Average Soil Water Retention Curves Measured by Neutron Radiography.
Water retention curves are essential for understanding the hydrologic behavior of partially saturated porous media and modeling flow and transport processes within the vadose zone. We directly measured the main drying and wetting branches of the average water retention function obtained using two-dimensional neutron radiography. Flint sand columns were saturated with water and then drained and rewetted under quasi-equilibrium conditions using a hanging water column setup. Digital images (2048 by 2048 pixels) of the transmitted flux of neutrons were acquired at each imposed matric potential (∼10-15 matric potential values per experiment) at the National Institute of Standards and Technology Center for Neutron Research BT-2 neutron imaging beam line. Volumetric water contents were calculated on a pixel-by-pixel basis using Beer-Lambert's law after taking into account beam hardening and geometric corrections. To account for silica attenuation and remove scattering effects at high water contents, the volumetric water contents were normalized (to give relative saturations) by dividing the drying and wetting sequences of images by the images obtained at saturation and satiation, respectively. The resulting pixel values were then averaged and combined with information on the imposed basal matric potentials to give average water retention curves. The average relative saturations obtained by neutron radiography showed an approximate one-to-one relationship with the average values measured volumetrically using the hanging water column setup. There were no significant differences (P < 0.05) between the parameters of the van Genuchten equation fitted to the average neutron radiography data and those estimated from replicated hanging water column data. Our results indicate that neutron imaging is a very effective tool for quantifying the average water retention curve.


MIB-1, Ki67, and PCNA scores and DNA flow cytometry in intermediate grade malignant lymphomas.
To verify the correlation between MIB-1, Ki67, and proliferating cell nuclear antigen (PCNA-PC10) scores and S-phase fraction in intermediate grade non-Hodgkin's lymphomas (Working Formulation F); and their reliability in differently processed tissues. Forty one non-Hodgkin's lymphomas were classified as (F) intermediate grade malignant lymphomas according to the Working Formulation; mitotic counts and percentage of large cells were assessed for each case. Sections from formalin fixed, paraffin wax embedded tissues were stained with anti MIB-1 monoclonal antibody, after microwave oven processing, and anti-PCNA (PC10) monoclonal antibody using an avidin-biotin immunoperoxidase (ABC) method. One thousand cells from 10 representative fields were scored. Frozen sections from surgical specimens were stained with Ki67 monoclonal antibody using the ABC method; the fraction of Ki67 positive cells was calculated scoring 1000 cells. Flow cytometry analysis (FCM) was performed on cell suspensions from fresh tissues. Correlations between data were estimated using linear regression. A linear correlation was found between MIB-1 and Ki67 scores (r = 0.92; p < 0.00001); between MIB-1 and PCNA scores (r = 0.79; p < 0.00001); and between MIB-1 score and S-phase fraction (r = 0.51; p = 0.0006). A linear correlation was also found between Ki67 and PCNA scores (r = 0.85; p < 0.00001); between Ki67 score and S-phase fraction (r = 0.6; p = 0.0002); and between PCNA score and S-phase fraction (r = 0.74; p < 0.00001). A correlation was found between mitotic counts and MIB-1 (r = 0.56; p = 0.0001), PCNA (r = 0.51; p = 0.0007), or Ki67 scores (r = 0.47; p = 0.002); between the percentage of large cells and MIB-1 (r = 0.49; p = 0.0009), PCNA (r = 0.6; p = 0.00003), and Ki67 scores (r = 0.53; p = 0.0003) and S-phase fraction (r = 0.55; p = 0.0002). MIB-1, Ki67, and PCNA (PC10) scores and S-phase fraction are highly correlated and equally well represent the proliferative activity of intermediate grade non-Hodgkin's lymphomas in differently processed material. MIB-1 and PCNA stains can be applied even on small biopsy specimens. MIB-1 produces homogenous staining without background; it also strongly stains mitotic figures. It can be performed on routinely processed tissues, permitting the simultaneous evaluation of the morphology and tumour cell kinetics. The wide standard deviations of the proliferative indices found for intermediate grade NHL suggest that this category probably includes various degrees of malignancy.


Importance of asparagine-381 and arginine-487 for substrate recognition in CYP4Z1.
The human cytochrome P450 enzyme CYP4Z1 remains an understudied enzyme despite its association with poor prognosis and overexpression in breast cancer. Hence, CYP4Z1 has previously been suggested as an anti-breast cancer target. In the present study we employed extended mutation analysis to increase our understanding of the substrate binding mode of this enzyme. In a combined in vitro and in silico approach we show for the first time that residue Arg487 plays an important role in substrate recognition and binding of CYP4Z1. Using a large array of recombinant CYP4Z1 mutants we show that, apart from Asn381, all other postulated binding residues only play an auxiliary role in substrate recognition and binding. Different substrate interaction motifs were identified via dynamic pharmacophores (dynophores) and their impact on catalytically competent substrate binding was classified. These new insights on the substrate recognition and binding mode represent an important step towards the rational design of CYP4Z1 prodrugs and guide further investigations into the so far poorly understood physiological role of CYP4Z1.


IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases.
Immunoglobulin G4 (IgG4)-related disorders can occur in the respiratory system. However, the clinicopathologic characteristics have not been well clarified. In this study, we examined clinical and pathologic features of, and follow-up data on, IgG4-related lung and pleural lesions. The patients group consisted of 17 males and 4 females with an average age of 69 years (range: 42 to 76). Pulmonary lesions in 16 patients and pleural lesions in 5 patients were examined. Histologically, all lesions showed diffuse lymphoplasmacytic infiltration. Irregular fibrosis and obliterative vascular changes were more common in solid areas. Nine cases (43%) had eosinophilic infiltration with more than 5 cells per high-power field. Immunostaining revealed numerous IgG4-positive plasma cells in inflamed areas. Sclerosing inflammation was distributed with intrapulmonary connective tissue. Pulmonary lesions showed a variety of morphologic changes according to the predominant area of inflammation. Serum IgG4 concentrations were elevated in 9 of 11 patients tested (average 6.9 g/L; range 0.3 to 18.0 g/L; normal range <1.35 g/L). Extra-pulmonary and extra-pleural IgG4-related lesions were identified in 9 patients (43%), and developed simultaneously or asynchronously during follow up. All patients treated with steroids responded, but some radiologic abnormalities remained in 3 patients. Interestingly, 1 patient was found to have a primary adenocarcinoma against a background of IgG4-related lung disease during follow up. In conclusion, IgG4-related diseases show a greater variety of pulmonary and pleural lesions than previously thought. It is important, therefore, to know the morphologic variety and clinicopathologic characteristics of this disorder.


Biosensor-based kinetic characterization of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors.
Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs licensed for clinical use: nevirapine, delavirdine, and efavirenz. Mathematical evaluation of the experimental data with several interaction models revealed that the four inhibitors interacted with HIV-1 RT with varying degrees of complexity. The simplest adequate model accounted for two different conformations of the free enzyme, of which only one can bind the inhibitor, consistent with a previously hypothesized population-shift model including a preformation of the NNRTI binding site. In addition, a heterogeneous binding was observed for delavirdine, efavirenz, and MIV-150, indicating that two noncompetitive and kinetically distinct enzyme-inhibitor complexes could be formed. Furthermore, for these compounds, there were indications for ligand-induced conformational changes.


Glucocorticoid exposure and tissue gene expression of 11beta HSD-1, 11beta HSD-2, and glucocorticoid receptor in a porcine model of differential fetal growth.
Glucocorticoids play a critical role in fetal development, but inappropriate exposure is associated with reduced fetal growth. We investigated cortisol exposure and supply in a porcine model of differential fetal growth. This model compares the smallest fetus of a litter with an average-sized sibling at three stages of gestation. At day 45, small fetuses had reduced plasma cortisol (16.8 +/- 3.4 ng/ml) relative to average fetuses (34.4 +/- 3.4 ng/ml, P < 0.001). At day 65 levels had reduced in small and average fetuses to similar concentrations (5.7 +/- 1.0 vs 4.8 +/- 0.5 ng/ml, P = 0.128). By day 100, elevated levels were found in small fetuses (10.7 +/- 1.5 vs 7.6 +/- 0.7 ng/ml, P < 0.001). Maternal plasma cortisol was unchanged over gestation (day 45, 56.7 +/- 21.6 ng/ml; day 65, 57.8 +/- 14.4 ng/ml; day 100, 55.7 +/- 6.5 ng/ml). We examined the cause of altered cortisol by investigating the fetal hypothalamic-pituitary-adrenal axis through the measurement of adrenocorticotropic hormone and assessing exposure to maternal cortisol by quantifying placental 11beta-hydroxysteroid dehydrogenase-isoform 2 (11beta HSD-2) gene expression. These data suggest that altered cortisol supply was of fetal origin. We examined organ glucocorticoid (GC) metabolism by the measurement of GC receptor (GR) and 11beta-hydroxysteroid dehydrogenase-isoform 1 (11beta HSD-1) gene expression. We found that fetal organs have different temporal patterns of 11beta HSD-1 and GR expression, with the liver particularly sensitive to cortisol in late gestation. This study examines GC exposure in naturally occurring differential growth and simultaneously explores tissue GC sensitivity and handling, at three key stages of gestation.


