Outbreak of a novel Enterobacter sp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania.
Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla(CTX-M-15) in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla(CTX-M-15) gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla(CTX-M-15) on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92-98.8%. The data describe an outbreak of a novel bla(CTX-M-15)-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum β-lactamases as well as improvements in hygiene measures in developing countries.


Calmodulin regulates nucleotide hydrolysis activity of tissue transglutaminase.
The interaction of calmodulin with purified guinea pig liver transglutaminase was studied. The nucleotide (ATP and GTP) hydrolysis activity of this tissue transglutaminase was transiently increased and then gradually decreased depending on calmodulin concentration. The peak activation was obtained in the presence of a stoichiometric amount of calmodulin. The effect of calmodulin on the classical transglutaminase activity was minimal. Fluorescence spectroscopy demonstrated that the enzyme produced a significant blue shift in the emission peak of dansylated calmodulin. Interestingly, Ca2+ was not required for the interaction between the two proteins. The results described here give an additional regulatory role to calmodulin.


Chloro-s-triazine antagonism of estrogen action: limited interaction with estrogen receptor binding.
In an accompanying article (see pp. 183-196), it was reported that administration of very high doses of the chlorotriazine herbicides atrazine, simazine, and diaminochlorotriazine (DACT), a common metabolite, expressed antiestrogenic activity in uteri of female Sprague-Dawley rats without expressing intrinsic estrogenic activity. In the present article, studies of chlorotriazine interaction with rat uterine estrogen receptors (ER) are reported. Under equilibrium conditions, none of the triazine compounds showed an ability to compete against binding of radiolabeled estradiol to ER. A weak competition was evident only if cytosols were preincubated with triazines at 25 degrees C prior to introduction of tracer. Competition was very weak, with kl estimates of 10-100 microM. A limited Scatchard analysis suggested a competitive type of inhibition. Sucrose gradient analysis of cytosol incubations showed that triazine interaction with the 4S isoform of ER may be greater than with the 8S form. When administered to ovariectomized rats for 2 d at 300 mg/kg/d, atrazine, simazine, or DACT all reduced uterine ER binding capacity by approximately 30%. Results from the receptor binding studies indicated that triazine competition against ER binding occurred to a much lesser degree than inhibition of estrogen-mediated responses reported in accompanying articles. This suggests that the complete responses to triazines may include inhibition of events other than or in addition to ER binding of estrogen.


[Visual functions and quality of life in patients with keratoconus].
To evaluate quality of life and visual functions in patients with keratoconus wearing rigid gas permeable (RGP) contact lenses. Keratometry and objective refraction, uncorrected visual acuity, visual acuity with RGP contact lens, high order aberrations and letter contrast sensitivity before and after RGP application were measured in 22 keratoconus patients. Vision-related quality of life was examined by the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) The average spherical equivalent in the study group was -7.28 (+/- 5.53), the average keratometry was 50.04 D (+/- 4.24) and the average corneal astigmatism -3,44 Dcyl (+/- 2,72). The uncorrected visual acuity was 0.20 (+/- 0.18), the corrected visual acuity 0.78 (+/- 0.22). The improvement of visual acuity after RGP fitting was statistically significant (p < 0.001). The RGP fitting didn't cause significant changes in high order aberrations and in contrast sensitivity. The NEI-VFQ overall score was 79.2. Keratoconus was associated with lower scores in these categories: dependency, mental health and ocular pain. Keratoconus is a disease which may have a marked impact on the quality of life beacuse it affects young adults in their active years. The use of RGP correction can significantly improve visual acuity but, at least in our study group, did not lead to significant improvement in contrast sensitivity and corneal aberrations.


[Avoidance conditioning and morphometric characteristics of the sensorimotor cortex of rats exposed to social deprivation in early ontogeny].
Male Wistar rats were exposed to social deprivation in the period from the 22nd to 70th days of postnatal development. The characteristics of the learning of these rats at the age 110-120 days in the passive avoidance box and during training for active avoidance of electroshock were significant lower than those of control animals. Features of motor activities of the "isolants" in learning and testing, and in the "open field" may be related to their higher anxiety level. Morfometric studies of neurons and glial cells and neocortex thickness showed that significantly lower density of neural elements may be the result of the afferent sensory input limitation produced by the social deprivation.


On immunity against infections and vaccines: credo 2004.
Resistance of vertebrate hosts against infections comprises important natural or innate resistance combined with adaptive immune responses of T and B cells. Viruses, bacteria or classical parasites all probe the limit of immune responses and of immunity. They, therefore, offer an excellent opportunity to assess the biology, physiology and molecular aspects of immune responses and help in characterizing the three basic parameters of immunology-- specificity, tolerance and memory. Various experiments are summarized that indicate that the rules of antiviral, antitumour, antiorgan graft and of autoimmune responses are basically the same. The practical specificity repertoire of T and B cells is probably in the order of 10(4)-10(5) specificities expressed by T cells or by neutralizing antibodies. Tolerance is best defined by rules of reactivity to eliminate infections while avoiding destruction of normal cells by complete elimination of T cells that are specific for antigens persisting within the blood and lymphatic (lymphohaemopoietic) system. Induction of a T-cell response is the result of antigens newly entering lymph nodes or spleen, initially in a local fashion and exhibiting an optimal distribution kinetics within the lymphohaemopoietic system. Antigen staying outside lymphatic tissues are immunologically ignored (e.g. are non-events). Thus immune reactivity is regulated by antigen dose, time and relative distribution kinetics. Memory is the fact that a host is resistant against disease caused by reinfection with the same agent. Memory correlates best with antigen-dependent maintenance of elevated antibody titres in serum and mucosal secretions, or with an antigen-driven activation of T cells, such that they are protective immediately against peripheral reinfections in solid tissues. While antibodies transferred from mother to offspring are a prerequisite for the survival of otherwise unprotected immuno-incompetent offsprings, activated memory T cells cannot be transmitted. Thus, attenuation of infections in newborns and babies by maternal antibodies is the physiological correlate of man-made vaccines. T cells not only play an essential role in maintaining T-help-dependent memory antibody titres, but also in controlling the many infections that persist in a host at rather low levels (such as tuberculosis, measles and HIV).


An evaluation of the metabolic interaction with myogenic vascular reactivity during blood flow autoregulation.
An attempt was made to evaluate the possible metabolic interaction with myogenic vascular reactivity during autoregulation of blood flow in sympathectomized cat skeletal muscle. This was done by studying the extent to which a purely myogenic response, elicited by a standardized 2 s vascular transmural pressure impulse stimulus was altered when mean arterial inflow pressure was varied in the range from 160 down to 40 mmHg. The observations were made during the steady state blood flows encountered at the different pressure levels. The data were corrected for the effects of physical factors inherent in altered basal vascular tone and intravascular pressure with the aid of a mathematical model for purely myogenic responses. The results demonstrated a flow dependent decline in myogenic vascular reactivity during reduction of arterial pressure, even in the range where blood flow was autoregulated quite effectively. This suggested a significant metabolic interaction with myogenic reactivity, an interpretation corroborated by a similar decline in myogenic reactivity found during more defined activation of the vascular metabolic control system by graded light muscle exercise. The fact that a significant metabolic interaction was revealed even at such minute flow changes that occur in the autoregulatory range indicates a high 'gain' in the metabolic feedback interacting, directly or indirectly, with myogenic mechanisms in local vascular regulation.


Atrial natriuretic peptide during different pacing modes in a comparison with hemodynamic changes.
The study investigates the response of atrial natriuretic peptide (ANP) to different cardiac pacing modes in comparison with hemodynamic changes. Ten patients underwent Swan-Ganz catheterization during pacemaker implant. Atrioventricular and ventricular pacing were performed consecutively at three pacing rate levels (80, 100, and 110 ppm). Blood samples were taken from the pulmonary artery for ANP determination, both basally and at the end of each pacing period. Concomitantly, mean pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (PAP) were measured. Cardiac output (CO) was determined by thermodilution both basally and during the 110 ppm steps. During atrioventricular pacing, whereas no significant changes were observed for ANP, PCWP and PAP, CO increased significantly (P less than 0.0005). At the beginning of ventricular pacing hemodynamic parameters and ANP levels were comparable with those of baseline conditions. During subsequent ventricular pacing PCWP and ANP increased significantly at the 110 ppm rate step (P less than 0.05). PAP did not change significantly, whereas CO decreased in all cases (P less than 0.01). A positive correlation was observed between ANP and PCWP during ventricular (P less than 0.001), but not atrioventricular pacing. The results, while confirming the hemodynamic advantages of atrioventricular pacing, point to a major stimulation of ANP secretion during ventricular pacing. This fact, together with the observed drop in CO and the correlation between ANP and PCWP, suggest that the increase of ANP in ventricular pacing may be the expression of a compensatory mechanism to the hemodynamic disadvantages of atrioventricular asynchrony.


IL-38 restrains inflammatory response of collagen-induced arthritis in rats via SIRT1/HIF-1α signaling pathway.
To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established. The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including HE staining, ELISA, immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. IL-38 could alleviate CIA joint damage and restrain inflammatory response, could up-regulate the expression of OPG in CIA rats and could down-regulate the expression of RANKL and RANK. IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could up-regulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL and CLH groups. From the treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL-38 on inflammatory factors and regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. IL-38 can restrain the inflammatory response of CIA rats, can promote the expression of osteogenic factors, can inhibit neovascularization, and can alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway.


