Recovery From Heart Attack, Biomedicalization, and the Production of a Contingent Health Citizenship.
In this article, I explore the experience of recovery from a heart attack through an analytic autoethnography. I discuss the tensions inherent in biomedical subjectivities of health and ill-health during cardiac recovery through three key themes: (a) the transfer of responsibility and becoming a subject "at risk," (b) technologies of biomedicine and the disciplining of subjectivities, and (c) the transformation of a body toward a new pharmaceuticalized bodily normal. Through an analysis driven by the biomedicalization thesis of Clarke, alongside work on biopower and the governmentality of health by Foucault, Rose, and Rabinow, I seek to provide new insights into the process of cardiac recovery and the relationship between individual experience and broader socio-political processes. Key to this analysis is a focus on the contingent subjectivities brought into being through biomedicalization that constitute a new form of health citizenship that is otherwise not accounted for in narratives of recovery.


AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes.
The activation-induced cytidine deaminase (AID; also known as AICDA) enzyme is required for somatic hypermutation and class switch recombination at the immunoglobulin locus. In germinal-centre B cells, AID is highly expressed, and has an inherent mutator activity that helps generate antibody diversity. However, AID may also regulate gene expression epigenetically by directly deaminating 5-methylcytosine in concert with base-excision repair to exchange cytosine. This pathway promotes gene demethylation, thereby removing epigenetic memory. For example, AID promotes active demethylation of the genome in primordial germ cells. However, different studies have suggested either a requirement or a lack of function for AID in promoting pluripotency in somatic nuclei after fusion with embryonic stem cells. Here we tested directly whether AID regulates epigenetic memory by comparing the relative ability of cells lacking AID to reprogram from a differentiated murine cell type to an induced pluripotent stem cell. We show that Aid-null cells are transiently hyper-responsive to the reprogramming process. Although they initiate expression of pluripotency genes, they fail to stabilize in the pluripotent state. The genome of Aid-null cells remains hypermethylated in reprogramming cells, and hypermethylated genes associated with pluripotency fail to be stably upregulated, including many MYC target genes. Recent studies identified a late step of reprogramming associated with methylation status, and implicated a secondary set of pluripotency network components. AID regulates this late step, removing epigenetic memory to stabilize the pluripotent state.


Optimization of Chondrocyte Viability in Partially Decellularized Tracheal Grafts.
Advancements in tissue-engineered tracheal replacement (TETR) show promise for the use of partially decellularized tracheal grafts (PDTG) to address critical gaps in airway management and reconstruction. In this study, aiming to leverage the immunoprivileged nature of cartilage to preserve tracheal biomechanics, we optimize PDTG for retention of native chondrocytes. Comparison in vivo murine study. Research Institute affiliated with Tertiary Pediatric Hospital. PDTG were created per a shortened decellularization protocol using sodium dodecyl sulfate, then biobanked via cryopreservation technique. Decellularization efficiency was characterized by DNA assay and histology. Viability and apoptosis of chondrocytes in preimplanted PDTG and biobanked native trachea (control) was assessed with live/dead and apoptosis assays. PDTG (N = 5) and native trachea (N = 6) were orthotopically implanted in syngeneic recipients for 1-month. At the endpoint, microcomputed tomography (micro-CT) was employed to interrogate graft patency and radiodensity in vivo. Vascularization and epithelialization were qualitatively analyzed using histology images following explant. PDTG exhibited complete decellularization of all extra-cartilaginous cells and reduced DNA content compared to control. Chondrocyte viability and nonapoptotic cell populations were improved utilizing biobanking and shorter decellularization time. All grafts remained patent. Evaluation of graft radiodensity at 1 month revealed elevation of Hounsfield units in both PDTG and native compared to host, with PDTG showing higher radiodensity than native. PDTG supported complete epithelialization and functional reendothelialization 1-month postimplantation. Optimizing PDTG chondrocyte viability is a key component to successful tracheal replacement. Ongoing research seeks to evaluate the acute and chronic immunogenicity of PDTG.


'He does not see himself as being different': the perspectives of children and caregivers on relevant areas of functioning in cerebral palsy.
In the context of the development of the International Classification of Functioning, Disability and Health (ICF) Core Sets for children and adolescents with cerebral palsy (CP), we investigated the strengths and limitations in functioning important to children with CP, through either child self-reports or caregiver proxy reports, using components of the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY). We conducted semi-structured interviews with 10 children with CP (children self-reporting), 10 caregivers of children self-reporting (10 child-caregiver dyads), and 12 caregivers of children not self-reporting. Mean age 10 y 6 mo, range 4-16 y. A convenience sample was recruited representing Gross Motor Function Classification System (GMFCS) levels I to V. Interviews were audio-taped and the content covered all of the relevant ICF-CY components. The interviews were then transcribed verbatim and coded in N-Vivo 10 using the ICF-CY coding system. We identified 1956 themes that linked to 175 ICF-CY categories. Most of the themes were represented by the ICF-CY components activities and participation and environmental factors. The children interviewed discussed issues related to mobility, self-care, and recreation and leisure, whereas the caregivers focused more on physical limitations and on the environmental factors associated with everyday activities. The children and their caregivers described many of the same areas of functioning but provided unique perspectives. Children talked more frequently about their abilities with CP, whereas the caregivers interviewed talked more about their concern over the limitations and broader issues facing their child. The findings highlight the need to explore the perspectives of both the child and the caregiver when characterizing the functional profile of children with CP.


Genetic and biological diversity of the Pea seed-borne mosaic virus isolates occurring in Czech Republic.
Eight isolates of the Pea seed-borne mosaic virus (PSbMV) from the Czech Republic were studied regarding their biological and molecular characteristics. Molecular characterization using RT-PCR was done on the 5'(Nter)NIb-CP-UTR3' region amplified using universal CPUP/P9502 primer pair and the newly designed PSB8812/PSB944, and PSB8800/PSB9440 primer pairs, respectively. Sequential and phylogenetic analysis of CP-UTR3' region from all isolates showed that the available Czech and GenBank PSbMV isolates were distributed into 4 clusters in agreement with their diversification and according to their biological characteristics (i.e. pathotype). The molecular data were confirmed by biological testing on different pea cultivars. The Czech isolates were distributed into two pathotypes, the P-1 (7 isolates) and P-4 (1 isolate).


Towards a new classification of atrial fibrillation detected after a stroke or a transient ischaemic attack.
Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. Atrial fibrillation detected after stroke is associated with a lower prevalence of risk factors, cardiovascular comorbidities, and atrial cardiomyopathy than atrial fibrillation known before stroke occurrence. These differences might explain why it is associated with a lower risk of recurrence of ischaemic stroke than known atrial fibrillation. Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.


Fitness to plead and psychiatric reports.
The role of the psychiatrist in the determination of fitness to plead is reviewed by reference to 77 pre-trial psychiatric reports prepared on 31 Special Hospital patients detained under the provision of Section 5(1)(c) (Unfit to Plead) of the Criminal Procedure (Insanity) Act 1964. Each psychiatric report was analysed using a standardized checklist which addressed the legal criteria used to determine fitness to plead, the nature of the alleged offence and the clinical diagnosis. The results showed that almost 40% of the reports made no mention of fitness to plead at all and that only one-third of the reports made a statement about fitness to plead which was supported by reference to standard legal criteria. The results of this study support earlier work which has suggested that psychiatrists have a poor understanding of the issues surrounding fitness to plead and criminal responsibility. These findings are discussed in relation to recommendations made by the Report of the Committee on Mentally Abnormal Offenders, 1975 (Butler Report) and legislative changes introduced by the Mental Health Act 1983.


A new technique for visualization of the human retinal vasculature.
Adenosine diphosphatase, an endothelial cell ectoenzyme that hydrolyses adenosine 5'-diphosphate to adenosine monophosphate, has been used histochemically to study the human retinal vasculature in flat mounts or as flat-embedded tissue that can be sectioned. In all retinas, reaction product was confined almost exclusively to the vasculature, with arteries having more reaction product than veins or capillaries. Adenosine diphosphatase activity was observed in endothelium, smooth-muscle cells, pericytes, and erythrocytes. In the more elaborate version of the technique, the adenosine diphosphatase-incubated retinas were flat embedded in glycol methacrylate. This allowed study of the retinal vasculature in dual perspective: en bloc with the use of dark-field microscopy and specific areas of interest histologically sectioned for further evaluation. The technique is simple and preserves angioarchitecture because the retinas are intact, and patency of the vasculature can be determined.