Multislice first-pass cardiac perfusion MRI: validation in a model of myocardial infarction.
The purpose of this study was to validate a first-pass MRI method for imaging myocardial perfusion with multislice coverage and relatively small analyzable regions of interest (ROIs). A fast gradient-echo (FGRE) sequence with an echo-train (ET) readout was used to achieve multislice coverage, and a high dose of a contrast agent (CA) was used to achieve a high signal-to-noise ratio (SNR). Dogs (N = 6) were studied 1 day after reperfused myocardial infarction, and fluorescent microspheres were used as a standard for perfusion. First-pass MRI correlated well vs. microsphere flow, achieving mean R values of 0.87 (range = 0.82-0.93), 0.71 (range = 0.46-0.85), and 0.72 (range = 0.49-0.95) for subendocardial ROIs, transmural ROIs, and the endocardial-epicardial ratio, respectively. Additionally, analysis of myocardial time-intensity curves (TICs) indicated that 15.8 +/- 6 sectors, corresponding to 260 microl of endocardium, can be analyzed (R(2) > 0.95).


Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer.
There is an urgent need for a companion assay to work with mesothelin-targeted therapeutic agents and for noninvasive and accurate prognostication of malignant mesothelioma (MM) patients. We report the development and validation of a blood-based assay for megakaryocyte potentiating factor (MPF) and the evaluation of its effectiveness for prognosis in MM and lung cancer patients. Using electrochemiluminescence technology, we developed a sensitive MPF assay and performed both analytical and clinical validations. Further, the effectiveness of the MPF assay in predicting prognosis was evaluated for 95 MM and 272 lung cancer patients. We performed comprehensive analytical and clinical validation, including precision and accuracy, interference, preanalytical variables, sensitivity, and specificity for mesothelioma. In MM patients, increased serum MPF is a predictor of poor survival with a hazard ratio (HR) = 2.46 (log-rank P = 0.003; n = 95). In refractory MM patients, increased MPF is a strong predictor of poor outcome with an HR = 6.12 (log-rank P = 0.0007; n = 57). In a lung cancer patient cohort, increased MPF is a predictor of poor survival, with an HR = 1.57 (log-rank P = 0.003; n = 272). The MPF assay has robust technical characteristics, with strong analytic and clinical validation. Clinical studies indicate that increased serum MPF is a predictor of poor survival for MM patients, throughout the course of the disease. Increased MPF is also associated with poor overall survival for patients with newly diagnosed lung cancer.


The use and misuse of new antibiotics. A perspective.
Many new antimicrobial agents have become available recently. Several of the new antibiotics may offer an extended spectrum of activity or an improved toxic effect profile. However, they pose such problems as excessive cost and the emergence of drug-resistant organisms as a result of "selection pressure." The majority of common infections can be treated with conventional agents, either singly or in combination. A careful, bedside clinical evaluation, in conjunction with simple laboratory tests, often narrows down microbiologic possibilities and allows simpler antibiotic choices. This results in a cost-conscious approach of using conventional, inexpensive antibiotics in most situations, with new agents being reserved for judiciously selected indications. Such an approach will not only contain health care costs but will also help to preserve the microbiologic ecosystem.


The Adaptation of a Measure of Confidence in Assessing, Formulating, and Managing Suicide Risk.
Background: To date little has been done to evaluate the effectiveness of suicide risk formulation training. Aims: We aimed to investigate the psychometric properties of a new scale measuring clinicians' confidence in assessing, formulating, and managing suicide risk. Method: A total of 128 mental health practitioners from an UK National Health Service Trust completed the scale. Of them, 85 from an Improving Access to Psychological Therapies service did so before and after training in Risk Assessment, Formulation, and Management (RAFM); 28 practitioners from the Older Adults service also completed the measure. For test-retest analysis, a further 15 completed the scale again 1 week after baseline without attending any training. Of the training group, 52 (61%) completed the measure at the 6-month follow-up. Results: Analysis indicated a single-factor structure, good test-retest reliability, and statistically significant increases in confidence between pre- and posttraining and between pretraining and 6 month follow-up. Cohen's effect size values suggest a moderate-to-large effect. Limitations: The relatively small sample sizes indicate that this study should be considered a preliminary investigation of a new measure, which warrants further replication. Conclusion: This measure could be useful in gauging practitioners' confidence in the RAFM approach and in evaluating and developing training.


Comparative electroencephalographic and behavioral effects of phencyclidine, (+)-SKF-10,047 and MK-801 in rats.
Female Sprague-Dawley rats prepared with chronic i.v. cannulas and/or cerebrocortical electrodes were administered sequentially increasing doses of phencyclidine (PCP, 0.1-6.4 mg/kg/injection), (+)-SKF-10,047 [(+)-N-allynormetazocine] (0.4-25.6 mg/kg/injection) or MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate] (0.01-0.64 mg/kg/injection). Effects on overt behavior, cortical EEG power spectra, locomotor activity and rotarod performance were assessed. Quantitative EEG spectral parameters (peak, mean and edge frequency; total and relative power; time domain descriptors mobility and complexity) were analyzed from the global frequency range of 1 to 50 Hz. Increasing doses of each drug produced increases in EEG spectra power from 1 to 50 Hz which was associated with a slowing of the peak frequency. PCP and MK-801 produced decreases in the mean frequency, mobility and edge frequency whereas (+)-SKF-10,047 produced increases in these spectral parameters. Moreover, (+)-SKF-10,047 increased complexity whereas MK-801 decreased complexity and PCP did not change this parameter. Total spectral power from 20 to 50 Hz was increased by (+)-SKF-10,047 and PCP, but was not changed by MK-801. Each drug increased spontaneous locomotor activity. At the highest doses, PCP and MK-801 decreased activity whereas (+)-SKF-10,047 was lethal. Each drug disrupted rotarod performance. The rank order of potency for each effect was: MK-801 greater than PCP greater than (+)-SKF-10,047. The data indicate that subtle differences in the effects of these drugs can be detected using EEG power spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of autophagy inhibition and inflammatory response in glioma by Wnt signaling pathway.
The objective of this study was to investigate the mechanism of the function of Wnt signaling pathway in regulating autophagy and inflammatory response in glioma cells. Human brain glioma cells U118 were selected and divided into three groups: i) the Wnt signaling inhibitor IWR-1 group (the observation group); ii) the PBS negative control group (the PBS group) and iii) the blank control group. After 24 h culture, Wnt5a/β-catenin protein, autophagy marker, microtubule-associated-proteins-1A1B-light-chain-3C (LC-3) II and Beclin I, and inflammatory factors IL-6 and TNF-α protein expression levels were evaluated using western blotting. Compared with both control groups, Wnt5a/β-catenin, IL-6 and TNF-α protein expression levels were significantly lower, and LC-3II and Beclin I protein expression levels were significantly higher in the observation group. In conclusion, Wnt5a/β-catenin signaling pathway regulates autophagy and inflammatory response of glioma cells.


Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial.
Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. Within a randomized trial in LBW infants in Guinea-Bissau of early BCG vs the usual postponed BCG, a subgroup was bled 4 weeks after randomization. Levels of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured from whole-blood assays stimulated with innate agonists to Toll-like receptor (TLR)-2, -4 or -7/8, or purified protein derivative (PPD). Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation, particularly of the cytokines IL-1β, IL-6, TNF-α, and IFN-γ. Four weeks after immunization, BCG-vaccinated infants have a significantly increased production of cytokines upon heterologous challenge, particularly T helper cell type 1 polarizing and typically monocyte-derived pro-inflammatory cytokines. BCG may accelerate the development of the neonatal immune system, mediating comprehensive protection against infections and mortality.


Encoding the complete electric field of an ultraviolet ultrashort laser pulse in a near-infrared nonlinear-optical signal.
We introduce a variation on the cross-correlation frequency-resolved optical gating (XFROG) technique that uses a near-infrared (NIR) nonlinear-optical signal to characterize pulses in the ultraviolet (UV). Using a transient-grating XFROG beam geometry, we create a grating using two copies of the unknown UV pulse and diffract a NIR reference pulse from it. We show that, by varying the delay between the UV pulses creating the grating, the UV pulse intensity-and-phase information can be encoded into a NIR signal. We also implemented a modified generalized-projections phase-retrieval algorithm for retrieving the UV pulses from these spectrograms. We performed proof-of-principle measurements of chirped pulses and double pulses, all at 400 nm. This approach should be extendable deeper into the UV and potentially even into the extreme UV or x-ray range.


Particulate matter 10 induces oxidative stress and apoptosis in rhesus macaques skin fibroblast.
Particulate matter (PM) is a major air pollutant that affects human health worldwide. PM can pass through the skin barrier, thus causing skin diseases such as heat rash, allergic reaction, infection, or inflammation. However, only a few studies have been conducted on the cytotoxic effects of PM exposure on large-scale animals. Therefore, herein, we investigated whether and how PM affects rhesus macaque skin fibroblasts. Rhesus macaque skin fibroblasts were treated with various concentrations of PM10 (1, 5, 10, 50, and 100 μg/mL) and incubated for 24, 48, and 72 h. Then, cell viability assay, TUNEL assay, and qRT-PCR were performed on the treated cells. Further, the reactive oxygen species, glutathione, and cathepsin B levels were determined. The MTT assay revealed that PM10 (>50 μg/mL) proportionately reduced the cell proliferation rate. PM10 treatment increased TUNEL-positive cell numbers, following the pro-apoptosis-associated genes (CASP3 and BAX) and tumor suppressor gene TP53 were significantly upregulated. PM10 treatment induced reactive oxidative stress. Cathepsin B intensity was increased, whereas GSH intensity was decreased. The mRNA expression levels of antioxidant enzyme-related genes (CAT, GPX1 and GPX3) were significantly upregulated. Furthermore, PM10 reduced the mitochondrial membrane potential. The mRNA expression of mitochondrial complex genes, such as NDUFA1, NDUFA2, NDUFAC2, NDUFS4, and ATP5H were also significantly upregulated. In conclusion, these results showed that PM10 triggers apoptosis and mitochondrial damage, thus inducing ROS accumulation. These findings provide potential information on the cytotoxic effects of PM10 treatment and help to understand the mechanism of air pollution-induced skin diseases.


