Chronic social stress blunts core body temperature and molecular rhythms of Rbm3 and Cirbp in mouse lateral habenula.
Chronic social stress in mice causes behavioural and physiological changes that result in perturbed rhythms of body temperature, activity and sleep-wake cycle. To further understand the link between mood disorders and temperature rhythmicity in mice that are resilient or susceptible to stress, we measured core body temperature (Tcore) before and after exposure to chronic social defeat stress (CSDS). We found that Tcore amplitudes of stress-resilient and susceptible mice are dampened during exposure to CSDS. However, following CSDS, resilient mice recovered temperature amplitude faster than susceptible mice. Furthermore, the interdaily stability (IS) of temperature rhythms was fragmented in stress-exposed mice during CSDS, which recovered to control levels following stress. There were minimal changes in locomotor activity after stress exposure which correlates with regular rhythmic expression of Prok2 - an output signal of the suprachiasmatic nucleus. We also determined that expression of thermosensitive genes Rbm3 and Cirbp in the lateral habenula (LHb) were blunted 1 day after CSDS. Rhythmic expression of these genes recovered 10 days later. Overall, we show that CSDS blunts Tcore and thermosensitive gene rhythms. Tcore rhythm recovery is faster in stress-resilient mice, but Rbm3 and Cirbp recovery is uniform across the phenotypes.


[Urticaria and angioedema in children].
Urticaria in children is a common disorder often associated with angioedema. An overview on the pathophysiology, clinical presentation, investigation and treatment of urticaria and angioedema in children is presented. Many factors, immunologic and non-immunologic, cause histamine release from tissue mast cells and thus contribute to urticaria. Acute urticaria may be associated with infections and/or allergy. There is increasing evidence that chronic urticaria is an autoimmune disorder caused by functional auto-antibodies against IgE and the Fc-receptor on mast cells. Allergy testing may be helpful in cases of suspected food or drug allergy where the history is not diagnostic. Provocation test for physical urticaria should be performed when indicated. Further diagnostic procedures are seldom useful. Non-sedative antihistamines are the drugs of choice in urticaria and generally provide substantial symptom relief until spontaneous remission occurs.


Histone H1.2 is translocated to mitochondria and associates with Bak in bleomycin-induced apoptotic cells.
Bleomycin induces single- and double-stranded breaks in DNA, with consequent mitochondrial membrane aberrations that lead to the apoptotic cell death. It is poorly understood how DNA damage-inducing apoptotic signals are transmitted to mitochondria, from which apoptotic factors are released into the cytoplasm. Here, we investigated the localization of histone H1.2 in the bleomycin-treated human squamous carcinoma SCCTF cells. The presence of DNA double-strand breaks in the bleomycin-treated cells was examined by Western analysis using antibody against phosphorylated histone H2AX (gamma-H2AX). Incubation of SCCTF cells for 48 h with 10 microM bleomycin induced apoptosis, as determined by cleavage of lamin B1 to 28 kDa fragment and DNA ladder formation. The mitochondrial permeabilization causing apoptotic feature was also detected with MitoCapture in the bleomycin-treated cells. Histone H1.2 was translocated from the nucleus to the mitochondria after treatment with bleomycin and co-localized with Bak in mitochondria. Our present results suggest that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following double-stranded breaks of DNA by bleomycin.


Kinetic model for microbial uptake of insoluble solid-state substrate.
A kinetic model for anaerobic digestion of insoluble solid-state substrates was developed. Rate equations for cell growth and substrate consumption were derived based on the assumption that the microorganisms assimilate the substrate mainly at the point of contact where they grow. The model emphasizes effects of substrate particle size, organic loading, and cell concentration on the rates of cell growth and substrate utilization. Batch digestion of a stearic acid emulsion with a mean particle size of 2.0 microm and a biological sludge was conducted at 30 and 37 degrees C to verify the proposed model. Agreement between the experimental and calculated results indicated the validity of the model for describing the microbial degradation of insoluble solid-state substrates. Further examination of the model revealed that with low cell substrate affinity or at low cell concentration, it coincided with a Michaelis-Menten type kinetics in which the effect of particle size was taken into consideration.


Revealing the Chemistry and Morphology of Buried Donor/Acceptor Interfaces in Organic Photovoltaics.
With power conversion efficiencies (PCEs) of <13% and plagued by stability issues, organic photovoltaics (OPVs) still lack wide adoption, despite significant recent advances. Currently, the most progress in OPV device performance is achieved by "trial-and-error" preparation procedures that lead to complex and largely unknown-despite tremendous analytical efforts-morphologies. Here, we demonstrate a proof-of-principle, chemical imaging methodology that combines experimental high spatial sensitivity and chemical selectivity with theoretical modeling, capable of analyzing the three-dimensional composition and morphology of virtually any device. Allowing the precise measurement of composition and direct visualization of film morphology with depth, our approach reveals the intricate buried donor/acceptor (D/A) interface of a model polymer/fullerene system, poly(3-hexylthiphene-2,5-diyl)/[6,6]-phenyl-C61-butyric acid methyl ester (P3HT/PCBM). In particular, our technique is able to identify and quantify the D/A interface length, that is, the extent of molecular mixing at the D/A interface, a parameter crucial for device performance, yet never measured. Extracting this parameter allows demonstrating that, contrary to the general understanding, when starting with a fully mixed D/A phase in our model system, thermal annealing, which is known to substantially (however limited) increase the device performance by phase segregation, does not create but small amounts of pure phases, leaving the device mostly mixed, which limits the performance improvement.


FCS cell surface measurements--photophysical limitations and consequences on molecular ensembles with heterogenic mobilities.
Fluorescence Correlation Spectroscopy is a powerful method to analyze densities and diffusive behavior of molecules in membranes, but effects of photodegradation can easily be overlooked. Based on experimental photophysical parameters, calculations were performed to analyze the consequences of photobleaching in fluorescence correlation spectroscopy (FCS) cell surface experiments, covering a range of standard measurement conditions. Cumulative effects of photobleaching can be prominent, although an absolute majority of the fluorescent molecules would pass the laser excitation beam without being photo-bleached. Given a distribution of molecules on a cell surface with different diffusive properties, the fraction of molecules that is actually analyzed depends strongly on the excitation intensities and measurement times, as well as on the size of the reservoir of freely diffusing molecules. Both the slower and the faster diffusing molecules can be disfavored. Apart from quantifying photobleaching effects, the calculations suggest that the effects can be used to extract additional information, for instance about the size of the reservoirs of free diffusion. By certain choices of measurement conditions, it may be possible to more specifically analyze certain species within a population, based on their different diffusive properties, different areas of free diffusion, or different kinetics of possible transient binding.


DNA conformational transitions inferred from re-evaluation of m|Fo| - D|Fc| electron-density maps.
Conformational flexibility of DNA plays important roles in biological processes such as transcriptional regulation and DNA packaging etc. To understand the mechanisms of these processes, it is important to analyse when, where and how DNA shows conformational variations. Recent analyses have indicated that conventional refinement methods do not always provide accurate models of crystallographic heterogeneities and that some information on polymorphism has been overlooked in previous crystallographic studies. In the present study, the m|Fo| - D|Fc| electron-density maps of double-helical DNA crystal structures were calculated at a resolution equal to or better than 1.5 Å and potential conformational transitions were found in 27% of DNA phosphates. Detailed analyses of the m|Fo| - D|Fc| peaks indicated that some of these unassigned densities correspond to ZI ↔ ZII or A/B → BI conformational transitions. A relationship was also found between ZI/ZII transitions and metal coordination in Z-DNA from the detected peaks. The present study highlights that frequent transitions of phosphate backbones occur even in crystals and that some of these transitions are affected by the local molecular environment.


Circulating dendritic cells isolated from healthy seropositive donors are sites of human cytomegalovirus reactivation in vivo.
Primary infection with human cytomegalovirus (HCMV) is generally asymptomatic in healthy individuals and results in a lifelong infection of the host. In contrast, in immunosuppressed transplant recipients and late-stage AIDS patients, HCMV infection and reactivation can result in severe disease or death. In vivo, latency is established in bone marrow CD34(+) progenitor cells with reactivation linked with their differentiation to macrophages and dendritic cells (DCs). However, previous analyses have relied on ex vivo differentiation of myeloid progenitor cells to DCs in culture. Here, we now report on the isolation and analysis of circulating blood myeloid DCs, resulting from natural differentiation in vivo, from healthy HCMV-seropositive carriers. We show that these in vivo-differentiated circulating DCs are fully permissive for HCMV and exhibit a phenotype similar to that of monocyte-derived DCs routinely used for in vitro studies of HCMV. Importantly, we also show that these DCs from healthy HCMV-seropositive donors carry HCMV genomes and, significantly, are typically positive for viral immediate-early (IE) gene expression, in contrast to circulating monocytes, which carry genomes with an absence of IE expression. Finally, we show that HCMV reactivation from these circulating DCs is enhanced by inflammatory stimuli. Overall, these data argue that the differentiation in vivo of myeloid progenitors to circulating DCs promotes the reactivation of HCMV lytic gene expression in healthy individuals, thereby providing valuable confirmation of studies performed using in vitro generation of DCs from myeloid precursors to study HCMV reactivation.


IFPA meeting 2016 workshop report II: Placental imaging, placenta and development of other organs, sexual dimorphism in placental function and trophoblast cell lines.
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging; 2) sexual dimorphism; 3) placenta and development of other organs; 4) trophoblast cell lines.


