Induction of beta-R1/I-TAC by interferon-beta requires catalytically active TYK2.
The beta-R1/I-TAC (interferon-inducible T-cell alpha-chemoattractant) gene encodes an alpha-chemokine that is a potent chemoattractant for activated T-cells. We previously reported that beta-R1 was selectively induced by interferon (IFN)-beta compared with IFN-alpha and that the canonical type I IFN transcription factor interferon-stimulated gene factor 3 (ISGF3) was necessary but not sufficient for beta-R1 induction by IFN-beta. These findings suggested that beta-R1 induction by IFN-beta required an accessory component. To begin characterizing this signaling pathway, we examined the function of TYK2 protein in the IFN-beta-mediated induction of beta-R1. This study was motivated by the observation that beta-R1 could not be induced in TYK2-deficient U1 cells by IFN-beta (Rani, M. R. S., Foster, G. R., Leung, S., Leaman, D., Stark, G. R., and Ransohoff, R. M. (1996) J. Biol. Chem. 271, 22878-22884), an unexpected result because IFN-beta evokes substantial expression of IFN-stimulated genes (ISGs) in U1 cells through a TYK2-independent pathway. We now report beta-R1 expression patterns in U1 cells complemented with wild-type or mutant TYK2 proteins. Complementation with wild-type TYK2 rescued IFN-beta-inducible expression of beta-R1. Cells expressing kinase-deficient deletion or point mutants of TYK2 were refractory to induction of beta-R1 by IFN-beta despite robust expression of other ISGs. Transient transfection analysis of a beta-R1 promoter-reporter confirmed that transcriptional activation of beta-R1 by IFN-beta required competent TYK2 kinase. These studies indicate that the catalytic function of TYK2 is required for IFN-beta-mediated induction of beta-R1. Catalytic TYK2 is the first identified component in an accessory signaling pathway that supplements ISGF3/interferon-stimulated response element signaling for gene induction by type I IFNs.


Design and synthesis of conformationally-constrained MMP inhibitors.
A novel series of conformationally constrained matrix metalloprotease inhibitors was identified. The potencies observed for these inhibitors were highly dependent upon the substitution pattern on the caprolactam ring as well as the succinate moiety.


Strong π-stacking causes unusually large anisotropic thermal expansion and thermochromism.
π-stacking in ground-state dimers/trimers/tetramers of N-butoxyphenyl(naphthalene)diimide (BNDI) exceeds 50 kcal ⋅ mol-1 in strength, drastically surpassing that for the *3[pyrene]2 excimer (∼30 kcal ⋅ mol-1; formal bond order = 1) and similar to other weak-to-moderate classical covalent bonds. Cooperative π-stacking in triclinic (BNDI-T) and monoclinic (BNDI-M) polymorphs effects unusually large linear thermal expansion coefficients (α a , α b , α c , β) of (452, -16.8, -154, 273) × 10-6 ⋅ K-1 and (70.1, -44.7, 163, 177) × 10-6 ⋅ K-1, respectively. BNDI-T exhibits highly reversible thermochromism over a 300-K range, manifest by color changes from orange (ambient temperature) toward red (cryogenic temperatures) or yellow (375 K), with repeated thermal cycling sustained for over at least 2 y.


Genetic variation at the alcohol dehydrogenase locus in Drosophila melanogaster in relation to environmental variation: Ethanol levels in breeding sites and allozyme frequencies.
Ethanol levels in Drosophila breeding sites in seepages of unfortified wine inside wineries have been found to be similar to those in many decaying fruits and vegetables. Fortified wine seepages inside wineries have ethanol levels on average three times as high as other breeding sites. However there was no evidence that this variation in ethanol levels was associated with differences in Adh F frequencies in D. melanogaster at sites either within wineries or outside wineries. D. simulans was at lower frequencies at sites inside wineries compared to sites outside although this difference may not be related to ethanol levels. It is concluded that adaptation to natural levels of environmental ethanol by D. melanogaster does not necessarily modify Adh frequencies.


A real-time prediction model for post-irradiation malignant cervical lymph nodes.
To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation. One-hundred forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine-needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model. A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (P < .05). A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation.


Factors associated with pelvic floor dysfunction with emphasis on urinary and fecal incontinence and genital prolapse: an epidemiological study.
To describe a general population of women with regard to factors associated with urinary and fecal incontinence and genital prolapse symptoms. A questionnaire about medical background, urinary and fecal incontinence and genital prolapse symptoms was mailed to 100040-year-old and 100060-year-old Swedish women. Associations were described by odds ratios (ORs) with 95% confidence intervals (CIs). Sixty-seven percent answered the questionnaire. Multivariate analysis showed urinary incontinence to be associated with anal sphincter rupture [OR 4.4 (95% CI 1.0-18.8)], pelvic heaviness [3.8 (2.1-7.0)], body mass index (BMI) >or=30 kg/m2[3.7 (2.0-6.7)], multiparity [1.8 (1.0-3.4)], varicose veins surgery [1.9 (1.2-3.2)] and age [1.9 (1.2-3.2)]. Univariate analyses revealed statistically significant associations between urinary incontinence and incontinence for flatus [4.8 (3.0-7.8)], for liquid stool [5.0 (2.9-8.6)] and for solid stool [5.9 (2.4-14.2)]. Chronic bronchitis [5.7 (1.7-18.9)] was strongly associated with urinary incontinence but was only reported by the older age group. Prolapse symptoms were strongly associated with both urinary and fecal incontinence. Prolapse symptoms as opposed to urinary and fecal incontinence seemed to be associated more with injuries at delivery than with chronic pelvic floor strain. Women with urinary incontinence are also likely to suffer from fecal incontinence and prolapse and vice versa. Other associated factors for pelvic floor dysfunction were overweight, and especially obesity, chronic bronchitis, vaginal delivery and multiparity, age, heredity and diseases suggestive of collagen disorders. A multidisciplinary management of women with pelvic floor symptoms is suggested and possible prevention is discussed.


Application of a disease-specific mapping function to estimate utility gains with effective treatment of schizophrenia.
Most tools for estimating utilities use clinical trial data from general health status models, such as the 36-Item Short-Form Health Survey (SF-36). A disease-specific model may be more appropriate. The objective of this study was to apply a disease-specific utility mapping function for schizophrenia to data from a large, 1-year, open-label study of long-acting risperidone and to compare its performance with an SF-36-based utility mapping function. Patients with schizophrenia or schizoaffective disorder by DSM-IV criteria received 25, 50, or 75 mg long-acting risperidone every 2 weeks for 12 months. The Positive and Negative Syndrome Scale (PANSS) and SF-36 were used to assess efficacy and health-related quality of life. Movement disorder severity was measured using the Extrapyramidal Symptom Rating Scale (ESRS); data concerning other common adverse effects (orthostatic hypotension, weight gain) were collected. Transforms were applied to estimate utilities. A total of 474 patients completed the study. Long-acting risperidone treatment was associated with a utility gain of 0.051 using the disease-specific function. The estimated gain using an SF-36-based mapping function was smaller: 0.0285. Estimates of gains were only weakly correlated (r = 0.2). Because of differences in scaling and variance, the requisite sample size for a randomized trial to confirm observed effects is much smaller for the disease-specific mapping function (156 versus 672 total subjects). Application of a disease-specific mapping function was feasible. Differences in scaling and precision suggest the clinically based mapping function has greater power than the SF-36-based measure to detect differences in utility.


Developmental changes in sleep and breathing across infancy and childhood.
Sleep and breathing are physiological processes that begin in utero and undergo progressive change. While the major period of change for both sleep and breathing occurs during the months after birth, considered a period of vulnerability, more subtle changes continue to occur throughout childhood. The systems that control sleep and breathing develop separately, but sleep represents an activity state during which breathing and breathing control is significantly altered. Infants and young children may spend up to 12 hours a day sleeping; therefore, the effects of sleep on breathing are fundamental to understanding both processes in childhood. This review summarizes the current literature relevant to understanding the normal development of sleep and breathing across infancy and childhood.


Bilateral parietal activations for complex visual-spatial functions: Evidence from a visual-spatial construction task.
In this paper, we examine brain lateralization patterns for a complex visual-spatial task commonly used to assess general spatial abilities. Although spatial abilities have classically been ascribed to the right hemisphere, evidence suggests that at least some tasks may be strongly bilateral. For example, while functional neuroimaging studies show right-lateralized activations for some spatial tasks (e.g., line bisection), bilateral activations are often reported for others, including classic spatial tasks such as mental rotation. Moreover, constructive apraxia has been reported following left- as well as right-hemisphere damage in adults, suggesting a role for the left hemisphere in spatial function. Here, we use functional neuroimaging to probe lateralization while healthy adults carry out a simplified visual-spatial construction task, in which they judge whether two geometric puzzle pieces can be combined to form a square. The task evokes strong bilateral activations, predominantly in parietal and lateral occipital cortex. Bilaterality was observed at the single-subject as well as at the group level, and regardless of whether specific items required mental rotation. We speculate that complex visual-spatial tasks may generally engage more bilateral activation of the brain than previously thought, and we discuss implications for understanding hemispheric specialization for spatial functions.


VLA-4-dependent adhesion activities of U937 cells and guinea pig bronchoalveolar lavage leukocytes.
VLA-4-dependent binding to fibronectin (FN) and to a human vascular cell adhesion molecule (hVCAM-1)-transfected murine cell line was measured using U937 cells and guinea pig (GP) bronchoalveolar lavage (BAL) cells. A species cross-reactive, blocking monoclonal antibody directed against human VLA-4 (TY 21.6) inhibited U937/FN binding by 71 +/- 7%. The presence of TY21.6 inhibited the stimulated binding of U937 cells to hVCAM-1 by 84%. However, TY 21.6 was unable to inhibit the BAL/FN binding. With the addition of TY 21.6, the binding of PMA-stimulated BAL cells to hVCAM-1 was inhibited by 57 +/- 5%. In summary, human and guinea-pig leukocytes express binding activity to both FN and hVCAM-1. A specific VLA-4 blocking monoclonal antibody, TY 21.6, inhibited U937 and BAL cell binding to hVCAM-1, but only inhibited FN binding with U937 cells.