Pulse Rate and Transit Time Analysis to Predict Hypotension Events After Spinal Anesthesia During Programmed Cesarean Labor.
Prophylactic treatment has been proved to reduce hypotension incidence after spinal anesthesia during cesarean labor. However, the use of pharmacological prophylaxis could carry out undesirable side-effects on mother and fetus. Thus, the prediction of hypotension becomes an important challenge. Hypotension events are hypothesized to be related to a malfunctioning of autonomic nervous system (ANS) regulation of blood pressure. In this work, ANS responses to positional changes of 51 pregnant women programmed for a cesarean labor were explored for hypotension prediction. Lateral and supine decubitus, and sitting position were considered while electrocardiographic and pulse photoplethysmographic signals were recorded. Features based on heart rate variability, pulse rate variability (PRV) and pulse transit time (PTT) analysis were used in a logistic regression classifier. The results showed that PRV irregularity changes, assessed by approximate entropy, from supine to lateral decubitus, and standard deviation of PTT in supine decubitus were found as the combination of features that achieved the best classification results sensitivity of 76%, specificity of 70% and accuracy of 72%, being normotensive the positive class. Peripheral regulation and blood pressure changes, measured by PRV and PTT analysis, could help to predict hypotension events reducing prophylactic side-effects in the low-risk population.


Action sequencing deficit following frontal lobe lesion.
Frontal lobe patients carried out temporal sequencing tasks related to actions that differed in terms of their abstractness using both verbal and pictorial presentations. A generalized impairment was found: neither a type of action effect nor a modality of item presentation effect was present. The patients also carried out a corresponding action production task and produced actions quickly and without errors. The frontal lobe patients were also spared in generating verbal descriptions of actions: they were as accurate as normal controls both in terms of the details reported and in maintaining the temporal sequence. It has been argued that the difficulty in processing the temporal dimensions of actions following frontal lobe lesions is due to some form of disruption of the action representation. However, no action representational deficits were present in our frontal lobe patients. Thus, they cannot account for our findings. On the contrary, we suggest that the action sequencing deficit was a consequence of the difficulties patients experienced in rejecting wrong alternatives presented by the stimulus situation.


[Drug promiscuity].
It is essential for a successful drug to possess two basic characteristics: satisfactory pharmacological action with sufficient potency and selectivity; good druggability with eligible physicochemical, pharmacokinetic and safety profiles, as well as structural novelty. Promiscuity is defined as the property of a drug to act with multiple molecular targets and exhibit distinct pharmacological effects. Promiscuous drugs are the basis of polypharmacology and the causes for side effects and unsuitable DMPK. Drug promiscuity originates from protein promiscuity. In order to accommodate, metabolize and excrete various endo- and exogenous substances, protein acquired the capability during evolution to adapt a wide range of structural diversity, and it is unnecessary to reserve a specific protein for every single ligand. The structures of target proteins are integration of conservativity and diversity. The former is represented by the relatively conservative domains for secondary structures folding, which leads to overlapping in ligand-binding and consequent cross-reactivity of ligands. Diversity, however, embodies the subtle difference in structures. Similar structural domain may demonstrate different functions due to alteration of amino acid sequences. The phenomenon of promiscuity may facilitate the "design in" of multi-target ligands for the treatment of complicated diseases, whereas it should be appropriately handled to improve druggability. Therefore, one of the primary goals in drug design is to scrutinize and manipulate the "merits and faults" of promiscuity. This review discusses the application of promiscuity in drug design for receptors, enzymes, ion channels and cytochrome P450. It also briefly describes the methods to predict ligand promiscuity based on either target or ligand structures.


Stepwise phase transition in the formation of lithium amidoborane.
A stepwise phase transition in the formation of lithium amidoborane via the solid-state reaction of lithium hydride and ammonia borane has been identified and investigated. Structural analyses reveal that a lithium amidoborane-ammonia borane complex (LiNH(2)BH(3).NH(3)BH(3)) and two allotropes of lithium amidoborane (denoted as alpha- and beta-LiNH(2)BH(3), both of which adopt orthorhombic symmetry) were formed in the process of synthesis. LiNH(2)BH(3).NH(3)BH(3) is the intermediate of the synthesis and adopts a monoclinic structure that features layered LiNH(2)BH(3) and NH(3)BH(3) molecules and contains both ionic and dihydrogen bonds. Unlike alpha-LiNH(2)BH(3), the units of the beta phase have two distinct Li(+) and [NH(2)BH(3)](-) environments. beta-LiNH(2)BH(3) can only be observed in energetic ball milling and transforms to alpha-LiNH(2)BH(3) upon extended milling. Both allotropes of LiNH(2)BH(3) exhibit similar thermal decomposition behavior, with 10.8 wt % H(2) released when heated to 180 degrees C; in contrast, LiNH(2)BH(3).NH(3)BH(3) releases approximately 14.3 wt % H(2) under the same conditions.


Recent Advances in Silver Nanowires Electrodes for Flexible Organic/Perovskite Light-Emitting Diodes.
Flexible organic light-emitting diodes and perovskite light-emitting diodes (PeLEDs) have been investigated as an innovative category of revolutionary LED devices for next-generation flat display and lighting applications. A transparent conductive electrode is a key component in flexible OLEDs and PeLEDs, and has been the limitation of the development in this area. Silver nanowires (AgNWs) have been regarded as the most suitable alternative material in TCEs, due to the economical solution synthesis and compatibility with roll-to-roll technology. This mini-review addresses the advances in silver nanowires electrodes for flexible organic/perovskite light-emitting diodes, and the relationship between electrode optimization and device performance is demonstrated. Moreover, the potential strategies and perspectives for their further development of AgNWs-based flexible OLEDs and PeLEDs are presented.


Synthesis and receptor-binding examination of 16-hydroxymethyl-3,17-estradiol stereoisomers.
The four 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers were synthesized and tested in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities are lower than 2.0% relative to that of the reference molecule estra-1,3,5(10)-triene-3,17beta-diol. The affinities of the tested compounds for the androgen and progesterone receptors are very low (K(i)> 100 microm and 1 microM, respectively). The prepared 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers are therefore estrogen receptor-selective molecules.


Patterns and predictors of primary mental health service use following bushfire and flood disasters.
Mental health care services play an important role following disasters (Reifels et al., 2013). The aim of this study is to examine patterns and predictors of primary mental health care service use, following two major Australian natural disaster events. Utilizing referral and session data from a national minimum dataset, descriptive and regression analyses were conducted to identify levels and predictors of the use of the Access to Allied Psychological Services (ATAPS) program over a 2-year period following two major Australian bushfire and flood/cyclone disasters. Predictor variables examined in negative binomial regression analysis included consumer (age, gender, household structure, previous mental health care history, and diagnosis) and event characteristics (disaster type). The bushfire disaster resulted in significantly greater service volume, with more than twice the number of referrals and nearly three times the number of sessions. Service delivery for both disasters peaked in the third quarter. Consumers affected by bushfires, diagnosed with depression, anxiety, or both of these disorders utilized sessions at significantly higher rates. The substantial demand for primary mental health services following disaster can vary with disaster type. Disaster type and need-based variables as key drivers of service use intensity indicate an equitable level of service use. Established usage patterns assist with estimating future service capacity requirements. Flexible referral pathways can enhance access to disaster mental health care. Future research should examine the impact of program- and agency-level factors on mental health service use and factors underpinning treatment non-adherence following disaster.


Multilevel quantum interference in the formation of high-order fractional molecular alignment echoes.
We theoretically investigate the formation of the high-order fractional alignment echo in OCS molecule and systematically study the dependence of echo intensity on the intensities and time delay of the two excitation pulses. Our simulations reveal an intricate dependence of the intensity of high-order fractional alignment echo on the laser conditions. Based on the analysis with rotational density matrix, this intricate dependence is further demonstrated to arise from the interference of multiple quantum pathways that involve multilevel rotational transitions. Our result provides a comprehensive multilevel picture of the quantum dynamics of high-order fractional alignment echo in molecular ensembles, which will facilitate the development of "rotational echo spectroscopy."


Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.
The effect of surfactant chain lengths [sodium caprylate (C8), Tween 20 (C12), Tween 80 (C18)] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties.