Dobutamine restores the reduced efficiency of energy transfer from total mechanical work to external mechanical work in stunned porcine myocardium.
In order to determine whether the relatively high oxygen consumption of stunned myocardium is related to decreased mechanical efficiency, myocardial oxygen consumption (MVO2) and its major determinants were studied in 10 open chest anaesthetised pigs. According to the time varying elastance concept, MVO2 is determined by contractility (Emax) and total mechanical work (PLA), which is the sum of the external work (EW) and potential energy (PE). Mechanical efficiency (EW/MVO2) equals the product of EW/PLA (= efficiency of energy transfer or EET) and PLA/MVO2. Emax is the slope of the end systolic pressure-segment length relationship, determined by gradually clamping the aorta. PLA is the area enclosed by the end systolic pressure-segment length relationship and the pressure-segment length trajectory. EW is the area of the pressure-segment length loop. Systemic haemodynamics, regional segment shortening, and MVO2 were determined at baseline, during stunning (two sequences of 10 min occlusion and 30 min of reperfusion), after a subsequent 50 beats.min-1 increase in heart rate by atrial pacing and additional infusion of 2 micrograms.kg-1.min-1 dobutamine. Stunning decreased segment shortening from 18.2(SEM 1.9)% to 10.2(1.5)%, MVO2 from 4.16(0.27) x 10(-2) to 2.84(0.25) x 10(-2) mumol.beat-1.g-1, and Emax from 47(9) to 23(3) mm Hg.mm-1 (all p < 0.05). PLA decreased by 13(4)%, as EW decreased by 42(6)%, and PE tended to increase. Although EET decreased from 0.58(0.04) to 0.40(0.03) (p < 0.05), there was no decrease in the mechanical efficiency, as an increase in PE caused an increase in PLA/MVO2 which compensated for the decrease in EET. Dobutamine infusion increased Emax and EW per beat to 120(23)% and 67(8)% of baseline, respectively, while MVO2 [4.12(0.53) mumol.beat-1.g-1] and EET [0.57(0.04)] returned to baseline. In stunned myocardium, mechanical efficiency is not decreased despite a decrease in EET. The increase in EET after dobutamine may explain the lack of the excessive increase in MVO2.


Preparation of superhydrophobic coatings on zinc as effective corrosion barriers.
Stable superhydrophobic films with a contact angle of 151 +/- 2 degrees were prepared on zinc substrates by a simple immersion technique into a methanol solution of hydrolyzed 1H,1H,2H,2H-perfluorooctyltrichlorosilane [CF3(CF2)5(CH2)2SiCl3, PFTS] for 5 days at room temperature followed by a short annealing at 130 degrees C in air for 1 h. The superhydrophobic film provides an effective corrosion-resistant coating for the zinc interface when immersed in an aqueous solution of sodium chloride (3% NaCl) for up to 29 days. The corrosion process was investigated by following the change of the water contact angle over time and by electrochemical means. The results are compared to those of unprotected zinc interfaces.


Development of a chimaeric receptor approach to study signalling by tumour necrosis factor receptor family members.
Members of the tumour necrosis factor receptor family play a pivotal role in cell differentiation, function and apoptosis. However, signalling by many members of the family remains to be elucidated. In the present study, we developed a chimaeric receptor approach for studying signalling by receptors belonging to this family. The chimaeric receptor comprises the human Fas external domain linked to the transmembrane and cytoplasmic domains of a tumour necrosis factor receptor family member of interest. When the chimaera is expressed in mouse cells, the clustering of the chimaera induced by a human Fas-activating antibody activates the intracellular domain of the chimaera without affecting its endogenous counterpart. Since the antibody recognizes only human Fas, this approach can be used to dissect signalling by any tumour necrosis factor family member using any type of mouse cell including those endogenously expressing Fas. Moreover, we also showed that the chimaeric receptor approach can be used to study signalling at any stage of cell differentiation or function.


Perspective-taking is two-sided: Misunderstandings between people with Asperger's syndrome and their family members.
Misunderstandings are social in nature, always having two sides. Yet the misunderstandings experienced by people with Asperger's syndrome are usually studied in terms of the individual with a diagnosis, with less emphasis on social relations. We use a two-sided methodology to map out misunderstandings within 22 dyads (n = 44) consisting of people with Asperger's syndrome and their family members. Both sides of the relationship were asked about 12 topics in terms of one's rating of Self, one's rating of Other and one's predicted rating by Other. The findings show that people with Asperger's are able to predict lower scores from family members, despite disagreeing with their view, and that family members often over-estimate the extent to which their relatives with Asperger's syndrome are egocentrically anchored in their own perspective. The research demonstrates that a two-sided methodology is viable, and it uses it to identify how representations of Asperger's syndrome can both support and hinder social understanding within relationships affected by Asperger's.


The Effects of Aromatherapy on Postpartum Women: A Systematic Review.
The postpartum period is the most crucial but also the most fragile stage of most pregnancies. The health benefits of aromatherapy have recently become more widely accepted among medical experts. Although a number of studies have examined these health benefits, no systematic reviews have been conducted to assess the effects of aromatherapy on the psycho-physiological health of postpartum women. This systematic review was conducted to evaluate the effectiveness of aromatherapy interventions on the psycho-physiological health of postpartum women, to determine the methods that were used to measure intervention effectiveness, and to identify the types of interventions that were used. We searched for studies that evaluated the effects of aromatherapy on postpartum women published in the Chinese or English languages before March 2018. We used online databases such as the Taiwan Journal Index, Centre for European Policy Studies, Cumulative Index for Nursing and Allied Health Literature, Cochrane Library, PubMed, and Social Sciences Citation Index. The search keywords used were "women," AND "postpartum," OR "postnatal" AND "aromatherapy," OR "aroma," OR "essential oils." Only randomized controlled trials including humans as study participants were included. The methodological quality of the trials was assessed using the modified Jadad scale. The quality of the full-text studies was assessed by three reviewers. The 15 studies that were included in this systematic review were performed in Iran, England, and the United States and included 2,131 participants in total. The numbers of participants in each study ranged between 35 and 635. The review found that the effective duration of aromatherapy varied according to the essential oils that were selected. The visual analog scale was the most frequently used measure of postpartum pain. Most of the studies found that the aromatherapy intervention improved postpartum physiological and psychological health, with positive effects shown on anxiety, depression, distress, fatigue, mood, nipple fissure pain, physical pain, post-cesarean-delivery pain, post-cesarean-delivery nausea, postepisiotomy pain, postepisiotomy recovery, sleep quality, and stress. Most of the studies reported no serious intervention-related side effects. This systematic review may serve as a reference for healthcare workers in caring for postpartum women. Aromatherapy may be applied as a noninvasive complementary intervention to promote physio-psychological comfort in postpartum women.


Lack of utility of metabolic screening in Ménière's disease.
The incidence of disturbances of carbohydrate and lipid metabolism were studied in two groups of patients; one group with Ménière's disease, the other with otosclerosis. Our observations do not support the notion that metabolic disturbances are the principal causes of the symptom complex in Ménière's disease. Results of thyroid function tests were also normal in all Ménière's patients tested.


A mathematical model of phloem sucrose transport as a new tool for designing rice panicle structure for high grain yield.
Rice (Oryza sativa) is one of the most important food crops in the world. Numerous quantitative trait loci or genes controlling panicle architecture have been identified to increase grain yield. Yet grain yield, defined as the product of the number of well-ripened grains and their weight, is a complex trait that is determined by multiple factors such as source, sink and translocation capacity. Mechanistic modelling capturing capacities of source, sink and transport will help in the theoretical design of crop ideotypes that guarantee high grain yield. Here we present a mathematical model simulating sucrose transport and grain growth within a complex phloem network. The model predicts that the optimal panicle structure for high yield shows a simple grain arrangement with few higher order branches. In addition, numerical analyses revealed that inefficient delivery of carbon to panicles with higher order branches prevails regardless of source capacity, indicating the importance of designing grain arrangement and phloem structure. Our model highlights the previously unexplored effect of grain arrangement on the yield, and provides numerical solutions for optimal panicle structure under various source and sink capacities.


Analysis of metal element distributions in rice (Oryza sativa L.) seeds and relocation during germination based on X-ray fluorescence imaging of Zn, Fe, K, Ca, and Mn.
Knowledge of mineral localization within rice grains is important for understanding the role of different elements in seed development, as well as for facilitating biofortification of seed micronutrients in order to enhance seeds' values in human diets. In this study, the concentrations of minerals in whole rice grains, hulls, brown rice, bran and polished rice were quantified by inductively coupled plasma mass spectroscopy. The in vivo mineral distribution patterns in rice grains and shifts in those distribution patterns during progressive stages of germination were analyzed by synchrotron X-ray microfluorescence. The results showed that half of the total Zn, two thirds of the total Fe, and most of the total K, Ca and Mn were removed by the milling process if the hull and bran were thoroughly polished. Concentrations of all elements were high in the embryo regions even though the local distributions within the embryo varied between elements. Mobilization of the minerals from specific seed locations during germination was also element-specific. High mobilization of K and Ca from grains to growing roots and leaf primordia was observed; the flux of Zn to these expanding tissues was somewhat less than that of K and Ca; the mobilization of Mn or Fe was relatively low, at least during the first few days of germination.


Stochastic fluctuations in epidemics on networks.
The effects of demographic stochasticity on the long-term behaviour of endemic infectious diseases have been considered for long as a necessary addition to an underlying deterministic theory. The latter would explain the regular behaviour of recurrent epidemics and the former the superimposed noise of observed incidence patterns. Recently, a stochastic theory based on a mechanism of resonance with internal noise has shifted the role of stochasticity closer to the centre stage, by showing that the major dynamic patterns found in the incidence data can be explained as resonant fluctuations, whose behaviour is largely independent of the amplitude of seasonal forcing, and by contrast very sensitive to the basic epidemiological parameters. Here we elaborate on that approach, by adding an ingredient which is missing in standard epidemic models, the 'mixing network' through which infection may propagate. We find that spatial correlations have a major effect on the enhancement of the amplitude and the coherence of the resonant stochastic fluctuations, providing the ordered patterns of recurrent epidemics, whose period may differ significantly from that of the small oscillations around the deterministic equilibrium. We also show that the inclusion of a more realistic, time-correlated recovery profile instead of exponentially distributed infectious periods may, even in the random-mixing limit, contribute to the same effect.


