4420638A/G and -317H1/H2 polymorphisms of APOC1 gene among Chinese patients with pre-eclampsia].
To assess the association of apolipoprotein (apo) C1 (APOC1) gene rs4420638A/G and -317H1/H2 polymorphisms with the risk of pre-eclampsia (PE) and the influence of their genotypes on the clinical and metabolic indexes among Chinese women. In total 289 PE patients and 824 women with uncomplicated pregnancies were included. The rs4420638A/G genotype was determined by a Taqman real-time PCR allelic discrimination assay. The -317H1/H2 genotype was measured through PCR and restriction fragment length polymorphism analysis. Serum lipid and apo levels were measured by an enzymatic kit and a PEG-enhanced immunoturbidimetric assay. Allelic and genotypic frequencies of the APOC1 gene rs4420638A/G and -317H1/H2 were not significantly different between the two groups (all P> 0.05). However, patients carrying the G allele of the rs4420638A/G locus had higher serum levels of triglyceride, non-HDL-C and apoB, and a higher apoB/apoA1 ratio compared with those with an AA genotype (all P< 0.05). Patients carrying the H2 allele of the -317H1/H2 polymorphism had smaller delivery gestational weeks compared with those with the H1H1 genotype (P< 0.05). Polymorphisms of the APOC1 gene rs4420638 and -317H1/H2 sites may be associated with abnormal lipoprotein metabolism among Chinese patients with PE, though no association was found between variants of the APOC1 gene and the risk of PE among them.


Microvasculature, blood flow, and vasoreactivity in rabbit sinus mucosa after surgery.
To study the circulatory integrity of the sinus mucosa following surgery, the vascular anatomy, blood flow, and vasoconstrictor response of the regenerated microcirculatory network were analyzed. Forty-six New Zealand White rabbits were operated on unilaterally with either a modified radical operation (MRO) or middle meatal antrostomy (MMA), using the nonoperated sinus for control purposes. After surgery, the animals were left to heal for 1 month. Vascular casts were prepared with a low-viscosity methyl methacrylate resin and studied by scanning electron microscopy. Blood flow was measured by means of radiolabeled microspheres (tin 113 [113Sn]). The vasoconstrictor response to oxymetazoline at increasing concentrations was measured with laser Doppler flowmetry. The number of vessels increased significantly in the regenerated mucosa. The vascular casts displayed a rich microcirculation with local signs of angiogenesis. However, there was no difference in blood flow between the operated cavities and their control sides. Following MRO the regenerated mucosa was more sensitive to the vasoconstrictor effect of oxymetazoline, compared with the control side. This difference was not evident in the MMA-operated sinuses. In this model, surgery does not seriously interfere with the sinus blood flow, although the regenerated mucosa did display an altered vasoreactivity. These findings should be considered in relation to the effects of surgery intended to limit local inflammation and to ensure the ventilation of the sinuses.


Highly Efficient Conversion of Greenhouse Gases Using a Quadruple Mixed Oxide-Supported Nickel Catalyst in Reforming Process.
The greenhouse gas reduction as well as the utilization of more renewable and clean energy via a dry reforming reaction is of interest. The impact of a CeMgZnAl oxide quad-blend-supported Ni catalyst on performance and anticoking during dry reforming reactions at 700 °C was studied. A high Ce-Mg/Zn ratio, as seen in the CeMg0.5ZnAl-supported nickel catalyst, enhances lattice oxygen, and the presence of strong basic sites, along with the creation of the carbonate intermediate species, is accompanied by the production of gaseous CO through a gasification reaction between the carbon species and Ni-COads-lin site. The phenomena caused the outstanding performance of the Ni/CeMg0.5ZnAl catalyst-CH4 (84%),CO2 (83%) conversions, and the H2/CO (0.80) ratio; moreover, its activity was also stable throughout 30 h.


Axial resolution analysis in compressive digital holographic microscopy.
Digital holographic microscopy with compressive sensing (CDHM) has successfully achieved tomography and has been applied in many fields. However, the enhancement of axial resolution in CDHM remains to be elucidated. By deducing accurate formulas for the lateral and axial resolutions without paraxial approximation, we quantized the elongation effect of a digital holography (DH) system in this study. Thus, we revealed that the elongation effect, which is affected only by the system's numerical aperture (NA), is an inherent property of DH systems. We present a detailed analysis herein on the physical significance of the coherence parameter, which is the ratio of a system's limit axial resolution to the interlayer spacing more thoroughly than in previous research. Further, we achieved the tomography of a fiber by using a DH system with a 10 × microscope, with CS to eliminate the elongation effect, and experimentally validated our theoretical results. By applying these theoretical guidelines, we distinguished crossed fibers at distances of 36.4 μm and 48.5 μm, respectively, using the same experimental setup. There would be potential applications of this theory in tomography and observation of microscale objects in the areas of biological and fluid.


Recombinant tissue-type plasminogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alone in acute ischemic stroke: propensity score-matched post hoc analysis.
The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial demonstrated safety of recombinant tissue-type plasminogen activator (r-tPA) plus eptifibatide in acute ischemic stroke (AIS). CLEAR-ER randomized AIS patients (5:1) to 0.6 mg/kg r-tPA plus eptifibatide versus standard r-tPA (0.9 mg/kg). Interventional Management of Stroke III randomized AIS patients to r-tPA plus endovascular therapy versus standard r-tPA. Albumin in Acute Stroke Part 2 randomized patients to albumin±r-tPA versus saline±r-tPA. Our aim was to compare outcomes in CLEAR-ER combination arm patients to propensity score-matched r-tPA only subjects in Albumin in Acute Stroke Part 2 and Interventional Management of Stroke III. The primary outcome was 90-day severity-adjusted modified Rankin score (mRS) dichotomization based on baseline National Institutes of Health Stroke Scale. Secondary outcomes were 90-day mRS dichotomization as excellent (mRS, 0-1); mRS dichotomization as favorable (mRS, 0-2); and nonparametric analysis of the ordinal mRS. Eighty-five combination arm CLEAR-ER subjects were matched with 169 Albumin in Acute Stroke Part 2 and Interventional Management of Stroke III trials' r-tPA only patients (controls). Median age in CLEAR-ER and control subjects was 68years; median National Institutes of Health Stroke Scale in the CLEAR-ER subjects was 11 and in control subjects 12. At 90 days, CLEAR-ER subjects had a nonsignificantly greater proportion of patients with favorable outcomes (45% versus 36%; unadjusted relative risks, 1.24; 95% confidence intervals, 0.91-1.69; P=0.18). Secondary outcomes were 52% versus 34% excellent outcomes (relative risks, 1.51; 95% confidence intervals, 1.13-2.02; P=0.007); 60% versus 53% favorable outcome (relative risks, 1.13; 95% confidence intervals, 0.90-1.41; P=0.31); and ordinal Cochran-Mantel-Haenszel P=0.10. r-tPA plus eptifibatide showed a favorable direction of effect that was consistent across multiple approaches for AIS outcome evaluation. A phase III trial to establish the efficacy of r-tPA plus eptifibatide for improving AIS outcomes is warranted.