"I know this is bad for me, but...": a qualitative investigation of women with irritable bowel syndrome and inflammatory bowel disease: part II.
Individuals with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) experience similar symptoms; however, individuals with IBD have alterations in their digestive tract and an increased probability of developing colorectal cancer, whereas individuals with IBS do not. Although not well documented within the literature, individuals with gastrointestinal (GI) disorders may engage in adverse behaviors regarding their intake of food, regardless of the fact that the "offending agents" have been identified. Further study into these negative behaviors is warranted for healthcare professionals to be provided with a better understanding of the behaviors that individuals with GI disorders knowingly engage in, despite the negative consequences. The overall objective of this research was to explore the lived experience of women diagnosed with the GI disorders IBD and/or IBS, with an emphasis on the dietary patterns of the women before and after diagnosis. Specifically, this article examines the adverse behaviors that women engaged in with respect to the consumption of food, beverages, and medications. Eight women diagnosed with IBD or IBS were recruited from a university campus in southwestern Ontario, Canada. Participants completed a background questionnaire, a 14-day food diary, and a semistructured interview consisting of 8 open-ended questions. Three major themes were identified: family and friend support, control, and adverse behaviors. The focus of this article, the theme of adverse behaviors, consisted of 2 major subthemes: dietary restrictions and issues with medication. All women engaged in adverse behaviors regarding their food intake and/or consumption of medications as related to food intake. Semistructured interviews with women diagnosed with IBD and IBS revealed that all women felt governed by their bowels to varying degrees. In addition, all women within this sample knowingly engaged in behaviors concerning food/beverages that had the potential to be detrimental to their conditions. A myriad of reasons were given for consuming foods/beverages. Implications for nursing practitioners are discussed.


Nutrition and ecosystems in Sarawak: The role of the areca nut.
The effects of population pressure on agricultural sustainability in the delicate tropical and subtropical ecosystems have often been thought to explain high prevalence rates of malnutrition in rural South-East Asia. However, recent studies in rural Sarawak suggest that processes of modernisation have resulted in increased variations in energy nutritional status in adults. A contributory factor may be consumption of the areca nut (Malay pinang, of the palm Areca catechu). This is thought to influence energy balance through effects on appetite and resting metabolic rate. Body mass index (BMI, kg/m2) data for 325 Iban men and 438 non-pregnant Iban women, measured in 1990 and again in 1996, have been analysed in relation to areca use, smoking behaviour, socio-economic status, and reported morbidity. Body composition derived from skinfold thickness measurements for 313 men and 382 women was also analysed. The results suggest that use of areca nut is associated with significantly lower age-related increments in BMI and percentage body fat in women after allowing for age, smoking, reported morbidity, and confounding socio-economic factors. Therefore, the impact of recent economic and social development seen in rising prevalences of 'over-nutrition' may be modulated by use of the areca nut.


Combined nuclear-molecular resonance inelastic scattering of x rays.
We report on theoretical and experimental studies of nuclear inelastic scattering in a molecular crystal, whose atoms experience both molecular and lattice vibrations. In this case scattering proceeds as combined nuclear-molecular resonance inelastic scattering. The lattice vibrations give rise to inelastic scattering around the molecular resonances with an energy dependence identical to that around the nuclear resonance. The incoherent nature of the scattering in the molecular resonances results in a proper balance of elastic and inelastic components, which has important implications for studies of heterogeneous systems.


Thyroid hormone induces sprouting angiogenesis in adult heart of hypothyroid mice through the PDGF-Akt pathway.
Study of physiological angiogenesis and associated signalling mechanisms in adult heart has been limited by the lack of a robust animal model. We investigated thyroid hormone-induced sprouting angiogenesis and the underlying mechanism. Hypothyroidism was induced in C57BL/6J mice by feeding with propylthiouracil (PTU). One year of PTU treatment induced heart failure. Both 12 weeks- (young) and 1 year-PTU (middle age) treatment caused a remarkable capillary rarefaction observed in capillary density. Three-day Triiodothyronine (T3) treatment significantly induced cardiac capillary growth in hypothyroid mice. In cultured left ventricle (LV) tissues from PTU-treated mice, T3 also induced robust sprouting angiogenesis where pericyte-wrapped endothelial cells formed tubes. The in vitro T3 angiogenic response was similar in mice pre-treated with PTU for periods ranging from 1.5 to 12 months. Besides bFGF and VEGF(164) , PDGF-BB was the most robust angiogenic growth factor, which stimulated notable sprouting angiogenesis in cultured hypothyroid LV tissues with increasing potency, but had little effect on tissues from euthyroid mice. T3 treatment significantly increased PDGF receptor beta (PDGFR-β) protein levels in hypothyroid heart. PDGFR inhibitors blocked the action of T3 both on sprouting angiogenesis in cultured LV tissue and on capillary growth in vivo. In addition, activation of Akt signalling mediated in T3-induced angiogenesis was blocked by PDGFR inhibitor and neutralizing antibody. Our results suggest that hypothyroidism leads to cardiac microvascular impairment and rarefaction with increased sensitivity to angiogenic growth factors. T3-induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF-BB, PDGFR-β and downstream activation of Akt.


Sigesbeckia orientalis L. Derived Active Fraction Ameliorates Perioperative Neurocognitive Disorders Through Alleviating Hippocampal Neuroinflammation.
Neuroinflammation is closely related to the pathogenesis of perioperative neurocognitive disorders (PNDs), which is characterized by the activation of microglia, inflammatory pathways and the release of inflammatory mediators. Sigesbeckia orientalis L. (SO) is a traditional Chinese medicine which demonstrates anti-inflammatory activities in different models. In this study, we aim to isolate the active fraction from the extract of SO with higher anti-inflammatory potential and confirm if the selected fraction exerts neuroprotection against the development of PND in an animal model. Moreover, the components in the selected fraction would be determined by UPLC-PDA analysis. Three fractions were prepared by column chromatography packed with three different macroporous resins. Anti-inflammatory activities of prepared fractions were accessed in microglial BV2 cultures by nitric oxide release, gene expression of inflammatory cytokines and activation of inflammatory JNK and NF-kB pathway molecules. Our results demonstrated that the fraction prepared from D101 macroporous resin (D101 fraction) exhibited a more potent anti-neuroinflammatory effect. The neuroprotective effect of D101 fraction was further examined in postoperative mice. Our results showed that surgery-induced cognitive dysfunction was attenuated by the D101 fraction treatment. This fraction also reduced microglial activation, inflammatory cytokines and inhibiting JNK and NF-kB pathway molecules in the hippocampus. In addition, surgery induced dendritic spine loss while D101 fraction ameliorated the spine loss in the hippocampus. For safety concerns, anti-thrombotic effect was examined by tail bleeding assay and no significant change of the bleeding pattern was found. UPLC-PDA analysis indicated that flavonoids (rutin, isochlorogenic acid A, isochlorogenic acid C) and terpenoid (darutoside) were the most important components in the D101 fraction. Our results support a therapeutic, as well as the translational potential for D101 fraction in ameliorating postoperative neuroinflammation and subsequent PND in the clinical setting without increasing bleeding tendencies.


Impact of electromagnetic radiation emitted by monitors on changes in the cellular membrane structure and protective antioxidant effect of vitamin A - In vitro study.
The increasing number of devices emitting electromagnetic radiation (EMR) in people's everyday life attracted the attention of researchers because of possible adverse effects of this factor on living organisms. One of the EMR effect may be peroxidation of lipid membranes formed as a result of free radical process. The article presents the results of in vitro studies aimed at identifying changes in malondialdehyde (MDA) concentration - a marker of lipid peroxidation and antioxidant role of vitamin A during the exposure of blood platelets to electromagnetic radiation generated by liquid-crystal-display (LCD) monitors. Electromagnetic radiation emitted by LCD monitors is characterized by parameters: 1 kHz frequency and 220 V/m intensity (15 cm from display screen). The time of exposure was 30 and 60 min. The study was conducted on porcine blood platelets. The samples were divided into 6 groups: unexposed to radiation, unexposed + vitamin A, exposed for 30 min, exposed for 30 min + vitamin A, exposed for 60 min, exposed for 60 min + vitamin A. The MDA concentration in blood platelets increases significantly as compared to control values after 60 min of exposure to EMR. A significant decrease in MDA concentration after the addition of vitamin A was noticed. In the blood samples exposed to EMR for 30 and 60 min the MDA concentration was significantly increased by addition of vitamin A. The results show the possibly negative effect of electromagnetic radiation on the cellular membrane structure manifested by changes in malondialdehyde concentration and indicate a possible protective role of vitamin A in this process. Int J Occup Med Environ Health 2017;30(5):695-703.


Comprehensive study of moiré deflectometry based on diffraction order filtering of fringes.
This paper presents a detailed investigation of the theory of moiré deflectometry through a comprehensive analysis of the higher-order diffraction of moiré fringes. We demonstrate the possibility of achieving always-high-resolution moiré fringes regardless of Ronchi grating positions and Talbot distance by filtering out the even diffraction orders of moiré fringes. Our theoretical studies lead to a comprehensive formulation of this technique, revealing the high potential of moiré deflectometry towards more precise measurement.