Serum cystatin C and emphysema: results from the National Health and Nutrition Examination Survey (NHANES).
Cystatin C (CysC) is a potent nonorgan-specific cysteine protease inhibitor and may contribute to elastolysis and tissue destruction by a mechanism of protease–antiprotease imbalance. Given the prevalence of CysC in the serum of smokers and its role in tissue destruction, we aimed to evaluate the association between CysC and emphysema. Pooled cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002 were used. Emphysema and chronic bronchitis were defined by a self-reported history ascertained using standardized questionnaires. Active smokers were defined as self-reported current smokers or measured serum cotinine ≥10 ng/mL. Nonactive smokers with a serum cotinine level >0.05 ng/mL were defined as environmental tobacco smoke (ETS)-exposed. The prevalence (95% CI) of emphysema was 1.3% (range = 0.9–1.8%). The mean (SE) CysC level in the emphysema group was significantly higher than in normal controls [1,139 (22) vs. 883 (8) μg/L; p = 0.001]. Upon stratification of the study population by C-reactive protein (CRP) concentrations, we demonstrated a progressive increase in the mean serum CysC level with serially increasing CRP concentrations. Active smokers with emphysema had 115.4 (46.5) μg/L higher mean (SE) CysC levels than the normal controls (p < 0.001). Upon adjusted analysis, we observed that nonactive smokers with significant ETS exposure had 31.2 (15.2) μg/L higher mean (SE) serum CysC levels as compared to ETS unexposed nonactive smokers (p = 0.04). In a large representative noninstitutionalized US population, we demonstrated an association between emphysema and serum CysC. Active smokers with emphysema had significantly higher CysC levels. These findings suggest that CysC may play a role in the pathogenesis of smoking-related emphysema.


Future in regional anesthesia and pain medicine: the pharmacological view.
Local anesthetics are still incompletely understood, and none of the currently available drugs are optimal. The primary target of local anesthetics is the voltage-gated sodium channel (VGSC), where they lead to a temporary interruption of nerve conduction. Unfortunately, local anesthetics are neither specific at blocking a specific VGSC isoform, nor a specific cell type. We realize now that the old classification of A and C fibers according to myelin thickness is outdated, that next to differing myelin configuration, cells differ also by their molecular biology, and that there are close to 20 different neuronal subgroups when function is concerned. The ideal local anesthetic would only block sensory impulses, or even only painful impulses. In the search for that drug, several research avenues have been followed. First, efforts have been undertaken to extend duration of local anesthetics, by additives or extended-release formulation. Second, blockade of specific pain fibers has been attempted by targeting permanently charged anesthetics specifically into nociceptors. Third, blockade of specific isoforms using antibodies, and adaptation of naturally occurring neurotoxins has shown promise. Lastly, combination of local anesthetics with other analgesics may improve their duration of action.


[Neodymium--Yag laser in the recanalization of arterial occlusions].
Failure of the guide-wire to recanalize some arterial total occlusion does not preclude balloon angioplasty. Nowadays there are recanalization devices such as the mechanical atherectomy and Lasers. The following report describes the successful use of the Nd: YG Laser in the recanalization of a common iliac artery total occlusion in a patient with claudication, rendering possible balloon angioplasty and a Palmaz Stent implantation, which is the first case performed in our country.


Structural remodeling of the N-terminus tunes TRPA1 channel activation and regulates behavioral responses in Drosophila.
Our bodies are constantly bombarded by a diversity of environmental stimuli, such as touch, taste, sound, smell, light, etc. To detect and process this broad array of signals, nature has evolved a variety of cellular sensory mechanisms and pathways that interface with the environment and transmit neural signals back to the CNS where they are translated into behavioral decisions. Transient Response Potential (TRP) cation channels were first identified in invertebrates (i.e., Drosophila) and represent a sizeable receptor/channel family in mammals, consisting of 28 individual members grouped into subclasses denoted TRPC, TRPV, TRPM, TRPML, TRPP and TRPA (for a recent review, see ref. 1). Although originally described as ion channels, we now know that many members of the TRP family also function as receptors for a range of stimuli, including temperature, pH, chemical compounds and membrane voltage. In fact, several TRP isoforms display multimodal sensitivity, meaning that they can respond to more than one stimulus. For example, TRPV1, or the capcaisin receptor, displays both thermal and chemical sensitivity, and the two stimuli may act synergistically to increase channel activity. Physiologically, TRP family members are expressed in a variety of sensory afferent nerves that feed environmental information to the CNS, and also in smaller C-type afferent fibers responsible for peripheral pain sensation and transmission. Therapeutically, manipulation of TRP channel activity may represent an effective strategy to treat peripheral pain associated with inflammation and chronic tissue injury.


Pilar sheath acanthoma.
A newly recognized, benign follicular tumor occurred in nine patients who ranged in age from 46 to 75 (median, 55) years. The neoplasms were solitary, asymptomatic, skin-colored nodules with a central pore-like opening plugged with keratin. All lesions had been present for years. Eight were on the skin of the upper lip and one was on the forehead. Histologically, a central cystic cavity showing epidermoid keratinization extended from the surface into the deep cutis. Multiple tumor lobules that were composed of hair sheath epithelium extended from the cyst wall into the surrounding corium. This neoplasm, which we have named "pilar sheath acanthoma," must be differentiated from trichofolliculoma and dilated pore.


Crystalglobulin-associated nephropathy presenting as MGRS in a case of monoclonal B-cell lymphocytosis: a case report.
Crystalglobulin-associated nephropathy (CAN), a rare subtype of monoclonal gammopathy, usually associated with multiple myeloma and occasionally monoclonal gammopathy of uncertain significance (MGUS), is characterized by occluding monoclonal pseudothrombi within renal glomerular capillaries and/or interstitial arterioles. Ultrastructurally, these pseudothrombi are unique for having a crystalline substructure. We describe a case of an adult patient with monoclonal B-cell lymphocytosis (MBL) and acute renal failure whose kidney biopsy revealed a rare diagnosis of CAN. A 63-year old male presented with a 2-month history of edema, arthralgia and malaise. He had acute kidney injury with hematoproteinuria on urine analysis. Serum and urine protein electrophoresis were both negative. A renal biopsy however revealed features of CAN. Organomegaly, bone pain and lymphadenopathy were absent. A repeat serum electrophoresis was positive for IgA kappa and a free light chain assay showed elevated free kappa light chains. Flow cytometry done subsequently revealed a diagnosis of MBL, chronic lymphocytic leukemia (CLL) type. CAN in association with MBL/CLL has not been previously described in literature, and our case highlights yet another instance of monoclonal gammopathy of renal significance (MGRS) where a small B-cell clone resulted in extensive renal pathology without systemic manifestations.


IL-10 is critical for host resistance and survival during gastrointestinal helminth infection.
Resistance to many intestinal nematodes is dependent on the induction of polarized type 2 cytokine responses, whereas type 1 responses can exacerbate these infections. The contributions of IL-4 and IL-13 to the development of resistance have been well described for a variety of intestinal parasites; however, the role of IL-10 has not been previously investigated. In this study we infected IL-10-, IL-10/IL-4-, IL-10/IL-12-, IL-4-, and IL-12-deficient mice with Trichuris muris to determine whether IL-10 contributes to the development of immunity. Interestingly, T. muris-infected IL-10-, IL-4-, and IL-10/IL-4-deficient mice failed to expel the parasite, and animals deficient in IL-10 displayed marked morbidity and mortality. In contrast, double IL-10/IL-12-deficient mice were completely resistant and mounted a highly polarized type 2 cytokine response, demonstrating that the increased susceptibility of IL-10-deficient mice was dependent on IL-12. Further study suggested that the susceptibility of IL-10- and IL-10/IL-4-deficient mice was probably attributable to a marked increase in type 1 cytokine production in those animals. The mortality observed in T. muris-infected IL-10- and IL-10/IL-4-deficient mice correlated with increased inflammation, loss of Paneth cells, and absence of mucus in the cecum. Interestingly, survival was enhanced in T. muris-infected IL-10/IL-4-deficient mice if a broad spectrum antibiotic was administered, suggesting that an outgrowth of opportunistic bacteria was contributing to the high degree of morbidity and mortality. Overall, these studies reveal a critical role for IL-10 in the polarization of Th2 responses, development of resistance during T. muris infection, and maintenance of barrier function in the colon.


Iron-containing micronutrient powder provided to children with moderate-to-severe malnutrition increases hemoglobin concentrations but not the risk of infectious morbidity: a randomized, double-blind, placebo-controlled, noninferiority safety trial.
A link between the provision of iron and infectious morbidity has been suggested, particularly in children with malnutrition. Two meta-analyses concluded that iron is not harmful, but malnourished children were underrepresented in most available studies. This study evaluated the effect of iron-containing micronutrient powder (iron MNP) on infectious morbidities when provided to children with moderate-to-severe malnutrition and anemia. A randomized, double-blind, placebo-controlled, noninferiority safety trial using a 2-mo course of daily iron MNP or placebo powder (PP) was conducted in 268 Bangladeshi children aged 12-24 mo with moderate-to-severe malnutrition (weight-for-age z score ≤ -2) and a hemoglobin concentration between 70 and 110 g/L. The primary endpoint was a composite of diarrhea, dysentery, and lower respiratory tract infection episodes (DDL) recorded through home visits every 2 d during the intervention and then weekly for 4 mo. The noninferiority margin was 1.2. Secondary endpoints included hemoglobin and anthropometric changes at 2 and 6 mo. All deaths and hospitalizations were documented. To capture seasonal variation, the study was repeated in the winter and summer with 2 distinct groups. An intention-to-treat analysis of recurrent events was performed by using the univariate Anderson-Gill model. The baseline characteristics of the subjects were similar. Analysis of phase-aggregated DDL data showed that iron MNP was not inferior to PP (relative risk: 0.81; 95% CI: 0.62, 1.04) and improved hemoglobin concentrations (P < 0.0001). We recorded no deaths, and hospitalizations were rare. Iron MNP is safe and efficacious when provided to children aged 12-24 mo with moderate-to-severe malnutrition and anemia. This trial is registered at clinicaltrials.gov as NCT00530374.