Effect of Temperature on Acetate Mineralization Kinetics and Microbial Community Composition in a Hydrocarbon-Affected Microbial Community During a Shift From Oxic to Sulfidogenic Conditions.
Aquifer thermal energy storage (ATES) allows for the seasonal storage and extraction of heat in the subsurface thus reducing reliance on fossil fuels and supporting decarbonization of the heating and cooling sector. However, the impacts of higher temperatures toward biodiversity and ecosystem services in the subsurface environment remain unclear. Here, we conducted a laboratory microcosm study comprising a hydrocarbon-degrading microbial community from a sulfidic hydrocarbon-contaminated aquifer spiked with 13C-labeled acetate and incubated at temperatures between 12 and 80°C to evaluate (i) the extent and rates of acetate mineralization and (ii) the resultant temperature-induced shifts in the microbial community structure. We observed biphasic mineralization curves at 12, 25, 38, and 45°C, arising from immediate and fast aerobic mineralization due to an initial oxygen exposure, followed by slower mineralization at sulfidogenic conditions. At 60°C and several replicates at 45°C, acetate was only aerobically mineralized. At 80°C, no mineralization was observed within 178 days. Rates of acetate mineralization coupled to sulfate reduction at 25 and 38°C were six times faster than at 12°C. Distinct microbial communities developed in oxic and strictly anoxic phases of mineralization as well as at different temperatures. Members of the Alphaproteobacteria were dominant in the oxic mineralization phase at 12-38°C, succeeded by a more diverse community in the anoxic phase composed of Deltaproteobacteria, Clostridia, Spirochaetia, Gammaproteobacteria and Anaerolinea, with varying abundances dependent on the temperature. In the oxic phases at 45 and 60°C, phylotypes affiliated to spore-forming Bacilli developed. In conclusion, temperatures up to 38°C allowed aerobic and anaerobic acetate mineralization albeit at varying rates, while mineralization occurred mainly aerobically between 45 and 60°C; thermophilic sulfate reducers being active at temperatures > 45°C were not detected. Hence, temperature may affect dissolved organic carbon mineralization rates in ATES while the variability in the microbial community composition during the transition from micro-oxic to sulfidogenic conditions highlights the crucial role of electron acceptor availability when combining ATES with bioremediation.


Dentin caries risk indicators in 1-year-olds. A two year follow-up study.
Early childhood caries (ECC) risk factors are suspected to vary between regions with different caries prevalence. Identify ECC risk factors for 1-year-olds predicting dentin caries at 3 years of age in a region with low caries prevalence. Caries risk was assessed by dental hygienist or dental assistant in 779 one-year-olds. The oral mutans streptococci (MS) score was performed from a tooth surface or (in pre-dentate children) from oral mucosa. A parental questionnaire with questions regarding family factors (siblings with or without caries), general health, food habits (night meals, breastfeeding, other beverage than water), oral hygiene habits and emerged teeth were answered by parents of the 1-year-olds. Dentin caries was assessed when the children were 3-year-olds. Simple and multiple logistic regression analyses were used for identification of caries-associated factors. An increased caries risk was assessed in 4.4% of the 1-year-olds. Dentin caries was found in 2.6% of the 3-year-olds. Caries risk at 1 year was associated with caries at 3 years (OR = 6.5, p = .002). Multiple regression analysis found the variables Beverages other than water (OR = 7.1, p < 0.001), Caries in sibling (OR = 4.8, p = .002), High level of MS (score 2-3) (OR = 3.4, p = .03) and Night meal (OR = 3.0, p = .03) to be associated with caries. The single variables Beverage other than water between meals and Caries in sibling were more reliable than Caries risk assessed performed by dental personnel. Behavioural, family and microbial factors are important when assessing caries risk among 1-year-olds in a region with low caries experience.


Assessment of hearing and hearing disorders in rock/jazz musicians.
The aim of this study was to assess hearing and hearing disorders among rock/jazz musicians. One hundred and thirty-nine (43 women and 96 men) musicians participated. The results are based on pure-tone audiometry and questionnaire responses. According to our definition of hearing loss, tinnitus, hyperacusis, distortion and/or diplacusis as hearing disorders, we found disorders in 74%, of the rock/jazz musicians studied. Hearing loss, tinnitus and hyperacusis were most common, and the latter two were found significantly more frequently than in different reference populations. The women showed bilateral, significantly better hearing thresholds at 3-6 kHz than the men. Hyperacusis, and the combination of both hyperacusis and tinnitus, were found to be significantly more frequent among women than among men. Hearing loss and tinnitus were significantly more common among men than among women. It is important to evaluate all kinds of hearing problems (other than hearing loss) in musicians, since they represent an occupational group especially dependent on optimal, functional hearing. On the basis of our results, we suggest that hearing problems such as tinnitus, hyperacusis, distortion and/or diplacusis should, in addition to hearing loss, be defined as hearing disorders.


[Changes in the cytokinetics of Mott's cells following sensitization to BCG under conditions of preliminary treatment of rats with soluble antigens of Mycobacterium tuberculosis].
The effect of pretreatment with tuberculins on BCG sensitization of rats was expressed in the transformation of precursors into Mott's cells. The tuberculins, particularly the old tuberculin, inhibited the MC-reaction; this seems to be connected with the tolerogenic action of the mycobacterial polysaccharides. An attempt was made to interpret the results from the point of view of the three-component system of the lymphoid cell cooperation during the formation of humoral antibodies, taking into account the competitive antagonistic relations between the delayed hypersensitivity (DH) and the humoral immunity. It postulated that this competition is effectuated through the repression of the B cell function by the T1 lymphocyte killer effectors of the DH committed to the same antigen against which the "blasts" or the plasmoblasts (subsequently transformed into MC) were produced. The author believes the latter to be the cells in which specific antiboty synthesis was blocked in the statu nascendi due to ectopic (not in the Golgi zone, but in the cisterns of the rough reticulum) and an excessive complex assembly of polysaccharides with the peptide chains of immunoglobulins.


Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins.
Bacterial pathogens utilize toxins to modify or kill host cells. The bacterial ADP-ribosyltransferases are a family of protein toxins that covalently transfer the ADP-ribose portion of NAD to host proteins. Each bacterial ADP-ribosyltransferase toxin modifies a specific host protein(s) that yields a unique pathology. These toxins possess the capacity to enter a host cell or to use a bacterial Type III apparatus for delivery into the host cell. Advances in our understanding of bacterial toxin action parallel the development of biophysical and structural biology as well as our understanding of the mammalian cell. Bacterial toxins have been utilized as vaccines, as tools to dissect host cell physiology, and more recently for the development of novel therapies to treat human disease.


Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation.
The tumor suppressor p53 is a nuclear phosphoprotein in which DNA-binding activity is increased on exposure to DNA-damaging agents such as UV or gamma radiation by unknown mechanisms. Because phosphorylation of p53 at the casein kinase (CK) II site activates p53 for DNA-binding function in vitro, we sought to determine the in vivo relevance of phosphorylation at this site after UV and gamma radiation. A polyclonal antibody was generated that binds to bacterially expressed p53 only when phosphorylated in vitro by CK II. Using this antibody, we showed that p53 is phosphorylated at the CK II site upon UV treatment of early passage rat embryo fibroblasts and RKO cells. In addition, DNA-binding assays indicated that phosphorylated p53 bound to a p53-responsive element, suggesting functional activation. However, gamma radiation, which also stabilizes p53, did not result in phosphorylation at the CK II site. These results indicate that phosphorylation at the CK II site is one of the post-translational mechanisms through which p53 is activated in response to UV radiation and that different mechanisms activate p53 after DNA damage by gamma radiation.


Effects of Concomitant Medication Use on Gefitinib-Induced Hepatotoxicity.
Gefitinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) patients. Severe hepatotoxicity was observed, but only a few cases have been reported on the hepatotoxicity of gefitinib. This study aimed to investigate the association between gefitinib-induced hepatotoxicity and various factors including concomitant medications in lung cancer patients. From January 2013 to December 2014, a retrospective study was performed with NSCLC patients who were treated with gefitinib. Associations between hepatotoxicity and various factors including concomitant drugs were analyzed. Based on multivariate models, it was found that H2 antagonists, proton pump inhibitors (PPIs), and H2 antagonists or PPIs increased hepatotoxicity by about 1.5- to 1.7-fold. Patients younger than 65 years showed 1.6 times higher hepatotoxicity than those older than 65 years. Patients with EGFR mutations had around 2-fold higher hepatotoxicity, and the percentage of incidence of hepatotoxicity because of exon 19 deletion was 32.7%. Our study showed that anti-acid-secreting agents in addition to age younger than 65 years and EGFR mutation were associated with gefitinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially for patients using anti-acid-secreting agents.


How domain growth is implemented determines the long-term behavior of a cell population through its effect on spatial correlations.
Domain growth plays an important role in many biological systems, and so the inclusion of domain growth in models of these biological systems is important to understanding how these systems function. In this work we present methods to include the effects of domain growth on the evolution of spatial correlations in a continuum approximation of a lattice-based model of cell motility and proliferation. We show that, depending on the way in which domain growth is implemented, different steady-state densities are predicted for an agent population. Furthermore, we demonstrate that the way in which domain growth is implemented can result in the evolution of the agent density depending on the size of the domain. Continuum approximations that ignore spatial correlations cannot capture these behaviors, while those that account for spatial correlations do. These results will be of interest to researchers in developmental biology, as they suggest that the nature of domain growth can determine the characteristics of cell populations.