Identification and Characterization of Botrytis Blossom Blight of Japanese Plums Caused by Botrytis cinerea and B. prunorum sp. nov. in Chile.
Blossom blight is a destructive disease of plums (Prunus salicina) when humid and temperate weather conditions occur in Chile. Disease incidence ranging from 4 to 53% has been observed. Symptoms include light brown petal necrosis, starting as light brown mottles or V-shaped necrosis at the margins of the petals, progressing to the stamen and pistils. In this study, the etiology of blossom blight of plums was determined. High- and low-sporulating isolates of Botrytis were obtained consistently from blighted blossoms and apparently healthy flowers of plums. Based on colony morphology, conidial production and molecular phylogenetic analysis, these high- and low-sporulating isolates were identified as B. cinerea and B. prunorum sp. nov., respectively. Phylogenetic analysis of the genes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), heat-shock protein 60 (HSP60), and DNA-dependent RNA polymerase subunit II (RPB2) grouped B. prunorum isolates in a single cluster, distantly from B. cinerea and other Botrytis species. The phylogenetic analysis of necrosis and ethylene-inducing protein (NEP1 and NEP2) genes corroborated these results. Analysis of the internal transcribed spacer region and large-subunit (26S) ribosomal DNA and detection of Boty and Flipper transposable elements, were not useful to differentiate between these Botrytis species. Both species were pathogenic on plum flowers and the fruit of plums, apples, and kiwifruits. However, B. prunorum was less virulent than B. cinerea. These pathogens were re-isolated from inoculated and diseased tissues; thus, Koch's postulates were fulfilled, confirming its role in blossom blight of plums. B. cinerea was predominant, suggesting that B. prunorum may play a secondary role in the epidemiology of blossom blight in plums in Chile. This study clearly demonstrated that the etiology of blossom blight of plums is caused by B. cinerea and B. prunorum, which constitute a species complex living in sympatry on plums and possibly on other stone fruit trees.


Composition of the isolated mitotic apparatus: analysis by polyacrylamide gel electrophoresis.
The mitotic apparatus (MA) from zygotes of the sea urchin Strongylocentrotus purpuratus were isolated and the components of the isolated MA were studied using one-dimensional polyacrylamide gel electrophoresis. MA were isolated using two different stabilization media, hexylene glycol and glycerol-dimethylsulphoxide ( MTM ), because previous studies have shown that MA isolated with these solutions have different properties. Both MA have at least 15-20 bands on gels. Whereas a few bands might be unique to one method of isolation, most bands are the same in hexylene glycol MA and MTM MA. Both kinds of MA differ from the general cytoplasm. Detailed descriptions of the appearances of the gels are given. The main difference between the two kinds of MA is in the relative intensities of the bands found in both MA. The physical and chemical properties of MA change during storage. After various durations of storage MA were extracted with 0.5 M KCl: more proteins were extracted from freshly isolated MA than from stored MA. There were changes in extractibility which occurred at the same time as the physiological changes, but the particular changes in hexylene glycol MA were not the same as those in MTM MA. Thus, there is no common denominator that would allow us to say that loss of extractibility is associated with changes in a certain protein of the isolated MA.


Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study.
Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI 0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI 1.52 to 53.22), but the confidence interval was wide. Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.


Improving the quality of Medicaid personal assistance through consumer direction.
As states seek to improve home and community-based services for people with disabilities, many are incorporating consumer-directed supportive services into their Medicaid programs. The national Cash and Counseling Demonstration uses a randomized design to compare an innovative model of consumer direction with the traditional agency-directed approach. This paper presents findings from the first demonstration program to be implemented, in Arkansas. Our survey of 1,739 elderly and nonelderly adults showed that relative to agency-directed services, Cash and Counseling greatly improved satisfaction and reduced most unmet needs. Moreover, contrary to some concerns, it did not adversely affect participants' health and safety.


Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure.
Gitelman's syndrome (GS), which is caused by homozygous or compound heterozygous mutations of the thiazide-sensitive sodium chloride cotransporter (NCC), usually manifests in children and is associated with low blood pressure. However, the prevalence of heterozygous NCC mutations and their association with blood pressure in children have not yet been studied. Five hundred unrelated children from the Taipei Children Heart Study were enrolled. Genomic DNA was isolated from peripheral blood and the SLC12A3 gene was amplified by polymerase chain reaction (PCR). The 15 NCC mutations previously identified in Chinese patients with GS were evaluated using restriction fragment length polymorphism (RFLP) analysis. Blood pressure, biochemistry and urine pH were measured. The allelic frequency of heterozygous NCC mutations and their association with low blood pressure were also investigated. RFLP analysis for the 15 NCC mutations revealed heterozygous T60M in 1 child, T163M in 1, S283Y in 4, R642C in 2, W844X in 2, R928C in 9 and R959frameshift in 10 children. The overall incidence of positive heterozygous NCC mutations was approximately 2.9%. There were no significant differences in systolic or diastolic blood pressure, biochemical profiles or urine pH between children with heterozygous NCC mutations (n = 29) and non-affected controls (n = 471), except for slightly higher fasting plasma glucose concentrations in NCC-heterozygous children (91 +/- 2.3 versus 88 +/- 0.4 mg/dL, P < 0.05). Examination among the different NCC mutations showed that these children also had comparable blood pressures. We found a relatively high prevalence of heterozygous NCC mutations in Chinese children, suggesting that GS may not be rare in this population. Heterozygous NCC mutations were not associated with lower blood pressure in these Chinese children.


Comprehensive Treatment Module for Medically Unexplained Physical Symptoms - A Guide for General Practitioners.
This study was aimed to develop a comprehensive treatment module that the general physician can use to manage patients with Medically Unexplained Physical Symptoms (MUPS) at a primary care level. Methods: This comprehensive module was developed after a literature review followed by its validation by a two-step Delphi technique with experts from internal medicine, psychiatry, and clinical psychology. The developed module for the patients with MUPS includes case diagnosis, initial evaluation, strategy for referral, and a comprehensive treatment module. The comprehensive treatment module includes symptom discussion, rapport establishment, physical health counselling, stress management, cognitive strategies for symptom control, comorbidities treatment, and medical management. Conclusion: The developed module has unique features, such as intensive sessions with these patients, a patient-specific treatment strategy, and a holistic approach incorporating pharmacological and non-pharmacological interventions. General Practitioners across the world can use this comprehensive treatment module for the management of patients with MUPS.


Clinical features of patients with dysthymia in a large cohort of Han Chinese women with recurrent major depression.
Dysthymia is a form of chronic mild depression that has a complex relationship with major depressive disorder (MDD). Here we investigate the role of environmental risk factors, including stressful life events and parenting style, in patients with both MDD and dysthymia. We ask whether these risk factors act in the same way in MDD with and without dysthymia. We examined the clinical features in 5,950 Han Chinese women with MDD between 30-60 years of age across China. We confirmed earlier results by replicating prior analyses in 3,950 new MDD cases. There were no significant differences between the two data sets. We identified sixteen stressful life events that significantly increase the risk of dysthymia, given the presence of MDD. Low parental warmth, from either mother or father, increases the risk of dysthymia. Highly threatening but short-lived threats (such as rape) are more specific for MDD than dysthymia. While for MDD more severe life events show the largest odds ratio versus controls, this was not seen for cases of MDD with or without dysthymia. There are increased rates of stressful life events in MDD with dysthymia, but the impact of life events on susceptibility to dysthymia with MDD differs from that seen for MDD alone. The pattern does not fit a simple dose-response relationship, suggesting that there are moderating factors involved in the relationship between environmental precipitants and the onset of dysthymia. It is possible that severe life events in childhood events index a general susceptibility to chronic depression, rather than acting specifically as risk factors for dysthymia.


Spinal anesthesia in surgical treatment of lumbar spine tumors.
This study aims to show the feasibility of spinal anesthesia in lumbar spinal tumor surgery; share our data and experience. A retrospective review of 14 patients with high risk for general anesthesia due to severe comorbidities was carried out. Patients who underwent surgeries under spinal anesthesia for lumbar vertebral column or spinal cord tumors at a single center between 2007-2019 were evaluated. The final pathological diagnosis, operation time, and surgical procedures were analyzed. Also, preoperative and postoperative advantages and disadvantages were determined. A comparison was performed with other 184 patients who were operated for spinal tumors in the same period under general anesthesia. Maximum operation time was found 220 min, and the average operation time was 166 min. The most primary diagnosis was vertebral column metastasis. The mean age was 65.5 years. None of the patients required general anesthesia during surgery; however, two patients needed additional spinal anesthesia preoperatively, which was performed by the surgeon. Lumbar decompression and fusion were the most performed procedures. Spinal anesthesia is a feasible and useful method of anesthesia in lumbar spinal tumor surgery for especially elderly patients with American Society of Anesthesiologists (ASA) 3 or 4 score and high risk of general anesthesia.


Science of Hyaluronic Acid Beyond Filling: Fibroblasts and Their Response to the Extracellular Matrix.
Loss of viscoelasticity is one of the primarily signs of skin aging, followed by appearance of visible wrinkles. Hyaluronic acid (HA)-based fillers are widely used to fill wrinkles and compensate for volume loss. Recent clinical observations demonstrate persistence of the filling effect longer than the biological availability of the filler. Stimulation of new collagen by cross-linked HA and up-regulation of elastin have been suggested as possible explanation to this observation and have been supported experimentally. Cross-linked HA substitutes for fragmented collagen in restoring extracellular matrix required for normal activity of fibroblasts, such as collagen and elastin production. To restore extracellular matrix efficiently, serial monthly treatments are required. Boosting of facial and nonfacial skin through fibroblast activation is a new indication for HA-based products. Injectable HA has also been recently registered in Europe as agents specific for the improvement of skin quality (Restylane Skinboosters). Further explanation of the possible mechanisms supported by long-term clinical examples is presented herein.