Inhibition of Listeria locomotion by mosquito oostatic factor, a natural oligoproline peptide uncoupler of profilin action.
Mosquito oostatic factor, a naturally occurring decapeptide (YDPAPPPPPP), strikingly resembles the primary structure of oligoproline-rich regions within the protein ActA, a bacterial surface protein required for Listeria motility in host cells. When microinjected into Listeria-infected PtK2 cells, the insect oostatic factor rapidly blocks Listeria-induced actin rocket tail assembly as well as intracellular locomotion of this pathogen. At intracellular concentrations of about 90 nM, transient inhibition of rocket tail formation and bacterial locomotion occurs, followed by full recovery of tail length and motility. However, at 0.9 microM oostatic factor, both processes are permanently arrested. Introduction of oostatic factor by microinjection also causes PtK2 peripheral membrane retraction in both Listeria-infected and uninfected cells. Epifluorescence microscopy with bodipy-phallacidin reveals that cells microinjected with the insect factor lose all actin stress fibers and accumulate F-actin in regions of membrane retraction. When the insect peptide is combined with profilin as an equimolar binary solution (1 microM [final concentration] each), intracellular addition fails to inhibit Listeria rocket-tail formation, fails to block intracellular bacterial movement, and no longer causes marked membrane retraction. The ability of profilin to neutralize the inhibitory action of oostatic factor is consistent with complex formation, and this finding suggests that profilin may interact directly with ActA peptide as well as a host cell peripheral membrane component to promote actin filament assembly by locally generating ATP-actin. Dispersal of profilin from such sites by oligoproline-rich peptide inhibitors suggests that profilin is directly involved in intracellular pathogen locomotion and reorganization of actin cytoskeleton of the host cell peripheral membrane.


Hunger relief: A natural experiment from additional SNAP benefits during the COVID-19 pandemic.
COVID-19 has directly affected millions of people. Others have been indirectly affected; for example, there has been a startling increase in hunger brought about by the pandemic. Many countries have sought to relieve this problem through public policy. This research examines the effectiveness of enhanced Supplemental Nutrition Assistance Program (SNAP) benefits in the U.S. to alleviate hunger. Using a biweekly cross-sectional survey and corresponding population weights from the U.S. Census Bureau, we estimate the effects of enhanced SNAP benefits on hunger in the U.S. as measured by food insufficiency. We use a Bayesian structural time series analysis to predict counterfactual values of food insufficiency. We supplement these findings by examining the effect of enhanced SNAP benefits on observed visits to a food pantry network in a midsized U.S. city. Our primary finding estimates that nationwide a total 850,000 (95% credible interval 0·24-1·46 million) instances of food insufficiency were prevented per week by the 15 percent increase in SNAP benefits enacted in January 2021. Secondarily, we find similar effects associated with SNAP benefit increases and local food pantry visits. Specifically, enhanced SNAP benefits resulted in fewer visits to the food pantry network than were predicted in the counterfactual model. These results not only indicate that the policies enacted to mitigate hunger caused by the COVID-19 pandemic helped, but also quantifies how much these benefits helped on a national scale. As a result, policymakers can use this data to benchmark future policy actions at scale. None.


Identification of yeast artificial chromosomes containing the inversion 16 p-arm breakpoint associated with acute myelomonocytic leukemia.
We report the cloning of the chromosome 16 p-arm breakpoint involved in inversion 16(p13;q22) associated with subtype of acute myelomonocytic leukemia (AMML) M4Eo. Inter-Alu polymerase chain reaction (PCR) products from a series of interspecific somatic cell hybrids that contain only small portions of the human chromosome 16 p-arm were generated for use as fluorescent in-situ hybridization (FISH) probes. When applied to patient cells, rapid and unambiguous identification of the inversion resulted. Using FISH analysis, cosmid clones associated with the hybrids were identified that bracketed the p-arm breakpoint. A repeat-free fragment of one of these cosmids (35B11) when used as probe on Southern blots from pulsed-field gels identified rearranged macrorestriction fragments in patient DNA. Yeast artificial chromosomes (YACs) were isolated using sequences derived from cosmids flanking 35B11 in a cosmid contig. Of 4 YACs so identified, 3 were shown by FISH to cross the inversion-16 p-arm breakpoint. Therefore, the breakpoint has been molecularly cloned, and identified as being within these 3 YACs. These clones will facilitate the unraveling of the genetic events associated with inversion-16 and are available tools with immediate clinical application.


Distinguishing mirror from glass: A "big data" approach to material perception.
Distinguishing mirror from glass is a challenging visual inference, because both materials derive their appearance from their surroundings, yet we rarely experience difficulties in telling them apart. Very few studies have investigated how the visual system distinguishes reflections from refractions and to date, there is no image-computable model that emulates human judgments. Here we sought to develop a deep neural network that reproduces the patterns of visual judgments human observers make. To do this, we trained thousands of convolutional neural networks on more than 750,000 simulated mirror and glass objects, and compared their performance with human judgments, as well as alternative classifiers based on "hand-engineered" image features. For randomly chosen images, all classifiers and humans performed with high accuracy, and therefore correlated highly with one another. However, to assess how similar models are to humans, it is not sufficient to compare accuracy or correlation on random images. A good model should also predict the characteristic errors that humans make. We, therefore, painstakingly assembled a diagnostic image set for which humans make systematic errors, allowing us to isolate signatures of human-like performance. A large-scale, systematic search through feedforward neural architectures revealed that relatively shallow (three-layer) networks predicted human judgments better than any other models we tested. This is the first image-computable model that emulates human errors and succeeds in distinguishing mirror from glass, and hints that mid-level visual processing might be particularly important for the task.


When Marriage Ends: Differences in Affluence and Poverty Among Older Adults in Israel.
Studies show that the economic benefits of marriage carry over into old age and that widowhood and divorce have detrimental economic consequences, especially for women. This study asks how affluence and poverty are affected by the timing of widowhood and divorce and tests whether they operate in symmetry. The study draws on Israel's annual Social Survey from multiple years (2013-2017), conducted by Israel's Central Bureau of Statistics. The sample is limited to older individuals, aged 55+ (n = 4824 men, 5643 women). The findings show that married people are less likely to be poor than unmarried people, but they are not always more likely to be affluent. Widowed men and women, and divorced men are more likely to achieve affluence than continuously married couples. The explanation may be that, in the Israeli context, the widowed tend to inherit benefits accumulated by their late spouse, whereas the divorced tend to divide resources when the marriage dissolves. Women incur higher and longer-term penalties for their change in marital status than do men, so that previously married women tend to have higher rates of poverty and lower rates of affluence than previously married men. The findings show that affluence and poverty do not operate in symmetry and that affluence does not simply mirror poverty, especially among men. For example, early widowed and late divorced men have higher odds of both poverty and affluence than married men. These findings demonstrate that poverty and affluence operate differently and examining both leads to new insights.


The Chemical Synthesis and Applications of Tropane Alkaloids.
Tropanes are an important class of alkaloid natural products that are found in plants all over the world. These compounds can exhibit significant biological activity and are among the oldest known medicines. In the early 19th century, tropanes were isolated, characterized, and synthesized by notable chemical researchers. Their significant biological activities have inspired tremendous research efforts toward their synthesis and the elucidation of their pharmacological activity both in academia and in industry. In this chapter, which addresses the developments in this field since 1994, the focus is on the synthesis of these compounds, and several examples of sophisticated synthetic protocols involving both asymmetric and catalytic approaches are described. In addition, the structures of more than 100 new alkaloids are included as well as the applications and pharmacological properties of some tropane alkaloids.


Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agents.
X-ray based micro-computed tomography (CT) and micro-digital subtraction angiography (DSA) are important non-invasive imaging modalities for following tumorogenesis in small animals. To exploit these imaging capabilities further, the two modalities were combined into a single system to provide both morphological and functional data from the same tumor in a single imaging session. The system is described and examples are given of imaging implanted fibrosarcoma tumors in rats using two types of contrast media: (a) a new generation of blood pool contrast agent containing iodine with a concentration of 130 mg/mL (Fenestratrade mark VC, Alerion Biomedical, San Diego, CA, USA) for micro-CT and (b) a conventional iodinated contrast agent (Isovue(R)-370 mg/mL iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro-DSA. With the blood pool contrast agent, the 3D vascular architecture is revealed in exquisite detail at 100 microm resolution. Micro-DSA images, in perfect registration with the 3D micro-CT datasets, provide complementary functional information such as mean transit times and relative blood flow through the tumor. This imaging approach could be used to understand tumor angiogenesis better and be the basis for evaluating anti-angiogenic therapies.