Vulnerability in elderly patients with gastrointestinal cancer--translation, cultural adaptation and validation of the European Portuguese version of the Vulnerable Elders Survey (VES-13).
"Vulnerable Elders Survey" (VES-13) is a questionnaire accurate in predicting functional decline and highly correlated with comprehensive geriatric assessment in identifying vulnerable elderly. The purpose of this study was to translate, cultural adapt and validate the first Portuguese cross-cultural version of VES-13 and to estimate the prevalence of vulnerability in Portuguese elderly gastrointestinal (GI) cancer patients. VES-13 European Portuguese translation and cultural adaptation was developed according to internationally accepted guidelines. Test-retest reliability and internal consistency were assessed by calculating the Kappa statistic and by analyzing the inter-item and item-total correlation matrices and calculation of Cronbach's alpha coefficients, respectively. Construct and criterion validity was assessed by Spearman's correlation coefficient between VES-13 and each EQ-5D-5 L dimension, clinical judgment and performance status. The translated and culturally adapted version of VES-13 revealed high test-retest reliability (test-retest Kappa ≥ 0.612; p < 0.001) in the pilot study (n = 22). For the validation phase 206 patients with GI cancer were recruited (median age: 73 years; colo-rectal cancer: 63 %). Criterion validity was confirmed by adequate correlations between VES-13 and clinical judgment of vulnerability, ECOG and KPS scores. Construct validity was confirmed by moderate correlations with most of EQ-5D-5 L dimensions. Cronbach's alpha of the questionnaire was 0.848. The estimated prevalence of vulnerability is 50 % (CI95% 0.43-0.56). The European Portuguese version of VES-13 is a valid and reliable approach to screening elderly cancer patients for geriatric needs. In our setting, one in two elderly patients was likely to be vulnerable or frail which stresses the importance of their correct identification to better inform cancer management.


[Immunotherapy against peritoneal dissemination by immunostimulatory CpG DNA].
Peritoneal dissemination is one of the most common causes of metastasis from malignancies in the abdominal cavity. However, the treatment of peritoneal dissemination is difficult; patients receiving normal chemotherapy have a 0-1% chance of surviving for 5 years. Milky spots in the greater omentum are considered to facilitate the adhesion and invasion of abdominal free cancer cells, and subsequently lymph node metastasis occurs. Since immune cells such as macrophages and lymphocytes are present in the greater omentum and lymph nodes, the activation of immune cells would be a promising strategy for treatment. Single-stranded oligonucleotides containing CpG dinucleotides (CpG DNA) are recognized by Toll-like receptor-9 on antigen-presenting cells such as macrophages to stimulate Th-1-type immune responses. However, a delivery system for CpG DNA to immune cells is essential to develop effective therapy against peritoneal dissemination. Here we review the pathophysiologic basis of peritoneal dissemination and introduce our approach that employs cationic liposomes as a carrier for CpG DNA as a new approach in the treatment of peritoneal dissemination.


Comments on the validity of the non-stationary generalized Langevin equation as a coarse-grained evolution equation for microscopic stochastic dynamics.
We recently showed that the dynamics of coarse-grained observables in systems out of thermal equilibrium are governed by the non-stationary generalized Langevin equation [H. Meyer, T. Voigtmann, and T. Schilling, J. Chem. Phys. 147, 214110 (2017); 150, 174118 (2019)]. The derivation we presented in these two articles was based on the assumption that the dynamics of the microscopic degrees of freedom were deterministic. Here, we extend the discussion to stochastic microscopic dynamics. The fact that the same form of the non-stationary generalized Langevin equation as derived for the deterministic case also holds for stochastic processes implies that methods designed to estimate the memory kernel, drift term, and fluctuating force term of this equation, as well as methods designed to propagate it numerically, can be applied to data obtained in molecular dynamics simulations that employ a stochastic thermostat or barostat.


Systematic review and meta-analysis of long-term outcomes in adults undergoing the Ross procedure.
The management of aortic valve disease is becoming increasingly complicated with the evolution of treatment options available to cardiac surgeons and cardiologist. Pulmonary autograft replacement of the aortic valve, commonly known as the Ross procedure, involves excision of the pulmonary valve from the right ventricular outflow tract and implantation in the aortic position. This systematic review aims to evaluate the long-term outcomes, following the Ross procedure. An electronic search strategy queried five online medical referencing databases from inception to 21 August 2020. All studies detailing the long-term outcomes of adults undergoing the Ross procedure were included. A random effects model was used to determine pooled continuous data. Enhanced secondary survival analysis was performed on reconstructed individual patient data. Twenty-three studies were included in the qualitative synthesis, including a total of 6,278 patients with a mean follow-up duration of 6.0±2.8 years. Long-term survival was 95.6%, 91.8%, 86.3% and 80.5% at five, ten, fifteen and twenty years, respectively. Freedom from autograft reoperation was 95.7%, 91.2%, 84.9% and 76.1% at five, ten, fifteen and twenty years, respectively. When performed in experienced centres and for appropriately selected patients, the Ross procedure represents a durable replacement of the aortic valve with excellent long-term survival.


[Future developments in genetic research. II. Psychological and social aspects].
Regarding the determination of genetic risk factors for serious diseases, the main question for a patient's young relatives is 'to know or not to know'. The answer depends among other things on the assessment of the severity of the disorder and the magnitude of the risk in relation to the population risk and on the availability of therapeutic or preventive measures. Experience with the requests for and the coping with results of the presymptomatic DNA test for untreatable neurodegenerative chorea of Huntington show that expectations about the effect of predictive DNA studies are often different from reality. A problem of a different nature arises in multifactorial diseases such as mammary or colonic carcinoma, because irrespective of the DNA study it remains uncertain whether or not the disease will occur. Nevertheless more than half of the healthy relatives of a patient with breast cancer requests DNA testing and a large majority of the proven carriers of a BCRAI and BRCA2 mutation chose for bilateral mastectomy and oophorectomy. Many questions about psychosocial consequences of predictive DNA testing remain to be answered: what will be the effect of early medicalization, how will relations be affected and which effect will carriership of genetic risk factors have on behaviour? Dutch legislation provides adequate guarantees against the use by third parties of results of genetic testing. The question remains, however, how future internationalization will work out in this respect. The possibly far-reaching social and psychological consequences of genetic research make some people feel that restraints should be imposed on this research. However, there are more grounds for curiosity and enthusiasm to constantly find new solutions for the new problems.


Chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, prevents fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment.
We hypothesized that chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, to young adult male rats would prevent/ameliorate fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment. Eighty 12-14-week-old young adult male Fischer 344 rats received either: (1) sham irradiation, (2) 40 Gy of fractionated whole-brain irradiation delivered as two 5 Gy fractions/week for 4 weeks, (3) sham irradiation plus continuous administration of 15 mg/L of ramipril in the drinking water starting 3 days before irradiation, or (4) fractionated whole-brain irradiation plus ramipril. Cognitive function was assessed using a perirhinal cortex-dependent version of the novel object recognition task 26 weeks after irradiation. Microglial activation was determined in the perirhinal cortex and the dentate gyrus of the hippocampus 28 weeks after irradiation using the ED1 antibody. Neurogenesis was assessed in the granular cell layer and subgranular zones of the dentate gyrus using a doublecortin antibody. Fractionated whole-brain irradiation led to: (1) a significant impairment in perirhinal cortex-dependent cognitive function, (2) a significant increase in activated microglia in the dentate gyrus but not in the perirhinal cortex, and (3) a significant decrease in neurogenesis. Continuous administration of ramipril before, during, and after irradiation prevented the fractionated whole-brain irradiation-induced changes in perirhinal cortex-dependent cognitive function, as well as in microglial activation in the dentate gyrus. Thus, as hypothesized, continuous administration of the angiotensin-converting enzyme inhibitor, ramipril, can prevent the fractionated whole-brain irradiation-induced impairment in perirhinal cortex-dependent cognitive function.


A post-insertion protocol for management of the Olympic Tracheostomy Button in neurosurgical patients.
This article describes and suggests a protocol for the monitoring and management of problems relating to the use of the Olympic Tracheostomy button with special emphasis on the needs of neurosurgical patients. A description of the Olympic Tracheostomy button is accompanied by a systematic checklist for nursing care supplemented by supporting rationale. The existence and availability of such a protocol for this patient group should focus the concern of all nursing personnel in a unified and orderly manner and heighten the index of suspicion for problems which may be subtle but potentially life-threatening.


Molecular basis of endothelial dysfunction in sepsis.
Sepsis is one of the major causes of mortality in critically ill patients and develops as a result of the host response to infection. A complex network of events is set into motion in the body by the infection and results in the pathogenesis of sepsis. This review article focuses on the molecular mechanisms and components involved in the pathogenesis of sepsis with a major emphasis on the endothelium. This includes sepsis-inducing bacterial components (e.g. endotoxins), cellular targets of these molecules and their responses, host reactions, intracellular and cytokine networks, individual susceptibility and new therapeutic targets in sepsis treatment.


