Revisiting the phylogenetic position of Caullerya mesnili (Ichthyosporea), a common Daphnia parasite, based on 22 protein-coding genes.
Caullerya mesnili is a common and virulent parasite of the water flea, Daphnia. It was classified within the Haplosporidia (Rhizaria) for over a century. However, a recent molecular phylogeny based on the 18S rRNA gene suggested it belonged to the Ichthyosporea, a class of protists closely related to animals within the Opisthokonta clade. The exact phylogenetic position of C. mesnili remained uncertain because it appeared in the 18S rRNA tree with a very long branch and separated from all other taxa, suggesting that its position could be artifactual. A better understanding of its phylogenetic position has been constrained by a lack of molecular markers and the difficulty of obtaining a suitable quantity and quality of DNA from in vitro cultures, as this intracellular parasite cannot be cultured without its host. We isolated and collected spores of C. mesnili and sequenced genomic libraries. Phylogenetic analyses of a newly generated multi-protein data set (22 proteins, 4998 amino acids) and of sequences from the 18S rRNA gene both placed C. mesnili within the Ichthyophonida sub-clade of Ichthyosporea, as sister-taxon to Abeoforma whisleri and Pirum gemmata. Our study highlights the utility of metagenomic approaches for obtaining genomic information from intracellular parasites and for more accurate phylogenetic placement in evolutionary studies.


The influence of massive jejunectomy on endocrine pancreas of diabetic Goto-Kakizaki.
Several bariatric surgeries have been related to the T2DM improvement in obese patients. Despite the different mechanism invoked for this improvement, many evidences showed that the pancreas cellularity is conditioned for the homeostatic physiological changes after these surgeries. Many authors reported the changes in beta-cell mass after some surgeries in healthy rats. We purpose to analyze the changes in β-cell cellularity and β-cell-mass after a severe malabsorptive surgical method. Thus, we studied several parameters of the islet morphometric composition after a massive jejunal resection. We employed Goto-Kakizaki diabetic non-obese rats, which underwent the 50% resection of middle portion of the jejunum versus a control group. After 3 months, rats were sacrificed and pancreas was immunohistochemicaly studied. The β-cell mass was analyzed and several parameters about the endocrine islet size distribution were studied. We report an increase of β-cell mass in massive resection surgical group versus controls. The islet distribution was significant different between both groups. Endocrine islets of surgical group were bigger with a different cellular distribution. According to the enteroendocrine changes related to surgeries in jejunum, as in other gastrointestinal portions, the cellularity of islets changes as an adaptive process to glycemic demands.


Hydrolysis of plasmalogen by phospholipase A1 from Streptomyces albidoflavus for early detection of dementia and arteriosclerosis.
To obtain an ethanolamine plasmalogen (PlsEtn)-hydrolyzing enzyme and to develop an assay that would help determine PlsEtn concentrations in human serum as an indicator of Alzheimer-type dementia and of arteriosclerosis. Phospholipase A1s, SaPLA1 and SvPLA1 from, respectively, Streptomyces albidoflavus NA297 and S. avermitilis JCM5070-but not phospholipase B from Streptomyces sp. NA684, PLA2-Nagase from S. avermitilis, PLA2IIL from S. violaceoruber nor LIPOMOD 699L (porcine phospholipase)-hydrolyzed choline plasmalogen (PlsCho) and PlsEtn (PlsCho preferred over PlsEtn). Using a combination of SaPLA1, lysoplasmalogen-specific phospholipase D (LyPls-PLD), with amine oxidase, an end-point assay was developed for measuring serum PlsEtn concentration. The standard curve, generated using various amounts of PlsEtn in this assay, was linear between 0 and 0.2 mM. PlsEtn concentrations in forty-seven serum samples, determined independently by this enzyme-based assay and (125)I-HPLC method, exhibited a linear relationship, indicating that the assay is suitable for fast and accurate measurement of serum PlsEtn concentration. An assay, developed using SaPLA1, LyPls-PLD, and AOX, selectively measured PlsEtn levels in blood samples. This assay could be a useful diagnostic tool for early stage detection of diseases such as Alzheimer-type dementia and arteriosclerosis.


Effect of sarcopenia, osteoporosis, and osteosarcopenia on spine fracture in American adults with prediabetes.
This study aimed to investigate the effect of sarcopenia, osteoporosis, and osteosarcopenia on spine fracture in patients with prediabetes. We collected and analyzed the data from the U.S. National Health and Nutrition Examination Surveys during the period from 2009 to 2018. Bone mineral density and the skeletal muscle mass index (SMI) were measured with dual-energy X-ray absorptiometry (DXA). The diagnosis of spine fracture was based on DXA and history. People with prediabetes were more likely to develop sarcopenia than normal glucose tolerance subjects (OR 1.33, 95% CI 1.07-1.66), while there was no significant increase of osteoporosis in prediabetes (OR 0.91, 95% CI 0.78-1.05). The SMI was independently associated with osteoporosis in prediabetes adults (OR 0.65, 95% CI 0.50-0.85). Both sarcopenia and osteoporosis were positively associated with spine fracture in prediabetes (OR 4.44, 95% CI 1.76-11.21, and OR 2.90, 95% CI 1.85-4.56, respectively). The risk of spine fracture was substantially higher in the presence of osteosarcopenia (OR 6.63; 95% CI, 1.34-32.94) than in the presence of sarcopenia or osteoporosis alone in prediabetes. In adults with prediabetes, both sarcopenia and osteoporosis are risk factors for spine fracture, and the combination of sarcopenia and osteoporosis further increases the prevalence of spine fracture.


Structure identification of a polysaccharide in mushroom Lingzhi spore and its immunomodulatory activity.
Ganoderma lucidum spore serves as a well-known immunomodulatory functional food in Asia. The polysaccharides in G. lucidum spore are responsible for the claimed immunomodulatory activity. However, the structural information of polysaccharides remains unclear. In this work, the leading water-soluble polysaccharide in G. lucidum spore (GLSP-I) with a molecular weight of 128.0 kDa was isolated and purified. The monosaccharide composition analysed by gas chromatography indicated that GLSP-I was a glucan. Three side chains, including Glc-(1 → 3)-Glc-(1 → 3)-Glc-(1 → 6)-Glc, Glc-(1 → 6)-Glc-(1 → 6)-Glc-(1 → 6)-Glc and Glc-(1 → 3)-Glc-(1 → 3)-Glc-(1 → 3)-Glc-(1 → 3)-Glc, were identified by UPLC-MS/MS. The structural characteristics were further identified by NMR spectra. The results indicated that the backbone of GLSP-I was (1 → 3)-β-D-glucan, with side chains linking at O-6. The proposed structure was drawn as below. The immunomodulatory activity assay indicated that GLSP-I could activate macrophages in a dose-dependent manner.


The rat nucleus paragigantocellularis as a relay station to mediate peripherally induced central effects of nicotine.
Previous electrophysiological studies have shown that intravenously administered nicotine in low doses indirectly excites noradrenergic locus coeruleus (LC) neurons. In the present study this effect of nicotine was attenuated (to about 25% of control response) by injection of lidocaine into the nucleus paragigantocellularis (PGi) whereas injection into the nucleus prepositus hypoglossi (PrH) had no effect in this regard. Whereas the basal firing rate of LC neurons was not affected by lidocaine injection into the PGi, more than 50% of the LC neurons displayed increased firing rate following lidocaine injection into the PrH. It is suggested that the peripherally induced effect of nicotine on LC neurons is indirectly mediated via activation of the PGi.


Ultrasonographic evaluation using the internal echo in normal and cirrhotic livers: Comparison of accuracy of gray-scale and binary black-and-white images and their intraobserver reproducibility and interobserver agreement.
We attempt to determine the possibility of classifying normal and cirrhotic livers by their internal echo texture alone, without using such basic ultrasonographic information as shape and surface character of the liver. We also assessed intraobserver reproducibility and interobserver agreement obtained using this classification to ascertain the diagnostic usefulness of the method. In this evaluation, we used both regional magnified B-mode images and binary black-and-white images, both derived from conventional B-mode images obtained from 10 patients with normal livers and 10 with cirrhotic livers. These 20 echograms were randomly divided into two groups and evaluated independently on two occasions by 12 observers who used the unaided eye and took only internal echo texture into consideration. Accuracy in distinguishing between normal and cirrhotic livers ranged from 41.7 percent to 100 percent. The intraobserver correlation coefficient r1 between evaluations of the regional magnified B-mode images was 0.63, while that for the binary black-and-white images was 0.80. Agreement between the decisions of the 12 observers in the first and second evaluations of the binary black-and-white images showedk values between 0 and 1.0 for binary black-and-white images and between -0.32 and 0.29 for regional magnified B-mode images. Subjective evaluation of normal and cirrhotic livers based on internal echo texture alone was possible: intraobserver correlation was good; and unexpectedly, agreement with black-and-white images was greater than that with the regional magnified B-mode images.


Determination of labile trace metals with screen-printed electrode modified by a crown-ether based membrane.
In this work, we have undertaken the construction of a screen-printed electrode modified by a specific membrane to protect the working surface from interferences during the analysis of trace metals by anodic stripping voltammetry. Different crown-ethers selected for their metals affinity have been incorporated into a membrane then deposed on the working surface of the electrode. Each modified electrode has been first tested in an acidified KNO3 10(-1) mol L(-1) solution (pH 2) doped by free Cd2+ and Pb2+ ions. The response and selectivity of the modified electrodes have been investigated according to different parameters: (i) the substrates (commercial ink or carbon based homemade ink), (ii) the electrode support (polystyrene or transparency film) and (iii) crown-ethers nature (dibenzo-24-crown-8 and tetrathiacyclododecane 12-crown-4). The influence of the substrate on the response of the electrode is clearly demonstrated. Homemade ink appears as the most appropriate substrate to modify the working surface of the screen-printed electrode by a crown-ether based membrane. The effect of the composition of the membrane has been shown too. The best membrane developed showed a detection limit of 0.6 x 10(-8) mol L(-1) for Cd and 0.8 x 10(-8) mol L(-1) for Pb and a quantification limit of 10(-8) mol L(-1) for Cd and 2 x 10(-8) mol L(-1) for Pb. This method, which integrates the extraction, preconcentration and measurement, was successfully applied to environmental samples without pretreatment.