Empirical and Methodological Challenges to the Model-Based Inference of Diversification Rates in Extinct Clades.
Changes in speciation and extinction rates are key to the dynamics of clade diversification, but attempts to infer them from phylogenies of extant species face challenges. Methods capable of synthesizing information from extant and fossil species have yielded novel insights into diversification rate variation through time, but little is known about their behavior when analyzing entirely extinct clades. Here, we use empirical and simulated data to assess how two popular methods, PyRate and Fossil BAMM, perform in this setting. We inferred the first tip-dated trees for ornithischian dinosaurs and combined them with fossil occurrence data to test whether the clade underwent an end-Cretaceous decline. We then simulated phylogenies and fossil records under empirical constraints to determine whether macroevolutionary and preservation rates can be teased apart under paleobiologically realistic conditions. We obtained discordant inferences about ornithischian macroevolution including a long-term speciation rate decline (BAMM), mostly flat rates with a steep diversification drop (PyRate) or without one (BAMM), and episodes of implausibly accelerated speciation and extinction (PyRate). Simulations revealed little to no conflation between speciation and preservation, but yielded spuriously correlated speciation and extinction estimates while time-smearing tree-wide shifts (BAMM) or overestimating their number (PyRate). Our results indicate that the small phylogenetic data sets available to vertebrate paleontologists and the assumptions made by current model-based methods combine to yield potentially unreliable inferences about the diversification of extinct clades. We provide guidelines for interpreting the results of the existing approaches in light of their limitations and suggest how the latter may be mitigated. [BAMM; diversification; fossils; macroevolutionary rates; Ornithischia; PyRate.].


Development of strong and bioactive calcium phosphate cement as a light-cure organic-inorganic hybrid.
In this research, light cured calcium phosphate cements (LCCPCs) were developed by mixing a powder phase (P) consisting of tetracalcium phosphate and dicalcium phosphate and a photo-curable resin phase (L), mixture of hydroxyethylmethacrylate (HEMA)/poly acrylic-maleic acid at various P/L ratios of 2.0, 2.4 and 2.8 g/mL. Mechanical strength, phase composition, chemical groups and microstructure of the cured cements were evaluated at pre-set times, i.e. before and after soaking in simulated body fluid (SBF). The proliferation of Rat-derived osteoblastic cells onto the LCCPCs as well as cytotoxicity of cement extracts were determined by cell counting and 3-{4,5-dimethylthiazol-2yl}-2,5-diphenyl-2H-tetrazolium bromide assay after different culture times. It was estimated from Fourier transforming infrared spectra of cured cements that the setting process is ruled by polymerization of HEMA monomers as well as formation of calcium poly-carboxylate salts. Microstructure of the cured cements consisted of calcium phosphate particles surrounded by polymerized resin phase. Formation of nano-sized needlelike calcium phosphate phase on surfaces of cements with P/L ratios of 2.4 and 2.8 g/mL was confirmed by scanning electron microscope images and X-ray diffractometry (XRD) of the cured specimen soaked in SBF for 21 days. Also, XRD patterns revealed that the formed calcium phosphate layer was apatite phase in a poor crystalline form. Biodegradation of the cements was confirmed by weight loss, change in molecular weight of polymer and morphology of the samples after different soaking periods. The maximum compressive strength of LCCPCs governed by resin polymerization and calcium polycarboxylate salts formation was about 80 MPa for cement with P/L ratio of 2.8 g/mL, after incubation for 24 h. The strength of all cements decreased by decreasing P/L ratio as well as increasing soaking time. The preliminary cell studies revealed that LCCPCs could support proliferation of osteoblasts cultured on their surfaces and no cytotoxic effect was observed for the extracts of them.


Morphometric Evaluation of Interrenal Gland and Kidney Macrophages Aggregates in Normal Healthy Rainbow Trout (Oncorhynchus mykiss) and after Bacterial Challenge with Yersinia ruckeri.
Macrophage aggregates (MA) occur in various organs of fish as discrete aggregations of pigmented macrophages. The study presented herein investigates the quantitative modifications from normal anatomical condition, of interrenal gland (IG) and kidney MA in six treatment groups of adult rainbow trout submitted to either specific or aspecific immune stimulation and subsequently challenged with Yersinia ruckeri. Routinely stained tissue sections from both IG and kidney were analysed. The percentage of tissues occupied by MA and the MA density (number/mm(2)) were calculated on at least 10 randomly selected nonoverlapping fields taken from each tissue section. MA morphometric findings from challenged fish were compared to those from a control group. Results showed that fish from control group displayed a statistically significant (P < 0.05) higher percentage of tissue occupied by MA and MA density. Among different treatment groups, anti-Yersinia ruckeri immunized fish, which did not show clinical signs of disease after bacterial challenge, displayed higher values of morphometric parameters compared with symptomatic fish from other groups. Our study demonstrates that the quantification of the area occupied by MA might be an efficient parameter to evaluate the general condition of a salmonid population since it positively correlates with the health status and negatively with stress factor such as the acute bacterial infection.


The costs of food at home and away from home and consumption patterns among U.S. adolescents.
This study examined the associations of prices of food at home groceries, prices of fast food away from home and the availability of food stores and restaurants with the number of days over the past week that adolescents consumed fruit and fruit juices, vegetables, meat, nonmeat protein, dairy, grains, and sweets. Individual-level data on adolescents were drawn from the Child Development Supplement of the Panel Study of Income Dynamics combined at the zip code level with external economic contextual data. Multivariate regression analyses were used to estimate the associations between food consumption categories and the economic contextual factors. Regressions were also estimated by households' poverty status. Fast food and food at home prices were not significantly associated with any of the food consumption categories in the full sample. However, among poor adolescents, higher fast food prices were associated with higher levels of nonmeat protein consumption. Food store outlet availability was found to have very small significant associations with some food consumption categories but no significant associations were found for restaurant outlets. Food away from home prices, such as fast food prices and supermarket and grocery store availability, were associated with some food consumption categories among low-income youths and related policies deserve further examination.


Is MRCP (U.K.) a redundant qualification for graduates of D.M. (Internal Medicine), University of the West Indies?
M.R.C.P.(U.K.) and D.M. (Internal Medicine), University of the West Indies, are postgraduate qualifications that did, or now do, evaluate and set the quality of specialist Internal Physician training. Since the inception of the degree, graduates of D.M. (Internal Medicine), University of the West Indies, have developed sub-specialty interests and have been recognized as being of consultant status throughout the region and the world. D.M. is of a higher standard as it is an exit examination whereas the MRCP(U.K.) diploma is an entrance examination. Acquisition of the MRCP (U.K.) is expensive; travel to the U.K. is mandatory. Possession of MRCP (U.K.) is considered by most graduates of D.M. (Internal Medicine), University of the West Indies, to be unnecessary; it has not advanced their career in any discernible way. It should no longer be encouraged in any way at the University of the West Indies.


Anti-obesity effects of Rapha diet® preparation in mice fed a high-fat diet.
The anti-obesity activities of Rapha diet® preparation containing silkworm pupa peptide, Garcinia cambogia, white bean extract, mango extract, raspberry extract, cocoa extract, and green tea extract were investigated in mice with dietary obesity. Male C57BL/6 mice were fed a high-fat diet (HFD) containing 3% Rapha diet® preparation for 8 weeks, and blood and tissue parameters of obesity were analyzed. The HFD markedly enhanced body weight gain by increasing the weights of epididymal, perirenal, and mesenteric adipose tissues. The increased body weight gain induced by HFD was significantly reduced by feeding Rapha diet® preparation, in which decreases in the weight of abdominal adipose tissue and the size of abdominal adipocytes were confirmed by microscopic examination. Long-term feeding of HFD increased blood triglycerides and cholesterol levels, leading to hepatic lipid accumulation. However, Rapha diet® preparation not only reversed the blood lipid levels, but also attenuated hepatic steatosis. The results indicate that Rapha diet® preparation could improve HFD-induced obesity by reducing both lipid accumulation and the size of adipocytes.


Heightened attention to supplementation is needed to improve the vitamin D status of breastfeeding mothers and infants when sunshine exposure is restricted.
Although exclusively breastfed infants are at increased risk of vitamin D (vit D) deficiency if vit D supplementation is lacking and sun exposure is limited, assessment of both risk factors in the first year of life is lacking. We evaluated the contribution of vit D intake and sunlight exposure to vit D status in 120 healthy, breastfeeding mother-infant dyads, who were followed up for 1 year. Vitamin D intake and skin sunlight exposure were evaluated using questionnaires. Serum 25-hydroxyvitamin D, parathyroid hormone (PTH) and alkaline phosphatase levels were determined post-natally in mothers at 4 weeks and in infants at 4, 26 and 52 weeks. Vitamin D supplementation was low (<20%) and sunlight exposure was common (93%) in study infants. At 4 weeks, 17% of mothers were vit D deficient (<50 nmol L(-1)) and 49% were insufficient (50-<75 nmol L(-1)), while 18% of infants were severely vit D deficient (<25 nmol L(-1)) and 77% were deficient (<50 nmol L(-1)). At 26 weeks, winter/spring birth season and shorter duration of months of exclusive breastfeeding were protective of vit D deficiency in infants. Vitamin D deficiency in infants decreased to 12% at 52 weeks with sunlight exposure. Serum PTH levels were significantly higher in severely vit D deficient than sufficient infants. Vitamin D deficiency was widespread in early post-partum breastfeeding mothers and infants, and declined to one in eight infants at 52 weeks due mostly to sunshine exposure. When sunlight exposure is limited or restricted, intensified vit D supplementation of breastfeeding mothers and infants is needed to improve vit D status.