Characterization of mechanisms involved in uptake of Streptococcus dysgalactiae by bovine mammary epithelial cells.
Bovine mammary epithelial cells were pretreated with inhibitors of protein kinase activity, actin polymerization and receptor-mediated endocytosis. In addition, mammary epithelial cells and Streptococcus dysgalactiae were pretreated with inhibitors of protein synthesis. Results showed that activity of tyrosine protein kinases, intact microfilaments and de novo eukaryotic protein synthesis was required for uptake of S. dysgalactiae by bovine mammary epithelial cells; a process that appeared to occur via receptor-mediated endocytosis. In contrast, de novo bacterial protein synthesis was not required for uptake of S. dysgalactiae by MAC-T cells. This study provides insight into bacterial and cellular mechanisms involved in early host-pathogen interactions, putting into perspective the role of mammary epithelial cells in the development and establishment of intramammary infections by S. dysgalactiae.


[Surveillance of postoperative wound infections: reference data of the Hospital Infection Surveillance System (KISS)].
Surgical site infections (SSI), the third-most-frequent nosocomial infection, are a problem in all fields of surgery. Assessing the level of one's own infection rates is often difficult, since there have been no suitable comparative data available in Germany in the past due to the lack of a uniform method of determining these rates. Based on an American model, the Hospital Infection Surveillance System (KISS) has been carrying out a standard recording of SSI since 1997 in meanwhile 132 surgical departments of 89 hospitals. Specially trained hygiene personnel record SSI according to CDC definitions in selected indicator operations. Since January 1997, 1,549 SSI have been recorded in 71,038 operations using 13 different surgical techniques. The risk-ratified SSI rates for each of these surgical techniques are provided and can serve as orientational data for other departments. The KISS reference data can help in assessing one's own SSI rates. A prerequisite is surveillance according to the KISS protocol.


Assessment of FTO Gene Polymorphism and its Association with Type 2 Diabetes Mellitus in North Indian Populations.
FTO gene polymorphism related to type 2 diabetes and obesity was studied in this north Indian population. This study was done, due to a continuous increase in the risk of obesity and type 2 diabetes in north Indian population, because of lifestyle and genetic variations. Clinically diagnosed subjects of type 2 diabetes mellitus (as per ADA criteria) were taken as cases and age and sex matched subjects without any associated illness were taken as controls. Obesity was estimated by calculating waist circumference and BMI in the study cases and controls. For genetic variation, DNA was isolated with Quaigen kit method and isolated DNA was amplified with PCR. Amplified DNA was resolved in 1% agarose gel electrophoresis. The Hardy-Weinberg equilibrium, OR, CI and P value were calculated using standard protocols. FTO gene polymorphism (SNP 9940128) was found to be significantly correlated with type 2 diabetes mellitus and obesity. The AG genotype frequency was observed to be higher (13.09%) with (P < 0.0001) in the cases as compared to controls. Logistic regression analysis was conducted for AG and GG genotypes with respect to AA. In this novel study genetic co-relation was observed between FTO gene polymorphisms and type 2 diabetes and obesity in the north Indian population.


[Satisfaction of geriatric patients with their pain therapy. Wish and reality].
The goal of this study was to determine the level of satisfaction of geriatric patients with their pain therapy, their wishes for improved treatment, and possible influencing factors. From April to November 2002, all patients able to communicate ( n=1432) were included in the study if they had reported pain in the previous 7 days or were taking regular analgesic medication without specifying pain. Of the geriatric patients reporting from home, 36.4% were not satisfied with their pain therapy up to that time, and 25.4% of surgical patients were dissatisfied as were 28.5% of patients treated in other departments. A total of 93.3% desired better pain treatment. Independent predictors for dissatisfaction with their therapy or wish for improvement were increasing pain intensity, frequent concomitant complaints in addition to pain, and the objectively perceived everyday competence. This study supports the observation that competent pain therapy is necessary and that there is room for improvement in geriatric facilities. Measuring pain intensity, posing questions pertaining to satisfaction with pain therapy, and determining whether patients desire better pain treatment are all indispensable for optimal care. Pain therapy should equally address reduction of pain intensity and management of other complaints.


Functional mitral regurgitation: a link to pulmonary hypertension in heart failure with preserved ejection fraction.
Patients with heart failure with preserved ejection fraction (HFpEF) may present with Pulmonary hypertension (PH) and functional mitral regurgitation (MR). Whether PH is linked to the presence of functional MR has not been investigated in HFpEF patients. Systolic pulmonary artery pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control subjects free of organic mitral valve lesions, significant valve disease, and comorbid conditions associated with PH. Whereas none of control subjects had more than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective regurgitant orifice, regurgitant volume, and regurgitant fraction 7 ± 3 mm,(2) 15 ± 8 mL, and 28 ± 14%, respectively). Pulmonary hypertension (sPAP >35 mm Hg) was significantly more prevalent in HFpEF patients with functional MR than in HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR remained an independent predictor of PH in HFpEF patients (P = .004) after adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022) and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in HFpEF patients than in control subjects (35 ± 9 vs 29 ± 8 mm Hg [P < .0001] and 13 ± 6 vs 11 ± 5 [P = .018], respectively). Systolic PAP remained greater in HFpEF patients than in control subjects after adjusting for E/e' (P = .002). Pulmonary hypertension appears to be linked to the presence of functional MR in HFpEF patients.


Lack of association between the brain-derived neurotrophin factor (C-270T) polymorphism and late-onset Alzheimer's disease (LOAD) in Brazilian patients.
After the identification of the apolipoprotein E gene isoform (APOE-epsilon4) as a risk factor for late-onset Alzheimer's disease (LOAD), the search for other polymorphisms associated with AD has been undertaken by many groups of investigators around the world. These studies have shown controversial results in many populations. More recently, a single nucleotide polymorphism in the promoter region of the brain-derived neurotrophin factor (BDNF) was found to be a risk factor for AD in two independent population studies. Here we report the analysis of this polymorphism in a group of 188 LOAD Brazilian patients compared to matched normal controls. A strong association between the APOE-epsilon4 polymorphism and LOAD was observed, but there was no significant association between this BNDF polymorphism and affected patients. The possibility that other polymorphisms or mutations in this gene play a role in the development of AD cannot be ruled out. However, the results of the present study suggest that in opposition to the two reported studies, this polymorphism does not seem to be implicated in LOAD Brazilian patients. It also shows the importance of replication studies in different populations, as susceptibility loci might differ in different ethnic groups; this will have important implications in future treatments with pharmacological agents.


Dissection of a complex seed phenotype: novel insights of FUSCA3 regulated developmental processes.
A T-DNA insertion mutant of FUSCA3 (fus3-T) in Arabidopsis thaliana exhibits several of the expected deleterious effects on seed development, but not the formation of brown seeds, a colouration which results from the accumulation of large amounts of anthocyanin. A detailed phenotypic comparison between fus3-T and a known splice point mutant (fus3-3) revealed that the seeds from both mutants do not enter dormancy and can be rescued at an immature stage. Without rescue, mature fus3-3 seeds are non-viable, whereas those of fus3-T suffer only a slight loss in their germinability. A series of comparisons between the two mutants uncovered differences with respect to conditional lethality, in histological and sub-cellular features, and in the relative amounts of various storage compounds and metabolites present, leading to a further dissection of developmental processes in seeds and a partial reinterpretation of the complex seed phenotype. FUS3 function is now known to be restricted to the acquisition of embryo-dependent seed dormancy, the determination of cotyledonary cell identity, and the synthesis and accumulation of storage compounds. Based on DNA binding studies, a model is presented which can explain the differences between the mutant alleles. The fus3-T lesion is responsible for loss of function only, while the fus3-3 mutation induces various pleiotropic effects conditioned by a truncation gene product causing severe mis-differentiation.


Rapid label-free colorimetric dual-functional aptasensor for β-lactoglobulin detection based on a rational tailoring strategy.
β-lactoglobulin (β-LG) is a nonnegligible allergenic protein found in cow milk. A label-free, enzyme-free, dual-functional aptameric sensor was constructed based on rational aptamer tailoring for β-LG detection. Via an established three-step rational tailoring strategy, the original aptamer was transformed from an inflexible antiparallel topology into the flexible, antiparallel/parallel hybrid topology, enlg2-pl3. enlg2-pl3 displayed the dual-functionality of not only binding with β-LG via the antiparallel conformation but also outputting signals via the parallel type. The dual-functionality depended on the conformational conversion of enlg2-pl3. The β-LG-driven conformational conversion to antiparallel type was the detection basis of aptasensor. The detection conditions were optimized regarding ions, hemin, chromogenic substrate, pH levels, and detection time. Furthermore, the aptasensor offered advantages, such as cost-efficiency, simple operation, 40 min rapid detection, excellent specificity, and a sensitivity of a three-orders of magnitude linear range and an 8.23-fold linear curve slope, meeting the point-of-care testing (POCT) requirements for dairy analysis.


Co-design to deliver service improvement: What does this mean and how can we do it? A qualitative study with upper gastrointestinal cancer patients and professionals.
There is strategic objective to incorporate the principles and practice of co-design into routine service development and improvement. The aim was to explore the concept and feasibility of service co-design with patients and health professionals with regards to the upper gastrointestinal (UGI) cancer care pathway. Qualitative telephone interviews and face-to-face focus groups in one region of England. Twenty patients completed interviews. Nine patients and ten professionals formed two focus groups. Patients were referred through the urgent (two week) GP referral route and were within six months of receiving their first treatment for an UGI cancer. Professionals were working as service planners and providers of the UGI cancer care pathway. Thematic analysis was undertaken. Six themes emerged: Responsibilities and expectations, Knowledge and understanding, Valuing patient input, Building relationships, Environment for co-design activities, Impact and effectiveness. Based on the themes a checklist has been created to provide practical suggestions for both professionals and patients on approaching co-design for service improvement. This study offers policy and practice partners a clearer understanding of co-design and factors to consider when approaching co-design in real life settings.