Assessment of hazardous impact of nickel oxide nanoparticles on biochemical and histological parameters of gills and liver tissues of Heteropneustes fossilis.
The aim of the present study was to assess the hazardous impact of nickel oxide nanoparticles (NiO NPs) on gills and liver of Heteropneustes fossilis. Fishes were treated with four concentrations of NiO NPs for a period of 14 days. Nickel accumulation, lipid peroxidation, antioxidant enzymes activities (superoxide dismutase, catalase, glutathione s transferase & glutathione reductase), liver enzymes activities (aspartate amino transferase, alanine transaminase, & alkaline phosphatase), Na+/K+ ATPase activity, FTIR, metallothionein content, ethoxyresorufin-o-deethylase activity, immunohistochemistry, histology and scanning electron microscopy were analyzed in both gills and liver tissues. Results revealed increased accumulation of nickel in both the tissues of exposed fishes. Lipid peroxidation and activities of different antioxidant enzymes increased (except superoxide dismutase) in both the tissues after exposure. Fluctuations in liver enzymes activities and variation in the activity of Na+/K+ ATPase were also observed. FTIR data revealed shift in peaks position in both the tissues. Level of metallothionein and its expression as well as activity of ethoxyresorufin-o-deethylase and expression of CYP1A also increased in both the target tissues of treated fishes. Furthermore, histological investigation and scanning electron microscopy showed structural damages in gills as well as liver tissues of exposed fishes. Our results suggest that NiO NPs cause deteriorating effects on the gill and liver tissues of fish, therefore effluents containing these nanoparticles should be treated before their release into water bodies.


Identifying children at high somatic risk (alpha 1 antitrypsin deficiency): possible long-term effects on parents' reproduction, marital status and social class level.
Neonatal identification of children at high somatic risk due to inherited alpha 1 antitrypsin deficiency (ATD) has been found to elicit a negative emotional reaction in a majority of the parents, at least initially. This sub-study was conducted to determine whether the identification and follow-up of the children's ATD had negatively influenced the families' reproduction, marital status and social class level (defined by parental occupation) during the 5 years following the identification of the children's ATD. No such negative effects were found in comparing these characteristics among 61 families with a child with ATD versus 183 control families living in the same area and having a child of the same sex and age. Unexpectedly, the ATD-children's families (fathers) had a significantly higher social class level, raising the question of a possible gene advantage associated with ATD.


Community outreach: an expanding role for hospitals.
Pressures for paediatric institutions to expand their traditional roles have come from changes in morbidity patterns, training requirements and community needs. Planning for new models of health care delivery has led to the development of the Community Outreach Program (COP), a hospital-based model which utilizes existing community resources to provide early intervention services, training in community paediatrics and integration of hospital and community-based health care. A process evaluation of the COP was performed after 18 months operation. Eighty-eight children were seen in a 7 week period, 20% with complex problems requiring further assessment and community consultation. Staff at the community agencies serviced considered the COP to be a major contributor to health care in their areas. Medical trainees developed new assessment techniques and management strategies for children with problems not previously encountered. It appears that the COP is a useful model for the delivery of health care, in particular to disadvantaged communities.


Diffusion-weighted MR study of femoral head avascular necrosis in severe acute respiratory syndrome patients.
To evaluate the apparent diffusion coefficient (ADC) of femoral head avascular necrosis (AVN) in severe acute respiratory syndrome (SARS). Seventy-nine SARS patients with hip pain underwent both conventional and diffusion-weighted MRI (b-value=0-1000 seconds/mm(2)). The abnormal regions on the diffusion-weighted images were outlined by using the conventional images as guides, and the ADCs were calculated. The ADC differences between normal and AVN femoral heads were compared. Of the 158 hips examined, 28 had AVN (11 with bilateral hip AVN, three with right hip AVN, and three with left hip AVN). The mean ADC was markedly greater in the AVN femoral head (1.66 x 10(-3) mm(2)/second+/-0.20) than in the normal femoral head (0.47 x 10(-3) mm(2)/second+/-0.082; P<0.0001). There was no overlap between the normal and AVN femoral heads. DWI can provide valuable information regarding the diffusion properties of femoral head AVN, and markedly increased diffusion was identified in AVN.


A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene.
We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.


Renal vascular response to interruption of the renin-angiotensin system in normal man.
We assessed the role of the renin-angiotensin system in the response of the renal circulation to restriction of sodium intake in 38 normal patients. Both saralasin (10 to 30 ng/kg/min), an angiotensin antagonist, and SQ 20881 (30 to 300microgram/kg), a converting enzyme inhibitor, induced a dose-related increase in renal blood flow (xenon 133 washout) only when the resin-angiotension system was activated by restriction of sodium intake to 10 MEq/day. Increasing doses of saralasin (100 to 1,000 ng/kg/min) reduced renal blood flow, presumably due to the angiotensin-like action of this partial agonist. The renal vascular response to SQ 20881 paralleled the endocrine response: An identical threshold dose (30 microgram/kg) increased renal blood flow and reduced plasma angiotensin II concentration, which fell despite a progressive rise of plasma renin activity. Plasma bradykinin concentration did not change in response to SQ 20881, which also blocks kininase II. Both agents also induced a small but consistent and statistically significant reduction in arterial blood pressure, which will be important in assessing the pathogenetic significance of a blood pressure reduction in patients with hypertension. This study indicates that angiotensin mediates the renal vascular response to restriction of salt intake in normal man and provides an approach to assessing the role played by angiotensin in the pathogenesis of functional renal disease.


Evaluation of force requirements during use of recycled plastic syringes.
Forces required to withdraw the piston in recycled syringes were investigated. New disposable syringes were used as a reference. The force required in withdrawal of the piston for recycled syringes was between 3 and 8 times that required for the reference syringes. Lubrication reduced the force for the recycled syringes substantially. A modification of syringe recycling protocol is suggested.


Classifying presence or absence of calcifications on mammography using generative contribution mapping.
The purpose of this study was to verify the efficacy of generative contribution mapping (GCM), an explainable deep learning model for images, in classifying the presence or absence of calcifications on mammography. The learning dataset consisted of 303 full-field digital mammography (FFDM) images labeled with microcalcifications obtained from the public INbreast database without extremely dense images. FFDM images were divided into calcification and non-calcification patch images using a sliding window method with 25% overlap. The patch images of the mediolateral oblique (MLO) and craniocaudal (CC) views were divided into a training set of 70%, a validation set of 10%, and a testing set of 20%. The classification performance of GCM classifiers was evaluated and compared with that of EfficientNet classifiers. Visualization maps of GCM highlighted regions of interest more clearly than EfficientNet's gradient-weighted class activation maps. The results showed that GCM classifiers yielded an accuracy of 0.92 (CC), 0.91 (MLO), and an area under the receiver operating characteristic curve of 0.92 (CC), 0.94 (MLO). In conclusion, GCM could accurately classify the presence or absence of calcifications on mammograms and explain intuitively reasonable grounds for their classification with visualization maps highlighting regions of interest.


Role of positions 9 and 10 in the endothelin molecule for biological activity and discrimination of receptor subtypes.
The importance of residues 9 and 10 in endothelin-1 was assessed by studying the responses of the guinea-pig ileum to [Ala9]endothelin-1 and [Ala10]endothelin-1. Both analogues induced relaxation followed by contraction. [Ala9]Endothelin-1 showed similar ED50 values and maximum response to those of endothelin-1, whereas [Ala10]endothelin-1 showed a larger ED50 value and was a partial agonist. Endothelin-1 and [Ala10]endothelin-1 induced similar degrees of tachyphylaxis, whereas [Ala9]endothelin-1 induced very little tachyphylaxis, indicating that Lys9 is important for inducing tachyphylaxis. Apamin inhibited the relaxation induced by endothelin-1 and [Ala9]endothelin-1 but not that induced by [Ala10]endothelin-1. BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu), a specific endothelin ETA receptor antagonist, inhibited [Ala9]endothelin-1-, but not [Ala10]endothelin-1-induced contraction. Cross-tachyphylaxis and additivity studies indicated that [Ala9]endothelin-1, like endothelin-1, acts at the endothelin ETA receptor, whereas [Ala10]endothelin-1 behaved as an endothelin ETB receptor agonist, like sarafotoxin S6c. Thus, the residue at position 10 plays a significant role in receptor activation and is a candidate for further exploration of receptor antagonism.


The course of asthma during pregnancy, post partum, and with successive pregnancies: a prospective analysis.
We studied 366 pregnancies in 330 prospectively managed women with asthma to determine the effect of pregnancy on asthma. Asthma activity was assessed by (1) daily symptom and medication diaries and (2) monthly auscultation and spirometry during pregnancy and for 3 months post partum. At 3 months post partum, subjects were asked to assess the overall course of their asthma during pregnancy compared to the usual course for them, and the course of their asthma during the 3 months post partum compared to the asthma during pregnancy. Asthma worsened during pregnancy in 35% of the women, improved in 28%, and was unchanged in 33%. Based on diary-card analysis, asthma was significantly less frequent and less severe during the last 4 weeks of pregnancy than during any other gestational interval. In women whose asthma improved during pregnancy, diary-card analysis revealed a gradual improvement with progressive pregnancy, whereas in women whose asthma worsened during pregnancy, there was an increase in asthma symptoms during 29 to 36 weeks gestation. During labor and delivery, asthma symptoms occurred in 10% of women with approximately equal proportions of these women receiving either no treatment or inhaled bronchodilators; only two subjects required intravenous aminophylline. During the 3 months post partum, asthma reverted toward its prepregnancy course in 73% of women. In 34 subjects prospectively studied for two successive pregnancies, there existed a significant concordance between the asthma course during the first and second pregnancies. The mechanistic and clinical implications of these findings are discussed.