The cellular basis of the aggressive acrorhagial response of sea anemones.
Some sea anemones possess structures called acrorhagi at the base of the tentacles. The acrorhagi are utilized solely for aggression. Acrorhagial aggression involves very exquisite intra- and interspecific recognition. This study examined acrorhagi and putative acrorhagial analogues or homologues in four species of sea anemone. The morphology and ultrastructure of tentacles, pseudoacrorhagi, column vesicles, and verrucae (adhesive column vesicles) differed from that of acrorhagi. Coral capitate tentacles and acrorhagi have different surface morphology, nematocysts, and functions. Besed on morphology, acrorhagi seem more likely to be homologous to tentacles than to verrucae. Acrorhagial nematocyst discharge and ectodermal peeling, the culmination of the response, were shown to require prior acrorhagial expansion in Anthopleura krebsi and Bunodosoma cavernata. A mechanical mechanism is suggested where- by distention of the acrorhagus opens a ciliary pit on the nematocyte surface and exposes the pit wall and microvilli, which may contain the chemoreceptors for the peeling process, including nematocyst discharge. A similar system may also be responsible for changing the threshold of nematocyst discharge in sea anemone tentacles. A case of possible neurosecretion in an anthozoan was also shown in this study.


Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration.
Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.


Nifedipine--a calcium channel blocker--in asthmatic patients. Interaction with terbutaline.
Seven asthmatic patients were studied in a single-blind randomized, crossover study after oral administration of 20 mg nifedipine or placebo. Four increasing doses of i.v. terbutaline were then given with 30 min interval. The study was concluded with inhalation of five terbutaline puffs. FEV1 measurements 30 min after intake of nifedipine did not show any difference compared to placebo. During the terbutaline treatment, however, there was a more pronounced bronchodilation after nifedipine than after placebo (P less than 0.05). Terbutaline-induced skeletal muscle tremor was similar after nifedipine and placebo pretreatments. After nifedipine intake there was a decrease of diastolic blood pressure and a reflexogenic tachycardia. Thus, this study showed a small potentiation of the beta 2-adrenoceptor mediated bronchodilation, which is of importance when treating patients with simultaneous asthma and hypertension or angina pectoris.


Gaseous ammonia uptake in compost biofilters as related to compost water content.
Sewage sludge and yard waste compost were used as biofilter materials and tested with respect to their capacity for removing ammonia from air at different water contents. Ammonia removal was measured in biofilters containing compost wetted to different moisture contents ranging from air dry to field capacity (maximum water holding capacity). Filters were operated for 15 days and subsequently analyzed for NH3/NH4+, NO2-, and NO3-. The measured nitrogen species concentration profiles inside the filters were used to calculate ammonia removal rates. The results showed that ammonia removal is strongly dependent on the water content in the filter material. At gravimetric water contents below 0.25 g H2O g solids(-1) for the yard waste compost and 0.5 g H2O g solids(-1) ammonia removal rates were very low but increased rapidly above these values. The sewage sludge compost filters yielded more than twice the ammonia removal rate observed for yard waste compost likely because of a high initial concentration of nitrifying bacteria originating from the wastewater treatment process and a high airwater interphase surface area that facilitates effective ammonia dissolution and transport to the biofilm.


A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19.
The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.


Cognitive decline in normal aging and its prevention: a review on non-pharmacological lifestyle strategies.
The purpose of this study is to examine the effects of the selected non-pharmacological lifestyle activities on the delay of cognitive decline in normal aging. This was done by conducting a literature review in the four acknowledged databases Web of Science, Scopus, MEDLINE, and Springer, and consequently by evaluating the findings of the relevant studies. The findings show that physical activities, such as walking and aerobic exercises, music therapy, adherence to Mediterranean diet, or solving crosswords, seem to be very promising lifestyle intervention tools. The results indicate that non-pharmacological lifestyle intervention activities should be intense and possibly done simultaneously in order to be effective in the prevention of cognitive decline. In addition, more longitudinal randomized controlled trials are needed in order to discover the most effective types and the duration of these intervention activities in the prevention of cognitive decline, typical of aging population groups.


Biobanking in Estonia.
Estonia is a democratic, parliamentary republic with a health care system that is built on the principle of compulsory, solidarity-based insurance and the all-round availability of services of private service providers. Estonia has specific biobank legislation as well as oversight via data protection laws. Its population-based biobank, the Estonian Genome Center (EGCUT), established in 2001, is one of the largest biobanks in Europe, and its database may be used only for scientific research, public health research, and statistics. The EGCUT can issue data to a third party, but only in coded form. This comprehensive database of genotypic, phenotypic, health, and genealogical information represents about 5% of Estonia's adult population, and is the largest cohort ever gathered in Estonia. Government approval is required for international data sharing, and sharing can be further limited by the requirement of ethics approval and permission from Estonian government.


Chlorhexidine Monotherapy with Adjunctive Topical Corticosteroids for Acanthamoeba Keratitis.
To assess the efficacy of chlorhexidine monotherapy for Acanthamoeba keratitis, and to determine the therapeutic outcomes of concomitant topical corticosteroids. In this prospective interventional case series, 31 eyes of 31 patients with Acanthamoeba keratitis (AK) were treated with chlorhexidine 0.02% as monotherapy, from April 2010 to April 2011. The diagnosis of AK was made based on clinical manifestations and positive confocal microscopic (confoscan 3.4, Nidek Co. Ltd., Gamagori, Japan) results. We report the percentage of a favorable clinical response within two weeks of initiating treatment, worsening of the infection while receiving chlorhexidine, recovery of visual acuity (VA), duration of treatment with chlorhexidine and corticosteroids, necessity for addition of other anti-Acanthamoeba agents, presence of corneal scar at the end of the treatment, and need for penetrating keratoplasty (PK). Two weeks after initiation of chlorhexidine, improvement in signs and symptoms was observed in 26 (83.9%) patients but 3 eyes required the addition of propamidine. After initial improvement in one patient, the infection worsened, necessitating the addition of Polyhexamethylene Biguanide (PHMB) and propamidine. A total of 26 (83.9%) patients received topical corticosteroids with mean duration of 65.8 ± 45.1 days. In 22 (71%) eyes, final visual acuity was ≥0.80. Improved VA occurred in 29 eyes (93.5%). Optical PK was considered in 3 (9.7%) eyes and a corneal scar developed in 8 (25.8%) eyes. Chlorhexidine is effective for monotherapy in AK and could be a good choice for initiating treatment. After the initial response to anti-Acanthamoeba agents, corticosteroids can be used as adjunctive therapy depending on the clinical condition.


Previous studies in Sweden have focused on a number of indicators to assess and compare health conditions at regional levels over time. In this study we aimed to give a more complete picture of the health situation in Stockholm County compared to the rest of Sweden, by using the DALY measure (disability-adjusted life years). DALY combines life lost to premature death (YLL) and years lived with disability (YLD) in one measure, and also allow comparisons of fatal and non-fatal conditions. This approach reveals that low back and neck pain and ischemic heart disease dominated the disease burden in 2015. Moreover, the health progress in Stockholm County has been better than the rest of Sweden since 1990, and the main reason is the decrease in premature death (YLL). This can partly be explained by a decrease in risk factors such as unhealthy diets, high blood pressure, tobacco smoking, high BMI and physical inactivity. The development of YLD has been relatively constant since 1990 in both Stockholm County and the rest of Sweden, implying that Sweden has been more successful in preventing death than reducing disability.


The experience of stroke for men in retirement transition.
In this study, the authors aimed to explore how men manage when two significant life events, stroke and retirement, occur within a close time proximity. They selected 7 men purposively who were either in the process of planning to retire or had just retired when they had suffered a stroke, and used interpretive phenomenological analysis to guide data collection and to analyze the resulting transcripts. The authors derived three interrelated processes with eight subthemes. The three themes were associated with ambivalence about retirement, the impact of the stroke, and healing and adjustment. The themes suggested that significant interplay existed between the meanings made of the two life events. The emergent themes implied that stroke had a profound impact on the men's lives and affected them on a number of levels. The experience of suffering a stroke also led to some positive reframing of life.


Differences in Mate Pairings of Hatchery- and Natural-Origin Coho Salmon Inferred from Offspring Genotypes.
Captive breeding can affect how sexual selection acts on subsequent generations. One context where this is important is in fish hatcheries. In many salmon hatcheries, spawning is controlled artificially and offspring are reared in captivity before release into the wild. While previous studies have suggested that hatchery- and natural-origin fish may make different mate choice decisions, it remains to be determined how hatchery fish may be making different mate choice decisions compared with natural-origin fish at a genetic level. Using genotyping-by-sequencing, we identify single-nucleotide polymorphisms (SNPs) associated with variation in mate pairings from a natural context involving hatchery- and natural-origin coho salmon (Oncorhynchus kisutch). In both natural-origin and hatchery mate pairs, we observed more SNPs with negative assortment than positive assortment. However, only 3% of the negative assortment SNPs were shared between the two mating groups, and 1% of the positive assortment SNPs were shared between the two mating groups, indicating divergence in mating cues between wild and hatchery-raised salmon. These findings shed light on mate choice in general and may have important implications in the conservation management of species as well as for improving other captive breeding scenarios. There remains much to discover about mate choice in salmon and research described here reflects our intent to test the potential of ongoing advances in population genomics to develop new hatchery practices that may improve the performance of hatchery offspring, lessening the differences and thus potential impacts upon wild stocks.


The effect of Nigella sativa on inflammation-induced myocardial fibrosis in male rats.
Nigella sativa (NS) (Ranunculaceae) used as a protective and therapeutic traditional medicine. This study evaluates the effect of NS on inflammation-induced myocardial fibrosis, serum and tissue inflammatory markers, and oxidative stress status in male rats. Fifty male Wistar rats were divided into five groups: (1) control; (2) lipopolysaccharide (LPS), 1 mg/kg/day; (3) LPS + NS (hydroalcoholic extract), 100 mg/kg/day; (4) LPS + NS, 200 mg/kg/day; (5) LPS + NS, 400 mg/kg/day (n = 10 in each group). The duration of LPS administration was two weeks. At the end of the experiment, blood samples were taken and ventricles were homogenized and stained for histological evaluation. Serum nitrite levels were lower in LPS group than the control group (22.98 ± 1.03 vs 28.5 ± 0.93 μmol/L), in which they were significantly increased by NS treatment (P < 0.05). Higher levels of heart interlukine-6 (IL-6) and tumor necrosis factor-α (TNF-α) were observed in LPS group compared to the controls (IL-6: 6805 ± 656 vs 4733 ± 691 pg/mL; TNF-α: 6504 ± 501 vs 5309 ± 452 pg/mL), in which they were reduced by NS 400 mg/kg compared to LPS groups (P < 0.05). A significant increment of malondialdehyde and reduction in heart total thiol, superoxide dismutase and catalase concentrations were observed in LPS group (p < 0.05) which significantly restored with treatment by three doses of NS. Histopathological studies showed higher inflammatory cell infiltrates, cardiac fibrosis, and collagen deposition in LPS group, which were reduced by the administration of NS. Treatment by NS reduced myocardial fibrosis in inflammation-induced fibrosis, possibly through improving oxidative/anti-oxidative balance.


Detection of human papillomavirus in a urothelial carcinoma mimicking urethral caruncle.
Primary carcinoma of the female urethra is an uncommon diagnosis, accounting for less than 0.02% of all carcinomas in women. Urothelial carcinomas occupying the distal urethra in young females are considered to be extremely rare. Here we report what we believe to be the sixth case of primary urothelial carcinoma in the published English-language literature. The patient, a 26-year-old woman, presented with a distal urethral lesion that resembled a caruncle, but which was proved to be a urothelial carcinoma on histopathological examination of the resected specimen. Human papillomavirus type 51 DNA was detected in the tumor by polymerase chain reaction and in situ hybridization. These findings suggest that human papillomavirus might be involved in a subset of urothelial carcinomas of the urethra.


Patient-rated versus proxy-rated cognitive and functional measures in older adults.
Patients with cognitive impairment may have difficulty reporting their functional and cognitive abilities, which are important clinical outcomes. Health care proxies may be able to corroborate patient self-reports. Several studies reported discrepancy between patient and proxy ratings, though the literature is sparse on changes over time of these ratings. Our goals in this 12-month study were to compare patient and proxy reports on functioning, cognition, and everyday executive function, and to further elucidate correlates of patient-proxy discrepancy. This was a prospective cohort study of individuals older than 70 years who ranged from having no cognitive impairment to having moderate dementia who had a proxy available to complete instruments at baseline (N=76). Measurements included Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADLI), Neuro-QOL Executive Function, PROMIS Applied Cognition (PROMIS-Cog), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale. Patient- and proxy-rated ADCS-ADLI were correlated at baseline and at 1-year follow-up. Patient and proxy ratings were discrepant on Neuro-QOL Executive Function and PROMIS-Cog. Greater patient-proxy discrepancy on PROMIS-Cog was associated with younger age and less depression, and greater patient-proxy discrepancy on Neuro-QOL Executive Function was associated with less depression and worse cognitive impairment. Patient-proxy discrepancy increased over time for everyday executive function. Changes in proxy-rated but not patient-rated ADCS-ADLI correlated with MMSE changes. Patients and proxies generally agree in reporting on activities of daily living. Patient and proxy reports differ in their respective evaluation of cognitive functioning and everyday executive function. Ratings from both sources may be preferred for these two domains, though studies using gold standard measures are necessary. It is important that clinicians are aware of the differences between patient and proxy perspective to create an accurate clinical picture and guide treatment.


Pupillary Light Reflex and Multimodal Imaging in Patients With Central Serous Chorioretinopathy.
The purpose of this study was to investigate and compare the corresponding alterations of the pupillary response between acute and chronic central serous chorioretinopathy (CSC) and between different disease categories. We recruited patients with unilateral acute and chronic CSC. An eye tracker was applied to determine the pupillary light reflex (PLR) and evaluate the following PLR metrics in healthy eyes: pupil diameter, diameter changes, including relative constriction amplitude (AMP%), and re-dilation ratio (D1%). Baseline optical coherence tomography (OCT), and fluorescein and indocyanine green angiography (FA/ICGA) were performed to analyze the relationship between pupillary response and retinal/choroidal architecture. In total, 52 patients were enrolled, including 25 with acute CSC and 27 with chronic CSC. Compared to the chronic CSC group, the acute CSC group displayed a significantly larger baseline pupil diameter (BPD; of 5.51 mm, P = 0.015), lower AMP% (34.40%, P = 0.004), and higher D1% (93.01%, P = 0.002), indicating sympathetic overactivity. On OCT, the total macular volume was positively correlated with the D1% (r = 0.48, P = 0.005) and negatively with AMP (r = -0.47, P = 0.007). On ICGA, the intense choroidal vascular hyperpermeability (CVH) group displayed a greater BPD than the nonintense CVH group. Additionally, 9 cases with later recurrent episodes following therapy showed a lower AMP% and higher D1% than the nonrecurrent group. The PLR revealed sympathetic excitation in patients with acute CSC. The stronger D1% was significantly associated with greater total macular volume, and it may be a potential biomarker for predicting the later recurrence of CSC.


Synthesis, Physicochemical Properties, and Antimicrobial Studies of Iron (III) Complexes of Ciprofloxacin, Cloxacillin, and Amoxicillin.
Iron (III) complexes of ciprofloxacin, amoxicillin, and cloxacillin were synthesized and their aqueous solubility profiles, relative stabilities, and antimicrobial properties were evaluated. The complexes showed improved aqueous solubility when compared to the corresponding ligands. Relative thermal and acid stabilities were determined spectrophotometrically and the results showed that the complexes have enhanced thermal and acid stabilities when compared to the pure ligands. Antimicrobial studies showed that the complexes have decreased activities against most of the tested microorganisms. Ciprofloxacin complex, however, showed almost the same activity as the corresponding ligand. Job's method of continuous variation suggested 1 : 2 metals to ligand stoichiometry for ciprofloxacin complex but 1 : 1 for cloxacillin complex.


DXMSMS Match Program for Automated Analysis of LC-MS/MS Data Obtained Using Isotopically Coded CID-Cleavable Cross-Linking Reagents.
Cross-linking combined with mass spectrometry for the study of proteins and protein complexes is greatly facilitated by the use of isotopically coded cleavable cross-linking reagents. The isotopic coding of the cross-linker enables confident detection of the cross-link signals, while cleavage of the cross-linker provides masses of the individual peptides composing the cross-link and, therefore, facilitates unambiguous assignment of the cross-links. Here, we describe the DXMSMS Match program, designed for automatic analysis of LC-MS/MS mass spectrometric data obtained with isotopically coded CID-cleavable cross-linkers. The program verifies the assignments of the cross-links by precursor mass and by inspection of the MS/MS spectra for the fragments and the cleavage products of the cross-linked peptides. The program produces nonprobabilistic scores for matching the spectra to the theoretical fragmentation of the cross-links and a visual interface for the validation of the mass spectral matches.


Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa.
Mitogen-activated protein kinases (MAPK), also known as extracellular signal-regulated kinases (ERKs) are cytoplasmic and nuclear serine/threonine kinases involved in signal transduction of several extracellular effectors. Recently, we have demonstrated that ERKs are present in spermatozoa and are involved in the regulation of the process of capacitation. We report here the effect of progesterone, a well-known inducer of the acrosome reaction in mammalian spermatozoa, on the immunolocalization, phosphorylation and activity of ERKs in capacitated human spermatozoa. We demonstrated that short-term incubation of spermatozoa with progesterone induces phosphorylation and activation of ERKs, resulting in redistribution of the proteins from the post-acrosomal region to the equatorial segment within the sperm head. To investigate the role of ERKs on the biological effects of progesterone, we used the MAPK cascade inhibitor PD098059, which strongly inhibited progesterone-induced activation of ERK-2. This compound did not inhibit progesterone-induced acrosome reaction, although it prevented redistribution of the enzyme to the equatorial region of the sperm head. These results suggest that the two processes, although temporally related, are independent. In conclusion, we provide new insight into the signal transduction pathways involved in the non-genomic action of progesterone in spermatozoa and suggest a possible involvement of ERKs in the process of fertilization.


Time to TAVI: streamlining the pathway to treatment.
Severe aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI. The centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed. Mean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p<0.00001). The total pathway time from echocardiographic diagnosis to TAVI for the centre performing local workup was 89.9±67.6 days, which was also significantly shorter than referral to TAVI time from all other centres (p<0.003). Centres without local workup had a significantly lower percentage of patients accepted for TAVI (49.5% vs 97.8%, p<0.00001). A novel TAVI pathway with emphasis on local workup within a non-surgical centre significantly reduced both the time to TAVI and rejection rates from a Heart Valve Centre. If adopted across the other centres, this approach may help improve access to TAVI.


[Monocytes are more susceptible in vitro in rhesus macaques of Chinese origin to recombinant serotype 5 adenovirus with higher preexisting vector specific neutralizing antibody titer].
Human adenovirus serotype 5 (HAd5) infect dendritic cells with low efficiency which restricts the use of HAd5 as an antigen carrying vector in such cells. Aiming to find a novel strategy to detour the traditional method for more convenient clinical use, peripheral blood mononuclear cells isolated from Chinese rhesus macaques were chosen as the target cells for HAd5. In vitro infection protocol was optimized which indicated centrifugation at 1000g could ease the entry of adenovirus. By this protocol, CD14 positive monocytes were infected at high efficiencies (> 80%), and about 10% of natural killer cells were infected; while T and B lymphocytes were rarely infected. Interestingly and importantly, it was the first time to report that in our in vitro study monocytes were more susceptible to HAd5-EGFP in macaques with higher preexisting vector specific neutralizing antibody titers. This phenomenon indicates an expansion of application of adenovirus based vectors for vaccine development and clinical use, especially for the population with preexisting neutralizing antibodies.