Molecular and biochemical characterization of tomato farnesyl-protein transferase.
The prenylation of membrane-associated proteins involved in the regulation of eukaryotic cell growth and signal transduction is critically important for their subcellular localization and biological activity. In contrast to mammalian cells and yeast, however, the function of protein prenylation in plants is not well understood and only a few prenylated proteins have been identified. We partially purified and characterized farnesyl-protein transferase from tomato (Lycopersicon esculentum, LeFTase) to analyze its biochemical and molecular properties. Using Ras- and G gamma-specific peptide substrates and competition assays we showed that tomato protein extracts have both farnesyl-protein transferase and geranylgeranyl-protein transferase 1 activities. Compared with the heterologous synthetic peptide substrates, the plant-specific CaaX sequence of the ANJ1 protein is a less efficient substrate for LeFTase in vitro. LeFTase activity profiles and LeFTase beta-subunit protein (LeFTB) levels differ significantly in various tissues and are regulated during fruit development. Partially purified LeFTase requires Zn2+ and Mg2+ for enzymatic activity and has an apparent molecular mass of 100 kD Immunoprecipitation experiments using anti-alpha LeFTB antibodies confirmed that LeFTB is a component of LeFTase but not of tomato geranylgeranyl-protein transferase 1. Based on their conserved bio-chemical activities, we expect that prenyltransferases are likely integrated with the sterol biosynthesis pathway in the control of plant cell growth.


The Effect of Educational Program on Quality of Life in Menopausal Women: A Clinical Trial.
This study aimed to investigate the effect of Educational program on quality of life (QOL) in menopausal women in 2016 in Hamadan, Iran. In this clinical trial study, 100 postmenopausal women were randomly selected and allocated to case and control group (50 per group). Data collection tool included questionnaires of demographic information and Menopause QOL, which were completed by the samples before the intervention. In the case group, education program was run during 5 sessions for 45 to 60 minutes. Immediately and Three months after intervention, information were collected using questionnaire in both groups and they were analyzed using SPSS 16 software. The menopause women in both intervention and control groups had similar demographics. There was not a significant difference in the QOL mean scores in before of the intervention between the two groups of intervention and control in all dimension of QOL. There was a significantly difference in the mean of QOL scores between the two groups in immediately after the intervention and 3 months after the intervention in dimension of vasomotor, psychosocial, sexual and physical (P < 0.001). This study recommend that a unit in health and treatment centers be established for training menopausal women about health care by holding didactic classes.


Preloading Trifolded Grafts for Descemet Membrane Endothelial Keratoplasty Affects Scroll Formation.
The trifolded, endothelium-in approach to Descemet membrane endothelial keratoplasty (DMEK) facilitates tissue insertion into the anterior chamber. We hypothesized that preloading the trifolded donor grafts in a cartridge for 48 hours before insertion would induce biomechanical changes that decrease their scrolling tendency compared with those loaded immediately before insertion. Ten Descemet membrane donor grafts, peeled and cut to 8.0 mm, were prepared by a single eye bank technician. Each graft was trifolded and pulled into a DMEK cartridge and stored for 48 hours. They were then pulled with microforceps into a petri dish filled with balanced salt solution. A video was recorded of the graft becoming a scroll over a 2-minute period. Each graft, serving as its own control, was then trifolded, pulled into the cartridge, and the process repeated. Images from 1, 5, 10, 60, and 120 seconds were extracted from video recording of the procedures. Scroll width was analyzed by graders masked to group assignment. A paired t test was used to determine differences in scroll width at each time point between the 48-hour and instant trifolding conditions. All grafts scrolled after removal from the cartridge into balanced salt solution. We measured a significant difference at all time points 1 through 120 seconds (4.02 preloaded vs. 2.91-mm instant trifold, P = 0.035). Preloading DMEK grafts in a trifolded configuration for 48 hours reduces the scrolling tendency of Descemet membrane for at least 2 minutes.


Synthesis and SAR of novel Re/99mTc-labeled benzenesulfonamide carbonic anhydrase IX inhibitors for molecular imaging of tumor hypoxia.
Carbonic anhydrase IX (CA-IX) is upregulated in cancer in response to the hypoxic tumor microenvironment, making it an attractive molecular target for the detection of hypoxic solid tumors. A series of small molecule benzenesulfonamide based CA-IX inhibitors containing novel tridentate chelates complexed with the M(CO)(3) core (M = Re or (99m)Tc) were designed and synthesized. The in vitro binding affinity of the benzenesulfonamide rhenium complexes yielded IC(50) values ranging from 3 to 116 nM in hypoxic CA-IX expressing HeLa cells. One of the most potent compounds, 3d (IC(50) = 9 nM), was radiolabeled with technetium tricarbonyl ({(99m)Tc(CO)(3)}(+)) to afford the {(99m)Tc(CO)(3)}(+) complex in excellent yield and high purity. (99m)Tc(CO)(3)-3d bound specifically to CA-IX expressing hypoxic HeLa cells. This effort led to the identification of a diverse series of promising high affinity {(99m)Tc(CO)(3)}(+) radiolabeled CA-IX inhibitors with the potential to significantly impact diagnosis, staging, and treatment selection of hypoxic solid tumors.


[Antacids--gel or tablet. A randomized, double-blind, placebo-controlled study].
A double blind placebo controlled trial was conducted to compare the effect of two antacid brands (liquid and tablet form) on fasting and postprandial intragastric pH. In 9 healthy volunteers intragastric pH was continuously recorded by solid state memory on 6 occasions. 40 mmol of each antacid was given one hour before and after a standardized meal. The time during which pH was below 3.5 during the first hour following each medication was, in the fasting state, 56.7 +/- 2.1 min. with placebo tablets, 30.7 +/- 8.0 min. (p 0.05) with magaldrate tablets, 26.6 +/- 8.0 min. (p less than 0.01) with Al-Mg-hydroxide tablets, 46.1 +/- 6.1 min. with placebo liquid, 18.4 +/- 5.2 min. (p less than 0.01) with magaldrate liquid, and 21.5 +/- 6.2 min. (p less than 0.01) with Al-Mg-hydroxide liquid. Postprandially the respective periods of time were 48.3 +/- 4.9 min. with placebo tablets, 45.4 +/- 4.6 min. (n.s.) with magaldrate tablets, 48.9 +/- 5.6 min. (n.s.) with Al-Mg-hydroxide tablets, 46.7 +/- 7.9 min. with placebo liquid, 26.6 +/- 9.3 min. (p less than 0.05) with magaldrate liquid, and 28.0 +/- 7.1 min. (p less than 0.05) with Al-Mg-hydroxide liquid. Both tested brands were equally effective. With regard to pH activity, both tested forms were more effective in fasting state than postprandially; tablets showed no measureable activity postprandially and were less effective than the liquid form. The usefulness of the usual medication of low-dosed antacids, one hour postprandially, is open to doubt.


[Acetylcholinesterase activity during pregnancy and in the newborn].
Our purpose was to determine levels of acetyilcholinesterase (AchE) activity in total blood of women during pregnancy, and liverborns, and to analyze the correlation of the enzymatic activity between the capillary and venous sample. PATIENTS, MATERIAL, AND METHODS: We included 205 samples from pregnant (22), second (25), third trimester (36), full term pregnancy (65), non-pregnant women (28), and from Newborns (29). A bivaried analysis was used to analyse the AchE activity and its association with gestational age, body mass index, tobacco addiction, and use of pesticides at home, and hemoglobin concentration. Women at childbirth and at third trimester showed a significant increase in AcE levels by 5.75 + 1.15 U/mL and 4.98 +/- 0.87 U/mL respectively, respect to levels from non-pregnant women (4.59 +/- 0.79 U/mL). Activity in cord's blood was significatively minor (3.78 +/- 0.56 U/mL) compared with levels in non-pregnant women. There was no difference in AchE activity by tobacco addiction, hemoglobin levels, and use of insecticides at home. AchE activity by capillary and venous punction showed a correlation of 0.68 with p < 0.01 and IC 95% = 0.5171-0.8476. Enzymatic activity showed a normal distribution and could be considered like values from a non-exposure population. We determined that possible confounding factors like tobacco addiction and use of pesticides at home have no significant effects over AchE activity. Our results are important as reference values for studies about AchE activity in women from populations predominantly exposed to pesticides during gestation.


Chagas' disease in Latin American immigrants.
Chagas' disease is caused by Trypanosoma cruzi, a protozoan parasite that infects an estimated 10 to 12 million Latin Americans. Because infection is often lifelong, individuals from endemic areas may develop symptomatic chronic Chagas' disease years after emigrating to the United States. We report three immigrant patients from Latin America who illustrate the indeterminate phase and the symptomatic cardiac and gastrointestinal syndromes of this illness.


Avidin expression during chick chondrocyte and myoblast development in vitro and in vivo: regulation of cell proliferation.
Avidin is a major [35S]methionine-labeled protein induced by bacterial lipopolysaccharide (LPS) and interleukin 6 (IL-6) in cultured chick embryo myoblasts and chondrocytes. It was identified by N-terminal sequencing of the protein purified from conditioned culture medium of LPS-stimulated myoblasts. In addition, avidin was secreted by unstimulated myoblasts and chondrocytes during in vitro differentiation; maximal expression being observed in differentiated myofibers and hypertrophic chondrocytes. In developing chick embryos, immunohistochemistry revealed avidin in skeletal muscles and growth plate hypertrophic cartilage. Avidin was secreted into culture as a biologically active tetramer. Exogenous avidin added to the medium of proliferating chondrocytes progressively inhibited cell proliferation, whereas addition of avidin to differentiating chondrocytes in suspension allowed full cell differentiation. No toxic effects for the cells were observed in both culture conditions. Western blots of samples from cytosolic extracts using alkaline-phosphatase-conjugated streptavidin showed three biotin-containing proteins. Acetyl-CoA carboxylase was identified by specific antibodies. Based on these data, we propose that avidin binds extracellular biotin and regulates cell proliferation by interfering with fatty acid biosynthesis during terminal cell differentiation and/or in response to inflammatory stimuli.