How Do You Provide Humanistic Care During a Pandemic?
Because of the COVID-19 pandemic, we are at an unprecedented time in history. We practice at Monter Cancer Center in Lake Success, New York, which is part of Northwell Health, the largest health system in New York state, located in the initial epicenter of COVID-19 in the United States.


A Hands-On Guide to Generate Spatial Gene Expression Profiles by Integrating scRNA-seq and 3D-Reconstructed Microscope-Based Plant Structures.
Transcriptome profiles of individual cells in the plant are strongly dependent on their relative position. Cell differentiation is associated with tissue-specific transcriptomic changes. For that reason, it is important to study gene expression changes in a spatial context, and therefore to link those to potential morphological changes over developmental time. Even though great experimental advances have been made in recording spatial gene expression profiles, those attempts are limited in the plant field. New computational approaches attempt to solve this problem by integrating spatial expression profiles of few marker genes with single-cell/single-nuclei RNA-seq (scRNA-seq) methodologies. In this chapter, we provide a practical guide on how to predict gene expression patterns in a 3D plant structure by combining scRNA-seq data and 3D microscope-based reconstructed expression profiles of a small set of reference genes. We also show how to visualize these results.


Superior gluteal artery pseudoaneurysm after a gunshot wound to the buttock: A case.
Penetrating trauma to the buttock can rarely result into the development of a gluteal artery pseudoaneurysm. Here we present the case of a patient with a superior gluteal pseudoaneurysm after a gunshot wound to the left buttock. A 48-year-old male presented with fullness and tenderness at the left gluteal wound that resulted from a gunshot 18 days prior. At the time of initial trauma, imaging showed minimal extravasation of contrast at the left superior gluteal artery, but the bleeding stopped and patient was discharged. On his return, examination showed palpable fluctuance but no bleeding. A superior gluteal artery pseudoaneurysm was identified on CT scan. Patient also complained of intermittent subjective fever and new onset of SOB. CT chest demonstrated a pulmonary embolism at the right basilar segmental artery. Coil embolization was performed to treat the pseudoaneurysm and patient was subsequently started on anticoagulation therapy. Penetrating wounds to the buttock can result in associated vascular or visceral injuries. Pseudoaneurysms can develop days to years after the initial injury. On exam, presence of pain, swelling, tenderness, bleeding from wound, thrill, bruit or a pulsating mass should raise suspicion for pseudoaneurysm, which can be diagnosed on CT scan and treated with embolization. Proper management of traumatic wounds to the buttock with associated vascular injuries, with follow up protocols and patient education is necessary to prevent life-threatening complications such as hemorrhage from pseudoaneurysm.


X-ray diffraction and electron microscope study of osteons during calcification.
To obtain information on the changes in the inorganic bone fraction during calcification, low- and wide-angle X-ray diffraction techniques and electron microscopy have been applied to single osteon samples. The samples were cylindrically shaped and their axes corresponded to the axes of the Haversian canals. The selection was made according to the degree of calcification and the orientation of collagen bundles and inorganic particles. Osteons at both the initial and final stages of calcification were chosen. Arrangements of fiber bundles and inorganic particles in successive lamellae characteristic of three types of osteon were selected, that is, longitudinally structured osteons, transversely structured osteons, and alternately structured osteons. The results indicate that in osteonic lamellar bone there are two types of inorganic particles: (1) granules arranged in linear or needle-shapred entities with maximum width 40-45 A, which are regularly distributed at the level of the main band of the collagen fibrils where their maximum length reaches the length of the main band itself; that is , about 400 A; and (2) very long crystallites, with a diameter of 40-45 A, which grow with their crystallographic c-axis parallel to the collagen fibrils and cover much more than a major collagen period.


Effects of larval density on flight potential of the beet webworm, Loxostege sticticalis (Lepidoptera: Pyralidae).
Tethered-flight techniques were used to investigate the flight potential of 1-d-old adult beet webworm, Loxostege sticticalis L. (Lepidoptera: Pyralidae), reared at densities of1, 10, 20, 30, and 40 larvae per 650-ml jar. Larval density had a significant effect on the flight potential, including total flight duration, distance, average velocity, and longest flight duration. Adults reared at a density of 10 larvae per jar, and those reared in isolation displayed the greatest and poorest flight capacity,respectively, relative to the other density treatments. Larval density also significantly affected length of the preoviposition period. Females with longer preoviposition period usually showed greater flight potential, and preoviposition period was positively correlated with flight potential. Body weight, water content, and triglyceride content of the moths were significantly affected by larval density, whereas glycogen content was not. Triglyceride content of adults reared at the different larval densities corresponded to the observed differences inflight potential, whereas water content and body weight were not related to their flight potential. These results suggest that larval density exerts a significant influence on preoviposition period and triglyceride content, which in turn influence flight potential of adult L. sticticalis.


Certain biochemical changes in the ovary of a migratory bird, Calandrella acutirostris tibetana.
The changes in the ovarian cholesterol, glycogen and ascorbic acid of Bagheri, Calandrella acutirostris tibetana, during its non-breeding and breeding periods were studied. There was a significant increase in all the 3 biochemical constituents during the breeding period.


Interactions of the DNA intercalator acridine orange, with itself, with caffeine, and with double stranded DNA.
Caffeine (CAF) inhibits the intercalation of acridine orange (AO) into cellular DNA. Optical absorption and fluorescence spectroscopy were employed to determine the molecular interactions of AO with itself, with CAF, and with double stranded herring sperm DNA (dsDNA). AO dimerization was observed at concentrations >2 micromol. The sharp increase in fluorescence (lambda(em)=530 nm) at 5 micromol of AO was attributed to AO multimer formation. From 0.5 to 5.0 micromol, the AO self-association binding constant (K(assoc)) was determined to be 38620 mol(-1), however, the presence of 150 mmol NaCl increased K(assoc) to 118000 mol(-1) attributed to the charge neutralization. The K(assoc) for AO with CAF was confirmed to be 256 mol(-1). K(assoc) for the binding of AO with 20 micromol DNA ranged from, 32000 mol(-1) at 2 micromol AO, to approximately 3700 mol(-1) at 10 micromol AO, in the absence of NaCl. This AO concentration dependency of K(assoc) value with DNA was attributed to AO intercalation into dsDNA at high dsDNA/AO ratios, and electrostatic binding of AO to dsDNA at low AO ratios. The findings provide information used to explain fluorescence intensity values at lambda(em) at 530 nm from studies that combine AO, caffeine, and dsDNA.


[Problems posed by the adjusting of a dosage form of a drug for children].
The safe use of drugs for pediatric patients is based upon good conditions of administration, in order to ensure accuracy and reproducibility of the dose received. But dosage adjustment often needs also a transformation of the galenic form, and that involves many risks or error. Some solutions are proposed in order to standardize the methods of drug adjustment for pediatric use.


A multi-scale continuum model of skeletal muscle mechanics predicting force enhancement based on actin-titin interaction.
Although recent research emphasises the possible role of titin in skeletal muscle force enhancement, this property is commonly ignored in current computational models. This work presents the first biophysically based continuum-mechanical model of skeletal muscle that considers, in addition to actin-myosin interactions, force enhancement based on actin-titin interactions. During activation, titin attaches to actin filaments, which results in a significant reduction in titin's free molecular spring length and therefore results in increased titin forces during a subsequent stretch. The mechanical behaviour of titin is included on the microscopic half-sarcomere level of a multi-scale chemo-electro-mechanical muscle model, which is based on the classic sliding-filament and cross-bridge theories. In addition to titin stress contributions in the muscle fibre direction, the continuum-mechanical constitutive relation accounts for geometrically motivated, titin-induced stresses acting in the muscle's cross-fibre directions. Representative simulations of active stretches under maximal and submaximal activation levels predict realistic magnitudes of force enhancement in fibre direction. For example, stretching the model by 20 % from optimal length increased the isometric force at the target length by about 30 %. Predicted titin-induced stresses in the muscle's cross-fibre directions are rather insignificant. Including the presented development in future continuum-mechanical models of muscle function in dynamic situations will lead to more accurate model predictions during and after lengthening contractions.


Association of reduced carbon monoxide diffusing capacity with moderate or severe left ventricular diastolic dysfunction in obese persons.
To determine the association of reduced diffusing capacity of the lung for carbon monoxide (D(LCO)) with moderate or severe left ventricular diastolic dysfunction (LVDD) in obese persons. We investigated the association of D(LCO) with LVDD in 105 patients with a mean +/- SD body mass index of 49 +/- 5 kg/m2. An abnormal D(LCO) was < 80%. LVDD was investigated by Doppler and by tissue Doppler echocardiography. The Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether the D(LCO) was normal or abnormal. A university hospital. The 105 patients included 19 men and 86 women (mean age, 45 +/- 9 years). An abnormal D(LCO) was present in 62 of 105 patients (59%). Moderate or severe LVDD was present in 35 of 105 patients (33%). Moderate or severe LVDD was present in 25 of 62 patients (40%) with an abnormal D(LCO) and in 10 of 43 patients (23%) with a normal D(LCO) (p < 0.05). Obese patients with a decreased D(LCO) have an increased prevalence of moderate or severe LVDD.