A functional screen for regulatory elements that improve retroviral vector gene expression.
Recombinant retroviruses constitute the most common class of gene delivery vectors used in hematopoietic cell-based gene therapy. However, the use of these vectors can be limited by inadequate levels of transgene expression, often mediated by expression variegation and vector silencing due to chromosomal position effects. Toward the goal of addressing this problem, we sought to identify cis-regulatory elements from the human genome that can improve the level and stability of retroviral vector gene expression. Libraries of size-selected fragments from the human genome were cloned into the "double-copy" position of the gammaretroviral reporter vector MGPN2, and the resulting vectors underwent several rounds of transduction and selection for high-level vector GFP expression. From this screen we identified both enhancer-like elements and vector mutations associated with increased vector expression. One element, H-11, exhibited enhancer activity in a mouse bone marrow progenitor colony assay, a human promoter trap assay, and a long-term mouse bone marrow transplant assay. This element seems to be an orientation-dependent, tissue-independent enhancer.


Effect of plutonium-239 on the mitotic activity of mouse bone marrow cells.
Mitotic index of the bone marrow cells was studied in femoral bone marrow of mice given 313 kBq 239Pu kg-1. The attention was turned to the femoral midshaft and the mitosis concentration, intensified by Colcemid stathmokinetic effect, was evaluated in a sampling field from endosteal surface to the central venous canal, throughout 68 weeks. It has been found that the plutonium effect in the sampling band is rather uniform except the points in subendosteal zone early after plutonium injection, where the mitotic index was reduced in such a way that the mitotic gradient, observed in controls, was affected. The mitotic activity in femoral diaphysis of plutonium injected mice was mobilized approximately till the 30th week of contamination. Later it deteriorated progressively. The results are discussed and should not be regarded as representative for the entire bone marrow hemopoiesis.


Data on evolutionary hybrid neural network approach to predict shield tunneling-induced ground settlements.
The dataset presented in this article pertains to records of shield tunneling-induced ground settlements in Guangzhou Metro Line No. 9. Field monitoring results obtained from both the two tunnel lines are put on display. In total, 17 principal variables affecting ground settlements are tabulated, which can be divided into two categories: geological condition parameters and shield operation parameters. Shield operation parameters are specifically provided in time series. Another value of the dataset is the consideration of karst encountered in the shield tunnel area including the karst cave height, the distance between karst cave and tunnel invert, and the karst cave treatment scheme. The dataset can be used to enrich the database of settlement caused by shield tunneling as well as to train artificial intelligence-based ground settlement prediction models. The dataset presented herein were used for the article titled "Evolutionary hybrid neural network approach to predict shield tunneling-induced ground settlements" (Zhang et al., 2020).


Evidence of hypocalcemic factor from corpuscles of Stannius of the teleost Heteropneustes fossilis (Bloch).
The administration of acid extract of corpuscles of Stannius has no effect on the plasma calcium level, in the normal fish, whereas the same dose shows typical hypocalcemic response in hypercalcemic fish, H. fossilis. It is concluded that acid extract of corpuscles of Stannius is effective only in hypercalcemic condition.


Atypical capillary malformations with subsequent diplegia: A difficult case of capillary malformation-arteriovenous malformation syndrome.
Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare condition associated with mutations in the genes RASA1 and EPHB4. We present a challenging case of CM-AVM in a 17-month-old boy with permanent diplegia from an undiagnosed arteriovenous malformation underlying a large atypical capillary malformation over the lower thoracic spine. This case demonstrates that clinicians should have a low threshold for neuroimaging in the context of new neurologic symptoms in patients with atypical capillary malformations.


Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.
The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity.


Human lung cancer cells grown on acellular rat lung matrix create perfusable tumor nodules.
Extracellular matrix allows lung cancer to form its shape and grow. Recent studies on organ reengineering for orthotopic transplantation have provided a new avenue for isolating purified native matrix to use for growing cells. Whether human lung cancer cells grown in a decellularized rat lung matrix would create perfusable human lung cancer nodules was tested. Rat lungs were harvested and native cells were removed using sodium dodecyl sulfate and Triton X-100 in a decellularization chamber to create a decellularized rat lung matrix. Human A549, H460, or H1299 lung cancer cells were placed into the decellularized rat lung matrix and grown in a customized bioreactor with perfusion of oxygenated media for 7 to 14 days. Decellularized rat lung matrix showed preservation of matrix architecture devoid of all rat cells. All three human lung cancer cell lines grown in the bioreactor developed tumor nodules with intact vasculature. Moreover, the lung cancer cells developed a pattern of growth similar to the original human lung cancer. Overall, this study shows that human lung cancer cells form perfusable tumor nodules in a customized bioreactor on a decellularized rat lung matrix created by a customized decellularization chamber. The lung cancer cells grown in the matrix had features similar to the original human lung cancer. This ex vivo model can be used potentially to gain a deeper understanding of the biologic processes involved in human lung cancer.


Extraosseous distribution of 99mTc-diphosphonates during bone scintigraphy: review of the literature with case series presentation.
Technetium-99m (99mTc)-diphosphonates represent the most common radiopharmaceutical used for bone scintigraphy. Even if the uptake in bone tissue has been widely explored, atypical uptake could be seen in soft tissue malignancies during bone scintigraphy. Increased vascularization and endothelium permeability represent front-row players in the biodistribution of the tracer, albeit other causes have been identified such as trauma, necrosis, the presence of calcification in metastasis, the pH of the tissue and consequently the type of ion concentration. The aim of this paper is to summarize the state of art of atypical soft tissue uptake seen in cancer tissues. The research was conducted on PubMed. The analysis of the literature suggests that calcium metabolism and ionic saturation have a pivotal role in the biodistribution of bone tracers. This phenomenon ranks in a complex scenario that includes carcinogenesis and cancer environment aspects. We also report two cases in our Institution in which atypical uptake in cancer tissues was observed.


High-speed DNA-based rolling motors powered by RNase H.
DNA-based machines that walk by converting chemical energy into controlled motion could be of use in applications such as next-generation sensors, drug-delivery platforms and biological computing. Despite their exquisite programmability, DNA-based walkers are challenging to work with because of their low fidelity and slow rates (∼1 nm min(-1)). Here we report DNA-based machines that roll rather than walk, and consequently have a maximum speed and processivity that is three orders of magnitude greater than the maximum for conventional DNA motors. The motors are made from DNA-coated spherical particles that hybridize to a surface modified with complementary RNA; the motion is achieved through the addition of RNase H, which selectively hydrolyses the hybridized RNA. The spherical motors can move in a self-avoiding manner, and anisotropic particles, such as dimerized or rod-shaped particles, can travel linearly without a track or external force. We also show that the motors can be used to detect single nucleotide polymorphism by measuring particle displacement using a smartphone camera.


Identification of lysine 15 at the active site in Escherichia coli glycogen synthase. Conservation of Lys-X-Gly-Gly sequence in the bacterial and mammalian enzymes.
Glycogen synthases from Escherichia coli and mammalian muscle differ in many respects including regulation, sugar nucleotide specificity, and primary sequence. To compare the structure of the active sites in these enzymes, the affinity-labeling study of the E. coli enzyme was carried out using adenosine diphosphopyridoxal as the reagent. The E. coli enzyme was inactivated in a time- and dose-dependent manner when incubated with the reagent followed by sodium borohydride reduction. The inactivation was markedly protected by ADP-glucose and ADP, suggesting that the reagent was bound to the substrate-binding site. The stoichiometry of the bound reagent to the enzyme was approximately 1:1. Sequence analysis of the labeled peptide isolated from a proteolytic digest of the modified protein revealed that Lys15 is labeled. Based on the geometry of the reagent, the epsilon-amino group of this residue might be located close to the pyrophosphate moiety of ADP-glucose bound to the E. coli enzyme, like that of Lys38 in the rabbit muscle enzyme, which is labeled by uridine diphosphopyridoxal (Tagaya, M., Nakano, K., and Fukui, T. (1986) J. Biol. Chem. 260, 6670-6676; Mahrenholz, A. M., Wang, Y., and Roach, P. J. (1988) J. Biol. Chem. 263, 10561-10567). The importance of the conserved sequence of Lys-X-Gly-Gly is discussed in connection with the glycine-rich region found in many nucleotide-binding proteins.


Voices - Yvonne Coghill on how inclusivity would benefit the new nursing framework.
Last month, England's chief nursing officer Jane Cummings published a framework designed to help nurses deliver better patient outcomes and experience, while using resources more efficiently.


11,12-Secoprostaglandins. 5. 8-Acetyl- or 8-(1-hydroxyethyl)-12-hydroxy-13-aryloxytridecanoic acids and sulfonamide isosteres as inhibitors of platelet aggregation.
The synthesis of a series of 8-acetyl- (or 1-hydroxyethyl-) 12-hydroxy-13-aryloxytridecanoic acids and their sulfonamide isosteres is described. These compounds are formally derived from members of earlier reported series of modified secoprostaglandins by replacing the omega-butyl chain termini by substituted aryloxy groups. A number of these compounds are potent inhibitors of collagen-induced blood platelet aggregation in guinea pigs on oral administration.


Lymphocyte migration in the micro-channel of splenic sheathed capillaries in Chinese soft-shelled turtles, Pelodiscus sinensis.
The structural characteristics of the splenic sheathed capillary were investigated using light microscopy and transmission electron microscopy (TEM). This study mainly focused on lymphocyte migration to the splenic white pulp via micro-channels in Chinese soft-shelled turtles, Pelodiscus sinensis. The results showed that the sheathed capillaries in the turtle spleen were high endothelial venule (HEV)-like vessels. These capillaries consist of micro-channels that facilitate lymphocyte migration to the splenic white pulp. The micro-channel is a dynamic structure comprising processes of endothelial cells, supporting cells, and ellipsoid-associated cells (EACs), which provides a microenvironment for lymphocyte migration. The pattern of lymphocyte migration in the micro-channel of the turtle spleen includes the following steps: (i) lymphocyte first adheres to the endothelium of the sheathed capillary, passes through the endothelial cells, and traverses through the basement membrane of the sheathed capillary; (ii) it then enters into the ellipsoid combined with supporting cells and EACs; and (iii) lymphocyte migrates from the ellipsoid to the periellipsoidal lymphatic sheath (PELS) via the micro-channel. This study provides morphological evidence for lymphocyte migration in the micro-channels of turtle spleens and also an insight into the mechanism of lymphocyte homing to the splenic white pulp of reptiles.