Dependence of lethality induced by a direct DNA perturbation of synchronized human diploid fibroblasts on different periods of the DNA synthetic period (S phase).
The cytotoxic effect of a direct perturbation of DNA during various portions of the DNA synthetic period (S phase) of cultured human diploid fibroblasts was examined. The cells were synchronized by a period of growth in low serum with a subsequent blockage of the cells at the G1/S boundary by hydroxyurea. This method resulted in over 90% synchrony, although approximately 20% of the cells were noncycling. Synchronized cells were treated for each of four 2-hour periods during the S phase with 5-bromodeoxyuridine (0.1-10 microM), followed by irradiation with near-UV (5-10 min). The 5-bromodeoxyuridine-plus-irradiation treatment was cytotoxic, while treatment with 5-bromodeoxyuridine alone or irradiation alone was not cytotoxic. The cytotoxicity was dependent upon the periods of S phase during which treatment was administered. The highest lethality was observed for treatment in early to middle S phase, particularly in the first 2 hours of S phase, whereas scarce lethality was observed in late S phase. The extent of substitution of 5-bromodeoxyuridine for thymidine in newly synthesized DNA was similar in every period of the S phase. Furthermore, no specific period during S phase was significantly more sensitive to treatment with respect to DNA damage, as determined by an induction of unscheduled DNA synthesis. These results suggest that a certain region or regions in the DNA of human diploid fibroblasts, as designated by their specific temporal relationship in the S phase, may be more sensitive to the DNA perturbation by 5-bromodeoxyuridine treatment plus near-UV irradiation for cell survival.


Ultrasensitive photoelectrochemical immunoassay for matrix metalloproteinase-2 detection based on CdS:Mn/CdTe cosensitized TiO2 nanotubes and signal amplification of SiO2@Ab2 conjugates.
An ultrasensitive photoelectrochemical sandwich immunoassay was developed to detect matrix metalloproteinase-2 (MMP-2, antigen, Ag) based on CdS:Mn/CdTe cosensitized TiO2 nanotubes (TiO2-NTs) and signal amplification of SiO2@Ab2 conjugates. Specifically, the TiO2-NTs electrode was first deposited with CdS:Mn by successive ionic layer adsorption and reaction technique and then further coated with CdTe quantum dots (QDs) via the layer-by-layer method, forming TiO2-NTs/CdS:Mn/CdTe cosensitized structure, which was employed as a matrix to immobilize capture MMP-2 antibodies (Ab1); whereas, SiO2 nanoparticles were coated with signal MMP-2 antibodies (Ab2) to form SiO2@Ab2 conjugates, which were used as signal amplification elements via the specific antibody-antigen immunoreaction between Ag and Ab2. The ultrahigh sensitivity of this immunoassay derived from the two major reasons as below. First, the TiO2-NTs/CdS:Mn/CdTe cosensitized structure could adequately absorb the light energy, dramatically promote electron transfer, and effectively inhibit the electron-hole recombination, resulting in significantly enhanced photocurrent intensity of the sensing electrode. However, in the presence of target Ag, the immobilized SiO2@Ab2 conjugates could evidently increase the steric hindrance of the sensing electrode and effectively depress the electron transfer, leading to obviously decreased photocurrent intensity. Accordingly, the well-designed photoelectrochemical immunoassay exhibited a low detection limit of 3.6 fg/mL and a wide linear range from 10 fg/mL to 500 pg/mL for target Ag detection. Meanwhile, it also presented good reproducibility, specificity, and stability and might open a new promising platform for the detection of other important biomarkers.


A Theorem at the Core of Colliding Bias.
Conditioning on a shared outcome of two variables can alter the association between these variables, possibly adding a bias component when estimating effects. In particular, if two causes are marginally independent, they might be dependent in strata of their common effect. Explanations of the phenomenon, however, do not explicitly state when dependence will be created and have been largely informal. We prove that two, marginally independent, causes will be dependent in a particular stratum of their shared outcome if and only if they modify each other's effects, on a probability ratio scale, on that value of the outcome variable. Using our result, we also qualify the claim that such causes will "almost certainly" be dependent in at least one stratum of the outcome: dependence must be created in one stratum of a binary outcome, and independence can be maintained in every stratum of a trinary outcome.


THE EVOLUTION OF SPERM SIZE IN BIRDS.
Sperm size varies enormously among species, but the reasons for this variation remain obscure. Since it has been suggested that swimming velocity increases with sperm length, earlier studies proposed longer (and therefore faster) sperm are advantageous under conditions of intense sperm competition. Nonetheless, previous work has been equivocal, perhaps because the intensity of sperm competition was measured indirectly. DNA profiling now provides a more direct measure of the number of offspring sired by extrapair males, and thus a more direct method of assessing the potential for sperm competition. Using a sample of 21 species of passerine birds for which DNA profiling data were available, we found a positive relation between sperm length and the degree of extrapair paternity. A path analysis, however, revealed that this relationship arises only indirectly through the positive relationship between the rate of extrapair paternity and length of sperm storage tubules (SSTs) in the female. As sperm length is correlated positively with SST length, an increase in the intensity of sperm competition leads to an increase in sperm length only through its effect on SST length. Why females vary SST length with the intensity of sperm competition is not clear, but one possibility is that it increases female control over how sperm are used in fertilization. Males, in turn, may respond on an evolutionary time scale to changes in SST size by increasing sperm length to prevent displacement from rival sperm. Previous theoretical analyses predicting that sperm size should decrease as sperm competition becomes more intense were not supported by our findings. We suggest that future models of sperm-size evolution consider not only the role of sperm competition, but also how female control and manipulation of ejaculates after insemination selects for different sperm morphologies.


A Quartz Crystal Microbalance dew point sensor without frequency measurement.
This work deals with the design of a dew point sensor based on Quartz Crystal Microbalance (QCM) without measuring the frequency. This idea is inspired by the fact that the Colpitts oscillation circuit will stop oscillating when the QCM works in the liquid media. The quartz crystal and the electrode are designed through the finite element simulation and the stop oscillating experiment is conducted to verify the sensibility. Moreover, the measurement result is calibrated to approach the true value. At last a series of dew points at the same temperature is measured with the designed sensor. Results show that the designed dew point sensor is able to detect the dew point with the proper accuracy.


Can psychiatry residents be attracted to analytic training? A survey of five residency programs.
In the face of fewer psychiatrist applicants for psychoanalytic training, determining the interest of current psychiatric residents in psychoanalysis and psychodynamic psychiatry is a pressing concern. To gauge this interest, an anonymous online survey was sent to residents from five psychiatry residency programs in the Midwest and South. Seventy-five residents responded, for a return rate of 42%. The data suggest that residents value psychoanalytic concepts and most plan to incorporate the practice of psychodynamic psychotherapy into their careers after graduation; however, residents have little confidence in their level of skill and the adequacy of their training. While 46% express interest in further psychodynamic psychotherapy training, only 22% express interest in psychoanalytic training. Most cite the cost and time involved as reasons they would not pursue further training. This study demonstrates that psychiatric residents have strong interest in and respect for psychodynamic psychotherapy and psychoanalysis. The data suggest that psychiatric residents are a viable pool of applicants for psychoanalytic training, especially if barriers to training can be reduced and creative ways for psychoanalysts to engage residents can be fostered.


[Multiple sclerosis: diagnosis, clinical course and differential diagnosis].
Disease modifying treatment for multiple sclerosis has improved both relapse rate and prognosis. The diagnostic criteria of McDonald were designed for early diagnosis, with a crucial role for magnetic resonance imaging in the 2010 revision, as dissemination in space and time can be established by a single scan. These criteria are likely applicable in pediatric, Asian, and Latin America populations, and include neuromyelitis optica as a differential diagnosis. With recent modifications for widespread use, diagnostic sensitivity and specificity have been improved. Nevertheless, clinical and imaging red flags for atypical manifestations are needed for exclusion of alternative diagnosis.


Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug-Gene Networks: From Biology to Precision Therapeutics.
Interferon-γ (IFNγ) signaling plays a complex role in atherogenesis. IFNγ stimulation of macrophages permits in vitro exploration of proinflammatory mechanisms and the development of novel immune therapies. We hypothesized that the study of macrophage subpopulations could lead to anti-inflammatory interventions. Primary human macrophages activated by IFNγ (M(IFNγ)) underwent analyses by single-cell RNA sequencing, time-course cell-cluster proteomics, metabolite consumption, immunoassays, and functional tests (phagocytic, efferocytotic, and chemotactic). RNA-sequencing data were analyzed in LINCS (Library of Integrated Network-Based Cellular Signatures) to identify compounds targeting M(IFNγ) subpopulations. The effect of compound BI-2536 was tested in human macrophages in vitro and in a murine model of atherosclerosis. Single-cell RNA sequencing identified 2 major clusters in M(IFNγ): inflammatory (M(IFNγ)i) and phagocytic (M(IFNγ)p). M(IFNγ)i had elevated expression of inflammatory chemokines and higher amino acid consumption compared with M(IFNγ)p. M(IFNγ)p were more phagocytotic and chemotactic with higher Krebs cycle activity and less glycolysis than M(IFNγ)i. Human carotid atherosclerotic plaques contained 2 such macrophage clusters. Bioinformatic LINCS analysis using our RNA-sequencing data identified BI-2536 as a potential compound to decrease the M(IFNγ)i subpopulation. BI-2536 in vitro decreased inflammatory chemokine expression and secretion in M(IFNγ) by shrinking the M(IFNγ)i subpopulation while expanding the M(IFNγ)p subpopulation. BI-2536 in vivo shifted the phenotype of macrophages, modulated inflammation, and decreased atherosclerosis and calcification. We characterized 2 clusters of macrophages in atherosclerosis and combined our cellular data with a cell-signature drug library to identify a novel compound that targets a subset of macrophages in atherosclerosis. Our approach is a precision medicine strategy to identify new drugs that target atherosclerosis and other inflammatory diseases.


Functional analysis of a WRKY transcription factor involved in transcriptional activation of the DBAT gene in Taxus chinensis.
Although the regulation of taxol biosynthesis at the transcriptional level remains unclear, 10-deacetylbaccatin III-10 β-O-acetyl transferase (DBAT) is a critical enzyme in the biosynthesis of taxol. The 1740 bp fragment 5'-flanking sequence of the dbat gene was cloned from Taxus chinensis cells. Important regulatory elements needed for activity of the dbat promoter were located by deletion analyses in T. chinensis cells. A novel WRKY transcription factor, TcWRKY1, was isolated with the yeast one-hybrid system from a T. chinensis cell cDNA library using the important regulatory elements as bait. The gene expression of TcWRKY1 in T. chinensis suspension cells was specifically induced by methyl jasmonate (MeJA). Biochemical analysis indicated that TcWRKY1 protein specifically interacts with the two W-box (TGAC) cis-elements among the important regulatory elements. Overexpression of TcWRKY1 enhanced dbat expression in T. chinensis suspension cells, and RNA interference (RNAi) reduced the level of transcripts of dbat. These results suggest that TcWRKY1 participates in regulation of taxol biosynthesis in T. chinensis cells, and that dbat is a target gene of this transcription factor. This research also provides a potential candidate gene for engineering increased taxol accumulation in Taxus cell cultures.


Benefits of Alcohol on Arsenic Toxicity in Rats.
It has been demonstrated earlier that exposure to ethanol and/or arsenic compounds (such as sodium arsenite) produces toxic effects as shown by both in vitro and in vivo experiments. Chronic exposure of humans to arsenic through drinking water, pesticides or consumption of alcoholic beverages has produced major health problem and concern in recent years. Water being one of the main ingredients for alcohol formation (beer fermentation process) can lead to contamination with arsenic. Thus, people consuming such alcohol are getting continuously exposed to arsenic compounds as well along with alcohol. The present study was undertaken to investigate the effect of alcohol co-administration on arsenic induced changes in carbohydrate metabolic status in adult male albino rats. Adult male albino rats of Wistar strain (weighing~100g) were divided into three groups (n=8 rats/group) including Control or vehicle treated (C), Arsenic treated (As) and Arsenic treated alcohol co-exposed (As+Alc). Treatment with Sodium-arsenite included intra-peritoneal injection consecutively for 14 days at a dose of 5.55 mg/kg (equivalent to 35% of LD50) per day. Absolute alcohol (15% v/v) was fed at a dose of 0.5 ml/100 g body weight per day for five consecutive days from start of the treatment schedule. Distilled water (D/W) was used as vehicle. Blood Glucose (BG) level, levels of glycogen, Pyruvic Acid (PA), Free Amino Acid Nitrogen (FAAN), total protein, Glutamate Oxalate transaminase (GOT) and Glutamate Pyruvate Transaminase (GPT) activity, and glucose-6-phosphatase (G6Pase) activity were measured in tissues including liver, kidney and muscle. Treatment with arsenic decreased the levels of BG, liver glycogen and PA, tissue protein and G6Pase activity, GOT activity in liver and muscle, and increased free amino acid content in kidney and muscle, GPT activity in liver and kidney. Alcohol administration to rats co-exposed to arsenic treatment reversed these changes. Thus, it is suggested that combined administration of alcohol with arsenic can result in the suppression of the down-regulating action of arsenic on glucose homeostasis as evidenced by its hypoglycaemic effect and increased gluconeogenesis and transamination in liver.


Antiallodynic Effects of Intrathecal Areca Nut for Spinal Nerve-Ligated and Chemotherapy-Induced Neuropathic Pain in Rats.
This study examined the effects of intrathecal areca nut on spinal nerve-ligated and chemotherapy-induced neuropathic pain (NP), and investigated the relevance of spinal 5-hydroxytryptamine (5-HT) and α2-adrenergic receptors to those effects. For drug administration, intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats. NP was induced either by spinal nerve ligation (left spinal nerves L5 and L6) or by chemotherapeutic injection (intraperitoneal cisplatin, 2 mg/kg/day, once daily for 4 days). Paw withdrawal thresholds (PWT) were mechanically assessed using von Frey filaments. The involvement of 5-HT and α2-adrenergic receptors in antiallodynia was determined using antagonists with the following receptor specificities: nonselective 5-HT (dihydroergocristine), 5-HT7 (SB269970), nonselective α2-adrenoceptor (yohimbine), α-2A (BRL 44408), α-2B (ARC 239), and α-2C (JP 1302). Intrathecal areca nut significantly increased the PWT in both spinal nerve-ligated and chemotherapy-induced NP (‡ p < 0.001). Intrathecal dihydroergocristine, SB269970, yohimbine, BRL 44408, ARC 239, and JP 1302 significantly reversed the antiallodynic effects of areca nut in both NP states (‡ p < 0.001). Collectively, intrathecal areca nut suppressed mechanical allodynia induced by spinal nerve ligation and cisplatin injection. Furthermore, spinal 5-HT7 receptor and α2A, α2B, and α2C-adrenoceptors contributed to the antiallodynic effects of areca nut.


Actomyosin-ADP states, interhead cooperativity, and the force-velocity relation of skeletal muscle.
Despite intense efforts to elucidate the molecular mechanisms that determine the maximum shortening velocity and the shape of the force-velocity relationship in striated muscle, our understanding of these mechanisms remains incomplete. Here, this issue is addressed by means of a four-state cross-bridge model with significant explanatory power for both shortening and lengthening contractions. Exploration of the parameter space of the model suggests that an actomyosin-ADP state (AM( *)ADP) that is separated from the actual ADP release step by a strain-dependent isomerization is important for determining both the maximum shortening velocity and the shape of the force-velocity relationship. The model requires a velocity-dependent, cross-bridge attachment rate to account for certain experimental findings. Of interest, the velocity dependence for shortening contraction is similar to that for population of the AM( *)ADP state (with a velocity-independent attachment rate). This accords with the idea that attached myosin heads in the AM( *)ADP state position the partner heads for rapid attachment to the next site along actin, corresponding to the apparent increase in attachment rate in the model.