MinR 10/20 system: Quantitative and reproducible cranial landmark setting method for MRI based on minimum initial reference points.
The international 10/20 system is not only a fundamental method for describing positioning for electroencephalography (EEG), but also provides intermediate cranial landmarks for the probabilistic spatial registration methods that use a reference-MRI database. However, the presence of the inion, one of the four initial reference landmarks of the international 10/20 system, is inconspicuous and can be difficult to locate on MRIs. The MinR 10/20 system utilizes only three initial reference points, the nasion (Nz) and the right and left preauricular points (AR and AL), but does not employ the inion (Iz). With the MinR 10/20 system, first the most posterior point on the occipital protuberance, IIz (Imitated Iz), is identified as an exploratory alternative to the Iz point. Next, the other landmarks are calculated according to the conventional international 10/20 system referring to these four reference points (Nz, AL, AR and IIz). Holistic tendencies for landmark position estimations on the heads and cortices in MNI space did not vary greatly between MinR and international 10/20 systems. A comparison of MinR and international 10/20 systems applied to seventeen adult head MRIs revealed little variance in holistic tendencies for landmark position estimations on head and cortex surfaces in the MNI coordinate system. Furthermore, variability was smaller with the MinR 10/20 system than with the conventional international 10/20 system. The MinR 10/20 system proved to be a practical alternative to the conventional international 10/20 system in modern computational spatial analysis for scalp-based brain mapping methods.


Antiprotozoal activity of Khaya anthotheca, (Welv.) C.D.C. a plant used by chimpanzees for self-medication.
Khaya species, endemic to Africa and Madagascar, continues to be valuable in indigenous traditional medicine. Their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. In the Budongo rain forest of Western Uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed. Extracts were prepared by sequential fractionation with solvents of increasing polarities and assayed using standard procedures. Bioassay guided purification of the petroleum ether extract by column chromatography yielded three pure limonoids, Grandifolione (1), 7-deacetylkhivorin (2) and 1,3-deacetyldeoxyhavenensin (3). The antitrypanosomal, antileishmanial and antiplasmodial activities of pure compounds (1) and (2) were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi trypomastigotes (Tulahuen C4), and axenic Leishmania donovani MHOMET-67/L82 and for cytotoxicity against L6 rat skeletal myoblast cells, in parallel with standard drugs. Of the four extracts tested, the petroleum ether extract showed activity against Plasmodium falciparum (IC50 0.955 μg/ml) and Trypanosoma brucei rhodesiense (IC50 5.72 μg/ml). The pure compounds (1) and (2) demonstrated activity against Plasmodium falciparum (KI strain) and marginal activities against Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The present study provides evidence justifying the use of Khaya preparations in traditional medicine to treat fevers and microbial infections. The observed antiprotozoal activity of grandifolione and 7-deacetylkhivorin from the seed of Khaya anthotheca further confirms the ethnomedicinal potential of this plant and supports the hypothesis that non-human hominids (chimpanzees and baboons) too, eat the bitter bark and seeds for self-medication and in general, the use of Khaya plant material for medication by humans in disease endemic tropical areas. The antiprotozoal activity of gradifolione, and, the antitrypanosomal and antileishmanial activities of 7-deacetylkhivorin are reported here for the first time.


Plant neurobiology: an integrated view of plant signaling.
Plant neurobiology is a newly focused field of plant biology research that aims to understand how plants process the information they obtain from their environment to develop, prosper and reproduce optimally. The behavior plants exhibit is coordinated across the whole organism by some form of integrated signaling, communication and response system. This system includes long-distance electrical signals, vesicle-mediated transport of auxin in specialized vascular tissues, and production of chemicals known to be neuronal in animals. Here we review how plant neurobiology is being directed toward discovering the mechanisms of signaling in whole plants, as well as among plants and their neighbors.


Effect of connective tissue grafting on buccal bone changes based on cone beam computed tomography scans in the esthetic zone of single immediate implants: A 1-year randomized controlled trial.
Connective tissue grafting has a beneficial effect on the peri-implant mucosa, but the effect of grafting the buccal mucosa on buccal bone thickness (BBT) has not been investigated, although BBT is proposed to be a key factor for the soft-tissue contour. The aim of this trial was to assess the outcome of a connective tissue graft (CTG) in the esthetic zone of single immediate implants on the change of BBT according to cone beam computed tomography (CBCT) scan analysis. In a 1-year randomized controlled trial, 60 patients received an immediately placed implant and provisionalization, either combined with CTG (test group) or without CTG (control group). CBCTs were taken preoperatively (Tpre ) and 1 year after definitive restoration (T2 ). Any change in BBT was assessed at different implant levels. Additionally, the change in mid-buccal mucosal level (MBML) and approximal marginal bone level were assessed. Fifty-five patients were available for statistical analysis (test group, n = 28; control group, n = 27). At T2 , the average change in BBT was significantly larger in the test group (-0.84 ± 0.61 mm) than in the control group (-0.46 ± 0.54 mm, P = 0.02). A MBML gain of 0.07 ± 0.85 mm in the test and a MBML loss -0.52 ± 1.16 mm in the control group was observed at T2 . Average loss of marginal bone was 0.05 ± 0.33 mm and 0.01 ± 0.38 mm, respectively. The application of CTG in the esthetic zone of immediately placed and provisionalized implants is accompanied with more loss of BBT, but at the same time better maintains the mid-buccal mucosal level.


Energy and nitrogen budgets for larval and aduit Paropsis charybdis Stål (Coleoptera: Chrysomelidae) feeding on Eucalyptus viminalis.
| (1) Paropsis charybdis, the Eucalyptus tortoise beetle, is a serious defoliator of several Eucalyptus species in New Zealand. A series of laboratory experiments demonstrated the growth characteristics of larvae and adults when feeding on E. viminalis at 20°C. These were used as the data bases for quantifying its trophic relationships in terms of dry matter, energy and nitrogen. (2) The four larval stages lasted 4.0, 2.5, 3.0 and 9.5 days. Growth was exponential until the second day of the fourth instar, when the superficially inactive prepupal stage began. The pupal stage lasted 9.5 days. Female beetles started to lay eggs 15 days (av.) after eclosion. (3) Larvae attained a mean maximum dry weight (dwt) of 53.29 mg. Reproductive females weighed 63.40 mg, and males 46.71 mg. (4) The guts and their contents contributed up to 50% of total larval dry weight and 15% of adult dry weight. (5) Studies of the trophic relationships of P. charybdis larvae were based upon budgets whereby consumption (C) equals the sum of production (P), respiretion (R) and egesta (FU). Production was divided into gut-free larval production (P L* ) and exuvia (P EX)+R+FUin J: 3,561.5 = (491.3+43.4) + 284.5 +2,574.9 in mgN: 4.001 = (2.078 + 0.200) +1.657 (no R term) . P = P L* + P EX The derived R term (R c), calculated as: R c = C - FU - (P = P L* + P EX) = 34.84 (6) Daily budgets of an average adult, where ΔP AD reflects the change in body weight and P R=reproductive production, were: C =(ΔP AD + P R) + R +FU in mg dwt: 27.36 = (ΔP +2.25) +R + 14.53 in J: 591.1 = ΔP + 65.4) + 82.0 +362.6 in mgN: 0368 = (ΔP AD + 0.252) + 0.285. The budget assumes that male P R is zero and includes a corrected R term whereby R C=1.43 R M. ΔP AD can be assumed to equal zero over a long term, although fluctuations were apparent during the experimental period. (7) The amount of leaf material removed but not eaten by larvae (NU) was 22.6 mg, 462.4 J or 0.526 mgN. Thus, the total material removed (MR = C +NU) was 194.3 mg, 3978.9 J or 4.527 mgN. NU per day for an average adult was 4.86 mg, 99.5 J or 0.113 mgN. Therefore adults removed 32.33 mg, 659.9 J or 0.751 mgN per day. (8) Ecological efficiencies (energy) of P. charybdis larvae (using P = P L* + P EX and A = assimilation + C - FU ) were: net ecological efficiency (P.A.-1)=56.8%, gross ecological efficiency (P.C-1)=15.2%, assimilation efficiency (A.C.-1)=26.8%, P.R.-1=121.5%. Adult efficiencies were: P. A.-1=28.6%, P.C.-1=11.1%, A.C.-1=38.7% and P.R.-1=55.7%. Efficiencies in terms of nitrogen were (larval data followed by adult data in parentheses): P.A.-1=97.2 (71.4)%, P.C.-1=56.9 (39.5)% and A.C.-1=58.6 (55.3)%. (9) Regressions were calculated to link larval length (1) or larval live weight (lwt) and the dry weight of leaf material removed from a tree by that individual so that these results can be readily applied to field studies: logMR = -2.042 + 3.418 log1 logMR = -0.728 + 1.023 log 1wt.


Androgen receptor (AR) gene CAG trinucleotide repeat length associated with body composition measures in non-syndromic obese, non-obese and Prader-Willi syndrome individuals.
Total body mass impacts reproductive health and infertility which has increased in the United States with rising rates of obesity. Overlapping genetic and environmental factors contribute to obesity and infertility including the androgen receptor (AR), a steroid hormone-activated transcription factor that is key in regulating androgen activity and sensitivity to sex hormones, weight and body composition in both males and females. The AR gene which is X-linked contains a polymorphic CAG trinucleotide repeat which varies in length and inversely correlated with gene expression. We examined the AR gene CAG repeat length and measures of weight and body mass index (BMI) in 27 non-syndromic obese and 33 lean controls and for the first time compared with 28 individuals with Prader-Willi syndrome (PWS), a rare obesity-related genetic disorder with natural sex hormone deficits to examine the effects of AR gene CAG repeat length on androgen-mediated response and obesity-related factors relevant to human infertility and reproduction. Mean CAG repeat length in base pairs (278 ± 7.9) did not significantly differ by subject group (F = 2.6, p = 0.08) but was strongly positively correlated with height standard deviation (SD) among males (r = 0.31, p < 0.05), mainly lean and obese, but not PWS (r = 0.02, p = 0.94). A negative correlation was observed for weight SD among females (r = -0.29, p < 0.04) when grouped together. The results were consistent with an androgen-mediated effect on height and weight negligible in PWS and supporting the role of sex hormones and AR gene interaction in obesity and infertility, both cardinal features of PWS. CAG repeat length of the AR gene is a marker for increased androgen sensitivity with shorter lengths predicting smaller stature in non-PWS adult males possibly due to accelerating fusion of bone growth plates and reducing the growth phase. Increased androgen effects from shorter CAG repeat lengths in non-PWS females could impact pregnancy-related weight gain and pregnancy outcomes.