Does community social capital buffer the relationship between educational disadvantage and cognitive impairment? A multilevel analysis in Japan.
This study explored the relationship between community social capital and cognitive impairment, with a focus on the buffering role of community social capital in the association between educational disadvantage and cognitive impairment in community-dwelling older adults in Japan. We used data from two population-based, cross-sectional surveys targeting people aged ≥65 years in a suburban city of the Tokyo metropolitan area (n = 897; 49.8% men; average age = 74.4 years). Social capital included social support (emotional and instrumental support) and the strength of social networks (neighborly ties). To create district-level social capital indicators, we aggregated individual responses on social capital within each district. The Mini-Mental State Examination, Japanese version was used for the assessment of cognitive function. Using multilevel logistic regression analysis, we found that lower amounts of district-level emotional and instrumental support were associated with a greater likelihood of cognitive impairment among men. For women, district-level emotional support was associated with a greater likelihood of cognitive impairment. Additionally, a strong district-level social network buffered the relationship between low education and cognitive impairment in both sexes. Community social capital appears to have a protective role in determining cognitive function in old age. Our findings may facilitate the development of new community-based strategies to combat dementia.


[Physiological aspects of deglutition].
Mechanisms of deglutition physiology and fundamental characteristics that allow swallowing to accomplish its absolutely necessary vital function are shortly analysed.


EMG-driven fatigue-based self-adapting admittance control of a hand rehabilitation robot.
Upper-limb rehabilitation therapy sessions for post-stroke people generally contain rhythmic hand movements in a tiresome manner to rebuild the injured neural circuits. Fatigue formation causes breaks in the training and limits the therapy duration. Therefore, it is essential to establish a correlation between the patient's muscle condition and the rehabilitation exercises to improve the physiotherapy sessions. A self-adapting control method based on online fatigue detection in rhythmic arm movements is presented. Experimental tests were performed on twenty healthy subjects to validate the method's feasibility. Electromyography (EMG) and force signals considered the interfaces between users and the robot. In the first stage of the experiment, utilizing the frequency features from EMG signals, a neural network for fatigue detection trained; however, in the end, it substituted with a simple function as a refinement in the time-consuming aspect for the online employment. The initiation of the fatigue process is followed by reducing the admittance controller damping term based on the EMG signal processing. Trajectory tracking with the robot employs the self-adapting admittance controller (SAAC) method and the non-adapting admittance controller (NAAC). Movement accuracy and smoothness were measured and showed a better performance of the SAAC method related to the NAAC. Simulations with two different stiffness levels were performed on an upper-limb OpenSim model to study a stroke-injured arm and evaluate the proposed method's proficiency. The metabolic cost indicated the movement's superiority in a fatigue situation for reduced environment stiffness.


Current aspects of lactate exchange: lactate/H+ transport in human skeletal muscle.
Skeletal muscle is capable of producing and releasing large amounts of lactate and at the same time taking up lactate and using it as a respiratory fuel. The release and uptake of lactate both involve transmembrane transport, which is mediated mainly by a membrane protein called the monocarboxylate transporter (MCT). MCTs mediate membrane transport with an obligatory 1:1 coupling between lactate and H+ fluxes, and is therefore of great importance for pH regulation, especially during intense muscle activity. The total lactate and H+ transport capacity is higher in membranes from oxidative fibers than in membranes from more glycolytic fibers. There are two isoforms of MCT present in skeletal muscle, MCT1 and MCT4. In human muscle samples, there is a positive correlation between the proportion of type I fibers and MCT1 density. In contrast, the MCT4 density in human muscle is independent of fiber type and displays a large interindividual variation. Although the two isoforms have identical transport kinetics (Km), they may have different roles in muscle. MCT1 and MCT4 respond differently to a high-intensity training session, which suggests that these two isoforms are regulated differently.


The unique structural and biochemical development of single cell C4 photosynthesis along longitudinal leaf gradients in Bienertia sinuspersici and Suaeda aralocaspica (Chenopodiaceae).
Temporal and spatial patterns of photosynthetic enzyme expression and structural maturation of chlorenchyma cells along longitudinal developmental gradients were characterized in young leaves of two single cell C4 species, Bienertia sinuspersici and Suaeda aralocaspica Both species partition photosynthetic functions between distinct intracellular domains. In the C4-C domain, C4 acids are formed in the C4 cycle during capture of atmospheric CO2 by phosphoenolpyruvate carboxylase. In the C4-D domain, CO2 released in the C4 cycle via mitochondrial NAD-malic enzyme is refixed by Rubisco. Despite striking differences in origin and intracellular positioning of domains, these species show strong convergence in C4 developmental patterns. Both progress through a gradual developmental transition towards full C4 photosynthesis, with an associated increase in levels of photosynthetic enzymes. Analysis of longitudinal sections showed undeveloped domains at the leaf base, with Rubisco rbcL mRNA and protein contained within all chloroplasts. The two domains were first distinguishable in chlorenchyma cells at the leaf mid-regions, but still contained structurally similar chloroplasts with equivalent amounts of rbcL mRNA and protein; while mitochondria had become confined to just one domain (proto-C4-D). The C4 state was fully formed towards the leaf tips, Rubisco transcripts and protein were compartmentalized specifically to structurally distinct chloroplasts in the C4-D domains indicating selective regulation of Rubisco expression may occur by control of transcription or stability of rbcL mRNA. Determination of CO2 compensation points showed young leaves were not functionally C4, consistent with cytological observations of the developmental progression from C3 default to intermediate to C4 photosynthesis.


Segmental release of amino acid neurotransmitters from transcranial stimulation.
The present study used microdialysis techniques in an intact rabbit model to measure the release of amino acids within the lumbar spinal cord in response to transcranial electrical stimulation. Dialysis samples from the extracellular space were obtained over a stimulation period of 90 minutes and were examined using high pressure liquid chromatography. Neuronal excitation was verified by recording corticomotor evoked potentials (CMEPs) from the spinal cord. A significant increase in the release of glycine and taurine compared to sham animals was measured after 90 minutes of transcranial stimulation. Glutamate and aspartate release was not significantly elevated. GABA concentrations were consistently low. CMEP components repeatedly showed adequate activation of descending fiber pathways and segmental interneuron pools during dialysis sampling. Since glycine, and to a lesser extent taurine, have been shown to inhibit motor neuron activity and are closely associated with segmental interneuron pools, suprasegmental modulation of motor activity may be, in part, through these inhibitory amino acid neurotransmitters in the rabbit lumbar spinal cord.


Prevalence of Chlamydia trachomatis among women attending gynecology and infertility clinics in Gaza, Palestine.
Chlamydia trachomatis is an obligate intracellular bacterium characterized by a biphasic developmental cycle of replication. The organism is recognized as one of the major causes of sexually transmissible human bacterial infection throughout the world. Since there have been no previous studies dealing with chlamydial diagnosis in Palestine, this study was conducted to determine the prevalence of C. trachomatis infection among women attending gynecology and infertility clinics. Endocervical swabs were collected from 109 women, aged 18-52 years (median 29 years), attending gynecology and infertility clinics in Gaza. These specimens were processed using molecular (polymerase chain reaction, PCR) and enzyme immunoassay (EIA; IDEIA PCE Chlamydia) techniques. The results obtained show that the overall prevalence rate of C. trachomatis was 20.2%. The sensitivity was 73% for the EIA, 86% for the MOMP (major outer membrane protein gene)-based PCR, and 100% for the plasmid-based PCR. Meanwhile the specificity was 94% for the EIA, 98% for the plasmid-based PCR, and 100% for the MOMP-based PCR. In multivariate analysis, only cervical discharge was significantly associated with positivity for C. trachomatis (adjusted odds ratio 5.6, 95% confidence interval 2.0-15.5; p=0.001). The study revealed that a significant proportion of Palestinian women expressed evidence of exposure to C. trachomatis. Women with cervicitis are more likely to have been previously infected or exposed to Chlamydia infection. Furthermore, PCR proved to be superior and more efficient in the diagnosis of C. trachomatis than EIA.


Differentiation of human hair by colour and diameter using light microscopy, digital imaging and statistical analysis.
This research introduces and evaluates a novel method that offers the potential of providing objective criteria to forensic microscopical hair comparisons. The method combines hair diameter with numeric characterisations of red, green, and blue colour content as determined with the use of digital imaging at defined locations of the hair. Thirty hairs were collected from each of twenty participants, all with naturally coloured brown hair. The hairs were examined with an Olympus BX53® polarising light microscope and digital images were viewed with an Olympus DP72® camera under 400× magnification. Using Olympus cellSens™ Entry software, hair diameter was measured at 1000, 1500 and 2000 μm from the base of the root. The Olympus cellSens™ Entry software uses a red, green and blue (RGB) colour model to quantitatively define the colour of each pixel on an image based on its composition of these three principal colour components. This software was used to collect numerical characterisations of hair colour at each distance interval. The diameter and colour values for each hair were compared using discriminant analysis (DA) and principal component analysis. Although a large amount of intrapersonal variation was observed, the degree of interpersonal variation was greater and enabled the statistical model to differentiate between the hair samples from each participant. The DA model achieved sample reclassification with an error rate of 7.33%. A validation study was conducted on a subset of hair samples from which 18 of the 20 were correctly assigned to the participant from whom they originated. These results support the potential of this method to provide an objective addition to current microscopical hair comparison practices.