Digestive-vacuole genesis and endocytic processes in the early intraerythrocytic stages of Plasmodium falciparum.
The digestive vacuole of the malaria parasite Plasmodium falciparum is the site of haemoglobin digestion and haem detoxification, and is the target of chloroquine and other antimalarials. The mechanisms for genesis of the digestive vacuole and transfer of haemoglobin from the host cytoplasm are still debated. Here, we use live-cell imaging and photobleaching to monitor the uptake of the pH-sensitive fluorescent tracer SNARF-1-dextran from the erythrocyte cytoplasm in ring-stage and trophozoite-stage parasites. We compare these results with electron tomography of serial sections of parasites at different stages of growth. We show that uptake of erythrocyte cytoplasm is initiated in mid-ring-stage parasites. The host cytoplasm is internalised via cytostome-derived invaginations and concentrated into several acidified peripheral structures. Haemoglobin digestion and haemozoin formation take place in these vesicles. The ring-stage parasites can adopt a deeply invaginated cup shape but do not take up haemoglobin via macropinocytosis. As the parasite matures, the haemozoin-containing compartments coalesce to form a single acidic digestive vacuole that is fed by haemoglobin-containing vesicles. There is also evidence for haemoglobin degradation in compartments outside the digestive vacuole. The work has implications for the stage specificity of quinoline and endoperoxide antimalarials.


The Effects of Nordic Walking Compared to Conventional Walking on Aerobic Capacity and Lipid Profile in Women Over 55 Years of Age.
The purpose of this study was to investigate the effects of Nordic Walking compared to conventional walking on aerobic capacity, the lipid profile, left ventricular ejection fraction, body mass, and body mass index in women over 55 years old. The study was comprised of 74 women over 55 years of age. Participants were randomized to the Nordic Walking (n = 38) or conventional walking (n = 36) training groups. The echocardiogram, treadmill exercise stress test, lipid profile, and body mass were assessed at baseline (pretest) and after 12 weeks (posttest). The authors found a significant main effect over time in duration (effect size [ES] = 0.59, P < .0001), distance covered (ES = 0.56, P < .0001), peak oxygen consumption (ES = 0.43, P < .0001), metabolic equivalent (ES = 0.29, P < .0001), peak heart rate (ES = 0.2, P < .0001), peak diastolic blood pressure (ES = 0.11, P = .0045), total cholesterol (ES = 0.26, P < .0001), and low-density lipoprotein cholesterol (ES = 0.16, P = .0005). The authors did not observe a time versus group interaction or the effect between groups. Post hoc tests revealed significant pretraining to posttraining differences in low-density lipoprotein cholesterol after the Nordic Walking training program and in peak diastolic blood pressure after the conventional walking training program. The heart rate, systolic blood pressure, and diastolic blood pressure at rest, peak diastolic blood pressure, somatic parameters (body mass and body mass index), and left ventricular ejection fraction did not change in either group. Both training programs resulted in increases in aerobic capacity and decreases in total cholesterol.


What are the mature men who do not work, do not look for a job, and are not retired doing?
Reduced participation of the male population in economic activities is the result of their later entry and earlier leave from the labor market. This earlier exit is not only associated to "early" retirement. Between 1993 and 2013, there was an increase in the number of men aged 50-59 who were not working, not looking for a job, and were not retired (NER) . The literature stresses that work is the most important social event of a man's life, and the traditional gender contract establishes the breadwinner role for men and the caregiver one for women. This growth suggests changes in gender relations since a decrease was observed in the proportion of male household heads, and an increase in that of male spouses, and of those living with their parents. This may be a consequence of their difficulties in participating in the labor market, also given their low education level; therefore, requiring greater participation from women. This trend is contradictory with the new demographic regime. A later leave from economic activities is an important requirement to minimize the challenges brought about by the reducing workforce and aging population.


Component structure of event-related fMRI responses in the different neurovascular compartments.
In most functional magnetic resonance imaging (fMRI) studies, brain activity is localized by observing changes in the blood oxygenation level-dependent (BOLD) signal that are believed to arise from capillaries, venules and veins in and around the active neuronal population. However, the contribution from veins can be relatively far downstream from active neurons, thereby limiting the ability of BOLD imaging methods to precisely pinpoint neural generators. Hemodynamic measures based on apparent diffusion coefficients (ADCs) have recently been used to identify more upstream functional blood flow changes in the capillaries, arterioles and arteries. In particular, we recently showed that, due to the complementary vascular sensitivities of ADC and BOLD signals, the voxels conjointly activated by both measures may identify the capillary networks of the active neuronal areas. In this study, we first used simultaneously acquired ADC and BOLD functional imaging signals to identify brain voxels activated by ADC only, by both ADC and BOLD and by BOLD only, thereby delineating voxels relatively dominated by the arterial, capillary, and draining venous neurovascular compartments, respectively. We then examined the event-related fMRI BOLD responses in each of these delineated neurovascular compartments, hypothesizing that their event-related responses would show different temporal componentries. In the regions activated by both the BOLD and ADC contrasts, but not in the BOLD-only areas, we observed an initial transient signal reduction (an initial dip), consistent with the local production of deoxyhemoglobin by the active neuronal population. In addition, the BOLD-ADC overlap areas and the BOLD-only areas showed a clear poststimulus undershoot, whereas the compartment activated by only ADC did not show this component. These results indicate that using ADC contrast in conjunction with BOLD imaging can help delineate the various neurovascular compartments, improve the localization of active neural populations, and provide insight into the physiological mechanisms underlying the hemodynamic signals.


Evidence for ethylation of rat liver deoxyribonucleic acid after administration of ethionine.
1. Administration of a large dose (500mg/kg body wt.) of (3)H-labelled l-ethionine to rats resulted in the incorporation of a small amount of radioactivity into the liver DNA. Considerable evidence that this radioactivity was not due to contamination of the isolated DNA with labelled protein, RNA, S-adenosyl-l-ethionine or l-ethionine was obtained. 2. After acidic hydrolysis of the DNA isolated from the livers of rats treated with labelled l-ethionine, virtually all of the radioactivity present in the DNA was found in a fraction with similar chromatographic properties to 7-ethylguanine. 3. Treatment of rats with comparable doses of l-methionine did not lead to the formation of 7-methylguanine in the liver DNA. 4. These results are discussed in relation to the induction of liver tumours by ethionine.


A scientific evaluation of operative choledochoscopy in acute cholangitis.
A prospective study to determine the safety and effectiveness of choledochoscopy in acute cholangitis and acute suppurative cholangitis due to common bile duct stones was conducted on 70 patients. Common bile duct pressures determined on the first 20 patients showed that choledochoscopy was unlikely to cause cholangiovenous reflux. Laboratory and clinical parameters revealed that choledochoscopy did not cause septicemia, worsen cholangitis, or provoke acute pancreatitis. There was no iatrogenic injury during choledochoscopy, and the choledochoscopic views were minimally affected by cholangitis. Choledochoscopy detected overlooked stones after conventional methods of exploration of common bile ducts in 14.3% of patients and it helped to remove impacted stones in 2.9% of patients. As a result, the incidence of retained stones after choledochoscopy was 1.4%. Time spent in choledochoscopy was short, and the total postoperative septic complication rate was only 10%. There was no operative mortality. It is concluded that choledochoscopy is safe and effective in cholangitis.


Effects of introducing routinely ultrasound scanning during Ante Natal Care (ANC) clinics on number of visits of ANC and facility delivery: a cohort study.
Many countries have integrated antenatal care as an essential part of routine maternal health services. The importance of this service cannot be overemphasized as many women's lives are usually saved particularly through early detection of pregnancy related complications. However, while many women would attend at least one visit for ante natal care (ANC), completion of recommended number of visits (4+) has been a challenge of many health systems particularly in developing countries like Tanzania. We conducted a cohort study to include ultrasound scanning using a portable hand-held Vscan to test whether by integrating it in routine ANC clinics at dispensary and health centre levels would promote number of ANC visits by women. Health providers rendering ANC services in selected facilities were trained on how to use the simple technology of ultrasound scanning. Women living in catchment areas of the respective selected facilities were eligible to inclusion to the study when consented. A baseline status of the ANC attendance in the study area was established through baseline household and facility surveys. A total of 257 women consented and received the study treatment. Our results showed that, there was no a slight change between baseline (97.2 %) and endline (97.4 %) results among women attending ANC clinics at least once. However, there was a significant change in percentage of women attending ANC clinic four times or more (27.2 % during baseline and 60.3 %; p = 0001). We conclude that, introduction of the simplified ultrasound scanning technology at lowest levels of care has an effect to improving ANC attendance in terms of number of visits and motivate facility delivery.


RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma.
Metastasis is a complex process by which cancer cells escape from the primary tumor to colonize distant organs. RAC1 is a member of the RHO family of small guanosine triphosphatases that plays an important role in cancer migration, invasion, angiogenesis and metastasis. RAC1 activation has been related to most cancers, such as cutaneous melanoma, breast, lung, and pancreatic cancer. RAC1P29S driver mutation appears in a significant number of cutaneous melanoma cases. Likewise, RAC1 is overexpressed or hyperactivated via signaling through oncogenic cell surface receptors. Thus, targeting RAC1 represents a promising strategy for cutaneous melanoma therapy, as well as for inhibition of other signaling activation that promotes resistance to targeted therapies. In this review, we focus on the role of RAC1 in metastatic cutaneous melanoma emphasizing the anti-metastatic potential of RAC1- targeting drugs.


The Delphi technique: myths and realities.
To outline the key concepts and principles of the Delphi technique. Reference is made to a selection of studies that illustrate a variety of methodological interpretations. Drawing on Heshusius's concept of 'goodness criteria', particular emphasis is given to the question of scientific merit and means of evaluation. Although the technique should be used with caution, it appears to be an established method of harnessing the opinions of an often diverse group of experts on practice-related problems.


Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate.
To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis.


[Organizational culture and professional development in nursing].
There is a lot of talk about the importance of persons in organization and leadership, nothing that the keys to lead the organizational milieu in a positive and beneficial manner have been established for several decades. These keys are related to the values of nursing as a profession and to how these may constitute intangible assets. Nonetheless, identifying such values and intangible assets is not the exclusive responsibility of business managers in the nursing field.