Tissue plasminogen activator, plasminogen activator inhibitor-1 and von Willebrand factor in rheumatoid arthritis.
Tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF), all of endothelial origin and active in the haemostasis, were analysed in 74 patients with rheumatoid arthritis. The concentrations were related to extra-articular disease and to the incidence of thromboembolic events (TE) registered in a 2-year follow-up period. Patients with extra-articular disease had a significant increase in PAI-1 activity and reduced tPA release in the venous occlusion test. von Willebrand factor, PAI-1 and also haptoglobin and triglycerides were significantly increased in the group of patients who later suffered from TE. In a multiple regression model, in which cholesterol, triglycerides and lipoprotein (a) showed significant association with TE, vWF had the strongest additive explanatory value. No distinct acute phase pattern of PAI-1 was found in any patient subgroup.


Reliability of two methods for identifying the timing of medium latency responses in subjects with and without chronic ankle instability.
This study aims to: (1) to compare 2 methods of assessing the timing of medium latency responses (MLR), in regard to intrasession reliability and mean values, in subjects with and without chronic ankle instability (CAI), and (2) to analyze the influence of CAI in timing of MLR and in its reliability. Thirty six athletes with (16) and without (20) CAI participated. Bilateral electromyography of peroneus longus (PL), peroneus brevis (PB), tibialis anterior (TA) and soleus (SOL) muscles was collected during a unilateral sudden inversion perturbation to assess the timing of MLR onset, in both standing and perturbed positions, through a baseline-based method and a peak-response-based method. The group without CAI presented higher relative reliability of SOL and peroneal muscles MLR with the peak response-based method than with the baseline-based method. Compared with the group without CAI and in both methods, the group with CAI presented a delayed and less reliable TA MLR, as well decreased coefficient variation of PL MLR in the uninjured limb. In conclusion, regardless of the method subjects with CAI present delayed and less reliable TA MLR while in subjects without CAI the peak response-based method provides higher reliability.


Climate change mitigation and improvement of water quality from the restoration of a subtropical coastal wetland.
Coastal wetland restoration is an important activity to achieve greenhouse gas (GHG) reduction targets, improve water quality, and reach the Sustainable Development Goals. However, many uncertainties remain in connection with achieving, measuring, and reporting success from coastal wetland restoration. We measured levels of carbon (C) abatement and nitrogen (N) removal potential of restored coastal wetlands in subtropical Queensland, Australia. The site was originally a supratidal forest composed of Melaleuca spp. that was cleared and drained in the 1990s for sugarcane production. In 2010, tidal inundation was reinstated, and a mosaic of coastal vegetation (saltmarshes, mangroves, and supratidal forests) emerged. We measured soil GHG fluxes (CH4 , N2 O, CO2 ) and sequestration of organic C in the trees and soil to estimate the net C abatement associated with the reference, converted, and restored sites. To assess the influence of restoration on water quality improvement, we measured denitrification and soil N accumulation. We calculated C abatement of 18.5 Mg CO2-eq ha-1 year-1 when sugarcane land transitioned to supratidal forests, 11.0 Mg CO2-eq ha-1 year-1 when the land transitioned to mangroves, and 6.2 Mg CO2-eq ha-1 year-1 when the land transitioned to saltmarshes. The C abatement was due to tree growth, soil accumulation, and reduced N2 O emissions due to the cessation of fertilization. Carbon abatement was still positive, even accounting for CH4 emissions, which increased in the wetlands due to flooding and N2 O production due to enhanced levels of denitrification. Coastal wetland restoration in this subtropical setting effectively reduces CO2 emissions while providing additional cobenefits, notably water quality improvement.


The width of a gastric tube has no impact on outcome after esophagectomy.
We evaluated the impact of the size of gastric tubes on tissue blood flow of the anastomotic site, the frequency of leakage and the postoperative nutritional status. Forty-four patients were randomly allocated to either reconstruction using subtotal stomach (n = 22) or to reconstruction using slender gastric tube (n = 22) after esophagectomy. The tissue blood flow at the anastomotic site was measured. The postoperative nutritional status of 17 patients without recurrence was examined. Possible correlations between the type of esophageal substitute and the tendency to leakage as well as postoperative nutritional status were examined. There was no significant difference in the tissue blood and the frequency of leakage between the types of gastric tubes. There was no significant difference noted between the two in the postoperative nutritional status at 6 and 12 months after operation. The width of gastric tube has no impact on tissue blood flow, the frequency of leakage, and the postoperative nutritional status after esophagectomy.


Pixel-based criteria-oriented analysis of time-lapse Ca2+-fluorescence images.
Since its inception, the analysis of time-lapse video-images acquired during Ca2+ imaging experiments using fluorescence microscopy has been progressively optimized for achieving a high temporal resolution. In contrast, the spatial resolution of the acquired images is often compromised during analysis to varying degrees by the need to draw regions of interest (ROI). We developed a strategy to analyze images at the acquired spatial resolution-pixel-by-pixel, grouping all pixels based on criteria of interest (COI) in regard to their associated fluorescence values over time and visualizing the distributions of the pixel-groups detected in a pseudo-colored map. We applied this pixel-based COI-strategy to the analysis of relative intracellular free calcium levels (Ca(i)(2+)) in attached cultured embryonic hippocampal cells under baseline and experimental conditions designed to evaluate the contribution of extracellular Ca2+ (Ca(e)(2+)) to baseline Ca(i)(2+) levels. We discovered distinct groups of Ca(e)(2+)-dependent Ca(i)(2+) regulation patterns emergent during the earliest phases of hippocampal cell differentiation, which were not limited to inter-cell differences. Thus, pixel-based COI-analysis of time-lapse images can be used to disclose distinct patterns of Ca(e)(2+)-dependent Ca(i)(2+) levels and their corresponding subcellular distributions in developing hippocampal cells. Such a strategy should be useful in studying the emergence and distribution of Ca(i)(2+) signaling at subcellular levels of resolution using fluorescence microscopy.


Chemotherapeutic agents do not interact with neurotransmitter receptors.
The interactions of cisplatin, 5-fluorouracil, doxorubicin, mitomycin, carmustine (BCNU), cyclophosphamide, methotrexate and thio-TEPA were assessed at three neurotransmitter receptor binding sites. Each drug was inactive at concentrations as high as 10(-4) M in displacing the specific binding of 3H-spiperone to dopamine D2, 3H-pyrilamine to histamine H1, and 3H-quinuclidinyl benzilate to muscarinic cholinergic receptors. These data suggest that chemotherapy-induced nausea and vomiting are not due to interactions with neurotransmitter receptors.


Sex, war, and disease: the role of parasite infection on weapon development and mating success in a horned beetle (Gnatocerus cornutus).
While parasites and immunity are widely believed to play important roles in the evolution of male ornaments, their potential influence on systems where male weaponry is the object of sexual selection is poorly understood. We experimentally infect larval broad-horned flour beetles with a tapeworm and study the consequent effects on: 1) adult male morphology 2) male-male contests for mating opportunities, and 3) induction of the innate immune system. We find that infection significantly reduces adult male size in ways that are expected to reduce mating opportunities in nature. The sum of our morphological, competition, and immunological data indicate that during a life history stage where no new resources are acquired, males allocate their finite resources in a way that increases future mating potential.


Confirmation of lens hydration by Raman spectroscopy.
Lens hydration was monitored by laser Raman spectroscopy in WBN/Kob rats which form spontaneous diabetes at about 1 yr of age and develop cataracts approximately 6 months after the onset of diabetes. Lens hydration in response to chronic hyperglycemic stress in these rats appeared predominantly in the cortical region while the hydration state in the nuclear region was fairly preserved. The 9-month treatment of similarly diabetic rats with the aldose reductase inhibitor Ponalrestat sufficiently suppressed lens hydration in the cortical and nuclear regions.


The use of zeta potential as a tool to study phase transitions in binary phosphatidylcholines mixtures.
Temperature dependence of the zeta potential (ZP) is proposed as a tool to analyze the thermotropic behavior of unilamellar liposomes prepared from binary mixtures of phosphatidylcholines in the absence or presence of ions in aqueous suspensions. Since the lipid phase transition influences the surface potential of the liposome reflecting a sharp change in the ZP during the transition, it is proposed as a screening method for transition temperatures in complex systems, given its high sensitivity and small amount of sample required, that is, 70% less than that required in the use of conventional calorimeters. The sensitivity is also reflected in the pre-transition detection in the presence of ions. Plots of phase boundaries for these mixed-lipid vesicles were constructed by plotting the delimiting temperatures of both main phase transition and pre-transition vs. the lipid composition of the vesicle. Differential scanning calorimetry (DSC) studies, although subject to uncertainties in interpretation due to broad bands in lipid mixtures, allowed the validation of the temperature dependence of the ZP method for determining the phase transition and pre-transition temperatures. The system chosen was dipalmitoylphosphatidylcholine/dimyristoyl phosphatidylcholine (DMPC/DPPC), the most common combination in biological membranes. This work may be considered as a starting point for further research into more complex lipid mixtures with functional biological importance.