Molecular phylogeny of Anthyllis spp.
For the genus Anthyllis (Fam. Fabaceae, tribe Loteae), with few exceptions, little information is available on the genetic variation among and within species. This genus contains 20 species distributed throughout Europe, Africa, and the Mediterranean basin. The most widespread species is A. vulneraria, and over 30 intraspecies taxa have been identified based on plant morphology. To study the molecular phylogeny of the genus, the sequences of the internal transcribed spacers ITS1 and ITS2 of the nuclear ribosomal DNA of 10 Anthyllis species, including 11 subspecies of A. vulneraria and three subspecies of A. montana, were obtained and analysed together with sequences of five other species of the genus obtained from GenBank. Our results suggest that the genus Anthyllis is not monophyletic and is divided in two main clades: the Anthyllis sensu strictu and the "tetraphylla clade". The former includes most of the Anthyllis species, and the latter includes three annual species more closely related to Lotus. All the taxa were also analysed according to seven chloroplast microsatellites, and these data closely confirm the results obtained with the ITS phylogeny.


Revisiting frequencies of phonological sound classes in speech input: Change over time in child-directed speech.
The purpose of the current study was to revisit a controversial topic: whether frequencies of phonological consonant and vowel classes differ in speech directed to children and to adults. In addition, the current study investigated whether the frequency of phonological consonant and vowel classes changes with children's increasing chronological and/or developmental age. This study analyzed speech input from 44 adults to four different age groups of listeners (i.e., three groups of children at 6, 18, and 36 months of age and one group of adult listeners) in terms of frequency of occurrence of consonant and vowel classes. Results revealed that consonant stop, nasal, fricative and glide manner classes as well as all four consonant place classes were significantly different in speech directed to the four different age groups. A perspective is discussed to better understand the nature of frequency input of phonological sound classes.


Exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy.
To describe the exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy. An institutional review board-approved protocol for a clopidogrel pharmacogenetic program in a community pharmacy was developed to address feasibility and evaluate the pilot program. Subjects taking clopidogrel are asked to participate at the point of medication dispensing. A pharmacist schedules an appointment with subjects to discuss the study and collects a buccal swab sample for CYP2C19 testing. When the results are available, the pharmacist consults with the subject's prescriber regarding test result interpretation and associated recommendations, and schedules a second appointment with the participant to discuss results and review any physician-approved therapeutic changes. The intervention-associated consultation is then billed to the subject's insurance. Subject enrollment has begun. Community pharmacists may be valuable partners in pharmacogenetics.


Implementation of Thromboelastometry for Coagulation Management in Isolated Traumatic Brain Injury Patients Undergoing Craniotomy.
BACKGROUND Coagulopathy (CP) is a modifiable factor linked with secondary brain damage and poor outcome of traumatic brain injury (TBI). A shift towards goal-directed coagulation management has been observed recently. We investigated whether rotational thromboelastometry (ROTEM) based management could be successfully implemented in TBI patients and improve outcomes. MATERIAL AND METHODS A prospective, case-control study was performed. Adult patients with isolated TBI requiring craniotomy were included in this study. All patients underwent standard coagulation tests (SCT). Patients were identified as either in control group or in case group. Patients in the case group were additionally tested with ROTEM to specify their coagulation status. Management of the patients in the control group was based on SCT, whereas management of patients in the case group was guided by ROTEM. Outcome measures were as follows: CP rate, protocol adhesion, blood loss, transfusions, progressive hemorrhagic injury (PHI), re-intervention, Glasgow coma score (GCS) and Glasgow outcome score (GOS) at discharge, and in-hospital mortality. RESULTS There were 134 patients enrolled (65 patients in the control group and 69 patients in the case group). Twenty-six patients in the control group (40%) were found to be coagulopathic (control-CP subgroup) and 34 patients in the case group (49.3%) were found to be coagulopathic (case-CP subgroup). Twenty-five case-CP patients had ROTEM abnormalities triggering protocolized intervention, and 24 of them were treated. Overall ROTEM-based protocol adhesion rate was 85.3%. Postoperative ROTEM parameters of case-CP patients significantly improved, and the number of coagulopathic patients decreased. The incidence of PHI (control versus case group) and neurosurgical re-intervention (control-CP versus case-CP subgroup) was in favor of ROTEM guidance (P<0.05). Mortality and GCS and GOS at discharge did not differ significantly between groups. CONCLUSIONS ROTEM led to consistent coagulation management, improved clot quality, and decreased incidence of PHI and neurosurgical re-intervention. Further studies are needed to confirm benefits of ROTEM in cases of TBI.


Oropharyngeal and Sputum Microbiomes Are Similar Following Exacerbation of Chronic Obstructive Pulmonary Disease.
Growing evidence suggests that the airway microbiota might be involved in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Understanding this relationship requires examination of a large-scale population for a long duration to accurately monitor changes in the microbiome. This type of longitudinal study requires an appropriate sampling strategy; two options are the collection of sputum or oropharyngeal swabs. Comparative analysis of the changes that occur in these two specimen types has not been previously performed. This observational study was conducted to explore oropharyngeal microbial community dynamics over time and to examine the relationship between oropharyngeal swabs and sputum. A total of 114 samples were collected from four patients suffering from severe AECOPD. Bacterial and fungal communities were evaluated using 16S rRNA and ITS sequencing. Inter-individual differences were found in bacterial community structure, but the core genera were shared by both sample types and included 32 lineages. Most of the core genera were members of the phyla Proteobacteria, Firmicutes and Ascomycota. Although the oropharyngeal samples showed higher bacterial alpha diversity, the two sample types generated rather similar taxonomic profiles. These results suggest that the sputum microbiome is remarkably similar to the oropharyngeal microbiome. Thus, oropharyngeal swabs can potentially be used instead of sputum samples for patients with exacerbation of COPD.


Objectively Measured Sedentary Time and Cardiometabolic Biomarkers in US Hispanic/Latino Adults: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Sedentary behavior is recognized as a distinct construct from lack of moderate-vigorous physical activity and is associated with deleterious health outcomes. Previous studies have primarily relied on self-reported data, whereas data on the relationship between objectively measured sedentary time and cardiometabolic biomarkers are sparse, especially among US Hispanics/Latinos. We examined associations of objectively measured sedentary time (via Actical accelerometers for 7 days) and multiple cardiometabolic biomarkers among 12 083 participants, aged 18 to 74 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos of diverse backgrounds (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) were recruited from 4 US cities between 2008 and 2011. Sedentary time (<100 counts/min) was standardized to 16 hours/d of wear time. The mean sedentary time was 11.9 hours/d (74% of accelerometer wear time). After adjustment for moderate-vigorous physical activity and confounding variables, prolonged sedentary time was associated with decreased high-density lipoprotein cholesterol (P=0.04), and increased triglycerides, 2-hour glucose, fasting insulin, and homeostatic model assessment of insulin resistance (all P<0.0001). These associations were generally consistent across age, sex, Hispanic/Latino backgrounds, and physical activity levels. Even among individuals meeting physical activity guidelines, sedentary time was detrimentally associated with several cardiometabolic biomarkers (diastolic blood pressure, high-density lipoprotein cholesterol, fasting and 2-hour glucose, fasting insulin and homeostatic model assessment of insulin resistance; all P<0.05). Our large population-based, objectively derived data showed deleterious associations between sedentary time and cardiometabolic biomarkers, independent of physical activity, in US Hispanics/Latinos. Our findings emphasize the importance of reducing sedentary behavior for the prevention of cardiometabolic diseases, even in those who meet physical activity recommendations.


Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity - Optimization of nicotine loading efficiency.
Nicotine, obtained from tobacco leaves, has been used to promote the cessation of smoking and reduce the risk of COPD and lung cancer. Incorporating the active in lipid nanoparticles is an effective tool to minimize its irritation potential and to use the particles as intermediate to produce final products. However, as a hydrophilic active, it is a challenge to prepare nicotine loaded lipid nanoparticles with high drug loading. In this study, lipid-drug-conjugates (LDC) were formed by nicotine and different fatty acids to enable the production of sufficiently loaded nicotine lipid nanoparticles. The encapsulation efficiency of nicotine in LDC-containing SLN was about 50%, which increased at least fourfold compared to the non-LDC formulations (around 10%) due to the increased lipophilicity of nicotine by strong interactions between positively charged nicotine and negatively charged fatty acids (formation of LDCs). The z-average of all formulations (150-350 nm) proved to be in the required submicron size range with a narrow size distribution. In summary, nicotine loaded LDC lipid nanoparticles with high drug loading were successfully developed with Kolliwax® S and stearic acid as counter-ion forming the LDC and hydrogenated sunflower oil (HSO) as lipid particle matrix.


Preventive Effect on Seroma of Use of PEAK PlasmaBlade after Latissimus Dorsi Breast Reconstruction.
Postoperative seroma is still the main complication after a latissimus dorsi (LD) flap procedure. The etiology of seroma is currently thought to comprise tissue fluids resulting from inflammatory reactions in affected tissue caused by the use of monopolar electrocautery (EC). It is possible that seroma formation can be reduced by using alternative devices such as the PEAK PlasmaBlade (PPB), which provides atraumatic scalpel-like cutting precision while the blade temperature remains close to body temperature. The subjects were 44 patients who underwent breast reconstruction with LD flaps from August 2015 to April 2017. They were retrospectively split into groups treated with a PPB (n = 21) and with conventional EC (n = 23). Outcomes such as rate of seroma formation, total drain discharge volume, indwelling period of drainage at the donor site, length of hospital stay, and operation time were compared between the 2 groups. The incidence of seroma was significantly lower in the PPB group (19.0%) than in the EC group (47.8%). The total drain discharge volume was significantly lower and the indwelling period of drainage and length of hospital stay were significantly shorter in the PPB group. In summary, use of PPB in an LD flap procedure can reduce seroma formation and the lengths of the drainage period and the hospital stay.


miRNA-337-3p inhibits gastric cancer progression through repressing myeloid zinc finger 1-facilitated expression of matrix metalloproteinase 14.
Matrix metalloproteinase 14 (MMP-14), a membrane-anchored MMP that promotes the tumorigenesis and aggressiveness, is highly expressed in gastric cancer. However, the transcriptional regulators of MMP-14 expression in gastric cancer still remain largely unknown. In this study, through mining computational algorithm programs and chromatin immunoprecipitation datasets, we identified adjacent binding sites of myeloid zinc finger 1 (MZF1) and miRNA-337-3p (miR-337-3p) within the MMP-14 promoter. We demonstrated that MZF1 directly bound to the MMP-14 promoter to facilitate its nascent transcription and expression in gastric cancer cell lines. In contrast, endogenous miR-337-3p suppressed the MMP-14 expression through recognizing its binding site within MMP-14 promoter. Mechanistically, miR-337-3p repressed the binding of MZF1 to MMP-14 promoter via recruiting Argonaute 2 and inducing repressive chromatin remodeling. Gain- and loss-of-function studies demonstrated that miR-337-3p suppressed the growth, invasion, metastasis, and angiogenesis of gastric cancer cells in vitro and in vivo through repressing MZF1-facilitated MMP-14 expression. In clinical specimens and cell lines of gastric cancer, MZF1 was highly expressed and positively correlated with MMP-14 expression. Meanwhile, miR-337-3p was under-expressed and inversely correlated with MMP-14 levels. miR-337-3p was an independent prognostic factor for favorable outcome of gastric cancer, and patients with high MZF1 or MMP-14 expression had lower survival probability. Taken together, these data indicate that miR-337-3p directly binds to the MMP-14 promoter to repress MZF1-facilitatd MMP-14 expression, thus suppressing the progression of gastric cancer.


Lidocaine Injection in the Intramuscular Innervation Zone Can Effectively Treat Chronic Neck Pain Caused by MTrPs in the Trapezius Muscle.
An increasing number of people suffer from neck pain due to life style and prolonged use of computers. Research has revealed that myofascial trigger points (MTrPs) and the intramuscular innervation zone (IZ) are involved in neck pain. MTrPs are induced mainly by IZ dysfunction of the affected skeletal muscle and the 2 do not overlap in location. The question is whether injection treatment in MTrPs or in the IZ is more effective to relieve MTrPs-associated pains. The precise location and body-surface map of the intramuscular IZ in the trapezius muscle and a clinical injection study in the IZ may provide a useful answer to the question. This study aimed to investigate the efficacy of lidocaine injection in the intramuscular IZ for the treatment of chronic neck pain caused by MTrPs in the trapezius muscle. Prospective observational study, approved by the local research ethics. University hospital, departments of Anesthesiology and Anatomy. First, for the determination of IZ distribution and body-surface mapping, a modified intramuscular Sihler's neural staining technique was applied to elucidate nerve distribution patterns of the trapezius muscle. Then, 120 patients with myofascial pain syndrome (MPS) of the trapezius muscle were randomly divided into 5 groups for analysis. Group 1 (n = 24) received injections of saline (0.9% NaCl) at the MTrPs. Group 2 (n = 24) received injections of 0.5% lidocaine at the MTrPs. Group 3 (n = 24) received injections of saline (0.9% NaCl) at the mid-upper trapezius (Point E). Group 4 (n = 24) received injections of 0.5% lidocaine at Point E. Group 5 (n = 24) received a combined injection of 0.5% lidocaine treatment at both Point E and the lower trapezius (Point F). The injection dose was 4 mL at each injection site. All patients received injections once a week for 4 weeks. The visual analogue scale (VAS) and the frequency of painful days per month (FPD) were obtained before treatment and at 2, 4, and 6 months after treatment. The intramuscular terminal nerve branches presented a "dendritic" distribution in the trapezius muscle and were connected with each other to form an S-shaped IZ belt in the middle of the muscle belly. Compared with the MTrP injection group, lidocaine-injection therapy in the IZ significantly reduced the degree and frequency of neck pain in patients at 6 months after treatment, especially the combined lidocaine-injection therapy in the IZ of both the mid-upper trapezius and the lower trapezius are more effective (all P < 0.05). This study confirms that lidocaine-injection therapy in the IZ significantly reduces the degree and frequency of neck pain in patients at 6 months after treatment. The combined lidocaine-injection therapy in the IZ of both the mid-upper trapezius and the lower trapezius is more effective. In addition, this study establishes a clear distribution map of intramuscular nerves that will be conducive to the future use of chemical blockers and electrical stimulation in the nervous system in treating MPS of the trapezius muscle. The small number of patients and the short duration of follow-up.


Immune defects caused by mutations in the ubiquitin system.
The importance of the ubiquitin system in health and disease has been widely recognized in recent decades, with better understanding of the various components of the system and their function. Ubiquitination, which is essential to almost all biological processes in eukaryotes, was also found to play an important role in innate and adaptive immune responses. Thus it is not surprising that mutations in genes coding for components of the ubiquitin system cause immune dysregulation. The first defect in the system was described 30 years ago and is due to mutations in the nuclear factor κB (NF-κB) essential modulator, a key regulator of the NF-κB pathway. With use of novel sequencing techniques, many additional mutations in different genes involved in ubiquitination and related to immune system function were identified. This can be clearly illustrated in mutations in the different activation pathways of NF-κB, which result in aberrations in production of various proinflammatory cytokines. The inherited diseases typically manifest with immunodeficiency, autoimmunity, or autoinflammation. In this perspective we provide a short description of the ubiquitin system, with specific emphasis given to its role in the immune system. The various immunodeficiency conditions identified thus far in association with defective ubiquitination are discussed in more detail.