Rosuvastatin induces apoptosis in CD4(+)CD28 (null) T cells in patients with acute coronary syndromes.
CD4(+)CD28(null) cells represent an aggressive and long-living T cell subpopulation, capable of infiltrating atheromatous plaque, leading to destabilisation and resulting in acute coronary syndromes (ACS). The aim of this study was to evaluate whether statins decrease the number of circulating CD4(+)CD28(null) T cells by apoptosis in patients with ACS. Patients with troponin-positive ACS (n = 35) without cholesterol lowering drugs were randomised to placebo (n = 17) or rosuvastatin 20 mg (n = 18) once daily for 6 weeks. CD4(+)CD28(null) T cell abundance (>1%) was distributed equally among the two groups at entry (n = 10 per group). Within 72 h rosuvastatin treatment significantly reduced mean CD4(+)CD28(null) T cell numbers (37 × 10⁶/L vs. placebo 122 × 10⁶/L, n = 20, P = 0.041), IFN-γ production (62.6 vs. 101.5%, P = 0.049) and increased apoptosis of these T cells (63.4 vs. 12.3%, P < 0.001). The intrinsic mitochondria-dependent pathway measured by the anti-apoptotic protein expression of B cell lymphoma 2 (BCL-2) was significantly down-regulated (mean fluorescence intensity 16.08 vs. placebo 43.34, P < 0.001). The down-regulation of anti-apoptotic BCL-2 expression by statins induces apoptosis in CD4(+)CD28(null) T cells. Targeting CD4(+)CD28(null) T cells in ACS statins could provide one further therapeutic strategy to prevent acute life-threatening coronary events.


Discovery of the genus Leptophion Cameron, 1901, from Japan and the Palaearctic region, with description of two new species (Hymenoptera: Ichneumonidae: Ophioninae).
The genus Leptophion Cameron, 1901, which belongs to the subfamily Ophioninae Shuckard, 1840, is recorded from Japan and the Palaearctic region for the first time based on two new species, L. parvus sp. nov. from Amamioshima Island and L. septentrionis sp. nov. from Yakushima and Amamioshima Island. A key to the Japanese and Taiwanese species is also provided.


Functional abnormalities in the left ventrolateral prefrontal cortex during a semantic fluency task, and their association with thought disorder in patients with schizophrenia.
Thought disorder is one of the primary symptoms in schizophrenia, yet the neural correlates and related semantic processing abnormalities remain unclear. We aimed to investigate the relationship between functional prefrontal abnormalities and thought disorder in schizophrenia using 2 types of verbal fluency tasks: the letter fluency task (LFT) and the category fluency task (CFT). Fifty-six adult patients with schizophrenia and 56 healthy controls matched for age, gender, and IQ participated in the study. During completion of the 2 types of verbal fluency tasks, we measured oxy- and deoxy-hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) signal changes over a wide area of the bilateral prefrontal cortex, using a 52-channel near-infrared spectroscopy (NIRS) system. Thought disorder scores were evaluated using the positive and negative syndrome scale. CFT performance was significantly higher than LFT performance in both groups, while there was no significant difference in any prefrontal NIRS signal changes between the 2 tasks in either group. In both versions of verbal fluency task, healthy controls exhibited a significantly greater NIRS signal change than did patients with schizophrenia. On the CFT only, left ventrolateral prefrontal NIRS [deoxy-Hb] signals were significantly associated with thought disorder scores in patients with schizophrenia. Our results suggest that left ventrolateral prefrontal abnormalities in category fluency might be related to thought disorder in schizophrenia. This could lead to an improved understanding of the neural mechanisms within the left ventrolateral prefrontal cortex involved in mediating semantic processing, as well as the relationship between semantic processing abnormalities and thought disorder in schizophrenia.


A direct comparison of the sensitivity of CT and MR cardiac perfusion using a myocardial perfusion phantom.
Direct comparison of CT and magnetic resonance (MR) perfusion techniques has been limited and in vivo assessment is affected by physiological variability, timing of image acquisition, and parameter selection. We precisely compared high-resolution k-t SENSE MR cardiac perfusion at 3 T with single-phase CT perfusion (CTP) under identical imaging conditions. We used a customized MR imaging and CT compatible dynamic myocardial perfusion phantom to represent the human circulation. CT perfusion studies were performed with a Philips iCT (256 slice) CT, with isotropic resolution of 0.6 mm(3). MR perfusion was performed with k-t SENSE acceleration at 3 T and spatial resolution of 1.2 × 1.2 × 10 mm. The image contrast between normal and underperfused myocardial compartments was quantified at various perfusion and photon energy settings. Noise estimates were based on published clinical data. Contrast by CTP highly depends on photon energy and also timing of imaging within the myocardial perfusion upslope. For an identical myocardial perfusion deficit, the native image contrast-to-noise ratio (CNR) generated by CT and MR are similar. If slice averaging is used, the CNR of a perfusion deficit is expected to be greater for CTP than MR perfusion (MRP). Perfect timing during single time point CTP imaging is difficult to achieve, and CNR by CT decreases by 24%-31% two seconds from the optimal imaging time point. Although single-phase CT perfusion offers higher spatial resolution, MRP allows multiple time point sampling and quantitative analysis. The ability of CTP and current optimal MRP techniques to detect simulated myocardial perfusion deficits is similar.


Cannulation of the portal vein for cytotoxic liver perfusion in colorectal carcinomas: an alternative approach.
Cytotoxic liver perfusion via the portal vein has been used with some success as an adjuvant to surgery for colorectal carcinoma. We have used an alternative method of cannulating the portal vein at the time of operation and support the use of this method as well as the use of short-term 5FU infusion via the portal vein as being safe and of low systemic toxicity.


Denitrification of overlying water by microbial electrochemical snorkel.
A novel microbial electrochemical snorkel (MES) bioreactor was constructed by inserting an iron rod into the sediment of a simulated natural water body for the first time. Its nitrate removal performance and mechanism were investigated. The DNA high-throughput sequencing analysis indicates that denitrifying bacteria were grown on the iron rod in the overlying solution. The XRD analysis on the oxides formed on the surface of the iron rod indicates that they are goethite and green rust. In the MES system, the green rust on the iron rod can concentrate nitrate and denitrifying bacteria, forming an anaerobic biocathode. The denitrifying bacteria can reduce the nitrate into nitrogen with the electrons moved from the sediment. The nitrate removal efficiency reached 98% in 16days. This novel MES system showed excellent in-situ nitrate removal performance by moving and concentrating the electrons in sediment and the nitrate in overlying solution in an anaerobic microenvironment.


The Fos family of transcription factors and their role in tumourigenesis.
Members of the Fos family (c-Fos, FosB and its smaller splice variants, Fra-1 and Fra-2) dimerise with Jun proteins to form the AP-1 transcription factor complex. Based on the rapidly growing amount of data from experimental studies, animal models and investigations on clinical tumour samples, this review summarises the current knowledge about the role of these proteins in carcinogenesis. In addition to c-Fos, which has oncogenic activity and is frequently overexpressed in tumour cells, Fra-1 seems to play a role in the progression of many carcinomas. The results obtained from various studies show different implications for these transcription factors according to tumour type, i.e., Fra-1 overexpression enhances the motility and invasion of breast and colorectal cancer cells, but inhibits the tumourigenicity of cervical carcinoma cell lines. Knowledge about regulation of invasion and metastasis in different malignant tumours in vivo might open promising perspectives to targeted therapeutic approaches.


Efficacy and safety of anamorelin in patients with cancer cachexia: Post-hoc subgroup analyses of a placebo-controlled study.
Cachexia, a disorder associated with anorexia, inflammation, and muscle wasting, is frequent in cancer patients. We performed post-hoc analyses of the ONO-7643-04 study to investigate the efficacy and safety of anamorelin in subgroups of Japanese patients with non-small cell lung cancer (NSCLC). The patients were divided into subgroups by baseline characteristics, including sex, age, body mass index, prior weight loss, performance status (PS), concomitant anticancer therapy, and number of previous chemotherapy regimens. The changes from baseline through to 12 weeks for lean body mass (LBM), body weight, and appetite were calculated. Appetite was evaluated using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD) item 8 score. Responder rates were defined as the maintenance/improvement of LBM (≥0 kg), body weight (≥0 kg), or QOL-ACD item 8 score (≥0) from baseline to all evaluation time points. Safety was evaluated in patients subgrouped by age and PS. Anamorelin resulted in greater improvements versus placebo in LBM, body weight, and appetite in most subgroups. Anamorelin was also associated with greater LBM, body weight, and appetite responder rates than placebo in nearly all subgroups. Among anamorelin-treated patients, adverse drug reactions (ADRs) tended to be more frequent with increasing age (<65 years, 19.2%; ≥65 to <75 years, 45.9%; ≥75 years, 60.0%) and PS score (PS 0-1, 38.4%; PS 2, 60.0%). The frequency of serious ADRs was 2.7% and 0% in the PS 0-1 and PS 2 subgroups, respectively. This study of NSCLC patients with cancer cachexia revealed consistent improvements in LBM, body weight, and appetite across most subgroups of anamorelin-treated patients. This study also demonstrated the tolerability of anamorelin regardless of age and PS, with a low incidence of serious ADRs in each subgroup.


The effects of vasculitis on the gastrointestinal tract and liver.
Vasculitis can affect every organ of the digestive system. In many cases, it may first present with gastrointestinal symptoms. In several forms of vasculitis, including Churg Strauss syndrome, Henoch-Schönlein purpura, and lupus, the majority of patients have gastrointestinal involvement. The astute gastroenterologist should consider vasculitic causes of the symptoms seen in many patients. Making the correct diagnosis requires a thorough understanding of the potential role of vasculitis in causing these symptoms and the appropriate path to making a diagnosis. This article reviews the variety of manifestations of vasculitis on the digestive system, and emphasizes diagnosis and clinical manifestations.


The time course of lexical and sublexical phonological activation in Chinese written production.
The time course of sublexical processing in written production is scarcely investigated due to transparent sound-to-spelling correspondence in most alphabetical languages. By taking advantage of the opaque orthography of Chinese, we were able to dissociatively manipulate sublexical relatedness and lexical relatedness in a picture-word interference task. The ERP technique was also used to provide a fine-grained time course of sublexical processing. Participants were asked to handwrite picture names while ignoring distractors overlain on the pictures. Distractors were phonologically related to the picture names (lexically related), phonologically related to the phonetic radicals of picture names (sublexically related), or unrelated to picture names. ERP results revealed that sublexical relatedness affected ERPs in the time window of 370-470 ms after picture onset, which was later than the early time window (200-260 ms) of the effect of lexical relatedness. We suggest that the sublexical phonological activation happens in the stages of sublexical POC procedure and/or the graphemic output buffer in written production. The relatively later time window of the sublexical effect is consistent with the later loci of the sublexical processes in the model of written production.