Plants Respond to GSM-Like Radiation.
In this article, we propose that an organism's general architecture is of primary importance for its ability to perceive electromagnetic radiation. Animals develop mainly as volumes for internal assimilation and appendages to increase their mobility, while plants develop as surfaces to optimize interaction with the environment. As a consequence, the proportion of cells directly interacting with EMF radiation at the organism/environment interface is much higher in plants than it is in animals, making them especially suited to study EMF effects on life.


Intestinal bioavailability of n-3 long-chain polyunsaturated fatty acids influenced by the supramolecular form of phospholipids.
The aim of this work was to study the bioavailability of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), carried by marine phospholipids (PL) and formulated in different supramolecular forms. Marine PL were administrated in rats either (1) in bulk form, or (2) as an oil-in-water emulsion, or (3) as liposomes. Each dietary formulation was characterized by a similar fatty acid (FA) profile and provided the same n-3 LC-PUFA amount. Intestinal bioavailability of n-3 LC-PUFA was monitored in the lymph compartment in a duct fistula model. On the one hand, the emulsification of plant oils with PL increased the overall intestinal absorption of dietary FA by 84% without affecting the lymph FA profile compared with the bulk form, suggesting that emulsification favoured the absorption of the total dietary FA derived from both triglycerides (TG) and PL. On the other hand, the liposome form did not modify the lymph lipid amount compared with the bulk form, but specifically increased the n-3 LC-PUFA levels. The dietary forms of PL influenced the position of some FA on the glycerol backbone of lymph TG and PL. In conclusion, using marine PL as an emulsifier promoted total FA absorption independently of the dietary lipid carrier (TG or PL) and the FA type. Structuring PL as liposomes specifically increased the intestinal bioavailability of FA esterifed in this lipid class, such as DHA, resulting in a higher incorporation into lymph lipids. Thus, using specific PL supramolecular forms would guide n-3 LC-PUFA towards total lipid absorption or specific FA absorption, according to the dietary needs.


Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.
Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia. However, studies evaluating safety and effectiveness of hysteroscopic myomectomy under procedural sedation are lacking. This study aims to investigate whether hysteroscopic myomectomy under procedural sedation and analgesia with propofol is noninferior to hysteroscopic myomectomy under general anesthesia. This was a multicenter, randomized controlled noninferiority trial conducted in 14 university and teaching hospitals in the Netherlands between 2016 and 2021. Inclusion criteria were age ≥18 years, maximum number of 3 type 0 or 1 fibroids, maximum fibroid diameter 3.5 cm, American Society of Anesthesiologists class 1 or 2, and having sufficient knowledge of the Dutch or English language. Women with clotting disorders or with severe anemia (Hb < 5.0 mmol/L) were excluded. Women were randomized using block randomization with variable block sizes of 2, 4, and 6, between hysteroscopic myomectomy under procedural sedation and analgesia (PSA) with propofol or under general anesthesia (GA). Primary outcome was the percentage of complete resections, assessed on transvaginal ultrasonography 6 weeks postoperatively by a sonographer blinded for the treatment arm and surgical outcome. Secondary outcomes were the surgeon's judgment of completeness of procedure, menstrual blood loss, uterine fibroid related and general quality of life, pain, recovery, hospitalization, complications, and surgical reinterventions. Follow-up period was 1 year. The risk difference between both treatment arms was estimated, and a Farrington-Manning test was used to determine the p-value for noninferiority (noninferiority margin 7.5% of incomplete resections). Data were analyzed according to the intention-to-treat principle, including a per-protocol analysis for the primary outcome. A total of 209 women participated in the study and underwent hysteroscopic myomectomy with PSA (n = 106) or GA (n = 103). Mean age was 45.1 [SD 6.4] years in the PSA group versus 45.0 [7.7] years in the GA group. For 98/106 women in the PSA group and 89/103 women in the GA group, data were available for analysis of the primary outcome. Hysteroscopic resection was complete in 86/98 women (87.8%) in the PSA group and 79/89 women (88.8%) in the GA group (risk difference -1.01%; 95% confidence interval (CI) -10.36 to 8.34; noninferiority, P = 0.09). No serious anesthesiologic complications occurred, and conversion from PSA to GA was not required. During the follow-up period, 15 serious adverse events occurred (overnight admissions). All were unrelated to the intervention studied. Main limitations were the choice of primary outcome and the fact that our study proved to be underpowered. Noninferiority of PSA for completeness of resection was not shown, though there were no significant differences in clinical outcomes and quality of life. In this study, hysteroscopic myomectomy for type 0 and 1 fibroids with PSA compared to GA was safe and led to shorter hospitalization. These results can be used for counseling patients by gynecologists and anesthesiologists. Based on these findings, we suggest that hysteroscopic myomectomies can be performed under PSA in an outpatient setting. The study was registered prospectively in the Dutch Trial Register (NTR 5357; registration date: 11 August 2015; Date of initial participant enrollment: 18 February 2016).


Concerted evolution of duplicated mitochondrial control regions in three related seabird species.
Many population genetic and phylogenetic analyses of mitochondrial DNA (mtDNA) assume that mitochondrial genomes do not undergo recombination. Recently, concerted evolution of duplicated mitochondrial control regions has been documented in a range of taxa. Although the molecular mechanism that facilitates concerted evolution is unknown, all proposed mechanisms involve mtDNA recombination. Here, we document a duplication of a large region (cytochrome b, tRNAThr, tRNAPro, ND6, tRNAGlu and the control region) in the mitochondrial genome of three related seabird species. To investigate the evolution of duplicate control regions, we sequenced both control region copies (CR1 and CR2) from 21 brown (Sula leucogaster), 21 red-footed (S. sula) and 21 blue-footed boobies (S. nebouxii). Phylogenetic analysis suggested that the duplicated control regions are predominantly evolving in concert; however, approximately 51 base pairs at the 5' end of CR1 and CR2 exhibited a discordant phylogenetic signal and appeared to be evolving independently. Both the structure of the duplicated region and the conflicting phylogenetic signals are remarkably similar to a pattern found in Thalassarche albatrosses, which are united with boobies in a large clade that includes all procellariiform and most pelecaniform seabirds. Therefore we suggest that concerted evolution of duplicated control regions either is taxonomically widespread within seabirds, or that it has evolved many times.


Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat.
Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic "knockouts".


Primary pulmonary hypertension. Study of eight autopsy cases.
Eight autopsy cases of primary pulmonary hypertension were studied. All cases were diagnosed as primary plexogenic arteriopathy. Microscopical study of the lungs showed in every case hypertensive arterial changes of Grade II-VI after Health & Edwards' criteria. Truncal pulmonary artery of three cases revealed aneurysm or severe dilatation with thrombus, and dilation was also recorded in another three cases. Histology of gross pulmonary artery in several cases presented disruption and defect of elastic fiber and alcian-blue positive microcystic change in media, lymphoid cell infiltration in outer media and inner adventitia, adventitial thickening, and intimal fibrosis. The liver of 7 cases showed secondary congestive changes and in one case intrahepatic portal vasculitis.


Injury mortality in local communities in Sweden and in the three Baltic States: implications for prevention.
This study provides a comparative time-trend evaluation of injury mortality in local communities in Sweden and the three Baltic States, considering their national socio-political and economic situations and with analysis of local injury prevention structures and activities. Data for the period from 1990 to 2002 were gathered from national statistical offices for the cities of Borås, Tartu, Jelgava and Kaunas and from WHO databases for national level analyses. The death rates for Borås remained relatively stable over the time period, while the Baltic communities had increasing rates until 1994 and seemed to stabilize after 1997. The differences in injury mortality in the studied communities were highest for the 0 - 19 year age group and especially in the 20 - 64 year age group, but not for the 65+ year age group. Local communities in the Baltic States should consider coordinated safety promotion and injury prevention programmes as a complement to national safety promotion framework.


Laser 3D printing with sub-microscale resolution of porous elastomeric scaffolds for supporting human bone stem cells.
A reproducible method is needed to fabricate 3D scaffold constructs that results in periodic and uniform structures with precise control at sub-micrometer and micrometer length scales. In this study, fabrication of scaffolds by two-photon polymerization (2PP) of a biodegradable urethane and acrylate-based photoelastomer is demonstrated. This material supports 2PP processing with sub-micrometer spatial resolution. The high photoreactivity of the biophotoelastomer permits 2PP processing at a scanning speed of 1000 mm s(-1), facilitating rapid fabrication of relatively large structures (>5 mm(3)). These structures are custom printed for in vitro assay screening in 96-well plates and are sufficiently flexible to enable facile handling and transplantation. These results indicate that stable scaffolds with porosities of greater than 60% can be produced using 2PP. Human bone marrow stromal cells grown on 3D scaffolds exhibit increased growth and proliferation compared to smooth 2D scaffold controls. 3D scaffolds adsorb larger amounts of protein than smooth 2D scaffolds due to their larger surface area; the scaffolds also allow cells to attach in multiple planes and to completely infiltrate the porous scaffolds. The flexible photoelastomer material is biocompatible in vitro and is associated with facile handling, making it a viable candidate for further study of complex 3D-printed scaffolds.