Spatiotemporal aspects of sympathetic C-fiber afferent activity in pressor reflex during abdominal ischemia.
Activation of abdominal sympathetic visceral afferents during ischemia elicits excitatory cardiovascular reflexes. The present study examined the time course and discharge patterns of activation of ischemically sensitive sympathetic C-fiber afferents, and then the relationship between summated afferent activity and the pressor reflex induced by prolonged abdominal ischemia was determined. Single-unit activity of abdominal C-fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 30 min of ischemia. The reflex pressor response to abdominal ischemia was induced by occlusion of celiac and superior mesenteric arteries. Of 68 C-fiber afferents studied, 36 (approximately 53%) were activated during 30 min of ischemia, whereas the activity of the remaining 32 were not altered. Onset latencies of 36 C-fiber afferents activated by ischemia ranged from 1.0 to 17.4 min with an average of 6.1 +/- 0.8 min. The majority of activated afferents manifested a bursting pattern of discharge activity as ischemia was prolonged beyond 10 min. Summated response of activated afferents, but not individual afferent activity, was related closely to the reflex pressor response during 30 min of ischemia. These results suggest that both recruitment of sufficient numbers of C-fiber afferents and adequate discharge frequency of afferents constitute an encoding mechanism for the pressor reflex during abdominal ischemia.


Improved visual acuity after microsurgical clipping of a symptomatic anterior cerebral artery aneurysm: case report.
Background: Symptomatic aneurysms of the anterior cerebral artery causing visual impairments are rare and preponderantly lacking in the literature. It is further under discussion, whether operative clipping or endovascular coiling might be superior in order to achieve visual recovery. We therefore present a case of a patient with progressive visual loss caused by an aneurysm of the right A1-A2 segment compressing the ipsilateral optic nerve. Methods: A 57-year-old woman was admitted to our neurosurgical department with visual impairment of the right eye. On admission, visual acuity was 0.05 dpt. and visual field testings showed severe medial and lateral quadrant-anopia. MRI scans and angiography (DSA) demonstrated an aneurysm of the A1-A2 segment compressing the right optic nerve. During surgery, the aneurysm was clipped, the space-occupying dome removed and the nerve relieved from any adhesions. Instantaneously after surgery, visual acuity significantly improved from 0.05 to 0.9 dpt. Conclusions: Anterior cerebral artery aneurysms may present with acute visual impairments and surgical clipping significantly improves impaired visual acuity.


OsMPH1 regulates plant height and improves grain yield in rice.
Plant height is a major trait affecting yield potential in rice. Using a large-scale hybrid transcription factor approach, we identified the novel MYB-like transcription factor OsMPH1 (MYB-like gene of Plant Height 1), which is involved in the regulation of plant height in rice. Overexpression of OsMPH1 leads to increases of plant height and grain yield in rice, while knockdown of OsMPH1 leads to the opposite phenotypes. Microscopy of longitudinal stem sections indicated that a change in internode cell length resulted in the change in plant height. RNA sequencing (RNA-seq) analysis of transgenic rice lines showed that multiple genes related to cell elongation and cell wall synthesis, which are associated with plant height and yield phenotypes, exhibited an altered expression profile. These results imply that OsMPH1 might be involved in specific recognition and signal transduction processes related to plant height and yield formation, providing further insights into the mechanisms underlying the regulation of plant height and providing a candidate gene for the efficient improvement of rice yield.


The impact of income support systems on healthcare quality and functional capacity in workers with low back pain: a realist review.
Low back pain (LBP) is a leading cause of work disability. While absent from work, workers with LBP may receive income support from a system such as workers' compensation or social security. This study examines how and in what contexts income support systems impact the healthcare quality for people with work disability and LBP and their functional capacity. We performed a realist review. Five initial theories about the relationship between income support systems and outcomes were developed, tested, and refined by acquiring and synthesising academic literature from purposive and iterative electronic database searching. This process was supplemented with gray literature searches for policy documents and semistructured interviews with experts in income support, health care, and LBP. Income support systems influence healthcare quality through funding restrictions, healthcare provider administrative burden, and allowing employers to select providers. They also influence worker functional capacity through the level of participation and financial incentives for employers, measures to prove the validity of the worker's LBP, and certain administrative procedures. These mechanisms are often exclusively context-dependent, and generate differing and unintended outcomes depending on features of the healthcare and income support system, as well as other contextual factors such as socioeconomic status and labour force composition. Research and policy design should consider how income support systems may indirectly influence workers with LBP through the workplace.


Potential effects of sulforaphane to fight obesity.
Obesity is linked to the onset of many diseases such as diabetes mellitus, cardiovascular diseases and cancer, among others. The prevalence of obesity nearly doubled worldwide between 1980 and 2014. Simultaneously, in the last decade, the effects of sulforaphane as a potential treatment for obesity have been investigated, with promising results. Fruits and vegetables and their processed agri-food co-products are good sources of natural health-promoting compounds. Brassica crops are among the most produced crops in the world and are a good source of glucoraphanin, which, following hydrolysis, releases sulforaphane. The Brassicaceae family generates large amounts of co-products with no intended use, causing negative economic and environmental impact. Valorization of these co-products could be achieved through their exploitation for the extraction of bioactive compounds such as sulforaphane. However, the extraction process still needs further improvement for its economic feasibility. This article reviews the potential effects of sulforaphane in the treatment of obesity, linked to the relevance of giving Brassica co-products added value, which is of key importance for the competitiveness of farmers and the agri-food industry. © 2018 Society of Chemical Industry.


Correcting bulk in-plane motion artifacts in MRI using the point spread function.
A technique is proposed for correcting both translational and rotational motion artifacts in magnetic resonance imaging without the need to collect additional navigator data or to perform intensive postprocessing. The method is based on measuring the point spread function (PSF) by attaching one or two point-sized markers to the main imaging object. Following the isolation of a PSF marker from the acquired image, translational motion could be corrected directly from the modulation transfer function, without the need to determine the object's positions during the scan, although the shifts could be extracted if desired. Rotation is detected by analyzing the relative displacements of two such markers. The technique was evaluated with simulations, phantom and in vivo experiments.


Growth of enterotoxigenic Bacillus cereus on salmon (Oncorhynchus nerka).
We previously demonstrated the widespread presence of enterotoxigenic Bacillus cereus in marine foods. In view of the widespread consumption of raw fish, we sought to determine the ability of this organism to grow on the surface of wild Alaskan salmon at abusive temperatures (12, 16, and 20°C), using an isolate able to produce elevated levels of hemolysin BL enterotoxin and nonhemolytic enterotoxin. An incubation temperature of 37°C for colony formation was found to be selective for B. cereus grown on salmon held for up to 24 h at each temperature. A fivefold increase in log CFU per gram was observed after 26 and 22 h at 16 and 20°C, respectively, while a >4-log CFU/g increase occurred on salmon held at 12°C for 48 h. Generation times of 169.7, 53.5, and 45.6 min were observed at 12, 16, and 20°C. Nonhemolytic enterotoxin was detected when levels of B. cereus were in excess of 10(8) CFU/g. Nisin, at concentrations of 1 and 15 m g/g of salmon, reduced levels of B. cereus 2.5- and 25-fold, respectively. Our results indicate that fresh salmon can serve as an excellent substrate for enterotoxigenic B. cereus and that this organism can reach levels associated with foodborne illness following moderate temperature abuse.


The Influence of the Modulation Index on Frequency-Modulated Steady-State Visual Evoked Potentials.
Based on increased user experience during stimulation, frequency-modulated steady-state visual evoked potentials (FM-SSVEPs) have been suggested as an improved stimulation method for brain-computer interfaces. Adapting such a novel stimulation paradigm requires in-depth analyses of all different stimulation parameters and their influence on brain responses as well as the user experience during the stimulation. In the current manuscript, we assess the influence of different values for the modulation index, which determine the spectral distribution in the stimulation signal on FM-SSVEPs. We visually stimulated 14 participants at different target frequencies with four different values for the modulation index. Our results reveal that changing the modulation index in a way that elevates the stimulation power in the targeted sideband leads to increased FM-SSVEP responses. There is, however, a tradeoff with user experience as increased modulation indices also lead to increased perceived flicker intensity as well as decreased stimulation comfort in our participants. Our results can guide the choice of parameters in future FM-SSVEP implementations.


Polycyclic aromatic hydrocarbons in electrocautery smoke during peritonectomy procedures.
This study identified and quantified polycyclic aromatic hydrocarbons (PAHs) in electrocautery smoke during 40 peritonectomy procedures and investigated any correlations and/or differences between levels of PAHs and perioperative variables. PAHs were measured in personal and stationary sampling by 40 mm Millipore cassettes, for adsorption of both gaseous and particle-bound PAHs. Results. All 16 USEPA priority pollutant PAHs were detected during peritonectomy procedures, naphthalene being the most abundant. For the only two PAHs with Swedish occupational exposure limits (OELs), benzo[a]pyrene and naphthalene, limits were never exceeded. Amount of bleeding was the only perioperative variable that correlated with levels of PAHs. Low levels of PAHs were detected in electrocautery smoke during peritonectomy procedures, and an increased amount of bleeding correlated with higher levels of PAHs. For evaluation of long-term health effects, more studies are needed.


Fresnel diffraction at an opaque strip expressed by means of asymptotic representations of Fresnel integrals.
The paper presents an asymptotic expression of relative intensity distribution in a Fresnel diffraction pattern at an opaque straight strip illuminated with a spherical wave. The asymptotic expression is used in an analysis showing an area of validity where the asymptotic expression reduces to an asymptotic expression of relative intensity distribution in a Fresnel diffraction at a half plane. The area of validity is defined through width of the geometrical shadow in a Fresnel diffraction pattern at an opaque straight strip and distance of a point under study to the center of the Fresnel diffraction pattern. Within this area, relative intensity in the Fresnel diffraction pattern at an opaque straight strip shows sinusoidal behavior, which can be used in easy location of maxima or minima of the relative intensity. The result of the analysis is supported by experiments realized in the area of validity and outside it.


To coil or not to coil: application practices, perception and efficacy of mosquito coils in a malaria-endemic community in Ghana.
Although evidence of mosquito coils' impact on disease epidemiology is limited, they are popularized as mosquito-borne disease prevention devices. Their usage affects the environment, human and mosquito health. This study investigated the perception, usage pattern and efficacy of coils in a predominantly poor malaria-endemic Ghanaian peri-urban area. Information on protection methods, perception and usage pattern was garnered using questionnaires. The efficacy of commonly used coils in the area was then assessed on the malaria vector, Anopheles gambiae, in a glass chamber. Sole or co-application of mosquito control methods and risky usage practices were reported. Coils were deemed harmful to humans and mosquitoes, and their perceived effectiveness varied, with several factors influencing their purchase. High d-allethrin concentration coils induced quicker mosquito knockdown; however, mortality was less than 85%. The coil usage pattern compromises users' health and can enhance mosquito tolerance to d-allethrin. The coils were ineffective against the vector, outlining a dichotomy between the users' perception of efficacy and the observed efficacy. Hence, the usage of other safer and more effective vector control methods should be encouraged to protect households.


Contribution of Biogas Slurry-Derived Colloids to Plant P Uptake and Phosphatase Activities: Spatiotemporal Response.
The bioavailability for varied-size phosphorus (P)-binding colloids (Pcoll) especially from external P sources in soil terrestrial ecosystems remains unclear. This study evaluated the differential contribution of various-sized biogas slurry (BS)-derived colloids to plant available P uptake in the rhizosphere and the corresponding patterns of phosphatase response. Keeping the same content of total P input (15 mg kg-1), we applied different size-fractioned BS-derived colloids including nanosized colloids (NCs, 1-20 nm), fine-sized colloids (FCs, 20-220 nm), and medium-sized colloids (MCs, 220-450 nm) respectively to conduct a 45-day rice (Oryza sativa L.) rhizotron experiment. During the whole cultivation period, the dynamics of chemical characteristics and P fractions in each experimental rhizosphere soil solution were analyzed. The spatial and temporal dynamics examination of P-transforming enzymes (acid phosphatases) in the rice rhizosphere was visualized by a soil zymography technique after 5, 25, and 45 days of rice transplantation. The results indicated that the acid phosphatase activities and its hot spot areas were significantly 1) correlated with the relative bioavailability of colloidal P (RBAcoll), 2) increased with the colloid-free (truly dissolved P) and BS-derived NC addition, and 3) affected by the plant growth stage. With the nanosized BS colloid addition, the RBAcoll and plant biomass were respectively found to be the highest (64% and 1.22 g plant-1), in which the acid phosphatase-catalyzed hydrolysis of organic Pcoll played an important role. All of the above suggested that nanosized BS-derived colloids are an effective alternative to conventional phosphorus fertilizer for promoting plant P uptake and P bioavailability.


Transvaginal laparoscopic cholecystectomy (hybrid NOTES cholecystectomy).
Natural orifice transluminal endoscopic surgery (NOTES) is usually performed by using a flexible endoscope. However, this instrument shows several limitations in the manipulation of intra-abdominal organs. Using the laparoscope instead of the flexible endoscope eliminates the need for new instruments and technical skills. We used conventional laparoscopic instruments for improving operative efficiency and single-port access (SPA) to prevent air leakage from the vaginal port. A 54-year-old female patient was admitted to our hospital with uterine prolapse and symptomatic gallstones. She underwent a transvaginal laparoscopic cholecystectomy. The transvaginal hysterectomy was performed after the cholecystectomy by a gynecologist. The operative time for the cholecystectomy was 86 minutes. She was discharged on postoperative day 8. This technique combines the advantages of NOTES and SPA surgery. We think that this technique can be easily performed from using laparoscopic instruments.


An emergency call system for patients in locked-in state using an SSVEP-based brain switch.
Patients in a locked-in state (LIS) due to severe neurological disorders such as amyotrophic lateral sclerosis (ALS) require seamless emergency care by their caregivers or guardians. However, it is a difficult job for the guardians to continuously monitor the patients' state, especially when direct communication is not possible. In the present study, we developed an emergency call system for such patients using a steady-state visual evoked potential (SSVEP)-based brain switch. Although there have been previous studies to implement SSVEP-based brain switch system, they have not been applied to patients in LIS, and thus their clinical value has not been validated. In this study, we verified whether the SSVEP-based brain switch system can be practically used as an emergency call system for patients in LIS. The brain switch used for our system adopted a chromatic visual stimulus, which proved to be visually less stimulating than conventional checkerboard-type stimuli but could generate SSVEP responses strong enough to be used for brain-computer interface (BCI) applications. To verify the feasibility of our emergency call system, 14 healthy participants and 3 patients with severe ALS took part in online experiments. All three ALS patients successfully called their guardians to their bedsides in about 6.56 seconds. Furthermore, additional experiments with one of these patients demonstrated that our emergency call system maintains fairly good performance even up to 4 weeks after the first experiment without renewing initial calibration data. Our results suggest that our SSVEP-based emergency call system might be successfully used in practical scenarios.


Genetic transformation in the methanogen Methanococcus voltae PS.
Mutations causing requirements for histidine, purine, and vitamin B12 were obtained in strain PS of Methanococcus voltae (archaebacteria) upon irradiation with UV or gamma rays. The first two mutations were shown to revert at low frequencies and were used to demonstrate the occurrence of transformation with homologous, wild-type DNA. The transformation rates obtained for these presumably chromosomal markers were in the range of 2 to 100 transformants per microgram of DNA. Mutants resistant to 2-bromoethanesulfonate and to 5-methyl-DL-tryptophan were also isolated.