In vitro and in vivo delivery of artemisinin loaded PCL-PEG-PCL micelles and its pharmacokinetic study.
Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone with anticancer properties, but its application is limited because of its low water solubility. To increase the bioavailability and water solubility of ART, we synthesized three series of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) (PCL-PEG-PCL) tri-block copolymers. The structure of the copolymers was characterized by HNMR, FTIR, DSC and GPC techniques. ART was encapsulated inside micelles by a nanoprecipitation method which leading to the formation of ART/PCL-PEG-PCL micelles. The obtained micelles were characterized by DLS and AFM technique. The results showed that the average size of micelles was about 83.22 nm. ART was encapsulated into PCL-PEG-PCL micelles with encapsulation efficacy of 89.23 ± 1.41%. In vivo results demonstrated that this formulation significantly increased drug accumulation in tumours. Pharmacokinetic study in rats revealed that in vivo drug exposure of ART was significantly increased and prolonged by intravenously administering ART-loaded micelles when compared with the same dose of free ART. The MTT assay showed that bare PCL-PEG-PCL micelles is non-toxic to MCF7 and 4T1 cancer cell lines whereas the ART/PCL-PEG-PCL micelles showed a specific toxicity to both cancer cell lines. Therefore, the polymeric micellar formulation of ART based copolymer could provide a desirable process for ART delivery.


Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine.
1. The biotransformation of the triazolobenzodiazepine alprazolam (ALP) to its hydroxylated metabolites (4-OH-ALP and alpha-OH-ALP) was evaluated in human, monkey, rat, and mouse liver microsomes. 2. In all species 4-OH-ALP was the principal metabolite, accounting for 84% of clearance in human microsomes compared with 16% for alpha-OH-ALP. 3. Among the serotonin-specific reuptake inhibitors fluoxetine (FLU) and sertraline (SERT), and their respective demethylated metabolites norfluoxetine (NOR) and desmethylsertraline (DES), NOR was the most potent inhibitor (mean Ki for 4-OH-ALP formation in humans: 11 microM), FLU the weakest (Ki = 83 microM), with SERT and DES falling in between (Ki = 24 and 20 microM). 4. The in vitro data predict 29% inhibition of ALP clearance at mean FLU and NOR plasma concentrations of 77 ng ml-1 and 72 ng ml-1, respectively, after correction for liver:water partition ratios in the range of 12-14. The observed mean degree of inhibition in a previous in vivo study was 21%. 5. Ketoconazole was a potent inhibitor of ALP metabolism in vitro (Ki = 0.046 microM), suggesting that ALP hydroxylation is mediated by the cytochrome P450-3A sub-family. Quinidine was a weak inhibitor (Ki = 626 microM).


Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases.
Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming for z-average in the range of 100-300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z-averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z-average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology.


The structure of d(CGCGAAT[]TCGCG) . d(CGCGAATTCGCG); the incorporation of a thymine photodimer into a B-DNA helix.
In the light of the biological significance of thymine photodimers , studies of the energetics of the dodecanucleotide fragment d( CGCGAATTCGCG )2 have been carried out using the methods of molecular mechanics, with and without incorporation of a thymine dimer in the cis-syn configuration. The results of the calculations suggest that the thymine dimerized structures show no gross distortion in the double helix with the conformational changes relative to the normal B-DNA double helix restricted largely to the dimer region. The energetics of dTp[]dT reveal a number of conformers which are energetically almost equally favorable and are, as a group, qualitatively consistent with NMR studies on this molecule. The biological implications of the results of the conformational studies, reported here, have been examined vis-a-vis the currently available models for the recognition of DNA "damage" by repair enzymes.


Protective effect of interferon on target cells exposed to cellular cytotoxicity.
In order to explore by immunological methods the interferon-induced cell membrane modulation, the effect of interferon in parental and monkey-mouse hybrid cells was studied in the presence of sensitized lymphocytes from isologous mice. After primary immunization to the hybrids, both parental interferons increased the lymphocyte-induced specific cytotoxicity in the same hybrid cells used as targets. In addition, a significnt increase of spontaneous lysis due to the two interferons was observed. In contrast, after secondary sensitization, in spite of the higher specific cytotoxicity induced by the lymphocytes, the same interferon preparation significantly protected the cells. These results are probably related to a greater number of sensitized effector cells after secondary sensitizationn. It is likely that, although interferon increases the affinity of sensitized T lymphocytes for the target cell membrane, in case of unsuccessful encounters, the target cells become resistant to new hits. Interferon could augment the number of such immune cells.


Pattern of Pediatric Supracondylar Fracture Operated at A Rural Teaching Hospital of Nepal: A Descriptive Cross-sectional Study.
Supracondylar fracture of humerus is one of the common pediatric fractures encountered in our daily clinical practice. The purpose of this study is to determine the pattern of supracondylar fracture operated at rural teaching hospital of Jumla, Karnali Nepal. A descriptive cross sectional study was conducted at Jumla, Karnali after Institutional Review Committee approval. Operating room notes from 15 May 2017 to 16 November 2019 were retrieved to gather the following information: patients address, age, sex, side, injury mechanism, displacement, neurovascular injury, concurrent injuries, initial management by traditional bone setters, time between injury and surgery, operative technique. Data analysis was done using Statistical Package for Social Sciences version 20. Left side predominated with 88 (63.7%) and extension type was common in 135 (97.8%). Thirteen (9.4%) patients were initially managed by traditional bonesetters. A total of 138 children underwent operative fixation with mean age of 7.47 years and gender ratio of 2:1 boy to girl. Fall from cliff, ladders and rooftops were the prevailing cause of injury 73 (52.8%). Average time between injury and surgery was 5.2 days. Closed reduction was done in 100 (72.4%) patients whereas open reduction was necessary in 38 (27.5%) patients. Closed extension type pediatric supracondylar fracture was common in this study. Fall from cliff, rooftop and ladder are the major cause of fracture. Delayed presentation and initial management of the fracture by the traditional bonesetters makes supracondylar fracture more challenging in resource limited setting like ours.


Effect of magnesium depletion on 3H-ouabain binding site concentration in rat skeletal muscle.
In young (4-week-old) rats, dietary Mg depletion for 1.5 weeks was followed by a significant decrease in 3H-ouabain binding site or Na,K-pump concentration of up to 21% and in total K content of up to 11% in various hind limb muscles. K depletion was associated with a decrease in 3H-ouabain binding site concentration of up to 64% and in total K content of up to 31%. Mg depletion was associated with a similar correlation between the decrease in 3H-ouabain binding site concentration and total K content, as was K depletion (r = 0.98, p less than 0.001). Taken together, the results indicate that the decrease in the concentration of 3H-ouabain binding sites following Mg depletion is not primarily caused by Mg deficiency per se, but is probably secondary to the associated K deficiency. The decrease in Na,K-pump concentration may be of importance for the retardation of K repletion as well as the increase in digitalis toxicity observed with Mg deficiency.


Tissue CEA as prognostic indicator in a series of 31 cases of gastric cancer.
The role of tissue CEA localization as a complementary factor in prognosis of patients affected by gastric cancer is analyzed. In a group of 31 gastric tumors, tissue CEA was always present in the apical portion of the tumor cell cytoplasm and in the glandular lumen, while in 23 cases it was found in the stroma, and in superficial and deep cell cytoplasm in 26 and 20 cases respectively. The serum marker levels were over 3 ng/ml in 19 patients. A relationship between CEA localization and tumor stage was observed. The more the tumors were advanced, the more the marker was found in the stroma and in the cytoplasm of superficial and deep cells. The same was found for CEA localization and serum CEA levels. The opposite trend was evidenced for the degree of tumor differentiation. In well differentiated tumors in a high percentage of cases the marker was present in the stroma and in the cytoplasm of superficial and deep cells as compared with undifferentiated tumors. No relationship between the histologic type and CEA localization was found.


Gene expression profile of abdominal aortic aneurysm rupture.
To search for novel transcriptional pathways that are activated in abdominal aortic aneurysm rupture, cDNA microarrays were used to compare global mRNA expression at the aneurysm rupture edge to anterior sac, and selected results were confirmed using quantitative real-time-polymerase chain reaction (QRT-PCR). This study identified apoptosis, angiogenesis, and inflammation as potentially important participants during the process of aneurysm rupture.


Prominent Electron Penetration through Ultrathin Graphene Layer from FeNi Alloy for Efficient Reduction of CO2 to CO.
The chemical transformation of CO2 is an efficient approach in low-carbon energy system. The development of nonprecious metal catalysts with sufficient activity, selectivity, and stability for the generation of CO by CO2 reduction under mild conditions remains a major challenge. A hierarchical architecture catalyst composed of ultrathin graphene shells (2-4 layers) encapsulating homogeneous FeNi alloy nanoparticles shows enhance catalytic performance. Electron transfer from the encapsulated alloy can extend from the inner to the outer shell, resulting in an increased charge density on graphene. Nitrogen atom dopants can synergistically increase the electron density on the catalyst surface and modulate the adsorption capability for acidic CO2 molecules. The optimized FeNi3 @NG (NG=N-doped graphene) catalyst, with significant electron penetration through the graphene layer, effects exceptional CO2 conversion of 20.2 % with a CO selectivity of nearly 100 %, as well as excellent thermal stability at 523 K.