Pseudomonas aeruginosa Y12 play positive roles regulating larval gut communities when housefly encountered copper stress.
Heavy metal contamination has become a global concern that threatens the lives of animals and insects throughout the food chain. Pseudomonas is a commonly found genus of bacteria that colonizes the intestines of insects and constitutes a necessary part of the insect gut microbiota. This research analyzed the influence of different concentrations of Cu2+ on housefly larval development, gut microbial structure and antioxidant defense system, and investigated the regulatory mechanism of P. aeruginosa Y12 on the gut microbiota when houseflies were exposed to Cu2+. We found that adding Cu2+ to the larval diet inhibited larval growth, while the mixed addition of P. aeruginosa Y12 and Cu2+ to the diet reduced the inhibitory effects of Cu2+ on larval growth. Oral administration of Cu2+ significantly changed the gut community structure and increased larval gut bacterial diversity. In vitro analysis revealed that P. aeruginosa Y12 showed Cu2+ adsorption effects and increased Cu2+ aggregation. The mixed addition of low concentrations of P. aeruginosa Y12 and Cu2+ to the larval diet caused a dynamic shift in the gut microbiota and resulted in a novel gut community structure with an increase in beneficial bacteria and a decrease in pathogenic bacteria. Furthermore, P. aeruginosa Y12 treatment influenced the activity of antioxidant enzymes in housefly larvae, indicating that the addition of P. aeruginosa Y12 to the larval diet could further influence the antioxidant system through P. aeruginosa Y12-Cu2+ interactions. In conclusion, our research revealed that intestinal flora dysbiosis was the essential reason why copper inhibits housefly larval growth. However, proper supplementation with P. aeruginosa Y12 played positive roles in regulating larval gut communities and protecting insects from toxic heavy metals.


Methods and strategies to promote academic literacies in health professions: a scoping review.
Universities enroll students from diverse backgrounds every year, with 300 million students expected in higher education by 2025. However, with widening participation, increasing numbers of students enrolling in higher health education and future health professions will be underprepared to meet demands of academic literacies, i.e. ability to read, interpret and critically evaluate academic texts and communicating the understanding verbally or in writing. The aim of this scoping review was to describe and explore methods and strategies to promote development of academic literacies. Thirty-one relevant studies were included and analyzed according to scoping review guidelines. The results showed four strategies: (1) integrating learning activities to develop academic literacies in the regular curriculum, (2) changing the course design with new methods for teaching and learning, (3) establish collaborations amongst academics and librarian faculty, and (4) adding courses or foundation year focusing on development of academic literacies. The results are discussed in light of the United Nations Agenda 2030 Sustainable Development, Goal 4, Quality Education, and widening participation. Aspects of widening participation and inclusion in higher education have been debated, and increasing numbers of students from diverse backgrounds are expected to enter health studies in higher education. We encourage integration of teaching and learning activities targeting parallel learning of course materials and development of academic literacies, beyond study skills. Embracing epistemic complexity and diversity as well as choosing strategic work with academic literacies may provide a starting point toward realizing sustainable development goals and widening participation.


Fecundity, fruiting pattern, and seed dispersal in Piper amalago (Piperaceae), a bat-dispersed tropical shrub.
This paper describes the nightly and seasonal production of ripe fruit by Piper amalago (Piperaceae), a patchily distributed, bat-dispersed forest shrub, at Parque Nacional Santa Rosa, Costa Rica. Phenological observations over several years indicate that individuals produce a low (usually 1-3) and variable number of ripe fruit each night for 3-4 wks in the early wet season (June and July). Observations of the disappearance rates of marked fruits and fruit manipulation experiments indicate that fruit removal probabilities are high (often nearly 1.0) and independent of nightly and seasonal ripe fruit crop size. Data from previous feeding and foraging studies of the bat Carollia perspicillata (Phyllostomidae) are used to estimate the mobility of P. amalago's seeds. Most seeds (>90%) are deposited ≧50 m from parent plants under night feeding roosts. Relatively few seeds move >300 m, and movements this long are more likely to occur early and late in the fruiting season when bats change feeding sites more frequently. Seed experiments indicate that P. amalago seedling establishment probabilities are higher in light gaps than under forest canopy. The dispersal quality (sensu McKey 1975) of P. amalago's chiropteran seed dispersers is directly proportional to the number of seeds they excrete in actual or incipient light gaps.


Applications of DNA chips for genomic analysis.
A major frontier in medical genetics is the definition of the molecular basis of multifactorial diseases. This is especially relevant in the field of clinical psychiatry where the majority of common disorders display complex inheritance patterns, and are further influenced by environmental interactions. New technologies are needed to help address the pressing needs for discovering and deciphering the nature of such disease-associated genes. One such technology which has emerged within the past 3 years involves hybridization-based nucleic acid array (DNA chip) analysis. This technology has the potential to have a lasting impact on diverse genomic-based applications such as large-scale gene mapping studies, mutational analysis, and global expression level monitoring of all human genes. In this review we will describe the fundamental principles behind nucleic acid array-based assays, while focusing on their applications towards genome-wide DNA and RNA analysis. The current capabilities and limitations of these technologies will be discussed, with a focus on areas where future development will be needed for DNA chip-based assays to achieve their full potential.


Chronic exposure to nitrous oxide increases [3H]MK801 binding in the cerebral cortex, but not in the hippocampus of adult mice.
Chronic exposure of adult mice to inhalational anesthetic nitrous oxide (N2O) results in anesthetic tolerance. N2O is an NMDA (N-methyl-D-aspartate) antagonist. It has been demonstrated that chronic administration of members of the NMDA antagonist class of drugs (e.g., MK801) causes upregulation of NMDA receptors in certain brain regions that could, at least in part, explain the development of tolerance. We sought to determine whether the anesthetic tolerance resulting from chronic exposure to N2O reflects changes in the number and/or distribution of NMDA receptors. We exposed mice to either a 50- or 75-vol% N2O atmosphere continuously for 1 or 2 weeks and performed binding studies with [3H]MK801 and NR1 antibodies. Binding studies revealed a significant (P < 0.05) increase in [3H]MK801 binding in the cerebral cortex after 2 weeks of N2O (50- and 75-vol%) exposure. Immunocytochemical binding of NR1 antibodies in selected brain regions showed no changes in distribution pattern. The timing of this increase in [3H]MK801 binding correlates with the time period required for development of tolerance.


A dataset of the chemical composition and near-infrared spectroscopy measurements of raw cattle, poultry and pig manure.
Organic waste products (OWPs) from livestock have a high fertilizer value (N, P, K), but can also lead to environmental problems when applied in excessive quantities. Because their composition varies greatly, it is important to develop fast, reliable and inexpensive methods for determining their chemical contents. Near-infrared spectroscopy (NIRS) offers the possibility of rapid analysis of samples and requires little sample preparation, and previous studies have demonstrated that NIRS could be able to determine the most important compositional parameters of solid animal manure. The recent development of low-cost miniaturized spectrometers even enables manure-spreading equipment to be equipped with sensors to measure the composition in real time, and some applications are already being commercialized for the spreading of liquid OWPs. In-situ analysis of these very heterogeneous products (roughness, humidity) is a challenge for such applications, because spectral acquisition must be performed on raw samples with no preparation. To evaluate the accuracy with which NIRS estimates dry matter content, organic matter, total and ammonium nitrogen, phosphorus, potassium, calcium and magnesium contents, we created a large calibration database representative of raw solid animal manures encountered in Brittany. A total of 490 samples of solid OWPs from livestock farms were collected in the early spring from 270 farms in Brittany (western France), in 2 campaigns conducted in 2018 and 2019. The sampling was designed to capture the large diversity of animal species (mainly cattle, pigs and poultry), type of farming and storage modes. Compositional parameters were analyzed according to analysis methods certified by the French standards organization (AFNOR). Samples were scanned using a Q-interline AgriQuant B8 equipped with a patented spiral sampler, which aggregates the heterogeneity of the sample. NIRS measurements were made in triplicate. Because the dataset covers a wide range of variability in the composition of solid animal manure, these data are of great interest to chemometrics experts and agronomists in search of references on the fertilizing value of products.


The potential of liposomal drug delivery for the treatment of inflammatory arthritis.
To review the use of liposomes as a delivery agent in inflammatory arthritis. The literature on liposomes and liposomal drug delivery for the treatment of inflammatory arthritis was reviewed. A PubMed search of articles in the English-language journals from 1965 to 2007 was performed. The index words used were as follows: "rheumatoid arthritis," "liposomes," and "targeted delivery." Papers identified were reviewed, abstracted, and summarized. Liposomes have the capacity to be used as delivery and targeting agents for the administration of antirheumatic drugs at lower doses with reduced toxicity. In other areas of medicine, the pace of progress has been rapid. In the case of infectious diseases and cancer, liposomal drug delivery has progressed and developed into commercially viable therapeutic options for the treatment of fungal infections (amphotericin B), or metastatic breast cancer and Kaposi sarcoma (doxorubicin, daunorubicin), respectively. In arthritis, the efficacy of prednisolone-loaded long-circulating liposomes is currently being evaluated in a phase II clinical trial. Liposome's application to arthritis is still in its infancy but appears promising as new patents are filed. With improvements in liposomal formulation and targeted synovial delivery, liposomes offer increased therapeutic activity and improvement in the risk-benefit ratio. Recent research into synovial targets and improved liposomal formulations continues to improve our capacity to use liposomes for targeted delivery. With time, this approach has the potential to improve drug delivery and reduce systemic complications.


Matriderm versus Integra: a comparative experimental study.
To compare engraftment rates and vascularisation in a rat model using either Integra Artificial Skin or Matriderm. Matriderm and the dermal part of Integra were compared in a two-step procedure including matrix implantation and subsequent epidermal grafting. Neonatal rat epidermis was used as coverage to test for rapid and complete take. Efficiency and quality of vascularisation expressed by take rate of epidermis, and thickness of resulting neodermis, were identical for both matrices. This first comparison of Matriderm with Integra in a rat model revealed no major differences in engraftment rates or vascularisation.