Effects fo streptozotocin in the WDHA syndrome not amenable to radical surgery.
Two cases of Verner-MOrrison syndrome due to pancreatic carcinoma were treated H. h streptozotocin (STZ) according to the schedule suggested by the Division of Cancer Treatment of the National Cancer Institute. In both patients the drug caused a remission of the WDHA syndrome: therefore, this finding seems to recommend such treatment when the syndrome is not amenable to radical surgery. Renal toxicity is, however, an important limitation. It occurs mostly when STZ is administered by iv infusion. In one of the patients, after a serious impairment of renal function caused by STZ, prednisone controlled the syndrome for a long period of time.


Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans.
Imbalance in the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischemic acute renal failure. Human atrial natriuretic peptide (h-ANP) increases glomerular filtration rate in clinical acute renal failure. This would increase renal oxygen consumption due to increased tubular load of sodium. Loop diuretics are commonly used in acute renal failure. Data on the effects of loop diuretics on glomerular filtration rate and renal oxygen consumption in humans are, however, controversial. We evaluated the effects of h-ANP and furosemide on renal oxygen consumption, glomerular filtration rate, and renal hemodynamics in humans. Prospective two-agent interventional study in a university hospital cardiothoracic ICU. Nineteen uncomplicated, mechanically ventilated postcardiac surgery patients with normal renal function. h-ANP (25 and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9). Renal plasma flow and glomerular filtration rate were measured using the infusion clearance technique for (51)Cr-labeled EDTA and paraaminohippurate, corrected for by renal extraction of PAH. h-ANP increased glomerular filtration rate, renal filtration fraction, fractional excretion of sodium, and urine flow. This was accompanied by an increase in tubular sodium reabsorption (9%) and renal oxygen consumption (26%). Furosemide infusion caused a 10- and 15-fold increase in urine flow and fractional excretion of sodium, respectively, accompanied by a decrease in tubular sodium reabsorption (-28%), renal oxygen consumption (-23%), glomerular filtration rate and filtration fraction (-12% and -7%, respectively). The filtered load of sodium is an important determinant of renal oxygen consumption. h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects. In contrast, furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/demand relationship in clinical ischemic acute renal failure.


Mouse haemoglobin Beta chains. Sequence data on embryonic y chain and genetic linkage of the Y-chain locus to the adult beta-chain locus Hbb.
Embryonic haemoglobin y-chain types were determined by starch-gel electrophoresis for inbred Mus musculus strains Sec/ReJ and Au/SsJ (with Hbbs and Hbbp adult beta-chain alleles respectively) and for random-bred HA/ICR (Swiss) mice, which had been selected to be homozygous for the adult Hbbd beta-chain allele. The strain with the Hbbs allele had y1 embryonic beta chain and the strain with the Hbbd allele had y2. The strain with the Hbbp allele also had y2 chain. A breeding study showed that the maximum recombination frequency between the Hbb locus and the y-chain locus is 5.4% at the 95% confidence level. Embryonic y2 chain was sequenced for 39 positions from the N-terminus with an Edman-Begg sequenator. Some tryptic-peptide composition data were obtained on both y1 and y2 chains. No amino acid substitutions between y1 and y2 chains were found in the 40 positions for which there are common data on the two chains. y2 and adult beta chains are different in 12 of the first 21 positions, but show considerable similarity thereafter. It is suggested that homologous but unequal crossing-over between y-chain and adult beta-chain loci could have given rise to the adult beta-chain allele Hbbd, which produces structurally different major and minor beta chains from two closely linked genes.


Immediate Perineal Reconstruction After Extralevatory Abdominoperineal Excision: Buried Desepidermised Fasciocutaneous V-Y Advancement Flap.
According to National Cancer Institute, there are approximately 39,800 rectal cancer cases per year, 25% of which will need an abdominoperineal resection (APR). The key to avoid most of the complications related to pelvic defect that occurs after APR is choosing an appropriate reconstruction option for perineum. This study aims to introduce an easily applicable flap option for closure to address postoperative pelvic defect in low rectal cancer. This is a retrospective evaluation of 9 patients who have undergone perineal reconstruction for pelvic defects after extralevatory abdominoperineal excision with rectal cancer between 2014 and 2016. Reconstruction consists of a novel technique defined by our clinic, which is buried desepidermised fasciocutaneous V-Y advancement flap. All defects are closed successfully. Patients are followed postoperatively for complications such as perineal infection, wound dehiscence, seroma, perineal sinus, or fistula formation. Flaps are evaluated with magnetic resonance imaging postoperatively, for viability and effectiveness on defect closure. Mean follow-up time is 20 (±9) months. Mean average hospital stay is 8 (±2) days. We did not experience any total or partial flap loss or encounter any local complication related to the wound. Buried desepidermised fasciocutaneous V-Y advancement flap is a reasonably easy and time-saving operation. It is effective in filling the pelvic dead space while closing the sacral defect after APR and therefore decreases late term complications related to large perineal excision.


Salivary concentration of TNFalpha, IL1 alpha, IL6, and IL8 in oral squamous cell carcinoma.
The aim of this study was to compare the concentration of tumor necrosis factor alpha, interleukin 1 alpha, 6, and 8 in the saliva of oral squamous cell carcinoma patients with control group. In this study 18 subjects were involved, nine patients with oral squamous cell carcinomas and nine age-sex-matched healthy individuals that were matched for gingival conditions too. Active dental abscesses, collagen vascular diseases, and infectious diseases during one month before saliva sampling were considered as exclusion criteria. Unstimulated whole saliva was collected and after processing the samples were analyzed by Enzyme Linked Immune Assay. The concentration of salivary interleukin 6 in oral squamous cell carcinoma patients was higher than control group and it was statistically significant (p < 0.05). The concentration of salivary tumor necrosis factor alpha, interleukin 1 alpha and 8 in case group was higher than control group but it was not statistically significant (p > 0.05). These results shows that more studies are needed to accept the utility of these cytokines in predicting or diagnosis of oral squamous cell carcinoma or evaluation of treatment.


High-power, cascaded random Raman fiber laser with near complete conversion over wide wavelength and power tuning.
Cascaded Raman fiber lasers based on random distributed feedback (RDFB) are proven to be wavelength agile, enabling high powers outside rare-earth doped emission windows. In these systems, by simply adjusting the input pump power and wavelength, high-power lasers can be achieved at any wavelength within the transmission window of optical fibers. However, there are two primary limitations associated with these systems, which in turn limits further power scaling and applicability. Firstly, the degree of wavelength conversion or spectral purity (percentage of output power in the desired wavelength band) that can be achieved is limited. This is attributed to intensity noise transfer of input pump source to Raman Stokes orders, which causes incomplete power transfer reducing the spectral purity. Secondly, the output power range over which the high degree of wavelength conversion is maintained is limited. This is due to unwanted Raman conversion to the next Stokes order with increasing power. Here, we demonstrate a high-power, cascaded Raman fiber laser with near complete wavelength conversion over a wide wavelength and power range. We achieve this by culmination of two recent developments in this field. We utilize our recently proposed filtered feedback mechanism to terminate Raman conversion at arbitrary wavelengths, and we use the recently demonstrated technique (by J Dong and associates) of low-intensity noise pump sources (Fiber ASE sources) to achieve high-purity Raman conversion. Pump-limited output powers >34W and wavelength conversions >97% (highest till date) were achieved over a broad - 1.1μm to 1.5μm tuning range. In addition, high spectral purity (>90%) was maintained over a broad output power range (>15%), indicating the robustness of this laser against input power variations.


LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.
The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26. Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%). These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.


The reactions of para-halo diaryl diselenides with halogens. A structural investigation of the CT compound (p-FC6H4)2Se2I2, and the first reported "RSeI3" compound, (p-ClC6H4)SeI·I2, which contains a covalent Se-I bond.
The reactions of the diaryl-diselenides (p-FC(6)H(4))(2)Se(2) and (p-ClC(6)H(4))(2)Se(2) with diiodine have been investigated. Species of stoichiometry "RSeI" are formed when the ratio employed is 1:1. The solid-state structure of "(p-FC(6)H(4))SeI" has been determined, and shown to be a charge-transfer (CT) adduct, (p-FC(6)H(4))(2)Se(2)I(2), where the Se-Se bond is retained and the diiodine molecule interacts with only one of the selenium atoms. The Se-I bond in (p-FC(6)H(4))(2)Se(2)I(2) is 2.9835(12) Å, which is typical for a (10-I-2) Se-I-I CT system. When diiodine is reacted in a 3:1 ratio with (p-XC(6)H(4))(2)Se(2) (X = F, Cl) species of stoichiometry "RSeI(3)" are formed. The structure of "(p-ClC(6)H(4))SeI(3)" reveals that this is not a selenium(IV) compound, but is better represented as a selenium(II) CT adduct, (p-ClC(6)H(4))SeI·I(2). The Se-I bond to the diiodine molecule is typical in magnitude for a CT adduct, Se-I: 2.8672(5) Å, whereas the other Se-I bond is much shorter, Se-I: 2.5590(6) Å, and is a genuine example of a rarely observed covalent Se-I bond, which appears to be stabilised by a weak Se···I interaction from a neighbouring iodine atom. The reaction of (p-ClC(6)H(4))SeI with Ph(3)P results in the formation of a CT adduct, Ph(3)PSe(p-ClC(6)H(4))I, which has a T-shaped geometry at selenium (10-Se-3). By contrast, the reaction of (p-FC(6)H(4))SeI with Ph(3)P does not form an adduct, but results in the formation of Ph(3)PI(2) and (p-FC(6)H(4))(2)Se(2).


Chest CT features of coronavirus disease 2019 (COVID-19) pneumonia: key points for radiologists.
COVID-19 is an emerging infection caused by a novel coronavirus that is moving so rapidly that on 30 January 2020 the World Health Organization declared the outbreak a Public Health Emergency of International Concern and on 11 March 2020 as a pandemic. An early diagnosis of COVID-19 is crucial for disease treatment and control of the disease spread. Real-time reverse-transcription polymerase chain reaction (RT-PCR) demonstrated a low sensibility; therefore chest computed tomography (CT) plays a pivotal role not only in the early detection and diagnosis, especially for false negative RT-PCR tests, but also in monitoring the clinical course and in evaluating the disease severity. This paper reports the CT findings with some hints on the temporal changes over the course of the disease: the CT hallmarks of COVID-19 are bilateral distribution of ground glass opacities with or without consolidation in the posterior and peripheral lung, but the predominant findings in later phases include consolidations, linear opacities, "crazy-paving" pattern, "reversed halo" sign and vascular enlargement. The CT findings of COVID-19 overlap with the CT findings of other diseases, in particular the viral pneumonia including influenza viruses, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, etc. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. The aim of this article is to review the typical and atypical CT findings in COVID-19 patients in order to help radiologists and clinicians to become more familiar with the disease.


Models of knowledge in the assessment of postoperative pain.
This article illustrates a process of knowledge development and the interrelationship between knowledge and practice using Carper's fundamental patterns of knowing. It explores two kinds of knowledge, theoretical knowledge and practical knowledge, using postoperative pain assessment as an illustration. By using their theoretical knowledge and their practical experience, nurses can maintain and develop their professional knowledge and competence.


Donor-lymphocyte infusion following haploidentical hematopoietic cell transplantation with peripheral blood stem cell grafts and PTCy.
Donor-lymphocyte infusion (DLI) for relapse following haploidentical hematopoietic cell transplantation (haploHCT) with post-transplant cyclophosphamide (PTCy) has been described in recipients of bone marrow grafts, but not recipients of G-CSF mobilized peripheral blood (PB) grafts. We retrospectively identified patients who underwent DLI following PB-haploHCT with PTCy for relapse, or loss of chimerism (LOC). Twelve patients (57%) received DLI for hematologic relapse/persistent disease, seven (33%) for extramedullary relapse and two (10%) for LOC. Sixteen (76%) received chemotherapy prior to DLI, which did not correlate with response. The most common first dose was 1 × 106 CD3+ cells/kg. Two patients developed grade I aGvHD post DLI, one had grade II and two had grade III. One developed mild skin cGvHD 1361 days post DLI. Pre-DLI aGvHD predicted post-DLI aGvHD (P=0.025). Six patients achieved CR after DLI for overt relapse, one achieved full donor chimerism after LOC. Patients with LOC or EM relapse had superior relapse-free survival following DLI (P=0.029). DLI following PB-haploHCT with PTCy is a viable salvage therapy for overt relapse or LOC without a substantial increase in GvHD, and donor lymphocytes may be collected simultaneously with graft collection to facilitate availability in patients at high risk of relapse.


Natural Development of Antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Protein Antigens during the First 13 Years of Life.
Conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), three H. influenzae proteins, and five M. catarrhalis proteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year and then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies (r = 0.71 to 0.75; P < 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.


Psychometric characteristics of simulation-based assessment in anaesthesia and accuracy of self-assessed scores.
The purpose of this study was to define the psychometric properties of a simulation-based assessment of anaesthetists. Twenty-one anaesthetic trainees took part in three highly standardised simulations of anaesthetic emergencies. Scenarios were videotaped and rated independently by four judges. Trainees also assessed their own performance in the simulations. Results were analysed using generalisability theory to determine the influence of subject, case and judge on the variance in judges' scores and to determine the number of cases and judges required to produce a reliable result. Self-assessed scores were compared to the mean score of the judges. The results suggest that 12-15 cases are required to rank trainees reliably on their ability to manage simulated crises. Greater reliability is gained by increasing the number of cases than by increasing the number of judges. There was modest but significant correlation between self-assessed scores and external assessors' scores (rho = 0.321; p = 0.01). At the lower levels of performance, trainees consistently overrated their performance compared to those performing at higher levels (p = 0.0001).


The Role of Fecal Calprotectin in Evaluating Intestinal Involvement of Behçet's Disease.
One of the regions of involvement of Behçet's disease (BD), a systematic inflammatory vasculitis with unknown etiology, is the gastrointestinal (GI) tract. Upper GI endoscopy, colonoscopy, and capsule endoscopy are frequently used methods to diagnose the intestinal involvement of BD. The aim of this study was to investigate the role of fecal calprotectin (FC) in the evaluation of intestinal involvement in BD. Material and Method. A total of 30 patients who were diagnosed with BD and had no GI symptoms and 25 individuals in the control group were included in this study. Results. Levels of FC were statistically significantly higher in patients with BD compared to the control group (p < 0.001). The correlation analysis performed including FC and markers of disease activity revealed a positive and statistically significant correlation between FC level and CRP and erythrocyte sedimentation rate (r: 0.255, p < 0.049, and r: 0.404, p < 0.001, resp.). FC levels in patients who were detected to have ulcers in the terminal ileum and colon in the colonoscopic examination were statistically significantly higher compared to the patients with BD without intestinal involvement (p = 0.01). Conclusion. The measurement of FC levels, in patients with BD who are asymptomatic for GI involvement, may be helpful to detect the possible underlying intestinal involvement.


[Preparation and spectra of the complexes of the first series transition metals with diphenic acid].
The ligand diphenic acid has been synthesized and the corresponding complexes of transition metal Co, Ni and Mn with diphenic acid have been prepared and characterized by the elementary analysis, IR spectra and ultraviolet-visible spectra. The results of IR show that the vas and vs of -CO2- in the complexes are lower than those of ligand diphenic acid, which can be explained by the coordinating between metal and ligand. In addition, compared with the complex IR spectra, the IR spectra of ligand became complicated due to the ligand polymerization through hydrogen bond. The UV-Vis spectra show that the ligand has three absorption peaks at 288, 273 and 270 nm, respectively, and these are slightly shifted in the complexes. Because the metal d-d absorption is weak, only in Co(C14H8O4) x 2H2O there is a d-d absorption at 537 nm.


In search of controlled evidence for health care quality improvement.
The purpose of this study was to measure the efficiency of simple searches in retrieving controlled evidence about specific primary health care quality improvement interventions and their effects. Searches were conducted to retrieve evidence on seven interventions and seven effect variables. Specific words and the closest Medical Subject Headings (MeSH) recommended by professional librarians were used to search the MEDLINE database. Searches were restricted to the MeSH publication type "randomized controlled trial." Two reviewers independently judged retrieved citations for relevancy to the selected interventions and effects. In selecting MeSH terms, the average agreement among librarians was 64.3% (+/-26.1) for interventions and 57.1% (+/-19.9) for effects. Analysis of the 755 retrieved reports showed that MeSH term searches had an overall recall rate of 58% while the same rate for textword searches was significantly lower (11%, p < .001). The difference in overall precision rates was nonsignificant (26% versus 33%, p = .15). In the group of MeSH searches, overall precision and recall was significantly lower for effects than for interventions (12% versus 52%, p < .001 and 41% versus 69%, p < .001). Two textwords appeared in more than 25% of the benchmark collection: reminder (25.7%) and cost (25.0%). The results of this study indicate that information needs for health care quality improvement cannot be met by simple literature searches. Certain MeSH terms and combinations of textwords yield moderately efficient recall and precision in literature searches for health care quality improvement. Clinicians and physician executives gaining direct access to bibliographic database could probably be better served by structured indexing of critical aspects of randomized controlled clinical trials: design, sample, interventions, and effects.


Defining Optimal Length of Opioid Pain Medication Prescription After Common Surgical Procedures.
The overprescription of pain medications has been implicated as a driver of the burgeoning opioid epidemic; however, few guidelines exist regarding the appropriateness of opioid pain medication prescriptions after surgery. To describe patterns of opioid pain medication prescriptions after common surgical procedures and determine the appropriateness of the prescription as indicated by the rate of refills. The Department of Defense Military Health System Data Repository was used to identify opioid-naive individuals 18 to 64 years of age who had undergone 1 of 8 common surgical procedures between January 1, 2005, and September 30, 2014. The adjusted risk of refilling an opioid prescription based on the number of days of initial prescription was modeled using a generalized additive model with spline smoothing. Length of initial prescription for opioid pain medication. Need for an additional subsequent prescription for opioid pain medication, or a refill. Of the 215 140 individuals (107 588 women and 107 552 men; mean [SD] age, 40.1 [12.8] years) who underwent a procedure within the study time frame and received and filled at least 1 prescription for opioid pain medication within 14 days of their index procedure, 41 107 (19.1%) received at least 1 refill prescription. The median prescription lengths were 4 days (interquartile range [IQR], 3-5 days) for appendectomy and cholecystectomy, 5 days (IQR, 3-6 days) for inguinal hernia repair, 4 days (IQR, 3-5 days) for hysterectomy, 5 days (IQR, 3-6 days) for mastectomy, 5 days (IQR, 4-8 days) for anterior cruciate ligament repair and rotator cuff repair, and 7 days (IQR, 5-10 days) for discectomy. The early nadir in the probability of refill was at an initial prescription of 9 days for general surgery procedures (probability of refill, 10.7%), 13 days for women's health procedures (probability of refill, 16.8%), and 15 days for musculoskeletal procedures (probability of refill, 32.5%). Ideally, opioid prescriptions after surgery should balance adequate pain management against the duration of treatment. In practice, the optimal length of opioid prescriptions lies between the observed median prescription length and the early nadir, or 4 to 9 days for general surgery procedures, 4 to 13 days for women's health procedures, and 6 to 15 days for musculoskeletal procedures.


An International Survey of Mediastinal Staging Practices amongst Interventional Bronchoscopists.
In potentially curable non-small-cell lung cancer, different practice guidelines recommend invasive me-diastinal staging in tumors larger than 3 cm, central, or hy-permetabolic N1 lymph nodes. There is no consensus concerning the use of an endosonographic procedure or a mediastinoscopy in the first line in patients with a radiologically normal mediastinum, while in case of a mediastinal involvement, the latest European guidelines recommend the combination of endobronchial ultrasound (EBUS) and endoscopic ultrasound/endoscopic ultrasound with EBUS endoscope (EUS/EUS-B), using a systematic endosonographic procedure. This international survey was conducted to describe current medical practices in endoscopic mediastinal staging amongst interventional bronchoscopists. A survey was developed and sent to all members of different interventional pulmonology societies, with the purpose to describe who, when and how an endoscopic mediastinal staging was performed. One hundred and fifty-three bronchoscopists responded to the survey. Most of them practiced in Europe (n = 84, 55%) and North America (n = 52, 34%). In the first line, EBUS alone was the most widely used endoscopic procedure for mediastinal staging. Half of the responders performed a systematic endoscopic staging procedure, including a systematic examination of all accessible nodal stations and a sampling of all lymph nodes >5 mm in the short axis at each station. A higher proportion of bronchoscopists who have completed a dedicated fellowship program performed systematic endoscopic mediastinal staging. Few endoscopists routinely perform combined EBUS/EUS(-B) for mediastinal staging and use the combination only in selected cases. There are several areas of divergence between published guidelines and current practices reported by interventional bronchoscopists. EBUS alone is the most widely used endoscopic procedure for mediastinal staging in lung cancer, and a combined endoscopic approach is frequently omitted by the responders. A fellowship program appears to be associated with a higher rate of systematic endoscopic staging procedures.


A wearable multi-channel fNIRS system for brain imaging in freely moving subjects.
Functional near infrared spectroscopy (fNIRS) is a versatile neuroimaging tool with an increasing acceptance in the neuroimaging community. While often lauded for its portability, most of the fNIRS setups employed in neuroscientific research still impose usage in a laboratory environment. We present a wearable, multi-channel fNIRS imaging system for functional brain imaging in unrestrained settings. The system operates without optical fiber bundles, using eight dual wavelength light emitting diodes and eight electro-optical sensors, which can be placed freely on the subject's head for direct illumination and detection. Its performance is tested on N=8 subjects in a motor execution paradigm performed under three different exercising conditions: (i) during outdoor bicycle riding, (ii) while pedaling on a stationary training bicycle, and (iii) sitting still on the training bicycle. Following left hand gripping, we observe a significant decrease in the deoxyhemoglobin concentration over the contralateral motor cortex in all three conditions. A significant task-related ΔHbO2 increase was seen for the non-pedaling condition. Although the gross movements involved in pedaling and steering a bike induced more motion artifacts than carrying out the same task while sitting still, we found no significant differences in the shape or amplitude of the HbR time courses for outdoor or indoor cycling and sitting still. We demonstrate the general feasibility of using wearable multi-channel NIRS during strenuous exercise in natural, unrestrained settings and discuss the origins and effects of data artifacts. We provide quantitative guidelines for taking condition-dependent signal quality into account to allow the comparison of data across various levels of physical exercise. To the best of our knowledge, this is the first demonstration of functional NIRS brain imaging during an outdoor activity in a real life situation in humans.


Metal-Based Electrocatalysts for Methanol Electro-Oxidation: Progress, Opportunities, and Challenges.
Direct methanol fuel cells (DMFCs) are among the most promising portable power supplies because of their unique advantages, including high energy density/mobility of liquid fuels, low working temperature, and low emission of pollutants. Various metal-based anode catalysts have been extensively studied and utilized for the essential methanol oxidation reaction (MOR) due to their superior electrocatalytic performance. At present, especially with the rapid advance of nanotechnology, enormous efforts have been exerted to further enhance the catalytic performance and minimize the use of precious metals. Constructing multicomponent metal-based nanocatalysts with precisely designed structures can achieve this goal by providing highly tunable compositional and structural characteristics, which is promising for the modification and optimization of their related electrochemical properties. The recent advances of metal-based electrocatalytic materials with rationally designed nanostructures and chemistries for MOR in DMFCs are highlighted and summarized herein. The effects of the well-defined nanoarchitectures on the improved electrochemical properties of the catalysts are illustrated. Finally, conclusive perspectives are provided on the opportunities and challenges for further refining the nanostructure of metal-based catalysts and improving electrocatalytic performance, as well as the commercial viability.


[Selective pharyngeal brain cooling].
Whole-body cooling can be used in the treatment of various brain pathologies, for example, after hypoxic events. Potential complications include haemodynamic instability, coagulation disorders and infection. Selective brain cooling (SBC) would therefore appear to make good sense. In an animal model a new approach to SBC was therefore evaluated. A rat weighing 350 g was sedated with alpha-chloralose (40 mg/kg/h) and d-tubocurarine (4.05 mg/kg/h), mechanically ventilated and placed on a heating pad. A thermocouple was introduced into the somatosensory cortex to a depth of 2.5 mm. SBC was achieved using a novel approach: PTFE tubing (ID 100 microns) with an inlet and an outlet was wrapped around and glued to a piece of wood, and introduced non traumatically into the pharynx. The tubing was perfused with cold water (+4 degrees C). Under SBC the cortical temperature dropped from 38.4 degrees C to 27.7 degrees C while the core temperature remained stable. In an animal model SBC was successfully accomplished via the pharynx. Further studies should now be done to evaluate the effectiveness of this approach in larger animals with potentially different anatomical features.


[Clinical and preclinical efficacy of antimicrobial catheters].
Frequent use of polymeric material for diagnostic and therapeutic use has provoked an increase of so-called polymer-associated foreign body infections. The difficulties in correctly diagnosing catheter-related infections and the necessity to remove the device in case of suspected infection require preventive procedures in the first place. Therefore, several studies have dealt with surface treatment by coating with antibiotics, antiseptics and silver. Some of them remain in clinical trials or are already sold in the USA. Clinical failure of silver-sulfadiazine coated CVCs has been reported recently. Recently a rifampicinminocyclin-catheter has been shown to reduce efficiently material-associated infection in preclinical and clinical studies. Most of the substances retained on catheter surfaces are released only in small quantities resulting in ineffective suppression of bacterial growth. If substantial amounts of antimicrobials are incorporated into the biomaterial, release pattern and killing efficacy of each substance group has to be determined in order to reach bactericidal concentrations in the environment of adherent bacteria. Killing kinetics of antibiotics, antiseptics and silver to bacteria are strongly different. On the one hand killing kinetics of microorganism due to substantial quantities of antiseptics are fast, on the other hand antiseptics destroy structures of both, bacteria and blood cells. Bactericidal concentrations of Ag-ions show fibroblast inhibition. Antibiotics, however, show lowest toxicity due to the specific action to microorganisms. However, sustained release over time is needed to reach bactericidal concentrations, considering the slower bactericidal action of typical antibiotics. Development of allergic reaction is possible for all substances, whereas development of bacterial resistance can be prevented by use of antimicrobial combinations.


Retrotransposon-based profiling of mammalian epigenomes: DNA methylation of IAP LTRs in embryonic stem, somatic and cancer cells.
In the current study, we have used HT-TREBS to individually analyze the DNA methylation pattern of 4799 IAP LTR retrotransposons in embryonic stem, somatic and Neuro2A cells. According to the results, half of the loci within this family show constant methylation patterns between the three cell types whereas the remaining half display variable levels of methylation. About half of the variably methylated IAP LTRs tend to be hypomethylated in ES cells, and nearly all in this group are hypomethylated in Neuro2A cells. The observed hypomethylation in both cell types occur in a non-uniform, locus-specific manner and to various degrees of severity, with some of them being easily detectible by COBRA. Overall, this study demonstrates the feasibility of HT-TREBS to study DNA methylation changes at retrotransposons in a locus-specific manner in multiple cell types and further suggests the potential utility of this technique in developing epigenetic biomarkers for tracking disease progression.


Desert springs: deep phylogeographic structure in an ancient endemic crustacean (Phreatomerus latipes).
Desert mound springs of the Great Artesian Basin in central Australia maintain an endemic fauna that have historically been considered ubiquitous throughout all of the springs. Recent studies, however, have shown that several endemic invertebrate species are genetically highly structured and contain previously unrecognised species, suggesting that individuals may be geographically 'stranded in desert islands'. Here we further tested the generality of this hypothesis by conducting genetic analyses of the obligate aquatic phreatoicid isopod Phreatomerus latipes. Phylogenetic and phylogeographic relationships amongst P. latipes individuals were examined using a multilocus approach comprising allozymes and mtDNA sequence data. From the Lake Eyre region in South Australia we collected data for 476 individuals from 69 springs for the mtDNA gene COI; in addition, allozyme electrophoresis was conducted on 331 individuals from 19 sites for 25 putative loci. Phylogenetic and population genetic analyses showed three major clades in both allozyme and mtDNA data, with a further nine mtDNA sub-clades, largely supported by the allozymes. Generally, each of these sub-clades was concordant with a traditional geographic grouping known as spring complexes. We observed a coalescent time between ∼2-15 million years ago for haplotypes within each of the nine mtDNA sub-clades, whilst an older total time to coalescence (>15 mya) was observed for the three major clades. Overall we observed that multiple layers of phylogeographic history are exemplified by Phreatomerus, suggesting that major climate events and their impact on the landscape have shaped the observed high levels of diversity and endemism. Our results show that this genus reflects a diverse fauna that existed during the early Miocene and appears to have been regionally restricted. Subsequent aridification events have led to substantial contraction of the original habitat, possibly over repeated Pleistocene ice age cycles, with P. latipes populations becoming restricted in the distribution to desert springs.


Human trafficking risk factors, health impacts, and opportunities for intervention in Uganda: a qualitative analysis.
Human trafficking is a global public health issue that is associated with serious short- and long-term morbidity. To address and prevent human trafficking, vulnerabilities to human trafficking and forces sustaining it need to be better understood among specific subpopulations. We aimed to explore risk and protective factors for human trafficking, the health impact of exploitation, and barriers and facilitators of seeking help throughout the human trafficking trajectory among forced labor and sex trafficking victims in Kampala, Uganda. Between March and November 2020, in-depth, semi-structured qualitative interviews were conducted with 108 victims of forced labor and sex trafficking who had completed a human trafficking survey conducted by the Uganda Youth Development Link (UYDEL). Participants who experienced various forms of exploitation were purposively invited for qualitative interviews and a convenience sample was interviewed. Interviews explored personal history, trafficking recruitment, experiences of exploitation and abuse, and experiences seeking help. Interviews were analyzed using a combination of deductive and inductive thematic analysis. Themes and subthemes were organized using an adapted conceptual framework of human trafficking. Poverty and an abusive home life, frequently triggered by the death of a caretaker, underpinned vulnerability to human trafficking recruitment. Limited education, lack of social support, and survival needs pushed victims into exploitative situations. Victims of human trafficking were systematically exploited and exposed to dangerous working conditions. Victims suffered from sexually transmitted diseases, incontinence, traumatic fistulae, musculoskeletal injuries, and mental health symptoms. Lack of awareness of resources, fear of negative consequences, restrictions on movement, and dependence on the trafficker and exploitation income prevented victims from seeking help. The police and healthcare workers were the few professionals that they interacted with, but these interactions were oftentimes negative experiences. To address and prevent human trafficking, localized interventions are needed at all stages of the human trafficking trajectory. Health impacts of human trafficking are severe. As some of the few professionals trafficking victims interact with, police and healthcare workers are important targets for anti-trafficking training. Improved understanding of human trafficking drivers and barriers and facilitators to seeking help can inform the design of necessary interventions.


A Suite of Mobile Conversational Agents for Daily Stress Management (Popbots): Mixed Methods Exploratory Study.
Approximately 60%-80% of the primary care visits have a psychological stress component, but only 3% of patients receive stress management advice during these visits. Given recent advances in natural language processing, there is renewed interest in mental health chatbots. Conversational agents that can understand a user's problems and deliver advice that mitigates the effects of daily stress could be an effective public health tool. However, such systems are complex to build and costly to develop. To address these challenges, our aim is to develop and evaluate a fully automated mobile suite of shallow chatbots-we call them Popbots-that may serve as a new species of chatbots and further complement human assistance in an ecosystem of stress management support. After conducting an exploratory Wizard of Oz study (N=14) to evaluate the feasibility of a suite of multiple chatbots, we conducted a web-based study (N=47) to evaluate the implementation of our prototype. Each participant was randomly assigned to a different chatbot designed on the basis of a proven cognitive or behavioral intervention method. To measure the effectiveness of the chatbots, the participants' stress levels were determined using self-reported psychometric evaluations (eg, web-based daily surveys and Patient Health Questionnaire-4). The participants in these studies were recruited through email and enrolled on the web, and some of them participated in follow-up interviews that were conducted in person or on the web (as necessary). Of the 47 participants, 31 (66%) completed the main study. The findings suggest that the users viewed the conversations with our chatbots as helpful or at least neutral and came away with increasingly positive sentiment toward the use of chatbots for proactive stress management. Moreover, those users who used the system more often (ie, they had more than or equal to the median number of conversations) noted a decrease in depression symptoms compared with those who used the system less often based on a Wilcoxon signed-rank test (W=91.50; Z=-2.54; P=.01; r=0.47). The follow-up interviews with a subset of the participants indicated that half of the common daily stressors could be discussed with chatbots, potentially reducing the burden on human coping resources. Our work suggests that suites of shallow chatbots may offer benefits for both users and designers. As a result, this study's contributions include the design and evaluation of a novel suite of shallow chatbots for daily stress management, a summary of benefits and challenges associated with random delivery of multiple conversational interventions, and design guidelines and directions for future research into similar systems, including authoring chatbot systems and artificial intelligence-enabled recommendation algorithms.


[Effect of Astragalus polysaccharide on pancreatic cell mass in type 1 diabetic mice].
To study the effect of Astragalus polysaccharide (APS) on pancreatic beta cell mass in type 1 diabetic mice. Diabetic mice induced by multiple low dose streptozotocin (MLD-STZ) were administered either APS (100, 200, 400 mg x kg(-1) body weight) or saline intraperitoneally daily, and sacrificed after 15 or 30 days of treatment. Streptavidin-peroxidase immunohistochemical method with counterstain was performed to determine the effect of APS on insulitis. Indirect double immunofluorescence for Insulin/Ki67 (counterstained by Hoechst33258) and Insulin/Cleaved caspase-3 was used to evaluate pancreatic cell (besides beta cell) proliferation, beta cell neogenesis, beta cell apoptosis and beta cell mass. Semi-quantitative RT-PCR was utilized to characterize pancreatic regenerating protein 1 mRNA levels, and ELISA method was performed to measure the levels of cytokine IFN-gamma and IL-4 secreted by splenocytes. Attenuated insulitis, upregulated beta cell mass, increased number of neogenetic pancreas islets, decreased number of apoptosis beta cells and downregulation of Th1/Th2 cytokine ratio were significantly time-and dose-dependent on APS treatment, when compared to saline controls. However, no significant differences of the number of pancreatic proliferative cells or replicative cells and pancreatic regenerating protein 1 mRNA levels were demonstrated between APS (APS100, APS200 and APS400) and saline vehicle group on day 15 and 30 with APS treatment. APS can upregulate pancreatic beta cell mass in type 1 diabetic mice, strongly associated with improved autoimmunity.


Insight into a Fast-Phototuning Azobenzene Switch for Sustainably Tailoring the Foam Stability.
A photoresponsive surfactant of 4-octoxy-4'-[(trimethylamino)ethoxy]azobenzene (OTAEAzo) has been synthesized for developing a fast-phototuning foam switch based on its high sensitivity, reversibility, and fatigue resistance of the photoisomerization capability. Ultraviolet (UV)-light irradiation for 1 s enabled conversion from the trans isomer to the cis configuration, while exposure to visible (Vis)-light for 3 min induced a cis-to-trans transformation, which maintains an excellent cycling stability for 20 cycles of photoisomerization. The photoisomerization speed depended on the concentration of OTAEAzo, and a lower concentration facilitated a faster photoisomerization process. Because of the low critical micelle concentration (CMC), OTAEAzo with a small dosage of 0.2 g·L-1 showed foamability, which accelerated the photoisomerization speed, enabling it to become a highly efficient switch. The surface activities of trans-OTAEAzo presented distinct differences from those of cis-OTAEAzo, resulting in the foam stabilization effects of trans-OTAEAzo (t1/2 = 2.58 min) and the destabilization effects of cis-OTAEAzo (t1/2 = 0.38 min). Moreover, the foam properties varied slightly in the phototuning cycles. OTAEAzo with low CMC presents high sensitivity and reversible photoisomerization capability, providing an environmental and sustainable approach for tailoring the foam stability.