Age-related changes of fibroblast density in the human periodontal ligament.
Recently, research has focused intensely on age-related tissue changes, not only in the field of dermatology but also in dental sciences. Although many new insights into age-related morphological, ultrastructural and biochemical changes in the periodontal ligament tissue have been gained, the basic question of whether there is a quantitative change in cell number remains unanswered or, at least to date, unpublished. Thus, the aim of this study was to detect age-related changes of the periodontal ligament regarding fibroblast density. 33 lateral tooth-bearing segments of the maxilla were obtained from deceased human individuals of different age, ranging from 7 to 63 years. The buccal segment of the periodontal ligament of the mesiobuccal root of the first maxillary molar was evaluated histomorphometrically to obtain the fibroblast density. The results clearly indicate a steady and statistically significant decline of fibroblast number with age. It may be concluded that fibroblast density in the physiological human periodontal ligament tissue decreases with age, thus causing an initial delay in physiological, pathological or externally induced processes that require remodeling of the periodontal ligament, e.g. traumatic occlusion or orthodontic tooth movement. It may be assumed that an orthodontic tooth movement in elderly patients requires more time in the initial treatment phase and should be done with lighter forces.


Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders.
Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. • MRS-detected brain tissue lactate levels can be quantified. • MRS lactate and lactate/Cr are increased in children with mitochondrial disease. • CSF lactate is less suitable as marker of mitochondrial disease.


Congestive heart failure.
Congestive heart failure in adults should be conceptualized and dealt with as a clinical syndrome. It is neither a diagnosis nor a disease as such. Patients with heart failure present with clusters of symptoms that define sets of systemic congestion, pulmonary congestion, and inadequate cardiac output. Some have potentially correctable anatomic or metabolic defects, others have myocardial failure, and some have both as underlying causes of the syndrome. A careful analysis of the symptom clusters may provide important clues to the underlying etiologic diagnosis, which should be established before initiating therapy for heart failure.


Kinome-wide shRNA screen identifies the receptor tyrosine kinase AXL as a key regulator for mesenchymal glioblastoma stem-like cells.
Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified: mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers.


Child care and family processes: Bi-directional relations between child care quality, home environments, and maternal depression.
The current study examined whether within-family changes in child care quality and quantity predicted subsequent changes in home environment quality and maternal depression across early childhood (6 to 54 months of age). Data were drawn from the NICHD Study of Early Child Care and Youth Development (n = 1239; 77% White; 48% female; data collection from 1991 to 1996), and were analyzed using Random Intercept Cross-Lagged Panel Models. Within-family increases in child care quality predicted modest increases in home environment quality (β = .13-.17). These effects were most robust from child age 6 to 15 months. Increases in child care quality produced small, statistically non-significant, reductions in depression. Time-specific increases in child care quantity were not consistently predictive of either outcome.


Folk classification of wild mushrooms from San Isidro Buensuceso, Tlaxcala, Central Mexico.
An ethnomycological study was conducted to describe the fungus concept and the traditional fungus classification system for the Nahuas of San Isidro Buensuceso, in central Mexico. The study which provides information on the co-existence of various forms of classification, based on both cultural and biological characteristics. The research included conducting community interviews and forest forays in the company of mushroom pickers. The triad technique, pile sorting, and fresh mushroom sampling methods were used. Traditional names were analyzed to describe the Nahua classification system for fungi. The triad technique with non-utilitarian stimuli allowed the fungi to be identified as an independent group of plants and animals. The Nahua people of San Isidro classify fungi primarily based on their use, where they grow, and by humoral characteristics. The analysis of the names revealed a classification based on the criteria proposed by Brent Berlin. This study identified the detailed knowledge of fungi in this Nahua community. The criteria used for the recognition of the species are very reliable, since they use organoleptic, ecological, phenological, and morphological characteristics.


The behavioral effects of lesions of the septum: a review.
Many investigations have been conducted in an effort to deduce the nature of septal function. This paper is an overview of the work done by several researchers in their attempt to find the possible connections between overt behaviors and septal structures in the rat.


Single acetylcholine channel currents in sympathetic neurons.
Single acetylcholine (ACh) channel currents were studied by the gigaohm patch-clamp technique in cultured sympathetic neurons of the bullfrog, Rana catesbeiana. Recordings were made at 22 degrees C on cell-attached and excised membrane patches. When ACh (0.5-1 microM) was present in the pipette, a single class of inward currents was observed with a chord conductance of 30 pS and a reversal potential of -2 mV. The mean channel open time was 11.6 ms at -65 mV and showed little or no voltage-dependence over the range -85 to -45 mV. These channels appear to mediate the fast nicotinic excitatory postsynaptic current.


Geographic study of mortality due to mesothelioma in Peru and its evolution.
Peru has a public health problem because of asbestos imports. We analyzed the mortality trends for mesothelioma in Peru and its provinces from 2005 to 2014 and estimated their relationship with the amount of asbestos imported previously. We computed age-standardized mortality rates (ASMRs) per 100,000 population (direct method and SEGI world standard population reference), and the standardized mortality ratio (SMR). The relationship between the amount of asbestos imported annually along the period 1965-2010 and the number of mesothelioma deaths per year from 2005 to 2014 was estimated by log-linear Poisson regression models and Pearson correlation calculations. After correcting the number of deaths, Peru registered 428 cases (or 430 when corrected cases are rounded by sex) between 2005 and 2014. The highest ASMRs were in Arequipa and Callao (range: 0.40-0.41/100,000 population), followed by Huancavelica (0.36/100,000 population). This translates into approximately one death per each 68-111 of asbestos tons imported. The latency period for the higher level of positive correlation found was 8 years (r = 0.8). Male female sex ratio was lower in provinces such as Junin and Hunacavelica with geological asbestos risk. Two patterns of mesothelioma risk have been detected, occupational and environmental. During the 2002-2006 years, Peru increased the asbestos use. If crocidolite imports were also increased, this could be behind the 8 years latency period detected. Peru should boost strategies towards the total ban of all forms of asbestos.


Discovery of 1-(5-(1H-benzo[d]imidazole-2-yl)-2,4-dimethyl-1H-pyrrol-3-yl)ethan-1-one derivatives as novel and potent bromodomain and extra-terminal (BET) inhibitors with anticancer efficacy.
As epigenetic readers, bromodomain and extra-terminal domain (BET) family proteins bind to acetylated-lysine residues in histones and recruit protein complexes to promote transcription initiation and elongation. Inhibition of BET bromodomains by small molecule inhibitors has emerged as a promising therapeutic strategy for cancer. Herein, we describe our efforts toward the discovery of a novel series of 1-(5-(1H-benzo[d]imidazole-2-yl)-2,4-dimethyl-1H-pyrrol-3-yl)ethan-1-one derivatives as BET inhibitors. Intensive structural modifications led to the identification of compound 35f as the most active inhibitor of BET BRD4 with selectivity against BET family proteins. Further biological studies revealed that compound 35f can arrest the cell cycle in G0/G1 phase and induce apoptosis via decreasing the expression of c-Myc and other proteins related to cell cycle and apoptosis. More importantly, compound 35f showed favorable pharmacokinetic properties and antitumor efficacy in MV4-11 mouse xenograft model with acceptable tolerability. These results indicated that BET inhibitors could be potentially used to treat hematologic malignancies and some solid tumors.


Improved hearing with cochlear implantation in Fabry's disease.
To describe our center's experience with cochlear implantation in patients suffering from Fabry's disease, an inherited mutation resulting in an alpha-galactosidase A enzyme deficiency. Case report of two patients aged 49 and 59 at implant, with genetically confirmed Fabry's disease and progressive hearing loss. Surgical implantation of Clarion (Advanced Bionics) and Nucleus Freedom (Cochlear) cochlear implants. Cochlear implantation improves hearing discrimination by 60 points on the HINT scale. This suggests that cochlear implantation is a safe and effective intervention that improves hearing discrimination in patients suffering from Fabry's disease.


Exact stochastic mean-field approach to the fermionic many-body problem.
We investigate a reformulation of the dynamics of interacting fermion systems in terms of a stochastic extension of time-dependent Hartree-Fock equations. From a path-integral representation of the evolution operator, we show that the exact N-body state can be interpreted as a coherent average over Slater determinants evolving in a random mean-field. The imaginary time propagation is also presented and gives a similar scheme which converges to the exact ground state. In addition, the growth of statistical errors is examined to show the stability of this stochastic formulation.


HPLC-PDA-MS/MS as a strategy to characterize and quantify natural pigments from microalgae.
Interest in pigment composition of microalgae species is growing as new natural pigments sources are being sought. However, we still have a limited number of species of microalgae exploited to obtain these compounds. Considering these facts, the detailed composition of carotenoids and chlorophylls of two species of green microalgae (Chlorella sorokiniana and Scenedesmus bijuga) were determined for the first time by high-performance liquid chromatography coupled to diode array and mass spectrometry detectors (HPLC-PDA-MS/MS). A total of 17 different carotenoids were separated in all the extracts. Most of the carotenoids present in the two microalgae species are xanthophylls. C. sorokiniana presented 11 carotenoids (1408.46 μg g-1), and S. bijuga showed 16 carotenoids (1195.75 μg g-1). The main carotenoids detected in the two microalgae were all-trans-lutein and all-trans-β-carotene. All-trans-lutein was substantially higher in C. sorokiniana (59.01%), whereas all-trans-β-carotene was detected in higher quantitative values in S. bijuga (13.88%). Seven chlorophyll compounds were identified in both strains with different proportions in each species. Concentrations of chlorophyll representing 7.6% and 10.2% of the composition of the compounds present in the biomass of C. sorokiniana and S. bijuga, respectively. Relevant chlorophyll compounds are reported for the first time in these strains. The data obtained provide significant insights for microalgae pigment composition databases.


Assessment of percent positive agreement between fluorescent marker and ATPase for environmental cleaning monitoring during sequential application in an intensive care unit.
Terminal room cleaning is critical in preventing pathogen transmission; however, the optimal cleaning effectiveness assessment modality is still being investigated. We sequentially compared cleanliness assessment agreement between a fluorescent marker and an adenosine triphosphate bioluminescence method, finding no significant differences between modalities.


The efficacy and safety of epidural dexmedetomidine and clonidine with bupivacaine in patients undergoing lower limb orthopedic surgeries.
Alpha (α-2) adrenergic agonists have both analgesic and sedative properties when used as an adjuvant in regional anesthesia. A prospective randomized double-blind study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to bupivacaine with special emphasis on their quality of analgesia, sedation and the ability to provide the smooth intra-operative and postoperative course. The study was conducted in prospective, randomized and double-blind manner. It included 60 American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under epidural anesthesia. Patients were randomly divided into Group A receiving 0.5% isobaric bupivacaine 15 ml with dexmedetomidine 1 μg/kg and Group B receiving 0.5% isobaric bupivacaine 15 ml with clonidine 2 μg/kg epidurally. Onset and duration of sensory and motor blocks, duration of analgesia, sedation, and adverse effects were assessed. Demographic data, surgical characteristics cardio-respiratory parameters, side-effect profile were comparable and statistically not significant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant. The onset times for sensory and motor blocks were significantly shorter in Group A as compared to Group B. The duration of analgesia and motor block was significantly longer in A Group as compared to Group B. Dexmedetomidine is a superior neuraxial adjuvant to bupivacaine when compared to clonidine for early onset of analgesia, superior intra-operative analgesia, stable cardio-respiratory parameters, prolonged postoperative analgesia and providing patient comfort.


The prevalence and clustering of alcohol consumption, gambling, smoking, and excess weight in an English adult population.
The aim of this study was to examine the prevalence and clustering of four health risks (increasing-/higher-risk drinking, current smoking, overweight/obesity, and at-risk gambling), and to examine variation across sociodemographic groups in the English adult population. We analysed data from the 2012, 2015, 2016, and 2018 Health Survey for England (n = 20,698). Prevalence odds ratios (POR) were calculated to examine the clustering of risks. We undertook a multinomial multilevel regression model to examine sociodemographic variation in the clustering of health risks. Overall, 23.8% of the adult English population had two or more co-occurring health risks. The most prevalent was increasing-/higher-risk drinking and overweight/obesity (17.2%). Alcohol consumption and smoking were strongly clustered, particularly higher-risk drinking and smoking (POR = 2.68; 95% CI = 2.31, 3.11; prevalence = 1.7%). Higher-risk drinking and at-risk gambling were also clustered (POR = 2.66; 95% CI = 1.76, 4.01), albeit with a very low prevalence (0.2%). Prevalence of multiple risks was higher among men for all risk combinations except smoking and obesity. The odds of multiple risks were highest for men and women aged 35-64 years. Unemployed men and women with lower educational qualifications had a higher odds of multiple risks. The relationship between deprivation and multiple risks depended on the definition of multiple risks, with the clearest socioeconomic gradients seen for the highest risk health behaviours. An understanding of the prevalence, clustering, and risk factors for multiple health risks can help inform effective prevention and treatment approaches and may support the design and use of multiple behaviour change interventions.


Evidence for the release of newly acquired ascorbate and alpha-aminoisobutyric acid from the cytosol of adrenomedullary chromaffin cells through specific transporter mechanisms.
Primary cultures of bovine adrenomedullary cells actively take up ascorbic acid and alpha-aminoisobutyric acid (AIB). Following a brief incubation with L-[14C] ascorbic acid and alpha-[methyl-3H]aminoisobutyric acid, cells stimulated with the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide or by membrane depolarization with high [K+] or veratridine released newly acquired ascorbic acid (NA-ascorbate) and AIB. NA-ascorbate and endogenous catecholamines are differentially released under a variety of conditions suggesting that release of both substances cannot originate from the same subcellular compartment. In contrast, the release profile for NA-ascorbate and AIB, a putative cytosolic marker, suggest that both of these molecules are released from a cytosolic compartment. Cells permeabilized with the detergent digitonin release catecholamines only in the presence of external Ca2+, whereas release of NA-ascorbate and AIB is Ca2+-independent and time- and detergent concentration-dependent. If the osmolality of the external medium is made either hyper- or hypoosmotic, 1,1-dimethyl-4-phenylpiperazinium iodide-induced release of endogenous catecholamines is inhibited. Release of NA-ascorbate and AIB, however, is progressively inhibited with increasing osmolality and enhanced with decreasing osmolality. Furthermore, differential release of NA-ascorbate and AIB as compared to soluble acetylcholinesterase, which is apparently released form the cisternae of the endoplasmic reticulum, was also observed. To determine the mechanism by which NA-ascorbate and AIB are released from the cell, the requirements for their maximal release were investigated. Release of NA-ascorbate and AIB was sensitive to inhibitors (both metabolic and transport) and to changes in the external ionic environment. The metabolic inhibitors carbonyl cyanide p-trifluoromethoxyphenylhydrazone and KCN (when incubated simultaneously with 2-deoxyglucose) inhibited NA-ascorbate and AIB release by greater than 75%. In contrast, the Na+-K+-ATPase inhibitor ouabain enhanced veratridine-induced release of NA-ascorbate by nearly 100% and had an even greater effect on AIB release. Changes in the external ionic environment (i.e. Na+ and/or Cl- substitution) inhibited both NA-ascorbate and AIB release to varying degrees. Substitution of Cl- by various anions inhibited NA-ascorbate and AIB release to a much greater degree than endogenous catecholamine release. Complete substitution of NaCl with sucrose inhibited release of NA-ascorbate and AIB release by greater than 80%, while Na+ substituted with Li+ inhibited release of all three molecules by about 50%.(ABSTRACT TRUNCATED AT 400 WORDS)


TORCing up metabolic control in the brain.
Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.


Can handling a weapon make soldiers more unstable?
Gait stability in soldiers can be affected by task constraints that may lead to injuries. This study determined the effects of weapon handling and speed on gait stability in seventeen soldiers walking on a treadmill with and without a replica weapon at self-selected (SS), 3.5 km·h-1, 5.5 km·h-1, and 6.5 km·h-1 while carrying a 23-kg load. Local dynamic stability was measured using accelerometry at the sacrum (LDESAC) and sternum (LDESTR). No significant weapon and speed interaction were found. A significant effect of speed for the LDESAC, and a significant effect of speed and weapon for the LDESTR were found. Per plane analyses showed that the weapon effect was consistent across all directions for the LDESTR but not for LDESAC. Weapon handling increased trunk but did not affect pelvis stability. Speed decreased stability when walking slower than SS and increased when faster. These findings can inform injury prevention strategies in the military. Practitioner summary: We determined the effects of two constraints in soldier's walking stability, weapon handling and speed, measured at the trunk and sacrum. No constraints interactions were found, however, lower stability when walking slow and greater stability with the weapon at the trunk can inform preventive strategies in military training.


Thymoma: a continuing survey at the Massachusetts General Hospital.
An analysis is presented of the treatment of 103 patients with thymoma, 56 with myasthenia gravis and 47 without. In a 1966 report on the first 63 patients, it was stated that the presence of myasthenia and the finding of local tumor invasion at operation were ominous prognostic indicators. The augmented series suggests that myasthenia no longer carries this stigma, possibly because of improved methods in its management in patients who have undergone operation.


Methodological aspects in the assessment of severity of depression by the Hamilton Depression Scale.
Observer-rating scales are used for the evaluation of drug trials in depression. One of the most widely used depression rating scales is still the Hamilton Depression Scale (HAMD), which was developed at the time when the first antidepressants were becoming available. Due to its construction it seems to have a specific focus on drug effects of classical antidepressants. As a result of different methodological analyses such as principal component analysis, the Rasch model and facet analysis, a differentiation between core symptoms reflecting the severity of depression and additional symptoms describing other aspects of the symptomatology of depression seems meaningful. The use of the HAMD 6-item score, described primarily by Bech, as the main efficacy criterion in antidepressant drug trials gives a fair estimation of drug-induced changes of severity of depression and avoids bias such as the well-known bias of the HAMD total score in favour of tricyclic antidepressants. This is demonstrated by the evaluation of two sertraline-amitriptyline comparative studies.


Chimeric virus-like particles elicit protective immunity against serotype O foot-and-mouth disease virus in guinea pigs.
Foot-and-mouth disease (FMD) is an acute and highly contagious disease caused by foot-and-mouth disease virus (FMDV) that can affect cloven-hoofed animal species, leading to severe economic losses worldwide. Therefore, the development of a safe and effective new vaccine to prevent and control FMD is both urgent and necessary. In this study, we developed a chimeric virus-like particle (VLP) vaccine candidate for serotype O FMDV and evaluated its protective immunity in guinea pigs. Chimeric VLPs were formed by the antigenic structural protein VP1 from serotype O and segments of the viral capsid proteins (VP2, VP3, and VP4) from serotype A. The chimeric VLPs elicited significant humoral and cellular immune responses with a higher level of anti-FMDV antibodies and cytokines than the control group. Furthermore, four of the five guinea pigs vaccinated with the chimeric VLPs were completely protected against challenge with 100 50% guinea pig infectious doses (GPID50) of the virulent FMDV strain O/MAY98. These data suggest that chimeric VLPs are potential candidates for the development of new vaccines against FMDV.


The Long-Term Effectiveness and Cost Effectiveness of Organized versus Opportunistic Screening for Breast Cancer in Austria.
In 2014, Austrian health authorities implemented an organized breast cancer screening program. Until then, there has been a long-standing tradition of opportunistic screening. To evaluate the cost-effectiveness of organized screening compared with opportunistic screening, as well as to identify factors influencing the clinical and economic outcomes. We developed and validated an individual-level state-transition model and assessed the health outcomes and costs of organized and opportunistic screening for 40-year-old asymptomatic women. The base-case analysis compared a scenario involving organized biennial screening with a scenario reflecting opportunistic screening practice for an average-risk woman aged 45 to 69 years. We applied an annual discount rate of 3% and estimated the incremental cost-effectiveness ratio in terms of the cost (2012 euros) per life-year gained (LYG) from a health care perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. Compared with opportunistic screening, an organized program yielded on average additional 0.0118 undiscounted life-years (i.e., 4.3 days) and cost savings of €41 per woman. In the base-case analysis, the incremental cost-effectiveness ratio of organized screening was approximately €20,000 per LYG compared with no screening. Assuming a willingness-to-pay threshold of €50,000 per LYG, there was a 70% probability that organized screening would be considered cost-effective. The attendance rate, but not the test accuracy of mammography, was an influential factor for the cost-effectiveness. The decision to adopt organized screening is likely an efficient use of limited health care resources in Austria.


Effect of transient breathing cycle on the deposition of micro and nanoparticles on respiratory walls.
From various perspectives (e.g. inhalation exposure and drug delivery), it is important to provide insights into the behavior of inhaled particles in the human respiratory system. Although most of the experimental and numerical studies have relied on an assumption of steady inhalation, the transient breathing profile is a key factor in particle deposition in the respiratory tract. In this study, particle transportation and deposition were predicted in a realistic human airway model during a breathing cycle and the effects of steady-state and transient flows on the deposition fraction were observed using computational fluid dynamics. Two transient breathing cycles with different respiratory durations were considered to evaluate the effects of respiration duration on particle transport and deposition characteristics. Two types of steady breathing conditions with corresponding steady-state respiratory volumes were reproduced. The Lagrangian discrete phase model approach was used to investigate particle transportation and deposition under transient breathing conditions. Additionally, the Eulerian approach was used to analyze the transport of nanoparticles in the gas phase. A total of >50,000 monodispersed particles with aerodynamic diameters ranging between 2 nm and 10 μm were selected for comprehensive deposition predictions for particle sizes ranging from the nano- to microscale. The predicted results were compared with the experimental data. The particle deposition fraction in the nasal cavity and tracheal regions showed differences between the steady and transient simulations. In addition, particle analysis under steady inhalation conditions cannot accurately predict particle transportation and deposition in the lower airway. Furthermore, the breathing cycle had a significant effect on the deposition fraction of the particles and the behavior of the inhaled particles. Transient simulation mimicking the breathing cycle was observed to be an important factor in accurately predicting the transportation and deposition of particles in the respiratory tract.


Pleiotropic roles of polyglycerolphosphate synthase of lipoteichoic acid in growth of Staphylococcus aureus cells.
Lipoteichoic acid (LTA) is one of two anionic polymers on the surface of the gram-positive bacterium Staphylococcus aureus. LTA is critical for the bacterium-host cell interaction and has recently been shown to be required for cell growth and division. To determine additional biological roles of LTA, we found it necessary to identify permissive conditions for the growth of an LTA-deficient mutant. We found that an LTA-deficient S. aureus Delta ltaS mutant could grow at 30 degrees C but not at 37 degrees C. Even at the permissive temperature, Delta ltaS mutant cells had aberrant cell division and separation, decreased autolysis, and reduced levels of peptidoglycan hydrolases. Upshift of Delta ltaS mutant cells to a nonpermissive temperature caused an inability to exclude Sytox green dye. A high-osmolarity growth medium remarkably rescued the colony-forming ability of the Delta ltaS mutant at 37 degrees C, indicating that LTA synthesis is required for growth under low-osmolarity conditions. In addition, the Delta ltaS mutation was found to be synthetically lethal with the Delta tagO mutation, which disrupts the synthesis of the other anionic polymer, wall teichoic acid (WTA), at 30 degrees C, suggesting that LTA and WTA compensate for one another in an essential function.


Inhibition of ROS production in peripheral blood mononuclear cells from type 2 diabetic patients by autologous plasma depends on Akt/PKB signaling pathway.
To compare the role of Akt/PKB signaling pathway in the modulation of reactive oxygen species (ROS) production by autologous plasma in peripheral blood mononuclear cells (PBMNC) from type 2 diabetic patients and healthy subjects. This study was approved by Santa Casa Ethical Committee and has included patients diagnosed with diabetes type 2 (DM2) and control group (non-diabetic) (ND). PBMNC were purified utilizing Ficoll-hypaque gradient. ROS was quantified by luminol-dependent chemiluminescence. The Akt/PKB phosphorylation was measured using a CASE kit. Statistical analyses were made with t Student test and chi-square (chi(2)). p<0.05 was considered significant. 12, 13-Phorbol dibutyrate (PDB) stimulated the production of higher levels of ROS in PBMNC from type 2 diabetic patients than that from healthy subjects. Autologous plasma, however, inhibited induced or not ROS production in PBMNC in both groups. The inhibition of PBMNC-ROS derived by autologous plasma from healthy subjects was higher than that from type 2 diabetic patients. Plasma phosphorylated (activated) Akt/PKB. The percentage of phosphorylation induced by autologous plasma in PBMNC from patients and healthy control were 14% and 93%, respectively. Inhibition of ROS production in PBMNC from DM2 were similar for PBMNC+plasma; PBMNC+Akti; and PBMNC+plasma+Akti. However, in ND control, plasma showed a higher ROS inhibition than Akti or plasma plus Akti. Our results suggest that the low antioxidant capacity observed in autologous plasma from DM2 patients in conjunction with the decreased activation of PKB may cause an imbalance in the oxidizing/reducing responses, possible inducing an oxidative stress state, which could be associated with tissular damage.


Is fat-free mass-based gentamicin dosing regimen preferable than whole-body weight in neonates?
Body fluid dynamics and renal maturation status vary during the neonatal period. We hypothesized that differences in peak and trough gentamicin concentrations could be expected. To predict the peak and trough gentamicin concentrations in critically ill neonates and to predict the changes in the predicted peak plasma concentrations of gentamicin following fat-free mass dosing. Critically ill neonates that received gentamicin and have gentamicin concentration measured were recruited. Fat mass was estimated using skinfold thicknesses. Changes in the peak plasma concentrations (Cmax) using whole-body weight (estimated using the current dosing regimen) and predicted concentrations following the fat-free mass-based dosing were the outcome measures. Eighty-nine critically ill neonates were recruited. Sub-therapeutic Cmax was estimated using the current dosing regimen in 32.6%, and 22.5% neonates following the first and second doses of gentamicin. Preterm neonates had significantly higher fat mass compared to term neonates. All except one had Cmax above 12 μg/ml after the first dose and all had after the second gentamicin dose following the predicted fat-free mass-based gentamicin dosing. The recommended doses are as follows: extreme preterm: 7.95 mg/kg every 48 h; very preterm: 7.30 mg/kg every 36-48 h; late preterm: 5.90 mg/kg every 36-48 h; and term neonates at 5.10 mg/kg every 24 h. Fat-free mass dosing may be considered for obtaining optimal therapeutic effects in the neonatal population.


Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.
We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials.


Cystathionine beta-Synthase in hypoxia and ischemia/reperfusion: A current overview.
Besides its presence in the liver, brain, pancreas, and kidney, Cystathionine beta-Synthase (CBS) is also found in many other tissues, where it acts through regulation of hydrogen sulfide (H2S) generation and homocysteine (Hcy) metabolism, to interact with other molecules during hypoxia and ischemia/reperfusion (I/R). Despite all the advances accumulated in decades of research on CBS, there are still controversies, and the role of CBS in many tissues during hypoxia and I/R is still unclear. Herein, we overviewed the expression level, the role, and the mechanism through which CBS interacts with other molecules during hypoxia and I/R processes in tissues of humans and other organisms. CBS appeared to be deregulated under hypoxia and I/R, after which it mostly conduces the reparation in the concerned tissue after damage; however, it has been described that CBS could also play pathological effects (exacerbating the damage). From all findings, it emerges that variations in CBS expression in these conditions depend on the organism, tissue, or subcellular localization, CBS could play both protective and pathological effects; and artificially controlling CBS expression may help to provide novel strategies for treatment or prevention of hypoxia and I/R -related injury.


Cervical adenocarcinoma: tumor implantation in the episiotomy sites of two patients.
The spread of cervical carcinoma associated with parturition through a tumorous cervix is rarely demonstrated. This report details two patients with adenocarcinoma of the cervix who delivered term fetuses vaginally and subsequently presented with tumor nodules in the episiotomy scars. Although both patients appear to have had their recurrences treated successfully, follow-up on one patient has been only 10 months since the completion of therapy. Tumor implantation of the episiotomy wound is a potential risk associated with vaginal delivery in a pregnant patient with cervical carcinoma. However, this iatrogenic mechanism of tumor spread may permit an opportunity for successful treatment of the local recurrence.


Disorders of gastric emptying and the application of radionuclide techniques.
There has been a greatly increased understanding of the physiology of gastric emptying in normal subjects, and of the pathophysiology and pharmacological treatment of gastric emptying disorders associated with the development and application of methods to quantify gastric emptying in humans. The non-invasive measurement of gastric emptying by means of radionuclide-labelled food markers has widespread clinical and research applications.