Transurethral prostatic resection in the treatment of prostatism with high urinary flow.
There were 51 patients with prostatism who were selected for transurethral resection of the prostate using clinical nonurodynamic criteria. Urodynamic evaluation revealed that 13 patients had preoperative maximum urine flow rates greater than 15 ml. per second. The favorable postoperative outcome in clinical and urodynamic terms in this group of patients with high preoperative urine flow is discussed.


Fluoroscopic assist in anterior cruciate ligament reconstruction.
When creating the femoral tunnel during endoscopic anterior cruciate ligament reconstruction, the potential exists for penetration of the posterior femoral cortex. In addition, during placement of the proximal fixation screw, the screw can deviate from its intended path. We have used an image intensifier intraoperatively to obtain a lateral view of the knee to enable the assessment of tunnel placement and screw alignment. This technique assures the accurate placement of the tibial and femoral tunnels and helps avoid screw divergence from the graft.


Pertussis toxin reduces the antiadrenergic effect of 2-chloroadenosine on papillary muscle and the direct negative inotropic effect of 2-chloroadenosine on atrium.
2-Chloroadenosine reduced the contractile tension of guinea-pig atria directly, and inhibited the increase in tension produced by beta-adrenergic stimulation of guinea-pig papillary muscle. Both effects were reduced by 8-phenyltheophylline, a competitive antagonist at extracellular P1-purinoceptors. Treatment of guinea-pigs with pertussis toxin reduced the sensitivity of both atria and ventricles to 2-chloroadenosine. Atria were significantly affected after treatment with 125 micrograms/kg toxin, but not 100 micrograms/kg. 60 micrograms/kg toxin had no effect on the sensitivity of the ventricles, but 100 and 125 micrograms/kg significantly decreased the antiadrenergic effect of 2-chloroadenosine. We conclude that both the direct and antiadrenergic effects are mediated by an inhibitory guanine nucleotide binding protein.


High-Resolution Imaging of STIM/Orai Subcellular Localization Using Array Confocal Laser Scanning Microscopy.
The expression of chimeras that consist of a fluorescent protein (FP) conjugated with a protein of interest provides the ability to visualize, track, and quantify the subcellular localization and dynamics of specific proteins in biological samples. Array confocal laser scanning microscopy is an eminently suitable technique for live-cell imaging of FP-tagged fusion proteins. Here, we describe real-time monitoring of the subcellular dynamics of the stromal-interacting molecule 1 (STIM1) and Orai1, the key protagonists of store-operated Ca2+ entry (SOCE) under resting conditions, and upon Ca2+ mobilization from the endoplasmic reticulum (ER).


Vertigo/dizziness in pediatric emergency department: Five years' experience.
Vertigo/Dizziness in childhood is not a rare cause of visits to the emergency department (ED). We analyzed a selected group with vertigo/dizziness to identify signs and symptoms that may help to guide the diagnostic approach and management. A total of 616 children admitted for vertigo to the ED over a five-year period were retrospectively reviewed. Their medical history, clinical characteristics, laboratory and neuroimaging tests, final diagnoses and management were analyzed. Migraine and syncope were the most frequent causes. Two patients were affected by life-threatening cardiac syncope, while structural life-threatening central nervous system diseases were found in 15 patients, none of whom presented with vertigo as an isolated clinical finding. Most cases of vertigo/dizziness in childhood that consist mainly of migraine and syncope are of benign origin. The prompt identification of neurological or cardiological signs or symptoms associated with vertigo in children is mandatory to rule out life-threatening conditions.


Do Types of Information in an Animated Video Intervention Affect University Students' Autism Knowledge and Openness Towards Peers on the Autism Spectrum?
This pre-test post-test control group design sought to compare the effectiveness of delivering different types of information ([1] factual information vs. [2] factual information + descriptive and explanatory information vs. [3] factual information + descriptive, explanatory + directive information) in an animated video intervention in increasing university students' autism knowledge and openness toward peers on the autism spectrum. The sample consisted of 92 undergraduates (27 males, 65 females; age range = 18-36) from various universities in Singapore. Participants were randomly assigned to one of the three experimental conditions/videos, where they completed a measure of their autism knowledge and openness scale, before viewing a 5-minute long animated video containing different types of information about autism. After which, participants completed the measure of autism knowledge and openness scale again, followed by a measure of their empathy level. Results indicated that participants' autism knowledge improved following the viewing of the animated video. However, the three different videos containing different types of information did not differ in influencing participants' openness toward peers on the autism spectrum. Nevertheless, qualitative responses proposed that the video containing factual information, with descriptive, explanatory, and directive information was useful in helping participants to know how to interact with their peers on the autism spectrum. The findings of this study provide preliminary support for the most effective method to educate and raise awareness about autism, among the general student population in order to foster a supportive and inclusive environment.


Chondrolysis after partial lateral meniscectomy in athletes.
Rapid chondrolysis after partial arthroscopic lateral meniscectomy has been seldom reported in literature. Considering the relatively high number of partial lateral meniscectomy performed, we cannot understand why this complication is so rare. The purpose of this paper is to report a series of athletes developing a chondrolysis associated with posterolateral corner laxity after a partial lateral meniscectomy and attempt to hypothesize the pathogenesis of this devastating complication. Five male professional soccer players of Italian championship with a mean age of 26.8 years underwent a partial lateral meniscectomy because of a traumatic lateral meniscus tear. Patients showed a slight varus knee and there were clinical signs compatible with a meniscal tear. No other pathological sign were found. An MRI scan confirmed these findings. After surgery patients were unable to resume sport activities because of swelling and knee pain during training sessions. At a mean time of 8 months (range 6-12 months) from surgery patients were re-examined and a new MRI scan was performed. Clinical examination revealed a slight swelling of the knee and signs of posterolateral corner laxity. MRI scan revealed intra-articular fluid and pathological findings of knee posterolateral corner associated with a thinning of the articular cartilage. Arthroscopy showed free cartilagineous debris floating into the knee and a high grade of cartilage damage on the lateral compartment. The evaluation of lateral compartment, ruled-out a new tear of the meniscal remnant and showed a positive drive-trough sign with knee in the Fig. 4 positioning. All patients had an open re-tensioning of the posterior meniscofemoral capsule, and in one case, an augmentation of the popliteal tendon using a free semi-tendinous graft was also done. This surgery gave a complete resolution of symptoms and patients resumed sports activities without any restriction after a period between 4 and 5 months. Based on this experience we hypothesize that partial lateral meniscectomy may have a role in causing a subtle rotatory instability that combined with high stress of sports activity can dramatically increase the susceptibility of joint to chondrolysis, Varus knee seems to be a possible predisposing factor. Open surgery addressing the insufficiency of lateral or posterolateral corner has been found to be effective in improving knee function and resolve patients symptoms at a short-term follow-up.


A comparative study of initial changes in pulpal blood flow between clear aligners and fixed orthodontic appliances.
The objective of this study is to evaluate and compare the initial changes of pulpal blood flow (PBF) using clear aligner and fixed orthodontic treatment. A total of 45 subjects were subdivided into 2 groups: group 1; 25 subjects treated with preadjusted edgewise fixed appliance with 0.014″ nickel titanium as the alignment archwire and group 2; 20 subjects treated using clear aligner. In both groups, PBF was measured for the maxillary right and mandibular left teeth using Laser Doppler flowmetry at different time intervals (20 minutes, 48 hours, 72 hours, and 1 month) after the fitting of the nickel titanium archwire in group 1 and after the delivery of the second aligner in group 2. A repeated-measures analysis of variance and a Bonferroni post-hoc comparison test were applied to determine differences at the various time intervals. The PBF decreased in both types of appliances after force application. The maximum reduction in PBF was reached after 72 hours. It returned to its normal values within 1 month. The differences in PBF between the 2 groups did not reach any statistical significance. PBF in orthodontically treated teeth decreased 20 minutes after orthodontic force application in both fixed and clear aligner appliances. In both treatment groups, most changes occurred within 48 hours of force application. PBF returned to its normal values within 1 month. Changes in PBF in both treatment groups were comparable.


On the compressibility and poroelasticity of human and murine skin.
A total of 37 human and 33 murine skin samples were subjected to uniaxial monotonic, cyclic, and relaxation experiments. Detailed analysis of the three-dimensional kinematic response showed that skin volume is significantly reduced as a consequence of a tensile elongation. This behavior is most pronounced in monotonic but persists in cyclic tests. The dehydration associated with volume loss depends on the osmolarity of the environment, so that tension relaxation changes as a consequence of modifying the ionic strength of the environmental bath. Similar to ex vivo observations, complementary in vivo stretching experiments on human volar forearms showed strong in-plane lateral contraction. A biphasic homogenized model is proposed which allows representing all relevant features of the observed mechanical response.


Selective conversion of methane to cyclohexane and hydrogen via efficient hydrogen transfer catalyzed by GaN supported platinum clusters.
Non-oxidative liquefaction of methane at room temperature and ambient pressure has long been a scientific "holy grail" of chemical research. Herein, we exploit an unprecedented catalytic transformation of methane exclusively to cyclohexane and hydrogen evolution through effective surface-hydrogen-transfer (SHT) at the heterojunctions boundary consisting of electron-rich platinum cluster (Pt) loaded on methane-activating gallium nitride (GaN) host. The experimental analysis demonstrates that the interface-induced overall reaction starts with methane aromatization to benzene and surface-bound hydrogen initiated by the Ga-N pairs, followed by the hydrogenation of benzene to cyclohexane with surface-bound hydrogen. The in-situ activated hydrogen at electron-rich metal Pt cluster is crucial for the hydrogenation and enables an outstanding selectivity (up to 92%) and productivity (41 μmol g-1) towards cyclohexane and hydrogen evolution concurrently at 300 °C, which is well-delivered after 5 recycling runs.