Extending the phenotype associated with the CSNK2A1-related Okur-Chung syndrome-A clinical study of 11 individuals.
Variants in the Protein Kinase CK2 alpha subunit, encoding the CSNK2A1 gene, have previously been reported in children with an intellectual disability and dysmorphic facial features syndrome: now termed the Okur-Chung neurodevelopmental syndrome. More recently, through trio-based exome sequencing undertaken by the Deciphering Developmental Disorders Study (DDD study), a further 11 children with de novo CSNK2A1 variants have been identified. We have undertaken detailed phenotyping of these patients. Consistent with previously reported patients, patients in this series had apparent intellectual disability, swallowing difficulties, and hypotonia. While there are some shared facial characteristics, the gestalt is neither consistent nor readily recognized. Congenital heart abnormalities were identified in nearly 30% of the patients, representing a newly recognized CSNK2A1 clinical association. Based upon the clinical findings from this study and the previously reported patients, we suggest an initial approach to the management of patients with this recently described intellectual disability syndrome.


Attitudes and barriers towards participation in an acupuncture trial among breast cancer patients: a survey study.
As breast cancer patients increasingly use complementary and alternative medicine (CAM), clinical trials are needed to guide appropriate clinical use. We sought to identify socio-demographic, clinical and psychological factors related to willingness to participate (WTP) and to determine barriers to participation in an acupuncture clinical trial among breast cancer patients. We conducted a cross-sectional survey study among post-menopausal women with stage I-III breast cancer on aromatase inhibitors at an urban academic cancer center. Of the 300 participants (92% response rate), 148 (49.8%) reported WTP in an acupuncture clinical trial. Higher education (p = 0.001), increased acupuncture expectancy (p < 0.001), and previous radiation therapy (p = 0.004) were significantly associated with WTP. Travel difficulty (p = 0.002), concern with experimentation (p = 0.013), and lack of interest in acupuncture (p < 0.001) were significant barriers to WTP. Barriers differed significantly by socio-demographic factors with white people more likely to endorse travel difficulty (p = 0.018) and non-white people more likely to report concern with experimentation (p = 0.024). Older patients and those with lower education were more likely to report concern with experimentation and lack of interest in acupuncture (p < 0.05). Although nearly half of the respondents reported WTP, significant barriers to participation exist and differ among subgroups. Research addressing these barriers is needed to ensure effective accrual and improve the representation of individuals from diverse backgrounds.


The Occurrence of Oxidative Stress Induced by Silver Nanoparticles in Chlorella vulgaris Depends on the Surface-Stabilizing Agent.
Silver nanoparticles (AgNPs) are of great interest due to their antimicrobial properties, but their reactivity and toxicity pose a significant risk to aquatic ecosystems. In biological systems, AgNPs tend to aggregate and dissolve, so they are often stabilized by agents that affect their physicochemical properties. In this study, microalga Chlorella vulgaris was used as a model organism to evaluate the effects of AgNPs in aquatic habitats. Algae were exposed to AgNPs stabilized with citrate and cetyltrimethylammonium bromide (CTAB) agents and to AgNO3 at concentrations that allowed 75% cell survival after 72 h. To investigate algal response, silver accumulation, ROS content, damage to biomolecules (lipids, proteins, and DNA), activity of antioxidant enzymes (APX, PPX, CAT, SOD), content of non-enzymatic antioxidants (proline and GSH), and changes in ultrastructure were analyzed. The results showed that all treatments induced oxidative stress and adversely affected algal cells. AgNO3 resulted in the fastest death of algae compared to both AgNPs, but the extent of oxidative damage and antioxidant enzymatic defense was similar to AgNP-citrate. Furthermore, AgNP-CTAB showed the least toxic effect and caused the least oxidative damage. These results highlight the importance of surface-stabilizing agents in determining the phytotoxicity of AgNPs and the underlying mechanisms affecting aquatic organisms.


Congenital Achiasma.
In evaluating a 3-month-old boy with horizontal nystagmus, brain MRI revealed absence of the optic chiasm. The remainder of the brain was normal in appearance. Achiasma was confirmed with diffusion tensor imaging and best visualized with optimized probabilistic-based tractography.


Revision versus primary arthroscopic rotator cuff repair: a 2-year analysis of outcomes in 360 patients.
Symptomatic rotator cuff tears are often treated surgically. However, there is a paucity of information regarding the outcomes of revision arthroscopic rotator cuff repairs. To evaluate the outcome of revision arthroscopic rotator cuff surgery when compared with primary arthroscopic rotator cuff surgery in a large cohort of patients. Cohort study; Level of evidence, 3. A consecutive series of 50 revision arthroscopic rotator cuff repairs performed by a single surgeon, with minimum 2-year follow-up, were retrospectively reviewed using prospectively collected data. As a comparison, 3 primary arthroscopic rotator cuff repair cases (primary group; n = 310) were chosen immediately before each revision case, and 3 were chosen after. Standardized patient-ranked outcomes, examiner-determined assessments, and ultrasound-determined rotator cuff integrity were assessed preoperatively at 6 months and at a minimum of 2 years after surgery. The revision group was older (mean age, 63 years; range, 43-80 years) compared with the primary group (mean age, 60 years; range, 18-88 years) (P < .05) and had larger tear size (mean ± SEM) (4.1 ± 0.5 cm(2)) compared with the primary group (3.0 ± 0.2 cm(2)) (P < .05). Two years after surgery, the primary group reported less pain at rest (P < .02), during sleep (P < .05), and with overhead activity (P < .01) compared with the revision group. The primary group had better passive forward flexion (+13°; P < .05), abduction (+18°; P < .01), internal rotation (+2 vertebral levels; P < .001) and also significantly greater supraspinatus strength (+15 N; P < .001), lift-off strength (+9.3 N; P < .05), and adduction strength (+20 N; P < .01) compared with the revision group at 2 years. When compared with the primary group, the revision group was more satisfied with the overall shoulder function before surgery but was less satisfied with their shoulder function than the primary group at 2 years (P < .005). The retear rate for primary rotator cuff repair was 16% at 6 months and 21% at 2 years, while the retear rate for revision rotator cuff repair was 28% at 6 months and deteriorated to 40% at 2 years (P < .05). The short-term clinical outcomes of patients undergoing revision rotator cuff repair were similar to those after primary rotator cuff repair. However, these results did not persist, and by 2 years patients who had revision rotator cuff repair were twice as likely to have retorn compared with those undergoing primary repair. The increase in retear rate in the revision group at 2 years was associated with increased pain, impaired overhead function, less passive motion, weaker strength, and less overall satisfaction with shoulder function.


The role of arabidopsis WDR protein in plant growth and defense strategies.
Evidence indicates that the mechanisms controlling photosynthesis efficiency also regulate plant response to biotic and abiotic stress. Light-induced cell death is genetically maintained for the control of innate immunity. In a recent study we showed that the expression of AtWDR26 was induced by light, multiple plant hormones, and abiotic stress; increased AtWDR26 strongly upregulated gene groups related to chloroplast metabolism, disease resistance, and abiotic stress tolerance. Gain- and loss-of-function analyses in transgenic plants demonstrated the involvement of AtWDR26 in signaling pathways; these controls were osmotic as well as salt stress tolerance. More detailed transcriptome evidence suggested that AtWDR26 was a powerful inducer of gene expression associated with chloroplast metabolism. This included the electron transport chain of the photosystem, carbohydrate synthesis, and enzymatic activity involved in photorespiration. Moreover, genes in auxin synthesis (and perception) constituted a significant portion of those that were upregulated. Gene expression involved in disease resistance, control of cell wall flexibility, Zn uptake, and AP2/ERF transcription factors was also be upregulated. We concluded that AtWDR26 is one component in the regulatory network between light-regulated plant growth and the adaptation response to disease resistance and abiotic stress. Auxin signal acts downstream for AtWDR26 regulation and the adaptation response to biotic and abiotic stress: this occurs through modulating cell wall flexibility, Zn homeostasis, and controlling stress-related transcription factors.


Effects of frequency, instrumental family, and cochlear implant type on timbre recognition and appraisal.
The purpose of this study was to compare postlingually deafened cochlear implant recipients and normal-hearing adults on timbre (tone quality) recognition and appraisal of 8 musical instruments representing 3 frequency ranges and 4 instrumental families. The implant recipients were significantly less accurate than the normal-hearing adults on timbre recognition. The implant recipients gave significantly poorer ratings than did the normal-hearing adults to those instruments played in the higher frequency range and to those from the string family. The timbre measures were weakly correlated with speech perception measures, but were significantly correlated with 3 cognitive measures of sequential processing.