Rock magnetic finger-printing of soil from a coal-fired thermal power plant.
We present seasonal rock magnetic data for 48 surficial soil samples collected seasonally around a coal-fired thermal power plant on the southwest coast of India to demonstrate how fly ash from the power plant is transported both spatially and seasonally. Sampling was carried out during pre-monsoon (March), early-monsoon (June), monsoon (September) and post-monsoon (December) seasons. Low- and high-frequency magnetic susceptibility (χlf and χhf), frequency-dependent magnetic susceptibility (χfd), χfd %, isothermal remanent magnetization (IRM), "hard" IRM (HIRM), saturation IRM (SIRM) and inter-parametric ratios were determined for the samples. Scanning electron microscopy (SEM) was used on limited number of samples. NOAA HYSPLIT MODEL backward trajectory analysis and principal component analysis were carried out on the data. Fly ash samples exhibit an average HIRM value (400.07 × 10(-5) Am(2) kg(-1)) that is comparable to that of soil samples. The pre- and post-monsoon samples show a consistent reduction in the concentration of magnetically "hard" minerals with increasing distance from the power plant. These data suggest that fly ash has indeed been transported from the power plant to the sampling locations. Hence, HIRM may perhaps be used as a proxy for tracking fly ash from coal-fired thermal power plants. Seasonal data show that the distribution of fly ash to the surrounding areas is minimum during monsoons. They also point to the dominance of SP magnetite in early-monsoon season, whereas magnetic depletion is documented in the monsoon season. This seasonal difference is attributable to both pedogenesis and anthropogenic activity i.e. operation of the thermal power plant.


Noninvasive positive pressure ventilation reverses acute respiratory failure in select "do-not-intubate" patients.
To determine the outcome from the use of noninvasive positive pressure ventilation (NPPV) in "do-not-intubate" (DNI) patients in acute respiratory failure. Prospective observational study. University-affiliated large medical center. All patients with DNI status who received NPPV for a 1-yr period. None. Demographic, physiologic, and laboratory data were collected before initiation, 2 hrs after initiation, and each morning and evening for as long as NPPV was provided. Data were recorded on 137 episodes of acute respiratory failure in 131 DNI patients. Hospital mortality rate was 37.5% in 24 patients with an exacerbation of chronic obstructive pulmonary disease (COPD), 39% in 28 patients with acute cardiogenic pulmonary edema, 68% in nine patients with non-COPD hypercapnic ventilatory failure, 77% in 13 post-extubation respiratory failure patients, and 86% in 57 patients with hypoxemic respiratory failure. Advanced cancer was present in 40 patients and was associated with increased risk of death (85% mortality rate, p = .002). A score based on the Simplified Acute Physiology Score (SAPS) II and serum albumin level calculated before NPPV was predictive of hospital outcome. NPPV is successful in reversing acute respiratory failure and preventing hospital mortality in DNI patients with COPD and cardiogenic pulmonary edema but not in patients with post-extubation failure, hypoxemic respiratory failure, or end-stage cancer. An easy-to-calculate score combining SAPS II and serum albumin level is a good prediction of outcome in DNI patients receiving NPPV.


[Multi-morbidity and perioperative risk of total hip endoprosthesis].
Paper describes the worldwide first-time implantation of an artificial joint by Themistocles Gluck (1853-1942) in May, 22 th 1890 in Berlin. After that in a retrospective study are represented multimorbidity and perioperative complications of 2,000 patients with total hip joint replacement performed between 1979 and 1987. The fatality was 1.6%, the rate of fatal lung-embolism 1.85%. Value of actual thromboembolism-prophylaxis and intensive-care-unit is discussed.


Newly synthesized catalytic and regulatory components of adenylate cyclase are expressed in neurites of cultured sympathetic neurons.
Forskolin- and guanine nucleotide-stimulated adenylate cyclase activities were measured in microdissected sections of neurites from small explants and in dispersed cell cultures of sympathetic ganglion neurons to determine whether a competent system for regulated formation of cAMP, consisting of both catalytic units of adenylate cyclase and regulatory GTP binding proteins, is synthesized during neurite outgrowth and where it is distributed in the neuron. An increase in both guanine nucleotide- and forskolin-dependent activity of adenylate cyclase occurred concomitantly with neurite outgrowth and was directly proportional to neurite length. Separate analysis of adenylate cyclase activity in explant cell bodies or neurites showed that the increased activity was localized entirely in the neurites, while activity in the cell bodies remained virtually constant during growth. Concentric sections of neurites of approximately 500 microns width, which contained similar volumes of neurites as determined with the indicator BCECF (Rink et al., 1982), produced similar levels of cAMP, indicating an even distribution of adenylate cyclase in the neurites. Cell bodies, when stimulated by GTP gamma S, produced 236 +/- 46 attomol cAMP/min (30 degrees C)/cell body and an additional 52.6 +/- 20 attomol cAMP/min (30 degrees C)/neuron were produced with each day of neurite growth (approximately 400 microns). Assuming a turnover number of 2000 min-1, cell bodies and neurites were calculated to contain similar densities of catalytic unit molecules on their surface (9-28 molecules/micron 2). An abundant GTP binding protein, detected by ADP-ribosylation with pertussis toxin, was also widely distributed in the neuron.(ABSTRACT TRUNCATED AT 250 WORDS)


CASPASE-3 and CD-34 expression in prostate adenocarcinoma.
1. To evaluate the percentage of caspase-3 and CD-34 expression on adenocarcinoma; 2. to quantify caspase-3 and CD-34 in tumor cells; 3. to verify the relationship between biomarkers and its malignancy; 4. to correlate biomarkers themselves. Thirty-eight human malignant prostate specimens, Gleason's score, were immunohistochemically stained for caspase-3 and CD-34 protein. Quantification was done under Samba 4000 Immuno System reading, yielding two variables: label index and optical density. Statistical analyses were based on cross-methods involving univariate and bivariate as well as correlation factors among independent variables. Immunostaining was revealed in 25 plates for caspase-3 and 34 for CD-34. Caspase-3 expression for label index was over 50 in 76%, while for optical density was below 50 in 96%. CD-34 expression demonstrated label index over 50 in 59% and optical density below 50 in 56%. Correlation among expression and severity did not demonstrate to be statistically significant. There was no correlation between protein expression and Gleason's score. 1. Caspase-3 and CD-34 were present respectively in 73.5% and 100% of samples; 2. caspase-3 and CD-34 showed high expression regarding label index and low expression in optical density; 3. there was no statistical significance among expressions and tumor severity according to Gleason's score; 4. no significant correlation could be set between the biomarkers themselves.


The barriers and enablers to implementing the New South Wales Healthy School Canteen Strategy in secondary schools in the Illawarra and Shoalhaven regions - A qualitative study.
In 2017, the New South Wales Healthy School Canteen Strategy (Strategy) was introduced into primary and secondary schools. Studies have reported that secondary schools have a lower level of compliance with healthy canteen policies compared with primary schools. This study aims to identify and describe the barriers and enablers to implementing the Strategy in Department of Education (DoE) secondary schools in the Illawarra and Shoalhaven regions. The framework underpinning the study was the systems theory. Canteen managers (CM) and principals from the 21 DoE secondary schools in the Illawarra and Shoalhaven regions were invited to participate in semi-structured interviews. The interviews were structured around the five focus areas of the Strategy, including questions on school nutrition policies and the role of the canteen. Data were collated using the interview guides as a framework and qualitative content analysis, using manual coding, was undertaken. Eight (38%) schools participated with seven CMs and six principals interviewed. Barriers to implementing the Strategy included the changing role of the canteen, the increased demands placed on CMs and inconsistencies between the school food environment and the Strategy. Enablers included monitoring implementation, and internal and external support. This study also recognised that previously identified barriers to healthy canteen strategy implementation are ongoing. The school canteen is an integral part of the school environment and therefore needs whole-of-school support if successful implementation of the Strategy is to occur. Addressing the barriers and promoting the enablers identified in this study will support better nutrition policy implementation in secondary schools.


Physical properties of root cementum: Part 19. Comparison of the amounts of root resorption between the right and left first premolars after application of buccally directed heavy orthodontic tipping forces.
Previous studies have used the right and left sides of the same jaw to compare different force levels, types of movement, and durations of forces. However, the amounts of root resorption have not been compared between the right and left sides after applying the same amount of force. The aims of the study were to quantitatively compare the volumes of the root resorption lacunae between the right and left first premolars to determine whether 1 side can serve as a control to the other and to compare the volumes of root resorption lacunae of the first premolars between the maxilla and the mandible. Forty-four first premolars, orthodontically indicated for extraction from 11 patients (left and right maxillary and mandibular first premolars from each) were moved buccally by using beta-titanium-molybdenum alloy 0.017 × 0.025-in cantilever springs with continuous heavy (225 g) force. After the experimental period, the teeth were extracted under a strict protocol to prevent root cementum damage and then analyzed by using a microcomputed tomography scan x-ray system (1172; SkyScan, Aartselaar, Belgium) and specially designed software (Convex Hull 2D, University of Sydney, Sydney, Australia) for direct volumetric measurements. There were no statistically significant differences in the mean cube root volumes of root resorption craters between the right and left sides (P = 0.18) or between the maxillary and mandibular jaws (P = 0.10). There was also no statistical significance for the interception (P = 0.41), which indicated that the jaw and the side had independent effects. The amount of root resorption on the left and right sides of the jaw were similar in both the maxilla and the mandible. Therefore, for future root resorption studies, it is justifiable to use the split-mouth technique so that teeth from 1 side of the jaw can serve as the controls.


Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection.
Pseudomonas aeruginosa (PA) from acute and chronic (eg, cystic fibrosis (CF)) infections differ in several respects, but they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and to examine its role in clinical outcomes. A total of 114 CF subjects were divided into 3 cohorts: 1st infected individuals, CI children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were collected prospectively. In 1st infection, 45.2% +/- 9.1% of PA isolates secreted T3 proteins compared with 29.1% +/- 4.2% and 11.5% +/- 3.0% in CI children and CI adults, respectively (P < 0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r = -0.32, P < 0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inversely correlated with the forced expiratory volume in 1 s (FEV(1)) decline (r = -0.35, P = 0.02). In 1st infection, 82% of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P < 0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV(1) decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection.