Wettability-defined droplet imbibition in ceramic mesopores.
Wettability-defined liquid infiltration into porous materials in nature and several industrial applications is of fundamental interest. Direct observation of wetting-controlled imbibition in mesopores is anticipated to deliver important insights into the interplay between nanoconfined liquid movement and nanoscale wettability. We present a systematic study of water imbibition into mesoporous silica thin films with wetting properties precisely adjusted through chemical functionalization. We observe the liquid infiltration, resulting in an imbibition ring around the water droplet, by top-view imaging using a camera with collimated coaxial illumination. With decreasing hydrophilicity, the maximum imbibition area around the droplet decreases, accompanied by a simultaneous change in the imbibition kinetics and imbibition mechanism. Initially, the imbibition kinetics follow a modified Lucas-Washburn law that considers a strong influence of evaporation. However, with increasing imbibition time after reaching constant imbibition ring dimensions, the imbibition area starts to increase again, causing a deviation from the applied model. This observation is ascribed to water-mediated surface activation at the imbibition front, leading to a slightly increased wettability, which is also confirmed by water adsorption measurements. Furthermore, recently described spontaneous condensation-evaporation imbalances that cause oscillations of the imbibition front could be verified and were studied with regard to changing wetting properties. By increasing the contact angle of the material and therefore the partial pressure needed for capillary condensation, the amplitude of the imbibition front oscillations decreases. These results provide insights into the wettability-defined complex movement of water in mesoporous structures, which has practical implications, e.g., for nano/microfluidic devices and water purification or harvesting.


[Morphofunctional changes in animal skin during combined administration of zinc sulfate and vitamin A].
Morphological and histochemical skin properties were studied in male rats in single and successive peroral injections of Zinc sulphate and vitamin A. Long term (25 d) peroral administration of vitamin A 2 mg/100 g in dose was shown to cause hypozincaemia. Zinc sulphate and vitamin A are capable of influencing proliferation and protein metabolism of epidermal cells and number of lymphocytes and mast cells in dermis. With the aim of the drugs named thickness of epidermis, ratio of its layers thickness as well as the rate of protein synthesis in germinal layer of epidermis can be changed purposefully. These parameters depend both on the drug injection technique (single, separated or successive injections) and time periods. Perspective of obtaining a complexed biocoordinative compound on the base of vitamin A and microtrace element of Zinc is discussed.


Comparison of alpha/beta estimates from homogeneous (individual) and heterogeneous (population) tumor control models for early stage prostate cancer.
Radiobiological parameter estimates for prostate cancer are obtained from both a homogeneous (individual) and heterogeneous (population) tumor control model based on Poisson statistics and the linear quadratic model of cell survival. Parameter estimates for both models are highly correlated: statistically equivalent fits are achievable using either (1) linear quadratic (LQ) parameters with low numbers of radioresistant tumor stem cells, or (2) LQ parameters with corresponding larger number of radiosensitive tumor stem cells. A theoretical framework is developed to explain this correlation. A Monte Carlo error analysis based on binomial statistics is used to estimate confidence intervals for all parameter estimates. It was found that both the homogeneous and heterogeneous models produce approximately equivalent estimates of radiobiological parameters, including the alpha/beta ratio. However, the 95% confidence interval for the alpha/beta ratio derived from the heterogeneous model are considerably larger than those derived from the homogeneous model, which indicate the homogeneous model overestimates the statistical significance of the alpha/beta estimate.


Combined hereditary deficiency of factors VII and VIII: a distinct coagulation disorder due to the 'lack' of an autosomal gene controlling factor VII and VIII activation?
A patient with a combined hereditary deficiency of factors VII and VIII is presented together with a family study. The main bleeding manifestations were easy bruising and bleeding after tooth extractions. No hemarthrosis was ever observed. The main laboratory features consisted in a mild prolongation of prothrombin time and of partial thromboplastin time. TG test was abnormal and was corrected by the addition of adsorbed normal plasma. Specific assays revealed a moderate defect of factors VII and VIII. All other clotting factors were within normal limits. The factor VII antigen in the propositus was normal or nearly normal. The factor-VIII-associated antigen was also normal. Five additional family members presented the same coagulation pattern and were variably symptomatic. The hereditary transmission pattern seems to be autosomal dominant. The defect appears to be due to a structural abnormality of a gene controlling factors VII and VIII activation.


Screening of in vivo activated genes in Enterococcus faecalis during insect and mouse infections and growth in urine.
Enterococcus faecalis is part of the commensal microbiota of humans and its main habitat is the gastrointestinal tract. Although harmless in healthy individuals, E. faecalis has emerged as a major cause of nosocomial infections. In order to better understand the transformation of a harmless commensal into a life-threatening pathogen, we developed a Recombination-based In VivoExpression Technology for E. faecalis. Two R-IVET systems with different levels of sensitivity have been constructed in a E. faecalis V583 derivative strain and tested in the insect model Galleria mellonella, during growth in urine, in a mouse bacteremia and in a mouse peritonitis model. Our combined results led to the identification of 81 in vivo activated genes. Among them, the ef_3196/7 operon was shown to be strongly induced in the insect host model. Deletion of this operonic structure demonstrated that this two-component system was essential to the E. faecalis pathogenic potential in Galleria. Gene ef_0377, induced in insect and mammalian models, has also been further analyzed and it has been demonstrated that this ankyrin-encoding gene was also involved in E. faecalis virulence. Thus these R-IVET screenings led to the identification of new E. faecalis factors implied in in vivo persistence and pathogenic potential of this opportunistic pathogen.


Perinatal aspects of bilirubin metabolism.
Study of bilirubin metabolism in the fetus and newborn continues to reveal new insights into fetal physiology and maternal-fetal-neonatal relationships. Therapeutic advances directed toward prevention as well as treatment of hyperbilirubinemia continue to expand our understanding of both the basic metabolic pathways and previously unsuspected interplay between host and environment. Seemingly insignificant alterations in temperature, oxygen, carbohydrate, or light itself have been shown to affect the delicate balances in bilirubin metabolism. Similar impact upon other developing systems undoubtedly occur. Those who accept responsibility for the care of the fetus and newborn must recognize that all we do and all we fail to do in their care has a much greater potential for affecting the quality of life than at any other time.


Significant parameters in the evaluation of donor lungs in single-lung cellular ex vivo lung perfusion.
Typically, single-lung ex vivo lung perfusion (SL-EVLP) is preferred when there is concern of contamination from the opposite lung. However, a comprehensive assessment of the SL-EVLP has not been completed. The purpose of this study is to compare the physiological parameters of SL-EVLP and double-lung EVLP (DL-EVLP) in the assessment of transplant suitability. Seven pairs of rejected donor lungs were perfused in cellular EVLP, with a tidal volume of 6 ml/kg ideal body weight and a perfusion flow of 70 ml/kg/min. The transplant suitability of each side was judged in the DL-EVLP. Subsequently, the tidal volume and flow were reduced by half. The right SL-EVLP was maintained for 10 min by clamping the left main pulmonary artery and the bronchus. Similarly, left SL-EVLP was performed. The physiological parameters were compared between SL-EVLP and DL-EVLP. PO2/FiO2 ratio was significantly lower in SL-EVLP than in DL-EVLP [182.5 (127.5-309.5) vs 311.5 (257.5-377.0) mmHg, P < 0.001]. There was a significant correlation with a higher shunt fraction and PCO2 in the pulmonary vein in SL-EVLP when compared to DL-EVLP. There was no difference in peak inspiratory and plateau pressures between SL-EVLP and DL-EVLP. Suitable lungs (n = 6) were associated with better PO2/FiO2 ratios and lower airway pressures than non-suitable lungs (n = 8). In SL-EVLP, peak inspiratory and plateau pressures have clinical utility in the assessment of the transplant suitability. It is important that PO2/FiO2 ratio in SL-EVLP is appreciably lower than that in DL-EVLP. This discrepancy should be considered in the evaluation of the transplant suitability in SL-EVLP.


Neuro-Behçet's disease in childhood: a focus on the neuro-ophthalmological features.
Neuro-Behçet's disease (NBD) involves the central nervous system; peripheral nervous system involvement is not often reported. NBD is quite common in adult patients and occurs rarely during childhood and adolescence. Young patients may share symptoms and signs of NBD with other neuro-ophthalmological disorders (e.g. idiopathic intracranial hypertension); thus, making the differential diagnosis difficult. Neuroimaging is mandatory and necessary for a correct NBD diagnosis but in children radiological examinations are often difficult to perform without sedation. From 1971 to 2011, 130 patients aged ≤16 years have been reported with NBD, according to retrospective surveys, case series, and case reports. The origin of the reported cases met the well-known geographical distribution of Behçet's disease (BD); the mean age at presentation of neurological findings was 11.8 years, with male gender prevalence (ratio, 2.9:1). We considered in detail the neuro-ophthalmological features of the 53 cases whose neuroimaging alterations were described with an assigned radiological pattern of the disease (parenchymal: 14 cases, non-parechymal: 35 cases, and mixed: 4 cases). In 19/53 patients (36%), neuro-ophthalmological symptoms anticipated any pathognomonic sign for a BD diagnosis, or only occasional aphtae were recalled by the patients. Family history was positive in 17% of subjects. Headache was reported in 75% of the patients; in those presenting with cerebral vascular involvement, headache was combined to other symptoms of intracranial hypertension. Papilledema was the most frequently reported ophthalmological finding, followed by posterior uveitis. Treatment consisted of systemic steroids in 93% of patients, often combined with other immunosuppressive drugs (especially colchicine and azathioprine). Clinical recovery or improvement was documented in the large majority of patients. Nine subjects had definitive alterations, and one died. Based on our review and personal experience, a delayed diagnosis, and the consequently delayed immunosuppressive treatment, may favour permanent sequelae, in particular, optic atrophy.


Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples.
Next Generation Sequencing (NGS) has become a valuable tool for molecular landscape characterization of cancer genomes, leading to a better understanding of tumor onset and progression, and opening new avenues in translational oncology. Formalin-fixed paraffin-embedded (FFPE) tissue is the method of choice for storage of clinical samples, however low quality of FFPE genomic DNA (gDNA) can limit its use for downstream applications. To investigate the FFPE specimen suitability for NGS analysis and to establish the performance of two solution-based exome capture technologies, we compared the whole-exome sequencing (WES) data of gDNA extracted from 5 fresh frozen (FF) and 5 matched FFPE lung adenocarcinoma tissues using: SeqCap EZ Human Exome v.3.0 (Roche NimbleGen) and SureSelect XT Human All Exon v.5 (Agilent Technologies). Sequencing metrics on Illumina HiSeq were optimal for both exome systems and comparable among FFPE and FF samples, with a slight increase of PCR duplicates in FFPE, mainly in Roche NimbleGen libraries. Comparison of single nucleotide variants (SNVs) between FFPE-FF pairs reached overlapping values >90 % in both systems. Both WES showed high concordance with target re-sequencing data by Ion PGM™ in 22 lung-cancer genes, regardless the source of samples. Exon coverage of 623 cancer-related genes revealed high coverage efficiency of both kits, proposing WES as a valid alternative to target re-sequencing. High-quality and reliable data can be successfully obtained from WES of FFPE samples starting from a relatively low amount of input gDNA, suggesting the inclusion of NGS-based tests into clinical contest. In conclusion, our analysis suggests that the WES approach could be extended to a translational research context as well as to the clinic (e.g. to study rare malignancies), where the simultaneous analysis of the whole coding region of the genome may help in the detection of cancer-linked variants.


Molecular Authentication of the Medicinal Species of Ligusticum (Ligustici Rhizoma et Radix, "Gao-ben") by Integrating Non-coding Internal Transcribed Spacer 2 (ITS2) and Its Secondary Structure.
Ligustici Rhizoma et Radix (LReR), an important Chinese medicine known as "Gao-ben," refers to Ligusticum sinense Oliv. or Ligusticum jeholense Nakai et Kitag. However, a number of other species are commonly sold as "Gao-ben" in the herbal medicine market, which may result in a series of quality control problems and inconsistent therapeutic effects. The "Gao-ben" is commonly sold sliced and dried, making traditional identification methods difficult. Here, the mini barcode ITS2 region was examined on 68 samples representing LReR and 7 potential adulterant or substitute species. The results showed 100% success rates of PCR and sequencing and the existence of a barcoding gap. The neighbor-joining (NJ) tree indicated that all the tested samples could be exactly identified. The ITS2 secondary structure revealed a clear difference between true "Gao-ben" and three adulterant species. We therefore recommend the use of ITS2 as a mini barcode for distinguishing between closely or distantly related plant species that may be used in Chinese medicine.


Design of ultra-broadband terahertz polymer waveguide emitters for telecom wavelengths using coupled mode theory.
We use coupled mode theory, adequately incorporating optical losses, to model ultra-broadband terahertz (THz) waveguide emitters (0.1-20 THz) based on difference frequency generation of femtosecond infrared (IR) optical pulses. We apply the model to a generic, symmetric, five-layer, metal/cladding/core waveguide structure using transfer matrix theory. We provide a design strategy for an efficient ultra-broadband THz emitter and apply it to polymer waveguides with a nonlinear core composed of a poled guest-host electro-optic polymer composite and pumped by a pulsed fiber laser system operating at 1567 nm. The predicted bandwidths are greater than 15 THz and we find a high conversion efficiency of 1.2 × 10(-4) W(-1) by balancing both the modal phase-matching and effective mode attenuation.


New cell therapy using bone marrow-derived stem cells/endothelial progenitor cells to accelerate neovascularization in healing of experimental ulcerative colitis.
Inflammatory bowel disease (IBD): ulcerative colitis (UC) and Crohn disease (CD) are characterized by recurrent inflammation and ulceration of intestinal and/or colonic mucosa and an inappropriate and delayed healing. Current therapies with, e.g., anti-TNFα antibody (infliximab) and other anti-inflammatory drugs (e.g., mesalamine) do not induce sustained remission, complete healing or prevent recurrence of UC. Although the pathogenesis of UC is not fully understood, pathologic angiogenesis has been postulated as a critical pathogenic component in UC. Recent studies demonstrated that the poor healing, chronic inflammation in colon of UC could be the result of microvascular dysfunction and endothelial barrier defect, resulting in sustained tissue hypoperfusion and ischemia in the colon. Previously, regeneration of injured endothelium and neovascularization were believed to rely solely on the migration and proliferation of neighboring endothelial cells from existing blood vessels. However, accumulating evidence shows that additional mechanisms may exist, and may be mediated by the circulating pool of bone marrow-derived endothelial progenitor cells (BMD-EPC). Furthermore, stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 have been demonstrated to play an important role in the "homing" of BMD-EPC to injured sites and neovascularization in tissue repair. Recent studies by others and us showed reduced BMD-EPC levels in the circulation of IBD patients and rats with experimental UC. However, the potential therapeutic effect of BMD-EPC on neovascularization and colonic mucosal repair in UC has not been elucidated. In this review, we discussed the possibility that impaired contribution of BMD-EPC (i.e., decreased release of BMD-EPC from bone marrow to circulation and/or blocked/impaired homing of BMD-EPC to colonic lesions) may be a critical component of mechanisms in the incomplete/delayed healing of UC, and may offer a novel form of cell therapy for IBD.


Effects of egg and yolk weights on yolk antibody (IgY) production in laying chickens.
Twenty 35-wk-old chickens, including 10 Single Comb White Leghorn (SCWL) and 10 Rhode Island Red (RIR) hens, were used to examine the effects of egg and yolk weights on egg yolk antibody (IgY) production in the two strains of chickens immunized with BSA. The SCWL chickens had a greater (P < 0.01) percentage hen-day production and greater egg and yolk weights than did the RIR chickens. However, the anti-BSA antibody activities determined by ELISA in the serum and the egg yolk were similar (P > 0.05) between the SCWL and RIR chickens. Similarities between the two strains of hens were also observed in protein and total IgY contents (expressed as the percentage of wet weight of yolk) and the percentage of BSA-specific antibody in the total IgY. It was concluded that both the SCWL and RIR chickens immunized with BSA can produce egg yolk IgY containing similar proportions of BSA-specific antibodies. Therefore, the egg yolk weight and the percentage hen-day production, both of which are greater in the SCWL hens, are considered to be important factors for the efficient production of IgY.


Metabolically healthy/unhealthy obesity and breast cancer: A possible role of plasma-derived extracellular vesicles on the cancerous behavior of triple-negative breast cancer.
Obesity has known detrimental effects on breast cancer (BC) development and progression. However, it's essential to consider the obesity phenotype based on metabolic health. This study aims to evaluate the impact of circulating extracellular vesicles (EVs) from women with metabolically healthy or unhealthy normal weight, overweight, and obesity on MDA-MB-231 cell migration, invasion, and apoptosis. Plasma EVs were isolated from different obesity phenotypes in women. EVs were characterized and EVs uptake by MDA-MB-231 cells was assessed. MDA-MB-231 cell lines were treated with EVs obtained from various studied groups, and migration, invasion, MMP-2 and MMP-9 activity, Bax and Bcl-2 mRNA expression, p-53 and Thr55 p-p53 protein expression, and apoptosis were assessed. EVs from obese individuals, regardless of phenotype, increased invasion and MMP-2 activity compared to healthy normal-weight EVs. Normal-weight EVs led to higher invasion under unhealthy conditions. BC cell migration was enhanced by EVs from healthy obese individuals compared to healthy normal-weight EVs. EVs from unhealthy obese women exhibited significantly lower p53/p-p53 levels and reduced apoptosis compared to healthy obese groups. It appears that EVs from both normal-weight women with unhealthy conditions and those with obesity or overweight, irrespective of metabolic status, worsened the cancerous behavior of TNBC cells. Therefore, considering metabolic health, in addition to BMI, is crucial for understanding obesity-related disorders.


Development and implementation of a high-throughput compound screening assay for targeting disrupted ER calcium homeostasis in Alzheimer's disease.
Disrupted intracellular calcium homeostasis is believed to occur early in the cascade of events leading to Alzheimer's disease (AD) pathology. Particularly familial AD mutations linked to Presenilins result in exaggerated agonist-evoked calcium release from endoplasmic reticulum (ER). Here we report the development of a fully automated high-throughput calcium imaging assay utilizing a genetically-encoded FRET-based calcium indicator at single cell resolution for compound screening. The established high-throughput screening assay offers several advantages over conventional high-throughput calcium imaging technologies. We employed this assay for drug discovery in AD by screening compound libraries consisting of over 20,000 small molecules followed by structure-activity-relationship analysis. This led to the identification of Bepridil, a calcium channel antagonist drug in addition to four further lead structures capable of normalizing the potentiated FAD-PS1-induced calcium release from ER. Interestingly, it has recently been reported that Bepridil can reduce Aβ production by lowering BACE1 activity. Indeed, we also detected lowered Aβ, increased sAPPα and decreased sAPPβ fragment levels upon Bepridil treatment. The latter findings suggest that Bepridil may provide a multifactorial therapeutic modality for AD by simultaneously addressing multiple aspects of the disease.


Action of alpha 2A-adrenergic receptors in circular smooth muscle of canine proximal colon.
Addition of the alpha 2-adrenergic receptor agonist clonidine (1 microM) to tetrodotoxin-treated strips of canine colonic circular smooth muscle resulted in a significant increase in contractile force that was blocked by addition of the alpha 2-antagonist yohimbine (0.1 microM). The alpha 2-receptor antagonist radioligand [3H]rauwolsine bound rapidly and reversibly to a single class of saturable sites (Bmax, 38.4 +/- 6.2 fmol/mg protein) in colonic circular smooth muscle membranes with an affinity (KD = 5.1 +/- 0.9 nM) characteristic of alpha 2-adrenergic receptors in smooth muscle. Studies in cells freshly isolated from circular muscle of canine proximal colon verified the smooth muscle origin of these receptors. Rank order of potency of alpha 2-adrenergic receptor antagonists in competition for [3H]rauwolsine binding was yohimbine greater than oxymetazoline much greater than prazosin. Affinity of alpha 2-receptors for yohimbine was indistinguishable from that of its optical isomer, rauwolsine, in both competition studies (KI = 3.4 nM) and in saturation-binding experiments employing [3H]yohimbine directly (KD = 4.2 nM). The alpha-receptor agonist epinephrine, in competition studies employing [3H]rauwolsine, revealed high-affinity binding sites that were converted to low-affinity binding sites for agonist by addition of 100 microM GTP gamma S. Addition of the alpha 2 more-selective agonist clonidine (100 microM) resulted in inhibition of adenylate cyclase activity that was abolished by pretreatment of tissue strips with pertussis toxin suggesting coupling of the alpha 2-receptor in colon to adenylate cyclase via the GTP-binding protein Gi. Our data demonstrate a physiological role for adenylate cyclase-coupled receptors of the alpha 2A-subtype in canine colon circular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting.
This paper describes a protocol for induction of moderate psychological stress in a laboratory setting and evaluates its effects on physiological responses. The 'Trier Social Stress Test' (TSST) mainly consists of an anticipation period (10 min) and a test period (10 min) in which the subjects have to deliver a free speech and perform mental arithmetic in front of an audience. In six independent studies this protocol has been found to induce considerable changes in the concentration of ACTH, cortisol (serum and saliva), GH, prolactin as well as significant increases in heart rate. As for salivary cortisol levels, the TSST reliably led to 2- to 4-fold elevations above baseline with similar peak cortisol concentrations. Studies are summarized in which TSST-induced cortisol increases elucidated some of the multiple variables contributing to the interindividual variation in adrenocortical stress responses. The results suggest that gender, genetics and nicotine consumption can influence the individual's stress responsiveness to psychological stress while personality traits showed no correlation with cortisol responses to TSST stimulation. From these data we conclude that the TSST can serve as a tool for psychobiological research.


Severe primary malnutrition in US children.
We studied 16 children aged 18 months or less who had severe primary protein-calorie malnutrition. All were admitted to one urban pediatric teaching hospital for treatment of failure to thrive between Jan 1, 1980, and Aug 30, 1984. The definitions of malnutrition were based on those of the Wellcome Trust. The patients had no evidence of medical causes for their conditions and grew rapidly when they were refed in the hospital. Eight were products of teenage pregnancies. Eleven patients were receiving public aid, and four had no third-party coverage. All were markedly below the fifth percentile in weight for length; their mean percentage of expected weight for age was 0.55. The mean hospital stay was 18.5 days. Severe primary protein-calorie malnutrition does exist in the United States. Thorough nutritional evaluation in children with failure to thrive is indicated, and malnutrition should be a reportable condition in the United States.


The Escherichia coli argU10(Ts) phenotype is caused by a reduction in the cellular level of the argU tRNA for the rare codons AGA and AGG.
The Escherichia coli argU10(Ts) mutation in the argU gene, encoding the minor tRNA(Arg) species for the rare codons AGA and AGG, causes pleiotropic defects, including growth inhibition at high temperatures, as well as the Pin phenotype at 30 degrees C. In the present study, we first showed that the codon selectivity and the arginine-accepting activity of the argU tRNA are both essential for complementing the temperature-sensitive growth, indicating that this defect is caused at the level of translation. An in vitro analysis of the effects of the argU10(Ts) mutation on tRNA functions revealed that the affinity with elongation factor Tu-GTP of the argU10(Ts) mutant tRNA is impaired at 30 and 43 degrees C, and this defect is more serious at the higher temperature. The arginine acceptance is also impaired significantly but to similar extents at the two temperatures. An in vivo analysis of aminoacylation levels showed that 30% of the argU10(Ts) tRNA molecules in the mutant cells are actually deacylated at 30 degrees C, while most of the argU tRNA molecules in the wild-type cells are aminoacylated. Furthermore, the cellular level of this mutant tRNA is one-tenth that of the wild-type argU tRNA. At 43 degrees C, the cellular level of the argU10(Ts) tRNA is further reduced to a trace amount, while neither the cellular abundance nor the aminoacylation level of the wild-type argU tRNA changes. We concluded that the phenotypic properties of the argU10(Ts) mutant result from these reduced intracellular levels of the tRNA, which are probably caused by the defective interactions with elongation factor Tu and arginyl-tRNA synthetase.


Impact of unilateral denervation on transdiaphragmatic pressure.
The diaphragm muscle (DIAm) has a large reserve capacity for force generation such that in rats, the transdiaphragmatic pressure (Pdi) generated during ventilatory behaviors is less than 50% of maximal Pdi (Pd(imax)) elicited by bilateral phrenic nerve stimulation. Accordingly, we hypothesized that following unilateral denervation (DNV), the ability of the contralateral DIAm to generate sufficient Pdi to accomplish ventilatory behaviors will not be compromised and normal ventilation (as determined by arterial blood gas measurements) will not be impacted, although neural drive to the DIAm increases. In contrast, we hypothesized that higher force, non-ventilatory behaviors requiring Pdi generation greater than 50% of Pd(imax) will be compromised following DIAm hemiparalysis, i.e., increased neural drive cannot fully compensate for lack of force generating capacity. Pdi generated during ventilatory behaviors (eupnea and hypoxia (10% O2)-hypercapnia (5% CO2)) did not change after DNV and arterial blood gases were unaffected by DNV. However, neural drive to the contralateral DIAm, assessed by the rate of rise of root mean squared (RMS) EMG at 75 ms after onset of inspiratory activity (RMS75), increased after DNV (p<0.05). In contrast, Pdi generated during higher force, non-ventilatory behaviors was significantly reduced after DNV (p < 0.01), while RMS75 was unchanged. These findings support our hypothesis that only non-ventilatory behaviors requiring Pdi generation greater than 50% of Pd(imax) are impacted after DNV. Clinically, these results indicate that an evaluation of DIAm weakness requires examination of Pdi across multiple motor behaviors, not just ventilation.


Strength development and non-contact lower limb injury in academy footballers across age groups.
Non-contact lower limb injuries are common in academy football. Yet, the impact these injuries have on strength development in academy footballers remains unclear. This study aimed to investigate the impact of non-contact lower limb injury on hip, groin, and knee flexor strength development in male academy youth footballers. Furthermore, this study: reports normative strength data of emerging field-based tests that can be easily deployed in football academies; explores the effect of age on injury occurrence; and highlights the number of days lost from injury in male youth footballers. Assessments of hip adductor, abductor, and eccentric knee flexor strength were obtained from 195 academy football players during pre-season and at the end of season. In-season injuries were recorded by medical staff. Those footballers who sustained non-contact lower limb injury were compared with those who did not sustain a non-contact lower limb injury. No between-group differences were observed for any strength assessments when controlled for pre-season measures. Stronger footballers at pre-season experienced strength loses, while those weaker players gained strength across the season. Hip strength development was impaired in older age group footballers. Sustaining a non-contact lower limb injury had minimal impact on strength development. In the absence of in-season lower limb strength monitoring, development in academy youth footballers may not progress as expected, and in particular, stronger and older youth athletes may benefit from individualized strength training.


Hollow carbon nanospheres for targeted delivery of chemotherapeutics in breast cancer therapy.
We present novel hollow carbon nanospheres (HCNs) for targeted breast cancer therapy. The HCNs have a 40 nm-cavity for drugs loading, and the surface is covered with "natural" primary amine without any exogenous modification, equipped to conjugate with functional biomolecules. After modification with anti-HER2 antibody and loading of Doxorubicin (DOX) to the HCNs, the HER2@HCNs/DOX can specifically access HER2-positive breast cancer cells and significantly suppress the cells in vitro, causing ∼60% reduction of the volume of the HER2-positive tumours in vivo. The HCNs show great promise to become a multifunctional carrier in the field of high-loading capacity drug delivery for cancer therapy.


The society of nematologists at 50, and where to from here?
Nathan Cobb, as the father figure of the Society of Nematologists, set an example to later generations of nematologists in his studies of nematode biology. In the 50 years of the Society's existence nematological research has greatly expanded that knowledge base. Opportunities over the next 50 years are boundless in view of advancing technologies and emerging challenges, and this leads to speculation as to what future nematological research advances will enhance peoples' quality of life.


High genetic contribution to anterior cruciate ligament rupture: Heritability ~69.
We aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture. We used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twins, aged ≥17 years, to determine the familial risk and heritability of ACL rupture. The incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture. The genetic contribution to ACL rupture of ~69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.


Residents' exposure to aboriginal health issues. Survey of family medicine programs in Canada.
To determine whether Canadian family medicine residency programs currently have objectives, staff, and clinical experiences for adequately exposing residents to aboriginal health issues. A one-page questionnaire was developed to survey the details of teaching about and exposure to aboriginal health issues. Family medicine programs in Canada. All Canadian family medicine program directors in the 18 programs (16 at universities and two satellite programs) were surveyed between October 1997 and March 1998. Whether programs had teaching objectives for exposing residents to aboriginal health issues, whether they had resource people available, what elective and core experiences in aboriginal health were offered, and what types of experiences were available. Response rate was 100%. No programs had formal, written curriculum objectives for residency training in aboriginal health issues, although some were considering them. Some programs, however, had objectives for specific weekend or day sessions. No programs had a strategy for encouraging enrollment of residents of aboriginal origin. Eleven programs had at least one resource person with experience in aboriginal health issues, and 12 had access to community-based aboriginal groups. Core experiences were all weekend seminars or retreats. Elective experiences in aboriginal health were available in 16 programs, and 11 programs were active on reserves. Many Canadian family medicine programs give residents some exposure to aboriginal health issues, but most need more expertise and direction on these issues. Some programs have unique approaches to teaching aboriginal health care that could be shared. Formalized objectives derived in collaboration with other family medicine programs and aboriginal groups could substantially improve the quality of education in aboriginal health care in Canada.


Selecting Suitable Near-Native Lignins for Research.
There are several methods to isolate near-native lignins, including milled-wood lignin, enzymatic lignin, cellulolytic enzyme lignin, and enzymatic mild-acidolysis lignin. Which one is the most representative of the native lignin? Herein, near-native lignins were isolated from different plant groups and structurally analyzed to determine how well these lignins represented their native lignin counterparts. Analytical methods were applied to understand the molecular weight, monomer composition, and distribution of interunit linkages in the structure of the lignins. The results indicated that either enzymatic lignin or cellulolytic enzyme lignin may be used to represent native lignin in softwoods and hardwoods. None of the lignins, however, appeared to represent native lignins in grasses (monocot plants) because of substantial syringyl/guaiacyl differences. Complicating the understanding of grass lignin structure, large amounts of hydroxycinnamates acylate their polysaccharides and, when released, are often conflated with actual lignin monomers.


Influence of postoperative analgesia on systemic inflammatory response and postoperative cognitive dysfunction after femoral fractures surgery: a randomized controlled trial.
To investigate the possible effect of postoperatively applied analgesics-epidurally applied levobupivacaine or intravenously applied morphine-on systemic inflammatory response and plasma concentration of interleukin (IL)-6 and to determine whether the intensity of inflammatory response is related to postoperative cognitive dysfunction (POCD). This is a randomized, prospective, controlled study in an academic hospital. Patients were 65 years and older scheduled for femoral fracture fixation from July 2016 to September 2017. Inflammatory response was assessed by leukocytes, neutrophils, C reactive protein (CRP) and fibrinogen levels in four blood samples (before anesthesia, 24 hours, 72 hours and 120 hours postoperatively) and IL-6 concentration from three blood samples (before anesthesia, 24 hours and 72 hours postoperatively). Cognitive function was assessed using the Mini-Mental State Examination preoperatively, from the first to the fifth postoperative day and on the day of discharge. The study population included 70 patients, 35 in each group. The incidence of POCD was significantly lower in the levobupivacaine group (9%) than in the morphine group (31%) (p=0.03). CRP was significantly lower in the levobupivacaine group 72 hours (p=0.03) and 120 hours (p=0.04) after surgery. IL-6 values were significantly lower in the levobupivacaine group 72 hours after surgery (p=0.02). The only predictor of POCD in all patients was the level of IL-6 72 hours after surgery (p=0.03). There is a statistically significant association between use of epidural levobupivacaine and a reduction in some inflammatory markers. Postoperative patient-controlled epidural analgesia reduces the incidence of POCD compared with intravenous morphine analgesia in the studied population. NCT02848599.


TRPA1: a transducer and amplifier of pain and inflammation.
The transient receptor potential ankyrin 1 (TRPA1) ion channel on peripheral terminals of nociceptive primary afferent nerve fibres contributes to the transduction of noxious stimuli to electrical signals, while on central endings in the spinal dorsal horn, it amplifies transmission to spinal interneurons and projection neurons. The centrally propagating nociceptive signal that is induced and amplified by TRPA1 not only elicits pain sensation but also contributes to peripheral neurogenic inflammation through a peripheral axon reflex or a centrally mediated back propagating dorsal root reflex that releases vasoactive agents from sensory neurons in the periphery. Endogenous TRPA1 agonists that are generated under various pathophysiological conditions both in the periphery and in the spinal cord have TRPA1-mediated pro-nociceptive and pro-inflammatory effects. Among endogenous TRPA1 agonists that have been shown to play a role in the pathogenesis of pain and inflammatory conditions are, for example, methylglyoxal, 4-hydroxynonenal, 12-lipoxygenase-derived hepoxilin A3, 5,6-epoxyeicosatrienoic acid and reactive oxygen species, while mustard oil and cinnamaldehyde are most commonly used exogenous TRPA1 agonists in experimental studies. Among selective TRPA1 antagonists are HC-030031, A-967079, AP-14 and Chembridge-5861528. Recent evidence indicates that TRPA1 plays a role also in transition of acute to chronic pain. Due to its location on a subpopulation of pain-mediating primary afferent nerve fibres, blocking the TRPA1 channel is expected to have antinociceptive, antiallodynic and anti-inflammatory effects.


Insights into allosteric control of vinculin function from its large scale conformational dynamics.
Vinculin is an important constituent of both cell-cell and cell-matrix junctions, where it plays crucial roles in the regulation of cell adhesion and migration. When activated, it mediates the linkage between cadherins (cell-cell) or integrins (cell-matrix) and the actin cytoskeleton through interactions with various proteins. The activation of vinculin requires structural conversions from an autoinhibited conformation to the "open" conformations in which the occluded binding sites of its different ligands become exposed, while the structural dynamics underlying the vinculin activation remains largely unknown. Here we report the first computational study of large scale conformational dynamics of full-length vinculin. We find that the "holding" and "releasing" motions between vinculin tail and pincer-like structure formed by first three domains of vinculin are the dominant motions near the native state of vinculin, indicating that an inherent flexibility of vinculin has a large influence on its allostery. We also find a cooperative dissociation between the head and tail domains of vinculin with increasing temperature in both thermodynamic and kinetic simulations, implying that vinculin may function as an allosteric switch in response to external signals. We show that the kinetics of vinculin unfolding exhibits specific sequential patterns, suggesting that a sophisticated interplay between domains may synergistically contribute to vinculin activation. We further find that the interaction between vinculin-binding site peptide from talin and vinculin significantly destabilizes the intramolecular head-tail interactions, suggesting a direct role of talin binding in vinculin activation.


Amino acid requirement for the growth-hormone stimulation of incorporation of precursors into protein and nucleic acids of liver slices.
1. Incorporation of [(14)C]leucine into protein in rat liver slices, incubated in vitro, increased as the concentration of unlabelled amino acids in the incubation medium was raised. A plateau of incorporation was reached when the amino acid concentration was 6 times that present in rat plasma. Labelling of RNA by [(3)H]orotic acid was not stimulated by increased amino acid concentration in the incubation medium. 2. When amino acids were absent from the medium, or present at the normal plasma concentrations, no effect of added growth hormone on labelling of protein or RNA by precursor was observed. 3. When amino acids were present in the medium at 6 times the normal plasma concentrations addition of growth hormone stimulated incorporation of the appropriate labelled precursor into protein of liver slices from normal rats by 31%, and into RNA by 22%. A significant effect was seen at a hormone concentration as low as 10ng/ml. 4. Under the same conditions addition of growth hormone also stimulated protein labelling in liver slices from hypophysectomized rats. Tissue from hypophysectomized rats previously treated with growth hormone did not respond to growth hormone in vitro. 5. No effect of the hormone on the rate or extent of uptake of radioactive precursors into acid-soluble pools was found. 6. Cycloheximide completely abolished the hormone-induced increment in labelling of both RNA and protein. 7. It was concluded that, in the presence of an abundant amino acid supply, growth hormone can stimulate the synthesis of protein in rat liver slices by a mechanism that is more sensitive to cycloheximide than is the basal protein synthesis. The stimulation of RNA labelling observed in the presence of growth hormone may be a secondary consequence of the hormonal effect on protein synthesis. 8. The mechanism of action of growth hormone on liver protein synthesis in vitro was concluded to be similar to its mechanism of action in vivo.


Mechanism of increased BK channel activation from a channel mutation that causes epilepsy.
Concerted depolarization and Ca(2+) rise during neuronal action potentials activate large-conductance Ca(2+)- and voltage-dependent K(+) (BK) channels, whose robust K(+) currents increase the rate of action potential repolarization. Gain-of-function BK channels in mouse knockout of the inhibitory beta 4 subunit and in a human mutation (alpha(D434G)) have been linked to epilepsy. Here, we investigate mechanisms underlying the gain-of-function effects of the equivalent mouse mutation (alpha(D369G)), its modulation by the beta 4 subunit, and potential consequences of the mutation on BK currents during action potentials. Kinetic analysis in the context of the Horrigan-Aldrich allosteric gating model revealed that changes in intrinsic and Ca(2+)-dependent gating largely account for the gain-of-function effects. D369G causes a greater than twofold increase in the closed-to-open equilibrium constant (6.6e(-7)-->1.65e(-6)) and an approximate twofold decrease in Ca(2+)-dissociation constants (closed channel: 11.3-->5.2 microM; open channel: 0.92-->0.54 microM). The beta 4 subunit inhibits mutant channels through a slowing of activation kinetics. In physiological recording solutions, we established the Ca(2+) dependence of current recruitment during action potential-shaped stimuli. D369G and beta 4 have opposing effects on BK current recruitment, where D369G reduces and beta 4 increases K(1/2) (K(1/2) microM: alpha(WT) 13.7, alpha(D369G) 6.3, alpha(WT)/beta 4 24.8, and alpha(D369G)/beta 4 15.0). Collectively, our results suggest that the D369G enhancement of intrinsic gating and Ca(2+) binding underlies greater contributions of BK current in the sharpening of action potentials for both alpha and alpha/beta 4 channels.


Antigen-initiated release of platelet-activating factor (PAF-acether) from mouse bone marrow-derived mast cells sensitized with monoclonal IgE.
Mouse bone marrow mast cells sensitized with monoclonal IgE and activated with specific antigen released 2.8 +/- 0.5 ng of platelet-activating factor (1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) (PAF-acether)/ 10(6) cells. The PAF-acether was identified by its ability to aggregate fully aspirin-treated washed rabbit platelets in the presence of an adenosine diphosphate (ADP)-scavenger complex, by its co-chromatography with [3H]-labeled semi-synthetic PAF-acether and synthetic 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, and by its inactivation by phospholipases A2, C, and D and not by lipase A1. The antigen-initiated release of PAF-acether, leukotriene C4 (LTC4), and leukotriene B4 (LTB4), and the secretion of the granule marker beta-hexosaminidase were not diminished by washing the cells before challenge, indicating that they were due to the interaction of antigen with the IgE fixed on the cell membrane and not to phagocytosis of immune complexes formed in the fluid phase. The parallel antigen-induced dose-response relationship, along with the superimposable time-course of the extracellular appearance, of beta-hexosaminidase, PAF-acether, and both leukotrienes indicated that the origin of these diverse mediators was from a common cell type with IgE-Fc receptors. Ethanol extraction of antigen-stimulated bone marrow-derived mast cells revealed the early transient appearance of a cell-associated platelet-aggregating activity, the action of which on platelets, like PAF-acether, was independent of ADP and arachidonic acid metabolism. The cell-associated activity contained a novel product that eluted at 13 min during high performance liquid chromatography (HPLC) (solvent hexane:n-propanol:water, 46:46:8), permitting resolution from PAF-acether and lyso-PAF-acether (1-O-alkyl-sn-glyceryl-3-phosphorylcholine), which eluted at 29 min and 30 min, respectively. The cell-associated material, which differs from lyso-PAF-acether, the putative precursor of PAF-acether, in being active in the bioassay on platelets may represent a newly recognized intermediate in the generation of PAF-acether. As the transiently present cell-associated intermediate has not been previously recognized, its detection may depend upon the relatively unique properties of the bone marrow-derived mast cell system in which IgE-dependent activation leading to product generation is complete within 5 min.(ABSTRACT TRUNCATED AT 400 WORDS)


A variable degree of autoimmunity in the pedigree of a patient with type 1 diabetes homozygous for the PTPN22 1858T variant.
We investigated whether the PTPN22 C1858T polymorphism is associated with the autoimmune conditions present in the family of a child affected by type 1 diabetes (T1D) carrying the TT genotype (index patient) and the potential immunological effect of the variant. We found that nine family members carried the CT genotype and five suffered from autoimmunity. Interestingly, anti-ZnT8 antibodies were detected in T1D patients and in three healthy relatives. In the TT patient, we showed diminished T-cell proliferation and reduced interleukin-2 (IL-2) and interferon-gamma (IFN-γ) production. A marked reduction of IL-2 was also observed for all CT relatives with autoimmunity and a lack of IFN-γ production was observed for the younger brother of the index patient, heterozygous for the polymorphism. In this family, the C1858T variant might confer a high risk of autoimmunity. Moreover, our data confirm that impaired IL-2 production upon T-cell receptor stimulation is associated with autoimmunity in the carriers of the polymorphism. This study might prompt to extend the panel of risk markers in relatives of subjects affected by T1D.


Isotopic identification of the sources of lead contamination for white storks (Ciconia ciconia) in a marshland ecosystem (Doñana, S.W. Spain).
White storks (Ciconia ciconia) fed in contaminated waters resulting from the Aznacollar acid mining-sludge spillage into the R. Guadiamar, which feeds the eastern flank of the Guadalquivir marshes (Doñana), S.W. Spain. The sludge was rich in a range of toxic elements, and in organic pollutants such as the aromatic amines. Storks did not exhibit elevated metals in their blood immediately following the accident, but chick blood collected the year following the accident showed genotoxic damage compared to the controls. In this study lead isotope analysis was used to assess if the storks had ingested sludge-derived contaminants. The sludge lead isotope ratio was distinct from that of the Doñana sediments. The stork blood lead isotope ratios exactly matched that of the sludge. It was concluded that the storks had ingested sludge-derived contaminants. A detailed study of the lead contamination along the R. Guadiamar and the R. Guadalquivir (of which the Guadiamar is a tributary) was also conducted to place the white stork colony lead exposure in the context of the spatial contamination of the storks' habitat.


Prenatal Diagnosis of Lissencephaly Type 2 using Three-dimensional Ultrasound and Fetal MRI: Case Report and Review of the Literature.
Lissencephaly is a genetic heterogeneous autosomal recessive disorder characterized by the classical triad: brain malformations, eye anomalies, and congenital muscular dystrophy. Prenatal diagnosis is feasible by demonstrating abnormal development of sulci and gyri. Magnetic resonance imaging (MRI) may enhance detection of developmental cortical disorders as well as ocular anomalies. We describe a case of early diagnosis of lissencephaly type 2 detected at the time of routine second trimester scan by three-dimensional ultrasound and fetal MRI. Gross pathology confirmed the accuracy of the prenatal diagnosis while histology showed the typical feature of cobblestone cortex. As the disease is associated with poor perinatal prognosis, early and accurate prenatal diagnosis is important for genetic counseling and antenatal care.


Accurate and precise wavelength calibration for wide bandwidth array spectrometers.
Calibrating the wavelength scale of an array spectrometer typically involves measurements of lines at well-known wavelengths from a calibration lamp such as a mercury-argon source. This process is relatively straightforward when the lines are well separated, relative to the bandwidth of the spectrometer. When the spectrometer's bandwidth is large, compared with the distance between calibration wavelengths, it becomes increasingly difficult to accurately locate lines in the calibration spectrum. Even calibrations for instruments with a modest bandwidth of 12 nm can be difficult. Here we present results from a simple approach to improve the accuracy of wavelength calibration for an instrument with a large bandwidth (12 nm, center-to-center pixel spacing 3.3 nm). A monochromator has been used to filter the source so that each calibration line can be measured separately. For ten spectrometers, we were able to achieve accuracy better than 0.12 nm, or 0.09 nm on average; this is less than 3% of the pixel spacing. We anticipate this approach will be useful for improving the accuracy of measurements on array spectrometers and particularly in transferring multivariate calibrations between instruments.


Enhanced butyric acid production using mixed biomass of brown algae and rice straw by Clostridium tyrobutyricum ATCC25755.
A brown alga Saccharina japonica and rice straw are attractive feedstock for microbial butyric acid production. However, inefficient fermentation of mannitol (a dominant component in S. japonica) and toxicity of inhibitors in lignocellulosic hydrolysate are limitations. This study demonstrated that mixed biomass with S. japonica and rice straw was effective in butyric acid production over those restrictions. Mannitol was consumed only when acetic acid was present. Notably, acetic acid was not produced but consumed along with mannitol. By mixing S. japonica and rice straw to take advantage of glucose and acetic acid in rice straw, Clostridium tyrobutyricum effectively consumed mannitol by utilizing acetic acid in hydrolysate and acetic acid derived from glucose with the enhanced butyric acid production. Furthermore, cell growth was restored owing to the decreased inhibitor concentration. The results demonstrate the potential of butyric acid production from mixed biomass of macroalgae/lignocellulose overcoming the drawbacks of single biomass.


The oligosaccharide units of rabbit immunoglobulin G. Multiple carbohydrate attachment sites.
The carbohydrate structure of rabbit immunoglobulin G isolated from pooled sera was investigated. Amino sugar analysis of fragments of the molecule allowed three oligosaccharides to be located at separate sites on the H-chain. The corresponding glycopeptides were isolated. The average composition of the C1-oligosaccharide was 2 glucosamine, 1 mannose and 2 galactose residues. It appeared to be present in approx. 15% of the H-chains; the carbohydrate was coupled through the amide group of asparagine in a peptide containing asparagine, glycine and threonine within the Fd fragment of the molecule. The average composition of the C2-oligosaccharide was 1 galactosamine, 1 galactose and either 1 or 2 sialic acid residues. It was present on approx. 40% of the H-chains and was attached glycosidically to the OH group of threonine in a peptide Ser-Lys-Pro-Thr-Cys-Pro-Pro-Glu-Leu in the hinge region of the molecule. The average composition of the C3-oligosaccharide was 5 glucosamine, 2 galactose, 5 mannose, 1 fucose and 1 sialic acid residue. It appeared to be present in all the H-chains and was linked through the amide group of asparagine in a peptide Gln-Gln-Phe-Asn-Ser-Thr-Ile-Arg within the Fc fragment of the molecule.


Intracellular collagen and fibronexus in fibromatosis and other fibroblastic tumors.
Myofibroblasts are mesenchymal cells with combined function and structure for contraction and collagen synthesis. They are found in reparative responses, nodular fasciitis, fibromatosis, and myofibroblastic sarcoma. Ultrastructurally, myofibroblasts are characterized by a specialized cell surface structure called the fibronexus (FNX). In addition, intracellular collagen fibers (ICF) have been described in nodular fasciitis and fibromatosis, but their origin and nature are still controversial. The aim of the present work was, first, to assess the frequency of FNX and ICF in proliferative myofibroblastic conditions compared to diverse mesenchymal tumors with spindle-shaped cells, and, second, to determine what kind of organelles contain ICF and if they are related to phagocytosis or cell synthesis. Forty-two cases of aggressive fibromatosis and 11 of nodular fasciitis (group A) were compared to 82 spindle-cell mesenchymal tumors of diverse nature (group B) by electron microscopy study. The presence and frequency of FNX and ICF was compared in both groups, and the organelles containing ICF were recorded. FNX and ICF were constantly found in group A (69.8 and 84.9%, respectively), and rarely in group B (0 and 5.12%, respectively). Most frequently ICF were contained in tunnels and phagolysosomes, but also were found in Golgi vesicles and cisternae of rough endoplasmic reticulum. In the majority of cases (75%), ICF were similar to collagen fibers of the extracellular space, but in some cases (22.5%), they were in dissimilar stages of fibrogenesis. Fibromatosis and nodular fasciitis are characterized by proliferation of myofibroblasts and constantly show FNX and ICF. These structures are rarely found in other mesenchymal tumors. The ICF are found in organelles of digestion and also in others related to synthesis and transport.


Optimizing Differentiated HIV Treatment Models in Urban Zimbabwe: Assessing Patient Preferences Using a Discrete Choice Experiment.
Differentiated service delivery holds great promise for streamlining the delivery of health services for HIV. This study used a discrete choice experiment to assess preferences for differentiated HIV treatment delivery model characteristics among 500 virally suppressed adults on antiretroviral therapy in Harare, Zimbabwe. Treatment model characteristics included location, consultation type, healthcare worker cadre, operation times, visit frequency and duration, and cost. A mixed effects logit model was used for parameter estimates to identify potential preference heterogeneity among participants, and interaction effects were estimated for sex and age as potential sources of divergence in preferences. Results indicated that participants preferred health facility-based services, less frequent visits, individual consultations, shorter waiting times, lower cost and, delivered by respectful and understanding healthcare workers. Some preference heterogeneity was found, particularly for location of service delivery and group vs. individual models; however, this was not fully explained by sex and age characteristics of participants. In urban areas, facility-based models, such as the Fast Track model requiring less frequent clinic visits, are likely to better align with patient preferences than some of the other community-based or group models that have been implemented. As Zimbabwe scales up differentiated treatment models for stable patients, a clear understanding of patient preferences can help in designing services that will ensure optimal utilization and improve the efficiency of service delivery.


singlecellVR: Interactive Visualization of Single-Cell Data in Virtual Reality.
Single-cell assays have transformed our ability to model heterogeneity within cell populations. As these assays have advanced in their ability to measure various aspects of molecular processes in cells, computational methods to analyze and meaningfully visualize such data have required matched innovation. Independently, Virtual Reality (VR) has recently emerged as a powerful technology to dynamically explore complex data and shows promise for adaptation to challenges in single-cell data visualization. However, adopting VR for single-cell data visualization has thus far been hindered by expensive prerequisite hardware or advanced data preprocessing skills. To address current shortcomings, we present singlecellVR, a user-friendly web application for visualizing single-cell data, designed for cheap and easily available virtual reality hardware (e.g., Google Cardboard, ∼$8). singlecellVR can visualize data from a variety of sequencing-based technologies including transcriptomic, epigenomic, and proteomic data as well as combinations thereof. Analysis modalities supported include approaches to clustering as well as trajectory inference and visualization of dynamical changes discovered through modelling RNA velocity. We provide a companion software package, scvr to streamline data conversion from the most widely-adopted single-cell analysis tools as well as a growing database of pre-analyzed datasets to which users can contribute.


Validating Insomnia Severity Index (ISI) in a Bangladeshi Population: Using Classical Test Theory and Rasch Analysis.
The COVID-19 outbreak is associated with sleep problems and mental health issues among individuals. Therefore, there is a need to assess sleep efficiency during this tough period. Unfortunately, the commonly used instrument on insomnia severity-the Insomnia Severity Index (ISI)-has never been translated and validated among Bangladeshis. Additionally, the ISI has never been validated during a major protracted disaster (such as the COVID-19 outbreak) when individuals encounter mental health problems. The present study aimed to translate the ISI into Bangla language (ISI-Bangla) and validate its psychometric properties. First, the linguistic validity of the ISI-Bangla was established. Then, 9790 Bangladeshis (mean age = 26.7 years; SD = 8.5; 5489 [56.1%] males) completed the Bangla versions of the following questionnaires: ISI, Fear of COVID-19 Scale (FCV-19S), and Patient Health Questionnaire-9 (PHQ-9). All the participants also answered an item on suicidal ideation. Classical test theory and Rasch analyses were conducted to evaluate the psychometric properties of the ISI-Bangla. Both classical test theory and Rasch analyses support a one-factor structure for the ISI-Bangla. Moreover, no substantial differential item functioning was observed across different subgroups (gender, depression status (determined using PHQ-9), and suicidal ideation). Additionally, concurrent validity of the ISI-Bangla was supported by significant and moderate correlations with FCV-19S and PHQ-9; known-group validity was established by the significant difference of the ISI-Bangla scores between participants who experienced suicidal ideation and those without. The present psychometric validation conducted during the COVID-19 outbreak suggests that the ISI-Bangla is a promising and operationally adequate instrument to assess insomnia in Bangladeshis.


Characteristics of non-cerebral coenurosis in tropical goats.
The epidemiological, clinical, and biochemical profile of non-cerebral coenurosis in goats and the morphological characteristics of the responsible metacestodes (cysts) were examined in a cross-sectional survey of slaughtered goats in abattoirs of the United Arab Emirates (U.A.E.) originating from Abu Dhabi and various tropical countries. The age, country of origin, and location of each cyst in the body of goats were recorded. Blood samples collected from infected and matching healthy goats were subjected to biochemical analysis. Data on the morphological characteristics of the cysts as well as the clusters, scoleces, and rostellar hooks in one cyst from each affected carcass were collected. The data collected were subjected to statistical analysis. A total of 2,284 slaughtered goats were examined and 40 goats were diagnosed as infected with non-cerebral coenurus cysts. The prevalence of non-cerebral coenurosis was 1.75% and the degree of parasite aggregation (k) was 0.003, which is indicative of overdispersion (k<1). The only abnormalities observed in the infected goats were palpation of large single cysts in thigh muscles and higher serum aspartate aminotransferase (AST) value. A total of 76 non-cerebral coenurus cysts from 14 different body locations were collected. No cysts were found in the brain or spinal cord. Cysts located in psoas muscles had on average significantly bigger volumes and higher numbers of scoleces and clusters compared to cysts located in other body parts (P-value=0.000). Significant differences in the morphometric measurements of the rostellar hooks were observed between cysts found in goats from different countries of origin (P-value<0.05) perhaps due to initial steps of allopatric speciation by geographic isolation. A significant positive correlation was found between number of scoleces and volume of cysts (b=6.37>5; R-Sq=89.4%; P-value=0.000) and between number of clusters and number of scoleces (b=25.13>1; R-Sq=79.8%; P-value=0.000) indicative of following a positive allometric growth as well as between number of clusters and volume of cysts (b=0.25<0.5; R-Sq=69.4%; P-value=0.000) indicative of following a negative allometric growth. The biological significance of the observed allometries is not known, but perhaps for evolutionary reasons the parasite is investing its resources more on the growth of scoleces, less on the growth of cyst volume, and even less on the number of clusters.


Arterial Remodeling and Dysfunction in the ZSF1 Rat Model of Heart Failure With Preserved Ejection Fraction.
The interplay between the stiffened heart and vessels has long been viewed as a core mechanism in heart failure with preserved ejection fraction, but the incremental vascular molecular remodeling mechanisms from systemic arterial hypertension to heart failure with preserved ejection fraction remain poorly investigated. Our aim was to characterize central arterial remodeling and dysfunction in ZSF1 obese rats and to compare it with hypertensive ZSF1 lean and healthy Wistar-Kyoto controls. Twenty-week-old male ZSF1 obese (n=9), lean (n=9), and Wistar-Kyoto rats (n=9) underwent left ventricular pressure-volume loop evaluation and synchronous acquisition of ascending aortic flow and pressure. Aortic rings underwent functional evaluation, histology, and molecular biology studies. Although mean arterial pressure, characteristic aortic impedance, and reactivity to phenylephrine were similarly increased in hypertensive ZSF1 lean and obese, only ZSF1 obese showed impaired relaxation and upward-shifted end-diastolic pressure-volume relationships despite preserved systolic function indexes, denoting heart failure with preserved ejection fraction. ZSF1 obese phenotype further showed decreased aortic compliance, increased wave reflection, and impaired direct NO donor and endothelial-mediated vasodilation which were accompanied on structural and molecular grounds by aortic media thickening, higher collagen content and collagen/elastin ratio, increased fibronectin and α-5 integrin protein expression and upregulated TGF (transforming growth factor)-β and CTGF (connective tissue growth factor) levels. Functional, molecular, and structural disturbances of central vessels and their potentially underlying pathways were newly characterized in experimental heart failure with preserved ejection fraction rendering the ZSF1 obese rat model suitable for preclinical testing.


Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation.
Previous experimental evidence indicates that some cancer cells have an alternative glycolysis pathway with net zero ATP production, implying that upregulation of glycolysis in these cells may not be related to the generation of ATP. Here we use a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. We uncover a novel pathway for ATP generation that involves reactions from serine biosynthesis, one-carbon metabolism and the glycine cleavage system, and show that the pathway is transcriptionally upregulated in an inducible murine model of Myc-driven liver tumorigenesis. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate - but higher rate of alanine secretion. Thus, in cells using the standard - or the net zero ATP glycolysis pathways a significant portion of the glycolysis flux is always associated with ATP generation, and the ratio between the flux rates of the two pathways determines the rate of ATP generation and lactate and alanine secretion during glycolysis.


Monoclonal antibodies identify blastemal cells derived from dedifferentiating limb regeneration.
Blastemal cells arise after the amputation of limbs or tails in urodele amphibians. These histologically undifferentiated mesenchymal cells divide and subsequently differentiate to regenerate a new appendage. Various studies (reviewed in ref. 1) indicate that blastemal cells arise from tissues near the site of amputation, including muscle, cartilage, nerve and dermis. The multinucleated myofibre, however, is a controversial source of blastemal cells. The suggestion that myofibres can dedifferentiate is based on their histological appearance during the early stages of limb regeneration. This is contrary to the widely accepted view of muscle regeneration in higher vertebrates which attributes it to satellite cells. One prediction of the dedifferentiation hypothesis is that a population with properties of both myofibres and blastema cells should be present during the early stages of regeneration. Here we described the isolation of two monoclonal antibodies, one that recognizes an antigen found only in myofibres and another that recognizes an antigen restricted to blastemal cells. By using these antibodies as cell markers, we can detect a small population of cells in the regenerating limbs of adult newts that bear both the myofibre and blastemal cell antigens. The time and location of these double-labelled cells supports the idea that blastemal cells originate, in part, by dedifferentiation of myofibres.


[Current diagnosis, clinical course and treatment of acute colitis infection with Clostridium difficile].
Detection rate of G. intestionalis in feces with direct microscopy has been compared with the immuno-enzymatic technique detecting protein GSA 65 with Alexon Inc., ProSpec T/Giardia reagents kit. The results obtained with both methods have further been compared with those obtained by microscopic examination of the duodenal content. Detectability of Giardia intestinalis with EIA technique with the use of ready-made kit has been assessed. Feces have been collected from 371 patients. Protein GSA 65 has been present in 170 samples, 45.8%, examined with the use of ProSpec T/Gardia kit. Giardia intestinalis cysts have been detected microscopically in the feces of 37 patients, i.e. in 22.3%. Microscopic examinations carried out by three independent examiners have shown marked diversity in the rate of positive results, being 0.1% (examiner A), 28.6% (B), and 45.2% (C). Comparison of G. intestinale detectability of all 3 techniques used have shown absence of protein GSA 65 in 2 out of 9 examined patients. However, trophozoits have been present in the duodenal content. Test performed with kits made by Alexon Inc. and DIALAB have given 45.8% and 60.7% of the positive results, respectively.


Divergent dislocation of the ring and little finger carpometacarpal joints--a rare injury pattern.
Hand injuries due to longitudinal forces in the line of the metacarpals demonstrate unusual dislocation patterns. We describe a case of volar intra-articular fracture dislocation of the ring finger carpometacarpal joint in association with a pure dorsal dislocation of the little finger carpometacarpal joint. Open reduction supplemented with Kirschner wire fixation restored normal carpometacarpal joint anatomical relations and achieved an excellent clinical result.


Virus-based microRNA expression for gene functional analysis in plants.
Traditional virus-induced gene silencing (VIGS) is a powerful virus-based short interfering RNA-mediated RNA silencing technique for plant functional genomics. Besides short interfering RNAs, microRNAs (miRNAs) have also been shown to regulate gene expression by RNA silencing in various organisms. However, plant virus-based miRNA silencing has not been reported. In addition, a number of plant miRNAs have been identified or predicted, while their functions are largely unknown. Thus, there is an urgent need for the development of new technologies to study miRNA function. Here, we report that a modified cabbage leaf-curl geminivirus vector can be used to express artificial and endogenous miRNAs in plants. Using this viral miRNA expression system, we demonstrate that VIGS using artificial miRNAs, dubbed as "MIR VIGS," was effective to silence the expression of endogenous genes, including PDS, Su, CLA1, and SGT1, in Nicotiana benthamiana. Silencing of SGT1 led to the loss of N-mediated resistance to Tobacco mosaic virus. Furthermore, using this viral miRNA expression system, we found that viral ectopic expression of endogenous miR156 and miR165 but not their mutants in N. benthamiana resulted in earlier abnormal developmental phenotypes, and expression of miR165 induced abnormal chlorotic spots on leaves. These results demonstrate that the cabbage leaf-curl geminivirus-based miRNA expression system can be utilized not only to specifically silence genes involved in general metabolism and defense but also to investigate the function of endogenous miRNAs in plants.


Applicability of biomarkers in the early diagnosis of prostate cancer.
Early diagnosis of prostate cancer can increase the curative success rate for this disease. Although serum prostate-specific antigen measurement is regarded as the best conventional tumor marker available, there is little doubt that it has great limitations. The threshold above which biopsies are indicated has now decreased to a serum prostate-specific antigen value of 3 ng/ml, which results in a negative biopsy rate of 70-80%. This can readily be explained by the fact that prostate-specific antigen is not specific for prostate cancer. Clinicians need more sensitive tools to help diagnose prostate cancer and monitor progression of the disease. Molecular oncology is playing an increasing role in the fields of diagnosis and therapy for prostate cancer and has already been instrumental in elucidating many of the basic mechanisms underlying the development and progression of this disease. The identification of new prostate cancer-specific genes, such as DD3PCA3, would represent a considerable advance in the improvement of diagnostic tests for prostate cancer. This could subsequently lead to a reduction of the number of unnecessary biopsies.


Relation between dietary and circulating lipids in lacto-ovo vegetarians.
As factors that have a positive influence on health and specifically on serum lipids and blood pressure, the nature and composition of vegetarian diets is one of the most speculated issues in nutrition. The aim of the present study was to compare diet, lipid profile and blood pressure levels in Brazilian lacto-ovo vegetarians and non-vegetarians. A cross-sectional study was carried out involving 87 male and female adult volunteers (29 lactoovo vegetarians and 58 non-vegetarians). Two non-vegetarians were selected for each vegetarian (paired for age and gender) in order to enhance the power of the statistical tests. Mean age was 40 (13) years; 58.6% were males. No differences were found regarding nutritional status based on the BMI. This similarity may be explained by the similar energy intake and degrees of physical activity in both groups. Regarding blood pressure, the only difference between groups was systolic arterial pressure, which was higher among the non-vegetarians. Among the intake parameters analysed, only energy intake and the intake of polyunsaturated fat were similar between groups. Mean total cholesterol and LDL were higher among non-vegetarians. Mean serum TG was higher among the vegetarians. The greater consumption of carbohydrates among the vegetarians was reflected in the higher serum triglyceride levels. Although all products of animal origin have a greater amount of protein, fat and saturated fatty acids, the absence of meat from the diet may have accounted for the better lipid profile among the lacto-ovo vegetarians may also stem from the high intake of fibre and antioxidants.


Association of Bypass Surgery and Mortality in Moyamoya Disease.
Background Patients with moyamoya disease (MMD) have a high risk of stroke or death. We investigated whether extracranial to intracranial bypass surgery can reduce mortality by preventing strokes in patients with MMD. Methods and Results This nationwide retrospective cohort study encompassed patients with MMD registered under the Rare Intractable Diseases program via the Relieved Co-Payment Policy between 2006 and 2019, using the Korean National Health Insurance Service database. Following a 4-year washout period, landmark analyses were employed to assess mortality and stroke occurrence between the bypass surgery group and the nonsurgical control group at specific time points postindex date (1 month and 3, 6, 12, and 36 months). The study included 18 480 patients with MMD (mean age, 40.7 years; male to female ratio, 1:1.86) with a median follow-up of 5.6 years (interquartile range, 2.5-9.3; mean, 6.1 years [SD, 4.0 years]). During 111 775 person-years of follow-up, 265 patients in the bypass surgery group and 1144 patients in the nonsurgical control group died (incidence mortality rate of 618.1 events versus 1660.3 events, respectively, per 105 person-years). The overall adjusted hazard ratio (HR) revealed significantly lower all-cause mortality in the bypass surgery group from the 36-month landmark time point, for any stroke mortality from 3- and 6-month landmark time points, and for hemorrhagic stroke mortality from the 6-month landmark time point. Furthermore, the overall adjusted HRs for hemorrhagic stroke occurrence were beneficially maintained from all 5 landmark time points in the bypass surgery group. Conclusions Bypass surgery in patients with MMD was associated with a lower risk of all-cause and hemorrhagic stroke mortality and hemorrhagic stroke occurrence compared with nonsurgical control.


Changes in aquatic vegetation and floodplain land cover in the Upper Mississippi and Illinois rivers (1989-2000-2010).
Quantifying changes in the cover of river-floodplain systems can provide important insights into the processes that structure these landscapes as well as the potential consequences to the ecosystem services they provide. We examined net changes in 13 different aquatic and floodplain land cover classes using photo interpreted maps of the navigable portions of the Upper Mississippi River (UMR, above the confluence with the Ohio River) and Illinois River from 1989 to 2000 and from 2000 to 2010. We detected net decreases in vegetated aquatic area in nearly all river reaches from 1989 to 2000. The only river reaches that experienced a subsequent recovery of vegetated aquatic area from 2000 to 2010 were located in the northern portion of the UMR (above navigation pool 14) and two reaches in the Illinois River. Changes on the floodplain were dominated by urban development, which increased in nearly every river reach studied from 1989 to 2000. Agricultural lands declined in most river reaches from 2000 to 2010. The loss of agricultural land cover in the northern UMR was accompanied by increases in forest cover, whereas in the lower UMR and Illinois River, declines in agriculture were accompanied by increases in forest and shallow marsh communities. The changes in aquatic vegetation occupied between 5 and 20% of the total aquatic area and are likely associated with previously reported regional improvements in water clarity, while smaller (1-15% of the total floodplain area) changes in anthropogenic land cover types on the floodplain are likely driven by broad-scale socio-economic conditions.


Ultrafast Cardiac Imaging Using Deep Learning for Speckle-Tracking Echocardiography.
High-quality ultrafast ultrasound imaging is based on coherent compounding from multiple transmissions of plane waves (PW) or diverging waves (DW). However, compounding results in reduced frame rate, as well as destructive interferences from high-velocity tissue motion if motion compensation (MoCo) is not considered. While many studies have recently shown the interest of deep learning for the reconstruction of high-quality static images from PW or DW, its ability to achieve such performance while maintaining the capability of tracking cardiac motion has yet to be assessed. In this article, we addressed such issue by deploying a complex-weighted convolutional neural network (CNN) for image reconstruction and a state-of-the-art speckle-tracking method. The evaluation of this approach was first performed by designing an adapted simulation framework, which provides specific reference data, i.e., high-quality, motion artifact-free cardiac images. The obtained results showed that, while using only three DWs as input, the CNN-based approach yielded an image quality and a motion accuracy equivalent to those obtained by compounding 31 DWs free of motion artifacts. The performance was then further evaluated on nonsimulated, experimental in vitro data, using a spinning disk phantom. This experiment demonstrated that our approach yielded high-quality image reconstruction and motion estimation, under a large range of velocities and outperforms a state-of-the-art MoCo-based approach at high velocities. Our method was finally assessed on in vivo datasets and showed consistent improvement in image quality and motion estimation compared to standard compounding. This demonstrates the feasibility and effectiveness of deep learning reconstruction for ultrafast speckle-tracking echocardiography.


Pinus densiflora Sieb. et Zucc. alleviates lipogenesis and oxidative stress during oleic acid-induced steatosis in HepG2 cells.
Excess accumulation of lipids and oxidative stress in the liver contribute to nonalcoholic fatty liver disease (NAFLD). We hypothesized that Pinus densiflora Sieb. et Zucc. (PSZ) can protect against NAFLD by regulating lipid accumulation and oxidative stress in the liver. To investigate the effect of PSZ upon NAFLD, we used an established cellular model: HepG2 cells treated with oleic acid. Then, the extent of hepatic steatosis and oxidative stress was assessed and levels of inflammatory markers measured. Oleic acid-treated HepG2 cells, compared with controls, had greater lipid accumulation. PSZ decreased lipid accumulation by 63% in oleic acid-treated HepG2 cells. Additionally, PSZ decreased the target gene expression of lipogenesis such as sterol regulatory element binding protein-1c, fatty acid synthase, stearoyl-CoA desaturase-1, diacylglycerol O-acyltransferase-1, and acetyl-CoA carboxylase-1 by 1.75, 6.0, 2.32, 1.93 and 1.81 fold, respectively. In addition, Oleic acid-treated HepG2 cells elicited extensive accumulation of tumor necrosis factor-α (TNFα) by 4.53 fold, whereas PSZ-treated cells decreased the expression of TNFα mRNA by 1.76 fold. PSZ significantly inhibited oxidative stress induced by reactive oxygen species. These results suggest that PSZ has effects on steatosis in vitro and further studies are needed in vivo to verify the current observations.


Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression.
Malignant melanoma is a destructive and lethal form of skin cancer with poor prognosis. An effective treatment for melanoma is greatly needed. Ginsenoside Rg3 is a herbal medicine with high antitumor activity. It is reported that abnormal glycosylation is correlated with the tumor cell growth. However, the antitumor effect of Rg3 on melanoma and its mechanism on regulating glycosylation are unknown. We found that Rg3 did not only inhibit A375 melanoma cell proliferation in a dose-dependent manner, but also decreased the expression of fucosyltransferase IV (FUT4) and its synthetic product Lewis Y (LeY), a tumor-associated carbohydrate antigen (TACA). Knocking down FUT4 expression by siRNA dramatically reduced FUT4/LeY level and inhibited cell proliferation through preventing the activation of EGFR/MAPK pathway. Consistently, the inhibitory effect of the Rg3 and FUT4 knockdown on melanoma growth was also seen in a xenograft melanoma mouse model. In conclusion, Rg3 effectively inhibited melanoma cell growth by downregulating FUT4 both in vitro and in vivo. Targeting FUT4/LeY mediated fucosylation by Rg3 inhibited the activation of EGFR/MAPK pathway and prevented melanoma growth. Results from this study suggest Rg3 is a potential novel therapy agent for melanoma treatment.


Atopic dermatitis.
The prevalence of atopic dermatitis (AD), the most common inflammatory skin disease in children, has increased over the last decade. Although there is a genetic predisposition to AD, there is strong evidence suggesting a crucial role for environmental factors. The etiology of AD is probably multifactorial and includes interactions between the genetic predisposition and exogenous provocation factors. Many specific exogenous factors have been associated with the disease. These factors include, house dust mites, irritants, dietary allergens, air pollution, etc. In this chapter, we try to review the most important factors that have been implicated in the etiology of AD.


Interventions to Improve Social Climate in Acute Mental Health Inpatient Settings: Systematic Review of Content and Outcomes.
Quantification of the social climate of mental health care environments has received considerable attention. Investigations of the resulting measures indicate that social climate is associated with individual outcomes including patient satisfaction and staff burnout. Interest has grown in developing interventions to improve social climate in anticipation of subsequent related benefits. This study aimed to identify and critically review research about the effectiveness of interventions for improving social climate in inpatient adult acute mental health settings. Systematic review reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Comprehensive terms were used to search multiple electronic databases from inception to July 2019. Information about intervention type(s), complexity was extracted and study quality was assessed. Twenty-three papers met inclusion criteria of which 20 used a pretest-posttest study design and three employed randomized and/or controlled designs. Interventions were environmental/structural, operational/process-oriented and developmental/person-oriented in nature and they ranged in complexity. The Ward Atmosphere Scale was the most common outcome measure used. Following quality assessment, six studies were judged to be sufficiently robust in terms of quality, theory-base, user-inclusion, and outcomes evaluation to contribute credibly to the evidence base. Of these, four complex person- and process-oriented intervention studies and two less complex structural/environmental intervention studies resulted in positive outcomes. There is limited strong evidence that interventions positively influence measures of ward social climate in acute adult mental health settings. Such measures should not be the sole criterion of success when evaluating change. Decisions about implementing change to improve social climate should be informed by meaningful proxy measures including the views and preferences of service users and other stakeholders. Studies using stronger designs are required to establish the ability of interventions to improve social climate.


PSII photochemistry and antioxidant responses of a chickpea variety exposed to drought.
The effect of drought on the chickpea variety ILC 3279 was investigated at the vegetative stage. After 20 days from sowing, the plants subjected to drought stress for 3, 5 and 7 days imposed by withholding water were permitted to recover by rewatering for 2 days after 3, 5 and 7 days of drought. Shoot elongation, leaf production, fresh and dry biomass reduced while MDA and proline accumulation increased with extended duration of stress. The plants stressed for 3 days exhibited a rapid drop in their relative and absolute water contents. The quantum efficiency of PSII open centres in the dark-adapted and light-saturated state, excitation energy trapping of PSII and electron transport rate decreased significantly from the 5th day to the end of the drought treatments. Plants drought-stressed for 7 days brought about a marked increase in non-photochemical energy dissipation and a marked decline in photochemical quenching. After rewatering all chlorophyll a fluorescence characteristics except for F(M) completely recovered and reached the control values. Under 5 and 7 days of drought, the anthocyanin content increased gradually while the total chlorophyll content of leaves declined compared to the controls. The total carotenoid content remained unchanged during the experiments. The antioxidant enzyme response to drought treatments was quite variable. The total SOD activity upregulated with increasing duration of stress. On the other hand, the total APX activity was significantly higher only on the 7th day while the total POD activity increased from the 5th day. Differences in the total GR activity of treated groups were not statistically significant compared to their controls throughout the treatments. The present results indicate that the chickpea variety ILC 3279 withstands severe drought with its upregulated protective mechanisms at the vegetative stage.


Serum indoleamine 2,3-dioxygenase and kynurenine aminotransferase enzyme activity in patients with ischemic stroke.
We investigated the activation and pathophysiological roles of indoleamine 2,3-dioxygenase (IDO) and kynurenine aminotransferase (KAT) in patients with ischemic stroke. Patients were recruited from the acute stroke unit of a general hospital within 24 hours post-stroke. The immune transmission turbidity method was used to determine the concentration of serum high-sensitivity C-reactive protein (hsCRP), apolipoprotein A-1 and apolipoprotein B. The concentrations of triglyceride, cholesterol, high density lipoprotein (HDL), low density lipoprotein and non-esterified fatty acids were determined using an enzymatic method. Tryptophan (TRP), kynurenine (KYN) and kynurenine acid (KYNA) concentrations were determined by high performance liquid chromatography. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological deficits at admission and 3 weeks post-stroke. The IDO and KAT activity ratio were calculated by KYN/TRP and KYNA/KYN, respectively. The correlation between hsCRP and IDO, KAT and NIHSS score was also analyzed. A total of 81 patients with ischemic stroke and 35 normal controls were recruited. Lower TRP, KYNA, HDL and KAT activity ratio were found in the stroke group compared to the control group (p<0.05). The levels of hsCRP and IDO activity ratio were much higher in the stroke group than the control group (p<0.01). The IDO activity in patients with ischemic stroke showed a positive correlation with hsCRP (r=0.425, p=0.027). In addition, hsCRP and IDO levels were positively associated with the NIHSS score both at admission and 3 weeks post-stroke. These data suggest an inflammatory response characterized by up-regulated IDO activation in ischemic stroke, which might be closely relevant to its pathophysiology.


Introduction to clinical decision making.
In the last few years there has been a remarkable increase in the amount of clinical data in the average hospital chart, and more and more problem-solving algorithms have been developed. We need better "thinking tools" to help us handle the flow of information. The term "clinical decision making" is used to describe a systematic way to handle data and algorithms to decide on a best course of action. This introductory article discusses some of the problems in establishing a decision criterion, both for a population and for an individual patient. Comparing the probabilities and utilities of various diagnostic outcomes (true positive, false positive, etc.) leads to a diagnostic strategy. The article also discusses conditional probability. Bayes' theorem, and likelihood ratios.


Child care center exclusion policies and directors' opinions on the use of antibiotics.
We studied exclusion policies and child care center directors' opinions regarding antibiotic use for childhood illnesses. Among 135 respondents, 96.9% reported that they had written policies on exclusion of children for acute illnesses. Although 52.4% of respondents agreed that children are prescribed antibiotics unnecessarily, 89.1% believed that parents pressure physicians to prescribe unnecessary antibiotics.


Comparison of live human neutrophil and alveolar macrophage elastolytic activity in vitro. Relative resistance of macrophage elastolytic activity to serum and alveolar proteinase inhibitors.
Elastin is an extracellular matrix protein critical to the normal structure and function of human lung. Recently reported data indicate that live human alveolar macrophages can degrade purified elastin in vitro. In this study, we directly compared the elastolytic activity of alveolar macrophages with that of human neutrophils. In the absence of proteinase inhibitors, human neutrophils degrade much more elastin than do human alveolar macrophages. However, macrophages cultured in 10% human serum and in contact with purified 3H-elastin degraded 4.7 micrograms elastin/10(6) cells per 24 h, as compared to less than 1 microgram/10(6) cells/24 h for neutrophils. We observed a similar pattern when the two cells were cultured in human alveolar fluid. We determined that the relative resistance of macrophage elastolytic activity to serum or alveolar proteinase inhibitors was not simply due to phagocytosis of substrate by the larger macrophages. Live macrophages as well as neutrophils degrade 125I-elastin coupled to noningestible sepharose beads. Again in serum-free media, neutrophils degraded eight-fold more elastin than macrophages but only macrophages degraded sepharose-coupled elastin in the presence of 10% serum. Because of these findings, we compared the enzymatic mechanisms of elastin breakdown by macrophages with that of neutrophils. Macrophage elastolytic activity is largely (65-80%) due to a cysteine proteinase(s), at least part of which is Cathepsin B. Approximately half of the cysteine proteinase activity appeared to be expressed at or near the cell surface. These experiments defined two enzymatically distinct pathways of elastin breakdown by human inflammatory cells: the classic, neutrophil derived soluble elastase(s) that is sensitive to serum and alveolar proteinase inhibitors, and a macrophage-mediated pathway that is largely cell associated and relatively resistant to inhibitors. The function of the two pathways depends on the relative excess or deficiency of soluble inhibitors. At inflammatory sites rich in proteinase inhibitors, tissue macrophages may degrade more extracellular matrix elastin than neutrophils. In smokers without antiproteinase deficiency, pulmonary macrophages, which are known to be increased in number, may be the more important cause of elastin breakdown and emphysema.


Mechanisms for the oxidation of reduced gluthathione by stimulated granulocytes.
We have reported previously that human granulocytes have an irreversible fall in their endogenous reduced soluble sulfhydryls following zymosan stimulation. In the present study, we demonstrate that stimulated granulocytes release one or more reactive oxygen species (ROS) with the capacity to oxidize reduced glutathione (GSH). One or more of these compounds is stable enough to be detected in the supernatant. The formation of these stable oxidants appears to require H2O2 and heme or a heme-containing enzyme. However, once formed, the compound reacts with GSH without these factors. The ROS is not superoxide or hydroxyl radical, since neither superoxide dismutase nor the hydroxyl scavengers, mannitol and benzoic acid, change the rate of the reaction. Methionine has recently been demonstrated to be oxidized to a sulfoxide by a reactive oxygen species that is dependent on H2O2 and heme for its production. We found that methionine could directly react with the same ROS that degrades GSH. The ROS also has the capacity to oxidize iodide and fix halogen to proteins. Our data indicate that stimulated granulocytes release a ROS with the capacity to oxidize GSH, react with methionine, and oxidize and fix I- to protein. The compound, therefore, appears dependent on H2O2 and the myeloperoxidase system for its production, and is either hypochlorous acid (HOCI) or a compound derived from HOCI, such as a chloramine. The capacity of GSH to react with this ROS suggests an additional role for this tripeptide in cellular protection against oxidant injury.