Characterization of Biofilm Formation in [Pasteurella] pneumotropica and [Actinobacillus] muris Isolates of Mouse Origin.
[Pasteurella] pneumotropica biotypes Jawetz and Heyl and [Actinobacillus] muris are the most prevalent Pasteurellaceae species isolated from laboratory mouse. However, mechanisms contributing to their high prevalence such as the ability to form biofilms have not been studied yet. In the present investigation we analyze if these bacterial species can produce biofilms in vitro and investigate whether proteins, extracellular DNA and polysaccharides are involved in the biofilm formation and structure by inhibition and dispersal assays using proteinase K, DNase I and sodium periodate. Finally, the capacity of the biofilms to confer resistance to antibiotics is examined. We demonstrate that both [P.] pneumotropica biotypes but not [A.] muris are able to form robust biofilms in vitro, a phenotype which is widely spread among the field isolates. The biofilm inhibition and dispersal assays by proteinase and DNase lead to a strong inhibition in biofilm formation when added at the initiation of the biofilm formation and dispersed pre-formed [P.] pneumotropica biofilms, revealing thus that proteins and extracellular DNA are essential in biofilm formation and structure. Sodium periodate inhibited the bacterial growth when added at the beginning of the biofilm formation assay, making difficult the assessment of the role of β-1,6-linked polysaccharides in the biofilm formation, and had a biofilm stimulating effect when added on pre-established mature biofilms of [P.] pneumotropica biotype Heyl and a majority of [P.] pneumotropica biotype Jawetz strains, suggesting that the presence of β-1,6-linked polysaccharides on the bacterial surface might attenuate the biofilm production. Conversely, no effect or a decrease in the biofilm quantity was observed by biofilm dispersal using sodium periodate on further biotype Jawetz isolates, suggesting that polysaccharides might be incorporated in the biofilm structure. We additionally show that [P.] pneumotropica cells enclosed in biofilms were less sensitive to treatment with amoxicillin and enrofloxacin than planktonic bacteria. Taken together, these findings provide a first step in understanding of the biofilm mechanisms in [P.] pneumotropica, which might contribute to elucidation of colonization and pathogenesis mechanisms for these obligate inhabitants of the mouse mucosa.


Plasma somatomedin activity and urinary hydroxyproline excretion during administration of human growth hormone in children with short stature. Short-term effects.
15 prepubertal children with short stature and varying peak growth hormone (GH) levels were given daily injections of increasing doses of human growth hormone (hGH) for consecutive periods of 7 days. Somatomedin activity (SM-act) and total urinary hydroxyproline excretion (THP) were determined in each period. In patients with a varying degree of GH deficiency, but without non-pituitary dependent abnormalities, there was a high correlation between basal SM-act and height velocity. Patients with catch-up growth had an unproportionally low SM-act and the Prader-Willi and transient Cushing patients had an unproportionally high one. All patients showed increases of SM-act and THP on hGH administration, but there was considerable variation of the shape of the curve and of the amplitude of the response. 3 1/2 days after the last injection, SM-act was back to basal level. There was a good correlation between weight-for-height and SM-act during the first two hGH doses, which fits the hypothesis of GH and insulin synergism on SM generation.


Bilateral simultaneous rupture of the quadriceps tendons. A report of four cases and review of the literature.
Four patients with bilateral simultaneous rupture of the quadriceps tendons were each older than 70 years of age. In the first patient the diagnosis was missed and one side was managed conservatively, while the other side was surgically treated. A combination of inadequate postoperative immobilization and the use of chromic catgut sutures probably caused failure of the repair, requiring revision surgery. The other three patients were treated by bilateral operative repair and had satisfactory results. Nonabsorbable suture material use and a minimum period of six weeks of postoperative immobilization are recommended.


Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo.
The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment. We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays. We observed a very robust synergism between ITGB4 and E-/P-selectin for the regulation of tumor growth, accompanied by an increased recruitment of CD11b+ Gr-1Hi cells with low granularity (i.e., myeloid-derived suppressor cells, MDSCs) specifically into ITGB4-depleted tumors. ITGB4-depleted tumors undergo apoptosis and actively attract MDSCs, well-known to promote tumor growth in several cancers, via increased secretion of different chemokines. MDSC trafficking into tumors crucially depends on E-/P-selectin expression. Analyses of clinical samples confirmed an inverse relationship between ITGB4 expression in tumors and number of tumor-infiltrating leukocytes. These findings suggest a distinct vulnerability of ITGB4Lo tumors for MDSC-directed immunotherapies.


Hospitalisation and compulsion: the research agenda.
Keown et al's paper highlights the complex nature of social determinants of hospital admission and compulsory care. We review here how research into compulsion in mental health has progressed beyond epidemiological studies of rates of admission. There is now a wider recognition of the range of compulsory and coercive processes used and how they are experienced by patients. The results of recent studies have confirmed the importance of confronting the complexity that Keown et al have presented. They have also produced unexpected and intriguing findings that set the direction for future research.


Primary hyperparathyroidism due to solitary adenoma. A comparative multicentre study of early and long-term results of different surgical regimens.
Surgical regimens for treatment of solitary parathyroid adenoma were compared in a multicentre study in five departments of surgery in the United States and Europe. Three hundred and twenty-five patients fulfilled the inclusion criteria. Eight years after the operation 272 patients (84%) were available for follow-up investigation. Severe postoperative hypocalcaemia (less than 2.00 mmol) was significantly more common after bilateral than unilateral exploration (p less than 0.001), and in women (p less than 0.01). Neither age nor preoperative serum calcium concentration was related to the severity of postoperative hypocalcaemia. At follow-up, 96% of the patients who had had unilateral, and 89% of those who had had Bilateral exploration had remained normocalcaemic without further treatment. Of the patients who had had incisional biopsies of normal glands 8% had hypercalcaemia and 8% had hypocalcaemia. Of patients operated on without a biopsy being taken or who had had one whole normal gland removed 1% were hypercalcaemic and 4% were hypocalcaemic. Early and late hypocalcaemia are reduced by atraumatic handling of the normal parathyroid gland without increasing the risk of persistent or recurrent hypercalcaemia.


Experiences of peripartum depressive symptoms among Chinese middle-class migrant women in the Netherlands: a qualitative study of migrant motherhood.
A low educational level and poor economic status have repeatedly been identified as the main risk factors of peripartum depression among migrant women in existing studies. However, there is limited knowledge about a group of highly educated and middle-class migrant women, and how this group of migrant women deals with those risks and which protective factors facilitate a successful transition into motherhood in the host country. This study aims to shed light on the multifaceted psychosocial challenges during the peripartum period for Chinese migrant women in their relationships with intimate partners, mothers, and mothers-in-law. In this qualitative study, semi-structured in-depth interviews were conducted digitally with 46 pregnant and postpartum middle-class Chinese migrant women with peripartum depressive symptoms in the Netherlands. The interview data were analyzed using content analysis. The multifaceted psychosocial challenges for women with peripartum depressive symptoms were classified into three key categories: the ambivalence towards different mothering values, perceived inadequate and mismatching social support and adverse childhood experiences. Well-educated middle-class Chinese migrant women with peripartum depressive symptoms faced challenges in the transition into motherhood due to the unmet self-expectations regarding the pursuit of a good quality of life and a happy motherhood. The nurturing intimate relationships and adequate social support in the host country have mitigated recollections of their adverse childhood experiences. Future prevention programs and postpartum care should consider the contextual specificity based on the childhood history. International mental health research should pay more attention to the growing and potentially vulnerable group of well-educated middle-class migrant women.