Prostacyclin, thromboxane and antioxidant levels in pregnancy-induced hypertension.
1. Plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha, a major metabolite of prostacyclin), plasma thromboxane B2 (TXB2, a major metabolite of thromboxane A2) and five antioxidants (indirect markers of reactive oxygen species) namely, plasma thiol, erythrocyte lysate thiol, erythrocyte superoxide dismutase, plasma total glutathione and erythrocyte membrane thiol, were measured in 25 healthy non-pregnant women, 36 normotensive pregnant women and 35 women with pregnancy-induced hypertension (PIH). 2. The levels of TXB2 were significantly increased in normal pregnant women and PIH women with or without proteinuria compared with non-pregnant women. The concentrations of TXB2 in PIH women with proteinuria were higher than those without proteinuria (P < 0.05). 3. The levels of 6-keto-PGF1 alpha in healthy non-pregnant women and PIH women with or without proteinuria were significantly lower than that in normotensive pregnant women (all of three P < 0.01). There were no significant differences between healthy non-pregnant women and PIH women with and without proteinuria. 4. The ratio of TXB2 to 6-keto-PGF1 alpha was markedly elevated in PIH women with or without proteinuria compared with normotensive pregnant women and healthy non-pregnant women. The difference between PIH women with proteinuria and those without proteinuria was not significant (P > 0.05). 5. The levels of plasma thiol, superoxide dismutase and glutathione were significantly decreased in PIH women compared with normotensive pregnant women. 6. There were significant positive correlations between the levels of prostaglandins and antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS)


American College of Allergy, Asthma and Immunology members' preferred steps 1 to 3 asthma maintenance and reliever therapy and incomplete insurance coverage indicated as main practice hurdle.
New asthma guidelines (GINA, 2022; NAEPP EPR-4, 2020) include considerable changes in treatment recommendations, specifically regarding anti-inflammatory rescue and Single MAintenance and Reliever Therapy (SMART). To explore American College of Allergy, Asthma and Immunology members' preferred treatment and perceived hurdles. A survey (SurveyMonkey) regarding steps 1 to 3 asthma therapy was e-mailed to American College of Allergy, Asthma and Immunology members. The allergists completed 147 surveys (46% with >20 years of experience; 98% from United States; 29% academic, 75% [also] private practice). In addition, 69% follow the National Asthma Education and Prevention Program and 81% the Global Initiative for Asthma recommendations. Of 147 allergists, 117 (80%) indicated correctly what SMART strategy is; 21%/36%/50%/39% would use SMART in step 3 treatment of a below 5-year-old/5- to 11-year-old/12- to 65-year-old/above 65-year-old patient, respectively. In this group, 11% to 14% incorrectly chose inhaled corticosteroid (ICS) plus salmeterol and 9% ICS plus vilanterol for SMART. In a 4-year-old needing step 1 therapy (N = 129), 55% of the respondents would add anti-inflammatory therapy; for step 2 treatment, most would prescribe ICS 100 to 200 µg budesonide equivalent daily; in step 3, 49% would prescribe ICS plus long-acting beta-agonist (LABA). In a 7-year-old needing step 1 treatment (N = 134), 40% would prescribe only short-acting beta-agonist; in step 3, 45% would institute SMART strategy, but only 8 of 135 (6%) chose very-low dose ICS plus formoterol (as recommended in Global Initiative for Asthma); most (39%) use low-dose ICS plus formoterol. As for rescue therapy, 59% is now instituting some form of anti-inflammatory rescue. Finally, in a 25-year-old patient (N = 144): in step 1, 39% would prescribe exclusively short-acting beta-agonist; in step 2, 4% only anti-inflammatory rescue and the rest prescribes ICS maintenance; one-third begins SMART strategy at step 2 and 50% in step 3. Major hurdles for prescribing one's preferred strategy included incomplete insurance coverage, insurance not approving more than one canister of ICS-formoterol per month, and cost. Asthma therapy varies among physicians, with respondents suggesting underutilization of the recommended anti-inflammatory rescue and SMART therapy. A major hurdle is lack of insurance coverage of medication in line with the guidelines.


Prevalence and risk factors for nosocomial infections in hospitals of the Veneto region, north-eastern Italy.
The study aimed to assess prevalence and risk factors for nosocomial infection (NI) in 21 hospitals of the Veneto Region (Italy). In May 2003, a one-week-period prevalence study of NI was carried out in 21 hospitals, representing 63% of all hospital beds for acute patients of the Veneto Region. Intensive care units represented 84% of all intensive care beds of the Region. Long term care, neonatal intensive care, burn, psychiatric and dermatology units were excluded. Overall, 6,352 patients were surveyed. The prevalence of NI was 7.6% (range 2.6%-17.7%), while 6.9% of patients (range 2.6%-15.5%) were affected by at least one NI. The prevalence of patients with NI in medical, surgical and intensive care areas was 6.6%, 5.0% and 25.8%, respectively. The sites most frequently affected were the following: urinary tract (28.4%), surgical site (20.3%), blood stream (19.3%), pulmonary and lower respiratory tract (17.6%). At multivariate analysis risk factors independently associated to NI were: Charlson index score >1, severity of underlying disease, exposure to antibiotics, surgical intervention, trauma at admission, presence of central venous catheter >24 h, urinary catheter, intubation, tracheostomy, and duration since admission >15 days. The study provided baseline data of NI in the Veneto Region hospitals. It showed that NI are frequent, and display a wide inter-hospital variability of rates. The highest prevalence has been reported in intensive care units. The unusual high frequency of blood stream infections and the relatively lower prevalence rate of surgical site infections highlighted the limits of prevalence studies.


Evaluation of a polyacrylamide soil additive to reduce agricultural-associated contamination.
Polyacrylamide is an effective water treatment product used to reduce suspended sediment and associated contaminants. An anionic polyacrylamide-containing product was tested for sediment and associated contaminant reduction and potential toxicity in agricultural irrigation and rainfall runoff. The product effectively reduced turbidity, total suspended solids, and phosphate concentrations in the field when compared to the untreated runoff waters. Acute survival of Ceriodaphnia dubia and Pimephales promelas was not decreased compared to laboratory controls. No significant increases in toxicity were measured in 10-d sediment toxicity tests with Chironomus dilutus. Product applications were effective in controlling sediment and nutrient contamination without increasing measured toxicity.


The assessment of antibiofilm activity of chitosan-zinc oxide-gentamicin nanocomposite on Pseudomonas aeruginosa and Staphylococcus aureus.
In the present study, chitosan-zinc oxide (CS-ZnO) nanocomposite with/without gentamicin was synthesized and characterized which used as an antibiofilm agent to inhibit the biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) PAO1 and Staphylococcus aureus (S. aureus). Synthesized CS-ZnO nanocomposite was characterized with the DLS (Dynamic Light Scattering), FTIR (Fourier Transform Infrared), XRD (X-ray Diffraction) and SEM (Scanning Electron Microscope). The minimum inhibitory concentrations (MICs) against P. aeruginosa PAO1 and S. aureus determined using broth microdilution methods. The influence of sub-MIC (1/4 MIC) and MIC concentration of CS-ZnO nanocomposite and gentamicin alone and in combination on biofilm formation was also determined. A four-fold MIC reduction in S. aureus and P. aeruginosa PAO1 treated by the gentamicin loaded CS-ZnO nanocomposite, and 84% reduction of biofilm formation for P. aeruginosa PAO1 and 77% reduction of biofilm formation for S. aureus, was observed compared to the gentamicin alone (P < 0.05). This study showed the important role of nanocomposite in designing novel antibacterial and antibiofilm agents to combat the P. aeruginosa and S. aureus biofilm-related infections.


Endo-laparoscopic approach versus conventional open surgery in the treatment of obstructing left-sided colon cancer: long-term follow-up of a randomized trial.
We previously conducted a randomized trial comparing the endo-laparoscopic approach (i.e. placing self-expanding metallic stents followed by laparoscopic resection) and conventional open surgery in the treatment of obstructing left-sided colon cancer. This study is a follow-up of the previous randomized trial and aims to report the long-term outcomes of the two groups. Forty-eight patients from the randomized trial were followed up in an outpatient clinic with regular monitoring. Patients were compared for clinicopathological variables, disease recurrence and survival rates. Clinicopathological details were comparable between the two groups. During the median follow-up periods of 32 months for the open group and 65 months endo-laparoscopic group, no statistically significant difference was observed between the groups in disease recurrence rate, 5-year overall survival (27% vs 48%, P = 0.076) and 5-year disease-free survival rates (48% vs 52%, P = 0.63). Besides being a safe bridge to subsequent elective laparoscopic surgery, preoperative self-expanding metallic stents insertion does not adversely affect oncological outcomes and patient survival. Based on our data, the endo-laparoscopic approach is the treatment of choice for patients presenting with malignant left-sided colonic obstruction.


Inhibition of natural, interleukin-2 stimulated and bacillus Calmette-Guerin enhanced cytotoxicity with anti-CD16 antibodies.
We studied the cytolytic mechanism of nonstimulated, bacillus Calmette-Guerin (BCG) stimulated and interleukin (IL)-2 (Chiron Corp., Amsterdam, The Netherlands) stimulated peripheral blood mononuclear cells. We inhibited the cytotoxicity of nonstimulated, BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells against various target cells using 3 monoclonal antibodies directed against the CD16 receptor of natural killer cells or alternatively monoclonal antibodies against the alpha and beta subunits of the IL-2 receptor complex (IL-2R). The main target cell was the poorly differentiated transitional cell line T24. Of the 3 anti-CD16 antibodies tested only CLB FcR-gran/1 effectively inhibited natural, IL-2 stimulated and BCG enhanced cytotoxicity. Cytotoxicity was also markedly diminished after depletion of CD16+CD56+/- cells with CLB FcR-gran/1. An hour of pretreatment with CLB FcR-gran/1 was enough to reduce significantly the level of cytotoxicity evoked by overnight stimulation with BCG or IL-2. Simultaneous administration of anti-IL-2Ralpha and anti-IL-2Rbeta significantly decreased the killing of target cells by BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells. Within the stimulation times chosen the same killing mechanisms seemed to explain the nonstimulated, BCG stimulated and IL-2 stimulated cytotoxicity with CD16 positive cells as central effectors. Anti-CD16 antibodies may deliver a target cell independent down-regulatory signal to natural killer cells or alternatively mimic a nonIg ligand and block the detection of the target cell.