Prompting asthma intervention in Rochester-uniting parents and providers (PAIR-UP): a randomized trial.
A disproportionate number of impoverished and minority children have asthma and receive suboptimal preventive care. To evaluate whether the Prompting Asthma Intervention in Rochester-Uniting Parents and Providers (PAIR-UP) intervention, administered in primary care offices, improves the delivery of preventive care and reduces morbidity for urban children with asthma. Cluster randomized trial in which 12 urban primary care practices were matched based on size and type and randomly allocated to the PAIR-UP intervention or usual care (UC). We enrolled 638 children aged 2 to 12 years with persistent or poorly controlled asthma in the waiting room prior to a visit with a clinician for any reason from October 2009 to January 2013. Blinded interviewers called caregivers within 2 weeks to inquire about preventive measures taken at the visit and called them 2 and 6 months later to assess symptoms. Children enrolled at PAIR-UP practices received prompts for the caregiver and clinician at the time of the visit that outlined the child's asthma severity or control as well as specific guideline-based recommendations to enhance preventive care. These practices also received educational resources and periodic feedback on their asthma care performance. The UC practices received copies of the asthma guidelines. The primary outcome was symptom-free days (SFDs) per 2 weeks at the 2-month follow-up. We enrolled 638 children (participation rate of 80%; 36% were black, 36% were Hispanic, and 68% had Medicaid insurance). Groups were similar in demographic characteristics and asthma severity at baseline. At the index visit, more children in the PAIR-UP group received a preventive medication action (new medication, increased dose, recommendation to restart preventive medication) than in the UC group (58% vs 33%; odds ratio [OR] = 2.8; 95% CI, 1.9 to 3.9). More children in the PAIR-UP group than in the UC group received an asthma action plan (61% vs 23%; OR = 8.3; 95% CI, 3.7 to 18.7), discussions regarding asthma (93% vs 78%; OR = 4.5; 95% CI, 2.8 to 7.2), and secondhand smoke counseling (80% vs 63%; OR = 2.6; 95% CI, 1.2 to 5.5). At the 2-month follow-up, children in the PAIR-UP group had more SFDs per 2 weeks than those in the UC group (mean difference, 0.78 days; 95% CI, 0.29 to 1.27). At 6 months, the improvement in SFDs was no longer statistically significant (mean difference, 0.56; 95% CI, -0.14 to 1.25). The PAIR-UP intervention improved the delivery of preventive asthma care and reduced asthma morbidity for high-risk urban children with persistent asthma at 2 months, but the improvement in SFDs was no longer significant at 6 months. clinicaltrials.gov Identifier: NCT01105754.


Impact of Thermal Control Measures on the Imaging Quality of an Aerial Optoelectronic Sensor.
The image resolution is the most important performance parameter for an aerial optoelectronic sensor. Existing thermal control methods cannot eliminate the sensor's temperature gradient, making the image resolution difficult to further improve. This article analyzes the different impacts of temperature changes on the imaging resolution and proposes modifications. Firstly, the sensor was subjected to thermo-optical simulation by means of finite element analysis, and the different impacts of temperature changes on the imaging quality were analyzed. According to the simulation results, an active thermal control method is suggested to enhance the temperature uniformity of the sensor. Considering the impacts of active and passive thermal control measures, thermal optical analysis was carried out to predict the performance of the sensor. The results of the analysis show that the imaging quality of the sensor has been significantly improved. The experimental results show that the image resolution of the optoelectronic sensor improved from 47 to 59 lp/mm, which demonstrates that the sensor can produce a high image quality in a low-temperature environment.


Expressing sexuality in nursing homes. The experience of older women: A qualitative study.
In nursing homes, a number of barriers to the expression of sexuality exist, such as the lack of privacy, certain attitudes on behalf of the staff and the family, the lack of a sexual partner, and physical limitations. The aim of this study was to describe the lived experience of sexuality in elderly Spanish women residing in nursing homes. A qualitative phenomenological approach was followed. Data were collected over an 18-month period between 2013 and 2015. Purposeful sampling was conducted with Spanish residents in nursing homes in Madrid. Data were collected using unstructured and semi-structured interviews. The data were analyzed using thematic analysis. Twenty female residents participated. Three main themes emerged from the data: a) expressing sexuality, b) sexuality as a duty and c) respecting vows. Female residents reported key elements influencing how they manage their sexuality in Nursing Homes. These results serve to improve our understanding regarding the expression of sexuality in older female nursing home residents.


[Primary arachnoid cyst in an adult (author's transl)].
Primary arachnoid cyst in adults seems to be relatively rare. Our case was a 42-year-old female, who complained of diplopia, dizziness, mild headache, and showed papilledema. Right carotid angiograms revealed the characteristic findings. Right fronto-parietal craniotomy was then performed. In the operation, a large, thin walled cyst was found on the surface of the right cerebral hemisphere. When the membrane was removed, essentially normal, but slightly atrophi gyri, could be seen. Aspiration of encapsulated fluid, and extirpation of the cyst wall resulted in an excellent improvement. Microscopically, the wall of the cyst was lined with normal arachnoid cells. The case was presumed to be a primary arachnoid cyst for the reasons that no definited etiological factor could be found in this case an no abnormal findings other than the cyst itself could be found in the operation and in the histological specimen. We discuss reported cases in our review, and about pathological findings, symptoms, diagnosis, and treatment of this disease.


Biochemical markers of brain injury: could they be used as diagnostic adjuncts in cases of inflicted traumatic brain injury?
Child abuse is the leading cause of serious traumatic brain injury (TBI) in infants and young children (Billmire & Myers, 1985; Bruce & Zimmerman, 1989). The incidence of serious or fatal inflicted traumatic brain injury (iTBI) in children < 1 year of age is approximately 1 in 3,300 ( Keenan et al., 2003); since many cases of iTBI are of mild or moderate severity, the incidence is probably significantly higher. Even at an incidence of 1 in 3,300, iTBI is as common as the incidence of cystic fibrosis (CF), the most common genetic recessive disease in the Caucasian population. Proper diagnosis of iTBI is difficult even for experienced and astute physicians because its presentation can be subtle and important historical data are often lacking. As a result, misdiagnosis is common and can have catastrophic medical consequences for patients and significant financial consequences for society ( Ewing-Cobbs et al., 1998; Jenny, Hymel, Pitzen, Reinert, & Hay, 1999). Unlike CF for which there are several well established screening tests, there are currently no diagnostic adjuncts to help physicians screen for possible iTBI.


Species differences of serum albumins: II. Chemical and thermal stability.
The chemical and thermal stability of five species of mammalian serum albumins (human, bovine, dog, rabbit, and rat) were investigated, and conformational stabilities were compared to obtain structural information about the different albumins. The chemical stability was estimated by using guanidine hydrochloride (GdnCl), and monitored by fluorometry and circular dichroism (CD). Thermal stability was evaluated by differential scanning calorimetry (DSC). In human, bovine, and rat albumin, two transitions were observed when GdnCl-induced denaturation was monitored fluorometrically, indicating at least one stable intermediate, although, in dog and rabbit albumin, only one transition was observed. However, GdnCl denaturation, as monitored by the ellipticity, showed a two-state transition in all species used in this study. Since these proteins, showing two transitions, contained a conserved tryptophan residue within domain II, these structural changes might have occurred in domain II during intermediate formation. DSC measurements showed that human, bovine, and rat albumin exhibited single sharp endotherms and these were clearly consistent with a two-state transition, while the deconvolution analysis of broad thermograms observed for dog and rabbit albumin showed that the absorption peaks could be approximated by a two-component composition, and were consistent with independent transitions of two different cooperative blocks. These experimental results demonstrate that species differences exist with respect to the conformational stability and the mechanism of the unfolding pathway for mammalian albumin.


Occurrence of Nematodes of the Genus Anisakis in Mediterranean and Atlantic Fish Marketed in Sardinia.
Anisakiasis is a gastrointestinal fish-borne zoonosis caused by the ingestion of third stage larvae of the genus Anisakis. Between January and December 2013, 1112 specimens of four commercial fish species (Engraulis encrasicolus, Merluccius merluccius, Scomber colias and Trachurus mediterraneus) marketed in Sardinia (Italy) were examined for Anisakis sp. The overall prevalence of Anisakis spp larvae was 39.9%, all morphologically identified as Type I. Scomber colias showed the highest prevalence (100%), followed by M. merluccius (Atlantic 91.0%, Mediterranean 71.2%), T. mediterraneus (32.7%) and E. encrasicolus (25.9%). All the larvae found in Mediterranean hosts were genetically identified as Anisakis pegreffii, whereas 90.0% of the larvae found in the Atlantic M. merluccius belonged to Anisakis simplex sensu stricto and 10.0% to A. pegreffii. The mean abundance of Anisakis sp. larvae was positively correlated with fish size in E. encrasicolus, Atlantic M. merluccius and local M. merluccius. The prevalence of infection was greater in the body cavity (37.9%) than in the edible muscle (9.4%). However, 1.8% of the examined fish were infected exclusively in the muscle. Therefore, the risk associated to the consumption of raw or undercooked fishery products poses the need of measures such as visual inspection and preventive treatments to guarantee consumers' health.


[Response of Straw and Straw Biochar Returning to Soil Carbon Budget and Its Mechanism].
Direct straw returning and straw carbonization returning are the main measures of straw returning. Because of the differences in structure and nature as well as returning process between straw and straw biochar, the soil respiration and soil carbon budget after returning must have significant differences. In this study, outdoor pot experiment was carried out to study the response of soil respiration and carbon budget to straw and straw biochar returning and its possible mechanism. The results showed that soil respiration of straw biochar returning [mean value 21. 69 µmol.(m2.s)-1] was significantly lower than that of direct straw returning [mean value 65.32 µmol.(m2.s)-1], and its soil organic carbon content ( mean value 20. 40 g . kg-1) and plant biomass (mean value 138. 56 g) were higher than those of direct straw returning (mean values 17. 76 g . kg-1 and 76. 76 g). Considering the carbon loss after the biochar preparation process, its soil carbon budget was also significantly higher than that of direct straw returning, so it was a low carbon mode of straw returning. Direct straw returning significantly promoted soil dehydrogenase activity, soil β-glycosidase activity and soil microorganism quantity, leading to higher soil respiration, but straw biochar did play an obvious role in promoting the microbial activity index. Easily oxidizable carbon (EOC) and biodegradability of straw biochar were lower than those of straw, which showed that straw biochar had higher stability, and was more difficult to degrade for soil microorganisms so its soil microbial activity was generally lower, and could be retained in the soil for a long time.