Identification and functional analysis of an ADAMTSL1 variant associated with a complex phenotype including congenital glaucoma, craniofacial, and other systemic features in a three-generation human pedigree.
Developmental glaucoma can occur as an isolated or syndromic condition and is genetically heterogeneous. We describe a three-generation family affected with developmental glaucoma, myopia, and/or retinal defects associated with variable craniofacial/dental, auditory, brain, renal, and limb anomalies. Whole-exome sequencing identified a heterozygous c.124T> C, p.(Trp42Arg) allele in ADAMTSL1; cosegregation analysis confirmed the presence of this allele in four affected family members. The mutation affects a highly conserved residue and is strongly predicted to have a deleterious effect on protein function. Trp42 is normally modified by protein C-mannosylation, an unusual post-translational modification. Comparison of ADAMTSL1-WT (also known as punctin-1) and ADAMTSL1-p.Trp42Arg in vitro demonstrated that the latter was not secreted from transfected cells but retained intracellularly. Moreover, ADAMTSL1-p.Trp42Arg reduced secretion of cotransfected wild-type ADAMTSL1, suggesting a dominant negative effect for this mutation. These data imply a multisystem role for ADAMTSL1 and present the first disease-associated variant affecting a C-mannosylation motif.


Characterization of a DNA exit gate in the human cohesin ring.
Chromosome segregation depends on sister chromatid cohesion mediated by cohesin. The cohesin subunits Smc1, Smc3, and Scc1 form tripartite rings that are thought to open at distinct sites to allow entry and exit of DNA. However, direct evidence for the existence of open forms of cohesin is lacking. We found that cohesin's proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. Mutation of this interface abolished cohesin's ability to stably associate with chromatin and to mediate cohesion. Electron microscopy revealed that weakening of the Smc3-Scc1 interface resulted in opening of cohesin rings, as did proteolytic cleavage of Scc1. These open forms may resemble intermediate states of cohesin normally generated by the release factor Wapl and the protease separase, respectively.


Joint Learning of Multiple Latent Domains and Deep Representations for Domain Adaptation.
In domain adaptation, the automatic discovery of multiple latent source domains has succeeded by capturing the intrinsic structure underlying the source data. Different from previous works that mainly rely on shallow models for domain discovery, we propose a novel unified framework based on deep neural networks to jointly address latent domain prediction from source data and deep representation learning from both source and target data. Within this framework, an iterative algorithm is proposed to alternate between 1) utilizing a new probabilistic hierarchical clustering method to separate the source domain into latent clusters and 2) training deep neural networks by using the domain membership as the supervision to learn deep representations. The key idea behind this joint learning framework is that good representations can help to improve the prediction accuracy of latent domains and, in turn, domain prediction results can provide useful supervisory information for feature learning. During the training of the deep model, a domain prediction loss, a domain confusion loss, and a task-specific classification loss are effectively integrated to enable the learned feature to distinguish between different latent source domains, transfer between source and target domains, and become semantically meaningful among different classes. Trained in an end-to-end fashion, our framework outperforms the state-of-the-art methods for latent domain discovery, as validated by extensive experiments on both object classification and human action-recognition tasks.


Preschool speech, language skills, and reading at 7, 9, and 10 years: etiology of the relationship.
To examine the etiology of the relationship between preschool speech and language, and later reading skills. One thousand six hundred seventy-two children from the Twins Early Development Study (B. R. Oliver & R. Plomin, 2007) were given a comprehensive speech and language assessment at 4(1/2) years. Reading was assessed at 7, 9, and 10 years. Twin analyses were applied to the data to assess the contributions of genetic and environmental factors to the longitudinal relationships between speech and reading, and language and reading. Phenotypically, there is a moderate and stable relationship between 4(1/2)-year speech and language scores and reading at 7, 9, and 10 years. Etiologically, at the individual-differences level, both genetic and shared environmental factors contribute to the links between language skills and reading. By contrast, genetic factors account for most of the relationship between early speech and later reading. At the extremes, there appears to be an even stronger role for genetic factors in accounting for the prediction from early speech and language impairments to later reading outcome. Both genetic and environmental factors contribute to the relationship between early language skills and reading, whereas genetic factors play a dominant role in the relationship between early speech and reading.


RNA-Seq Analysis of the Liver Transcriptome Reveals the Networks Regulating Treatment of Sitagliptin Phosphate plus Fuzhujiangtang Granule in the Zucker Diabetic Fatty Rats.
Diabetes is one of the most serious chronic diseases. Numerous drugs including oral agents and traditional Chinese medicines, such as sitagliptin phosphate (SP) and Fuzhujiangtang granules (FJG), have been discovered to treat diabetes and used in combination in clinical practice. However, the exact effect and underlying mechanism of using combined medicine is not clear. In this study, we compared the antidiabetic effect of SP, FJG, and SP plus FJG (SP-FJG) using forty 8-week-old Zucker diabetic fatty (ZDF) rats and 10 age-matched Zucker lean rats as the normal control group. ZDF rats were treated with different therapies, respectively, for 6 weeks. The study showed that the fast blood glucose, random blood glucose (RBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index, triglyceride (TC), superoxide dismutase, and malondialdehyde of each treatment group were improved when compared with the diabetes mellitus (DM) control group. Using SP-FJG in combination had better improvements in OGTT, fast serum insulin levels, TNF-α, and IL-6 compared with using SP individually. Besides, the increased LDL and TC caused by using SP was attenuated by using FJG in combination. Meanwhile, compared with the DM group, 1781 differentially expressed genes (DEGs) (including 1248 mRNA, 211 ncRNA, 202 cirRNA, and 120 miRNA) were enriched in 58 pathways. Through analysis of ceRNA networks, we found that rno-miR-326-3p, rno-miR-423-5p, rno-miR-15b-5p, rno-let-7c-5p, and rno-let-7b-5p were related to pharmacodynamics in different groups. By analyzing the protein-protein interaction (PPI) and coexpression networks of the transcriptomes of different groups, it is inferred that Lrrk2 and Irak3 may be pharmacodynamic genes for type 2 diabetes mellitus (T2DM). Our research compared the treatment of SP, FJG, and SP-FJG and acquainted the PPI network, coexpression network, mutations, and pharmacodynamics genes, which reveals the new mechanisms of pathogenesis of T2DM.


Temperament and Character Traits of Parents of Children With ADHD.
This study investigates the relationship between ADHD and the personalities of parents of children with ADHD. Personality traits of parents of children with ADHD (study group; n = 135) and parents of children without ADHD (control group; n = 122) were compared. Psychiatric comorbidities were excluded with Structured Clinical Interview for DSM-IV Axis I Disorders, Clinical Version [SCID-I-CV]. Personality is assessed with Temperament and Character Inventory, and inattention (IA) and hyperactivity (HI) are assessed with Turgay Scale. Harm avoidance and persistence scores were higher, and self-directedness (SD) scores were lower in the study group than the control group. Being in ADHD group predicted lower SD scores. Positive correlations were found between harm avoidance and IA and HI, and between persistence and HI. Negative correlations were found between SD and both IA and HI. Our data suggest that there is relationship between ADHD in children's and parents' personalities. Common etiologic properties and personalized psychoeducation and treatment options for families should be discussed.


Novel perturbation approach for the structure factor of the attractive hard-core Yukawa fluid.
A novel perturbation approach for the structure factor S(k) of the Lennard-Jones-type Yukawa fluid with z=1.8 is presented. An approach is based on a new reference system, that is, the short-range Yukawa model with z0>z=1.8. By choosing for the reference system the value z0=6, it is shown that (i) the proposed approach for S(k) performs much better than the traditional hard-sphere reference perturbation method does; (ii) the use of an approximate mean spherical (MSA) description of the reference structure factor provides the results for S(k) that are more accurate as those obtained from the direct MSA computations; and (iii) the results obtained for S(k) tend to reproduce "exact" simulation results when accurate simulation data for the reference system are used.


Maximizing automation in LC/MS high-throughput analysis and purification.
Here, we describe a system for LC/MS-based analysis and purification of compounds aiming at the minimization of manual interference in the overall process. Key elements of the concept are automated identification of the target compounds, automated assignment of optimized preparative gradients for purification of the target compounds, and automated purity assessment of fractions with subsequent pooling of validated product fractions. Additional support is provided by an automated solvent and waste management system. One person can easily process 100-200 compounds on a 150-mg scale per day on that system, while still the maximization of purity and yield after purification is guaranteed. Reduced demands with respect to purity or yield can lead to significantly higher throughput numbers.


Natural resources for morality: commentary.
Loewy makes an extraordinary and audacious claim. He does not only reject virtue ethics, casuistry, the "Kantian injunction of respect for persons based on their capacity for self-legislation," and the utilitarian greatest good as possible groundings for clinical ethics. He even offers another grounding that he qualifies explicitly as "universally acceptable." Of course we have to analyze what it is that he offers. But prior to that, we must analyze what he means by "grounding." Grounding suggests an evidence that can neither be rationally grounded again nor rationally questioned but that other concepts can be rationally grounded upon. And it is at least doubtful whether the alternatives he quotes are groundings in that strict sense....