Template-Free Electrochemical Growth of Ni-Decorated ZnO Nanorod Array: Application to an Anode of Lithium Ion Battery.
ZnO nanorods (NRs) decorated with Ni nanoparticles were synthesized using a template-free electrochemical deposition in an ultra-dilute aqueous electrolyte and a subsequent galvanic reaction. The electrochemical properties of the ZnO NRs as an anode material for rechargeable Li-ion batteries were evaluated for different binder morphologies (film and close-packed spherical particles) of polyvinylidene fluoride (PVDF). Results showed that the close-packed spherical PVDF simultaneously improved electrochemical capacity and cyclability because the free-volume between the spherical PVDF helped to accommodate the volume change in the anode caused by the Li ions discharge and charge processes. Furthermore, the Ni nanoparticles decorated on the surface of ZnO NRs enhanced the electrical conductivity of the ZnO NR anode, which enabled faster electronic and ionic transport at the interface between the electrolyte and the electrode, resulting in improved electrochemical capacity. The free-volume formed by the close-packed spherical PVDF, and the decoration of metal nanoparticles are expected to provide insight on the simultaneous improvement of electrochemical capacity and cyclability in other metal oxide anode nanostructures.


Effects of a Personalized Music Intervention for Persons with Dementia and their Caregivers.
Given the challenges of developing disease-modifying treatments for Alzheimer's disease and related disorders, non-pharmacological interventions represent an increasingly promising approach in long-term care settings. Music-based interventions have been effective in improving the quality of life by influencing biopsychosocial factors that play a role in the progression of illnesses such as depression and anxiety. However, approaches have tended to focus exclusively on the person with dementia rather than integrating caregivers. This study aimed to determine the impact of a music-based intervention on the quality of life of persons with dementia and their caregivers. A mixed-methods study was conducted with seven dyads consisting of residents (aged 76-92) with diagnoses of dementia and their caregivers (aged 53-84) at a skilled nursing facility in Pennsylvania. Eight music intervention sessions were completed in the presence of the resident and caregiver using personalized playlists created for the dyad. Pre- and post-intervention questionnaires were administered during each session, and observational data for both residents and caregivers were collected. Caregivers reported feeling less overwhelmed after the intervention with a mean difference of -0.24±0.14, p = 0.016. Mean difference in the other 5 responses showed that listening to music had a beneficial impact for resident/caregiver dyads. Observations of interpersonal behavior supported the benefit of the intervention for these dyads. Quantitative analysis of a personalized music intervention for residents/caregivers showed positive trends in increasing personal connection, and qualitative data identified greater appreciation of the relationship and increased bonding.


Gonadotropin-releasing hormone and conception of Holsteins.
Effects of gonadotropin-releasing hormone (100 micrograms) and time of artificial insemination on fertility, were examined in lactating dairy cows at first, second, and third services. Inseminations were either soon after detected estrus (0 h) or 12 h later, and cows were given gonadotropin-releasing hormone or saline after inseminations. Conception at first service was not improved by hormone treatment. But conception rates at repeat services were improved by nearly 21% when cows were treated with gonadotropin-releasing hormone within 30 s after insemination. Inseminations soon after detection of estrus (0 h) followed by hormone treatment resulted in the highest conception rates for all services. Time of the insemination (0 versus 12 h) had no effect on conception. Administering gonadotropin-releasing hormone at repeat services should improve conception rate of lactating dairy cows.


Practical importance and modern methods of the evaluation of skin microcirculation during chronic lower limb ischemia in patients with peripheral arterial occlusive disease and/or diabetes.
Skin ischemia is one of the crucial phenomena during chronic lower limb ischemia in patients with peripheral arterial occlusive disease and/or diabetes. However, risk stratification for development of ischemic ulceration and/or skin necrosis in those patients is not easy, mostly due to the complex structure of the dermal vascular bed and limited possibilities for studying the skin capillaries in everyday practice. All definitions of critical limb ischemia thus far have considered mostly the clinical symptoms and the degree of macrocirculatory impairment. Despite the fact that the reduction of absolute dermal perfusion and improper distribution of perfusion in ischemic feet, primarily diminished perfusion or even a complete loss of blood flow in nutritional capillaries, rather than arterial occlusion per se, is the eventual reason for critical limb ischemia symptoms, the vessels of the microcirculation are not routinely assessed in clinical practice. Monitoring of microcirculatory parameters, as a part of integrated diagnostic approach, may have a considerable value in the evaluation of risk, progression of the disease and the effectiveness of therapeutic intervention in individual patients. Relative simplicity and availability of different non-invasive methods, including video capillaroscopy and laser Doppler fluxmetry, should constitute a premise to their wider application in clinical management of chronic limb ischemia.


Estimating allele frequencies of hypervariable DNA systems.
Several polymorphisms of human DNA have been shown to be hypervariable due to the recurrence of a variable number of tandem repeats (VNTRs) in the lengths of allelic restriction fragments. The recurrence of allelic variants in this novel class of polymorphisms seems to comply well with a model of continuous random variables. Based on this assumption, we have compiled some simple algorithms for classification of continuous data and estimation of classes of relative frequencies and have implemented these routines for the management of databases storing hypervariable single locus DNA genetic systems. The algorithms are compiled in BASIC language and can be incorporated in task-oriented computer programs. Three procedures are discussed, based in turn on: (a) using predetermined, arbitrary classes; (b) point estimations of frequencies for single fragments using error measurements associated with the kilobase value assignment; (c) estimates of phenotype frequencies according to error measurements. Error measurements are obtained from a statistic of values pertaining to several restriction fragments (genomic controls) repeatedly tested in different experiments. Problems related to these approaches are discussed.


Herpes oesophagitis in a healthy 8 year-old.
An 8 year-old, immunocompetent child developed a severe acute herpetic oesophagitis in the absence of oropharyngeal lesions. Intravenous treatment with the antiviral drug, acyclovir, relieved symptoms within 24 hours.


Correlation between plasma physostigmine concentrations and percentage of acetylcholinesterase inhibition over time after controlled release of physostigmine in volunteer subjects.
Five to six subjects ingested doses of controlled-release physostigmine salicylate tablets (9, 12, and 15 mg) followed by sequential blood drawing for measurement of plasma physostigmine concentrations and percentage of acetylcholinesterase (AChE) inhibition. Both plasma physostigmine concentrations and percentage of AChE inhibition demonstrated dose proportionality to three doses of ingested drug. Plasma physostigmine concentrations correlated with percentage of AChE inhibition across time by dose and across all doses and subjects tested. These data should be helpful to physicians in adjusting physostigmine dosing, enabling them to use the relatively simple and widely available AChE assay to approximate plasma physostigmine concentrations.


Resistance to oxyimino beta-lactams due to a mutation of chromosomal beta-lactamase in Citrobacter freundii.
The duplicative mutation of an Ala-Val-Arg sequence at positions 208 to 210 in the loop structure of Enterobacter cloacae class C beta-lactamase caused substrate specificity extension to oxyimino beta-lactam antibiotics and this chromosomal mutation provided bacterial cells with high resistance to the beta-lactams (M. Nukaga et al, 1995, J. Biol. Chem. 270, 5729-5735). In order to confirm the universality of this phenomenon among other class C beta-lactamases, the duplicative mutation was applied to a class C beta-lactamase of Citrobacter freundii, which has 74% homology to the E. cloacae beta-lactamase amino acid sequence. The counterpart sequence to the Ala-Val-Arg of the E. cloacae enzyme in C. freundii beta-lactamase was identified to be Pro-Val-His. A Pro-Val-His sequence was inserted just after the native Pro-Val-His sequence at positions 208 to 210 in the C. freundii beta-lactamase. The resulting mutant of C. freundii beta-lactamase obtained a striking characteristic that we expected, showing substrate specificity extension to oxyimino beta-lactams. Nearly the same result was obtained with the insertion of an Ala-Val-Arg sequence after the native Pro-Val-His sequence. These results indicate that structural modification of this locus commonly induces modification of the substrate specificity to unfavorable substrates for many chromosomal class C beta-lactamases produced by gram-negative bacteria.


Smart specification for sustainability.
This article details a study reviewing the potential for 'smart specification' of air filtration for air-handling units (AHUs) to offer NHS Trusts sustainability savings, including 'hard cost' reductions. The study, involving three separate NHS Trusts--Calderdale and Huddersfield NHS Foundation Trust, York Teaching Hospital NHS Foundation Trust, and Harrogate and District NHS Foundation Trust--proves that sustainability savings can be realised without significant financial investment. The key investment is manpower, and the study suggests that the use of a third-party supplier would offer the Trusts involved net productivity gains.


Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction.
The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2) via a direct protein-protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the α-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural α-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an α-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50-values in a biochemical fluorescence polarisation assay.