Glycemic control and healthcare utilization following pregnancy among women with pre-existing diabetes in Navajo Nation.
Native American communities experience greater burden of diabetes than the general population, including high rates of Type 2 diabetes among women of childbearing age. Diabetes in pregnancy is associated with risks to both the mother and offspring, and glycemic control surrounding the pregnancy period is of vital importance. A retrospective chart review was conducted at a major Navajo Area Indian Health Service (IHS) hospital, tracking women with pre-existing diabetes who became pregnant between 2010 and 2012. Logistic regression was performed to find patient-level predictors of our desired primary outcome-having hemoglobin A1c (HbA1c) consistently < 8% within 2 years after pregnancy. Descriptive statistics were generated for other outcomes, including glycemic control and seeking timely IHS care. One hundred twenty-two pregnancies and 114 individuals were identified in the dataset. Baseline HbA1c was the only covariate which predicted our primary outcome (OR = 1.821, 95% CI = 1.184-2.801). Examining glycemic control among pregnancies with complete HbA1c data (n = 59), 59% were controlled before, 85% during, and 34% after pregnancy. While nearly all women received care in the immediate postpartum period, only 49% of women visited a primary care provider and 71% had HbA1c testing in the 2 years after pregnancy. This is the first analysis of outcomes among women with diabetes in pregnancy in Navajo Nation, the largest reservation and tribal health system in the United States. Our findings demonstrate the positive impact of specialized prenatal care in achieving glycemic control during pregnancy, while highlighting the challenges in maintaining glycemic control and continuity of healthcare after pregnancy.


Serosurvey of Trypanosoma cruzi in persons experiencing homelessness and shelter workers of Brazil.
Although Chagas disease, caused by Trypanosoma cruzi, has been associated with social vulnerability worldwide, producing disability and mortality, no study to date has assessed this protozoal infection in persons experiencing homelessness. Accordingly, the present study aimed to assess anti-T. cruzi antibodies by Wiener Chagatest ELISA recombinant v.3.0 in serum samples of persons experiencing homelessness and related shelter workers in São Paulo, a city with reported vectors but no recent autochthonous case report. Overall, seropositivity to T. cruzi resulted in three of 203 (1.5%) persons experiencing homelessness and two of 87 (2.3%) shelter workers, with similar seroprevalence likely associated with their past social vulnerability. Although the seropositivity in persons experiencing homelessness and shelter workers was within 0 to 25.1% seroprevalence for chronic Chagas disease in the general Brazilian population, the disease has almost decreased 2-fold from the 1980s to 2000s, and such a wide range may not reflect the local disease status. In addition, the authors hypothesized that the similar seroprevalence and exposure between homeless persons and shelter workers herein may be more associated with shared past and present low-income social vulnerability than migratory movements, which may also include infection by sharing injecting drugs, vertical transmission, or blood transfusion. Thus, future studies are needed to confirm the active transmission of Chagas disease in São Paulo city. Moreover, Chagas disease should be considered as differential diagnosis in homeless persons and shelter workers, even in major disease-free Brazilian or other worldwide cities, mostly due to early exposure and vulnerable living conditions.


Metabolism of Poly-β1,4-N-Acetylglucosamine Substrates and Importation of N-Acetylglucosamine and Glucosamine by Enterococcus faecalis.
The ability of Enterococcus faecalis to use a variety of carbon sources enables colonization at various anatomic sites within a mammalian host. N-Acetylglucosamine (GlcNAc) is one of the most abundant natural sugars and provides bacteria with a source of carbon and nitrogen when metabolized. N-Acetylglucosamine is also a component of bacterial peptidoglycan, further highlighting the significance of N-acetylglucosamine utilization. In this study, we show that CcpA-regulated enzymes are required for growth on the poly-β1,4-linked GlcNAc substrate, chitopentaose (β1,4-linked GlcNAc5). We also show that EF0114 (EndoE) is required for growth on chitobiose (β1,4-linked GlcNAc2) and that the GH20 domain of EndoE is required for the conversion of GlcNAc2 to N-acetylglucosamine. GlcNAc is transported into the cell via two separate phosphotransferase system (PTS) complexes, either the PTS IICBA encoded by ef1516 (nagE) or the Mpt glucose/mannose permease complex (MptBACD). The Mpt PTS is also the primary glucosamine transporter. In order for N-acetylglucosamine to be utilized as a carbon source, phosphorylated N-acetylglucosamine (GlcNAc-6-P) must be deacetylated, and here, we show that this activity is mediated by EF1317 (an N-acetylglucosamine-6-phosphate deacetylase; NagA homolog), as a deletion of ef1317 is unable to grow on GlcNAc as the carbon source. Deamination of glucosamine to fructose-6-phosphate is required for entry into glycolysis, and we show that growth on glucosamine is dependent on EF0466 (a glucosamine-6-phosphate deaminase; NagB homolog). Collectively, our data highlight the chitinolytic machinery required for breaking down exogenous chitinous substrates, as well as the uptake and cytosolic enzymes needed for metabolizing N-acetylglucosamine. IMPORTANCE Enterococcus faecalis causes life-threatening health care-associated infections in part due to its intrinsic and acquired antibiotic resistance, its ability to form biofilms, and its nutrient versatility. Alternative nutrient acquisition systems are key factors that contribute to enterococcal colonization at biologically unique host anatomic sites. Although E. faecalis can metabolize an array of carbon sources, little is known of how this bacterium acquires these secondary nutrient sources in mammalian hosts. Our research identifies the glycosidase machinery required for degrading exogenous chitinous substrates into N-acetylglucosamine monomers for transport and metabolism of one of the most abundant naturally occurring sugars, N-acetylglucosamine. Disrupting the function of this N-acetylglucosamine acquisition pathway may lead to new treatments against multidrug-resistant enterococcal infections.


Treatment of frontal bone fracture sequelae through inversion of the bone fragment.
Treatment of frontal sinus fractures depends on the structures involved: the anterior wall, the posterior wall and the nasofrontal duct. It may vary from the correction of the defect in the anterior wall to the cranialization with obliteration of the nasofrontal duct. The inversion of the frontal sinus's anterior wall to correct the defect in the fractured region is a good treatment option for sequelae, since this technique eliminates or reduces the use of biomaterial in the area, and allows direct assessment of the permeability of the nasofrontal duct. This work describes the technique of fractured segment inversion for the treatment of frontal sinus fracture sequelae in a motorcycle accident victim.


Regulatory T cells in human lymphatic filariasis: stronger functional activity in microfilaremics.
Infection with filarial parasites is associated with T cell hyporesponsiveness, which is thought to be partly mediated by their ability to induce regulatory T cells (Tregs) during human infections. This study investigates the functional capacity of Tregs from different groups of filarial patients to suppress filaria-specific immune responses during human filariasis. Microfilaremic (MF), chronic pathology (CP) and uninfected endemic normal (EN) individuals were selected in an area endemic for Brugia timori in Flores island, Indonesia. PBMC were isolated, CD4CD25(hi) cells were magnetically depleted and in vitro cytokine production and proliferation in response to B. malayi adult worm antigen (BmA) were determined in total and Treg-depleted PBMC. In MF subjects BmA-specific T and B lymphocyte proliferation as well as IFN-gamma, IL-13 and IL-17 responses were lower compared to EN and CP groups. Depletion of Tregs restored T cell as well as B cell proliferation in MF-positives, while proliferative responses in the other groups were not enhanced. BmA-induced IL-13 production was increased after Treg removal in MF-positives only. Thus, filaria-associated Tregs were demonstrated to be functional in suppressing proliferation and possibly Th2 cytokine responses to BmA. These suppressive effects were only observed in the MF group and not in EN or CP. These findings may be important when considering strategies for filarial treatment and the targeted prevention of filaria-induced lymphedema.


Educational approaches.
Three papers were presented in the session focusing on educational approaches: Anu Narusk reported on an Estonian study on the influence of the family on adolescents' substance use, Bernadette Roussille presented a French mass media campaign aimed at reducing heavy drinking by young people, and Sally Casswell analysed the public discourse on alcohol, which is an important part of the social and political context in which decisions are taken about public policies. Each of the papers highlighted in its own way the complex relationships between people's behaviour, its social and cultural context, and the wider economic and political environment.


Rituximab in combination with CHOP improves survival in elderly patients with aggressive non-Hodgkin's lymphoma.
Diffuse large B-cell lymphoma (DLCL) is the most frequently diagnosed subtype of non-Hodgkin's lymphoma (NHL), and more than 50% of cases present in patients over 60 years of age. Although cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) is currently regarded as the gold standard treatment for DLCL, less than half of the elderly patients treated are cured. Therefore, it is essential that new strategies are developed. Rituximab is a chimeric monoclonal antibody that is directed against the B-cell-specific antigen CD20 that is expressed on 80% of NHLs. Pilot trials combining rituximab with CHOP have suggested an efficacy advantage in both indolent and aggressive B-cell NHL, with no significant impact on toxicity. The Groupe d'Etude des Lyphomes de l'Adulte LNH-98.5 trial is the first randomized clinical trial to compare rituximab plus CHOP with CHOP alone in lymphoma patients. The trial compared the two treatment regimens in elderly patients with aggressive DLCL. Interim data (18-month follow-up) from this trial showed that the addition of rituximab to CHOP results in a statistically superior benefit in survival compared with CHOP alone. These groundbreaking data are the first in 20 years to show statistical improvement over CHOP and this suggests that rituximab plus CHOP may become the new gold standard treatment for elderly patients with DLCL.