Anemia and hypoalbuminia as an adjunct to soil-transmitted helminthiasis among slum school children in Visakhapatnam, South India.
A longitudinal study was conducted over the period August 1993 to August 1994 on 217 children from a fishing community of Visakhapatnam, Andhra Pradesh. The subjects were aged between 7 and 13 years. Children were screened for Ascaris lumbricoides, Trichuris trichiura and hookworm. Intensity of infection was estimated by the formalin-ether sedimentation technique. Simultaneously, blood samples ware also collected for estimation of hemoglobin and serum proteins using standard techniques. Blood parameters and ova count were monitored both prior to and following treatment with albendazole, administered at a single oral dose of 400 mg/child in November 1993. Post-treatment recordings were done at the end of the second, fourth and fifth months while hemoglobin estimation was also monitored at the ninth month. Study showed a prevalence of 82% with intestinal helminths and a mean hemoglobin level of 9.7 g/dL + 1.7 (5-13 g/dL), with 88% of the children being anemic. Total serum protein level was normal (8.61 ± 1.03 g/dL), with an elevated serum globulin response (4.63 ± 0.88). Post-treatment observations showed the complete expulsion of worms with the significant lowering of globulin levels. However, moderate anemia persisted in the population with gradual improvement by the ninth month. Significant increase in weight was not registered at the end of the fifth month probably coinciding with the rapid establishment of infection. Sex-wise there was no significant deviation from the general trend.


[Role of aeroallergens in the etiopathogenesis of atopic dermatitis].
Atopic dermatitis is a chronic relapsing inflammatory skin disease. It is most frequent in childhood and its clinical manifestations vary with age. The etiopathogenic mechanisms that explain this process are still poorly understood; several studies performed in adults speculate on the possible role of aeroallergens through direct contact with the skin but, because the etiology of this disease varies with age, studies in children of different ages are required. (i) To determine whether children with atopic dermatitis are sensitized to inhalant allergens. (ii) To determine whether these inhalant allergens cause dermatitis or whether they provoke allergic respiratory disease (asthma, rhinitis) concomitant with atopic dermatitis. (iii) To evaluate whether sensitization to a particular allergen takes place at any age or whether there are differences according to age. This study was performed in the following groups: (i) 64 children with atopic dermatitis, divided into two subgroups, one consisting of 37 children who also presented allergic respiratory disease (asthma, rhinitis) (AR) and another subgroup of 27 patients who presented atopic dermatitis only. (ii) eight children who presented AR only, to determine whether this group reacted to patch testing with inhalant allergens. (iii) seven healthy children to rule out non-specific positive tests in the non-atopic population. All groups were divided by age according to the phases of atopic dermatitis: early childhood phase (< 2 years): 21, childhood phase (2-10 years): 37, adolescent phase (> 10 years): 21. In all children total serum IgE determination (RIA), allergen-specific IgE determination (RAST), prick- and patch test were performed. In the three tests the same allergens were used, consisting of the usual components of standardized inhalant and food allergens. When the results of patch testing were positive, biopsy and histopathological analysis were performed and monoclonal antibodies were used to determine reproducibility of the eczematous lesion. Sensitization was found to differ among patients with atopic dermatitis according to whether they presented respiratory symptoms and according to age with a clear predominance of food sensitization in the group aged less than 2 years. In the group aged 2-10 years, mixed sensitization predominated, mainly because of simultaneous respiratory involvement, but it is highly probably that inhalant allergens participate in the etiopathogenesis of atopic dermatitis. In children aged more than 10 years sensitization to inhalant allergens predominated as most presented respiratory symptoms. Patch testing was positive in 34.3 % of patients with atopic dermatitis and approximately half were positive to dust mites. The patch test is of great diagnostic value in atopic dermatitis and none of the tests were positive in the control group. All the biopsies of patch tests with inhalant allergens reproduced the lesions typical of eczema, demonstrating their involvement in the etiopathogenesis of dermatitis.


Using JPP to Identify Ni Bidentate Phosphine Complexes In Situ.
Identifying intermediates of Ni-containing reactions can be challenging due to the high reactivity of Ni complexes and their sensitivity toward air and moisture. Many Ni bidentate phosphine complexes are diamagnetic and can be analyzed in situ via 31P NMR spectroscopy, but the oxidation state of Ni is difficult to determine using 31P chemical shift analysis alone. The J-coupling between P atoms, JPP, has been proposed to correlate with oxidation state, but few investigations have looked at how JPP is affected by parameters such as length of the linker or identity of the phosphine or other ligands. The present investigation into the JPP values of Ni bidentate phosphine complexes with two-carbon and three-carbon linkers shows that the JPP values observed in 31P NMR spectra, |JPP|, are competent indicators of the oxidation state at Ni. For complexes with two-carbon linkers, |JPP| > 40 Hz is typical of Ni0 while |JPP| < 30 Hz is typical of NiII; this trend is reversed for complexes with three-carbon linkers. Additionally, the Lewis acidity of the Ni and Lewis basicity of the phosphine ligand affect JPP predictably. For example, increased P-to-Ni donation arising from more-donating phosphines or more-withdrawing ligands trans to the P atoms causes a more negative JPP. These results should enable the oxidation state of Ni and properties of ligands in Ni bidentate phosphine complexes to be determined in situ during reactions containing these species.


Isotopic variations of Zn in biological materials.
Variations in the isotopic composition of Zn present in various biological materials were determined using high-resolution multicollector inductively coupled plasma mass spectrometry (MC-ICPMS), following digestion and purification by anion exchange chromatography. To correct for differences in instrumental mass discrimination effects between samples and standards, Cu was employed as an elemental spike. Complementary analyses of Zn separates by sector field ICPMS instruments revealed that the concentrations of the majority of potentially interfering elements were reduced to negligible levels. Residual spectral interferences resulting from (35)Cl(16)O(2)(+), (40)Ar(14)N(2)(+), and (40)Ar(14)N(16)O(+) could be instrumentally resolved from the (67)Zn, (68)Zn, and (70)Zn ion beams, respectively, during measurement by MC-ICPMS. The only other observed interference in the Cu and Zn mass range that could not be effectively eliminated by high-resolution multicollection resulted from (35)Cl(2)(+), necessitating modification of the sample preparation procedure to allow accurate (70)Zn detection. Complete duplication of the entire analytical procedure for human whole blood and hair, as well as bovine liver and muscle, provided an external reproducibility of 0.05-0.12 per thousand (2sigma) for measured delta(66/64)Zn, delta(67/64)Zn, and delta(68/64)Zn values, demonstrating the utility of the method for the precise isotopic analysis of Zn in biological materials. Relative to the selected Zn isotopic standard, delta(66/64)Zn values for biological samples varied from -0.60 per thousand in human hair to +0.56 per thousand in human whole blood, identifying the former material as the isotopically lightest Zn source found in nature to date.


Detection of clone-specific immunoglobulin heavy chain genes in the bone marrow of B-cell-lineage lymphoma after treatment.
In order to determine the appropriate treatment of malignant lymphoma, it is important to know the degree to which extra-nodal invasion of lymphoma cells has occurred. We amplified complementarity-determining region (CDR) III genes in 64% of lymph node samples at the onset or relapse of B-cell-lineage non-Hodgkin's lymphoma (NHL) in 22 patients. By using a clone-specific CDR III probe in each patient, we were able to detect minimal residual disease (MRD) of lymphoma cells in the bone marrow and/or blood in 9 out of 14 cases (64.2%) at the onset of the disease or relapse, whereas abnormal cells in the bone marrow and/or blood were identified by routine morphological analysis in only 4 out of 22 cases (18.2%). This indicates that extranodal invasion of malignant cells may be common in patients with NHL. In some cases, the clone-specific CDR III gene was still expressed in the samples of bone marrow and/or peripheral blood even after chemotherapy, when other markers associated with NHL were no longer expressed. Five out of six cases in this group had a worse outcome associated with NHL. On the other hand, most of the cases whose clone-specific CDR III gene was no longer expressed in the bone marrow and/or in circulation after treatment had a relatively fair prognosis. These results indicate that the detection at molecular level of MRD in extranodal organs may prove useful as a predictor of prognosis for NHL.


Intra- and Interspecies Differences of Two Cecropia Species from Tabasco, Mexico, Determined through the Metabolic Analysis and 1H-NMR-Based Fingerprinting of Hydroalcoholic Extracts.
The genus Cecropia is used in the traditional medicine of Tabasco, Mexico, in diabetes and hypertension treatments, mainly without distinction of the species. This contribution aimed to carry out the metabolic analysis and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy-based fingerprinting of the hydroalcoholic leaf extracts of Cecropia peltata (Cp) and Cecropia obtusifolia (Co) collected in five sub-regions of the State of Tabasco (Cp1, "Centro"; Cp2, "Chontalpa"; Cp3, "Pantanos"; Cp4, "Ríos" and Co5, "Sierra"). Firstly, the extracts were evaluated for their Total Phenol Content (TPC) and Total Flavonoid Content (TFC) by spectrophotometric methods. In addition, metabolic analysis was performed using High-Performance Liquid Chromatography with Diode-Array Detection HPLC-DAD, which allowed the quantification of the chemical markers: chlorogenic acid, isoorientin, and orientin, as well as a vitexin analog. Finally, metabolomic analysis was carried out based on the 1H-NMR spectra. The Cp4 extract (C. peltata from the "Ríos" sub-region) presented the highest values of TPC (155 ± 9.1 mg GAE/g E) and TFC (724 ± 22.2 mg RE/g E). The metabolic analysis was similar among the five samples; the highest concentrations of the four chemical markers were found in Cp3 (C. peltata from the "Pantanos" sub-region) for chlorogenic acid (39.8 ± 2.3 mg/g) and isoorientin (51.5 ± 2.9 mg/g), in Cp4 for orientin (49.9 ± 0.6 mg/g), and in Cp2 (C. peltata from the "Chontalpa" sub-region) for the vitexin analog (6.2 ± 0.2 mg/g). The metabolic analysis and the 1H-NMR fingerprint analysis showed intraspecies differences among the C. peltata samples and interspecies between C. peltata and C. obtusifolia, which were attributed to variations in the metabolite groups as well as in the proportion of sugars such as glucose and xylose.