Hypogammaglobulinemia in pediatric systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease typically associated with elevated serum immunoglobulin G (IgG). Hypogammaglobulinemia in SLE patients has been attributed to immunosuppressive treatment or a transient effect associated with nephrotic syndrome. We retrospectively reviewed pediatric SLE patients from a single institution to identify patients with hypogammaglobulinemia and risk factors for hypogammaglobulinemia. A total of 116 pediatric SLE cases from 1997 to 2011 were reviewed and patients with hypogammaglobulinemia (IgG < 500 mg/dl) were identified. The two cohorts were evaluated for association with age, sex, presence of lupus nephritis at SLE diagnosis, disease activity at diagnosis, initial IgG level, and drug treatment. Eighty-six patients were included in our study, with a median age of 15 years and a median follow-up of 39.5 months. Seven percent (six of 86) of patients had hypogammaglobulinemia with a median onset of 27 months (0-72 months) after SLE diagnosis. Significant associations were noted for white race (p value 0.029), male sex (p value 0.009), and the presence of lupus nephritis at SLE diagnosis (p value 0.004). Use of immunosuppressive treatment did not show a statistical association with hypogammaglobulinemia, although two of the patients with hypogammaglobulinemia did receive rituximab. Most patients with hypogammaglobulinemia received intravenous immunoglobulin (IVIG) replacement therapy because of infections and/or concern for infection. Measurement of immunoglobulin levels during treatment in SLE could help identify patients with hypogammaglobulinemia who might require more aggressive follow-up to monitor for increased risk of infection and need for IVIG treatment. A prospective study is needed to validate associated risk factors identified in this study.


Efficacy assessment of interferon-alpha-engineered mesenchymal stromal cells in a mouse plasmacytoma model.
Bone marrow mesenchymal stromal cells (BM-MSCs) may survive and proliferate in the presence of cycling neoplastic cells. Exogenously administered MSCs are actively incorporated in the tumor as stromal fibroblasts, thus competing with the local mesenchymal cell precursors. For this reason, MSCs have been suggested as a suitable carrier for gene therapy strategies, as they can be genetically engineered with genes encoding for biologically active molecules that can inhibit tumor cell proliferation and enhance the antitumor immune response. We used BM-MSCs engineered with the murine interferon-alpha (IFN-α) gene (BM-MSCs/IFN-α) to assess in a mouse plasmacytoma model the efficacy of this approach toward neoplastic plasma cells. We found that IFN-α can be efficiently produced and delivered inside the tumor microenvironment. Subcutaneous multiple administration of BM-MSCs/IFN-α significantly hampered the tumor growth in vivo and prolonged the overall survival of mice. The antitumor effect was associated with enhanced apoptosis of tumor cells, reduction in microvessel density, and ischemic necrosis. By contrast, intravenous administration of BM-MSCs/IFN-α did not significantly modify the survival of mice, mainly as a consequence of an excessive entrapment of injected cells in the pulmonary vessels. In conclusion, BM-MSCs/IFN-α are effective in inhibiting neoplastic plasma cell growth; however, systemic administration of engineered MSCs needs to be improved to make this approach potentially suitable for the treatment of multiple myeloma.


Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival.
Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale. The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed. The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001). Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.


Chronic Exposure to Chlorpyrifos Damages Thyroid Activity and Imbalances Hepatic Thyroid Hormones Signaling and Glucose Metabolism: Dependency of T3-FOXO1 Axis by Hyperglycemia.
Early life exposure to Endocrine Disruptor Chemicals (EDCs), such as the organophosphate pesticide Chlorpyrifos (CPF), affects the thyroid activity and dependent process, including the glucose metabolism. The damage of thyroid hormones (THs) as a mechanism of action of CPF is underestimated because the studies rarely consider that TH levels and signaling are customized peripherally. Here, we investigated the impairment of metabolism/signaling of THs and lipid/glucose metabolism in the livers of 6-month-old mice, developmentally and lifelong exposed to 0.1, 1, and 10 mg/kg/die CPF (F1) and their offspring similarly exposed (F2), analyzing the levels of transcripts of the enzymes involved in the metabolism of T3 (Dio1), lipids (Fasn, Acc1), and glucose (G6pase, Pck1). Both processes were altered only in F2 males, affected by hypothyroidism and by a systemic hyperglycemia linked to the activation of gluconeogenesis in mice exposed to 1 and 10 mg/kg/die CPF. Interestingly, we observed an increase in active FOXO1 protein due to a decrease in AKT phosphorylation, despite insulin signaling activation. Experiments in vitro revealed that chronic exposure to CPF affected glucose metabolism via the direct modulation of FOXO1 activity and T3 levels in hepatic cells. In conclusion, we described different sex and intergenerational effects of CPF exposure on the hepatic homeostasis of THs, their signaling, and, finally, glucose metabolism. The data points to FOXO1-T3-glucose signaling as a target of CPF in liver.


An interface to support independent use of Facebook by people with intellectual disability.
Use of social networking sites, such as Facebook, is rapidly expanding, but people with intellectual disability are at risk for exclusion because sites like Facebook are not designed for cognitive access. The purpose of the present study was to describe the development and initial testing of a cognitively accessible prototype interface for Facebook, called Endeavor Connect, that was designed to support independent Facebook use by people with intellectual disability. The performance of young adults with intellectual disability when completing five common Facebook tasks was compared when using the Endeavor Connect and Facebook interfaces. Results suggest that, when using Endeavor Connect, young adults with intellectual disability completed more tasks independently with fewer errors and required fewer prompts. Implications for research and practice are discussed.


[Ladasten versus placebo effect self-evaluated by neurasthenia patients with different EEG alpha rhythm types].
The study was focused on the clinico-pharmacological analysis of differences between subjective and objective assessment of the effects of antiasthenic drug ladasten and placebo effects in patients with neurasthenia with different individual patterns manifested in their EEG alpha rhythms and MMPI findings. It is established that, in patients with neurasthenia characterized by reduced EEG alpha activity combined with emotional lability and inertness, the therapeutic action and effectiveness of ladasten and placebo was more robust (the subjective estimation was higher) than in patients with prominent alpha rhythm and sthenic personal traits. The self-assessment of the effect of single test doses of ladasten and placebo was independent of the individual differences of EEG alpha rhythm organization and personal traits with respect to tolerability, wish to continue the treatment, activating and calming effects. In long-term treatment, higher subjective estimations of the ladasten and placebo effect appeared in patients with reduced EEG alpha rhythm, and the difference corresponded to objective indices of the psychotropic action and effectiveness of the drug.


A well-defined (POCOP)Rh catalyst for the coupling of aryl halides with thiols.
This article describes a well-defined pincer-Rh catalyst for C-S cross-coupling reactions. (POCOP)Rh(H)(Cl) serves as an active precatalyst for the coupling of aryl chlorides and bromides with aryl and alkyl thiols under reasonable conditions (3% mol cat., 110 °C, 2-24 h, >90% yield). For select substrates, >90% yields were obtained with catalyst loading as low as 0.1%. Key mechanistic intermediates have been isolated and fully characterized, including (POCOP)Rh(Ph)(SPh) (6a) and (POCOP)Rh(SPh2) (6b). The aryl/bis(phosphinite) (POCOP)Rh system has been shown to favor aryl thiolate reductive elimination at elevated temperatures and in some cases at room temperature, compared with the analogous diarylamido/bis(phosphine) (PNP)Rh pincer system. Concerted reductive elimination has been studied with 6a directly and in the presence of aryl bromide and aryl chloride traps. This investigation demonstrates a clear rate dependence on aryl chloride concentration during catalysis, a dependence that is absent when using aryl bromides. The rate of catalysis is dramatically reduced or brought to zero for ortho-tolyl halides, which can be traced to slower C-S coupling and slower carbon-halogen oxidative addition for ortho-substituted aryls. The influence of the sterics in the thiol component is less straightforward. The S-H oxidative addition product (POCOP)Rh(H)(SPh) (16) has been fully characterized and its reactivity has been examined, resulting in the isolation of the sodium-thiolate adduct (POCOP)Rh(NaSPh) (19). The solid-state structure of 19 shows Na interactions not only with sulfur, but also with a neighboring Rh and the chelating aryl carbon of the pincer framework. The reactivity of 16 and 19 indicates that these potential side products should not hinder catalysis.


A comparative analysis of constitutive promoters located in adeno-associated viral vectors.
The properties of constitutive promoters within adeno-associated viral (AAV) vectors have not yet been fully characterized. In this study, AAV vectors, in which enhanced GFP expression was directed by one of the six constitutive promoters (human β-actin, human elongation factor-1α, chicken β-actin combined with cytomegalovirus early enhancer, cytomegalovirus (CMV), simian virus 40, and herpes simplex virus thymidine kinase), were constructed and introduced into the HCT116, DLD-1, HT-1080, and MCF-10A cell lines. Quantification of GFP signals in infected cells demonstrated that the CMV promoter produced the highest GFP expression in the six promoters and maintained relatively high GFP expression for up to eight weeks after infection of HCT116, DLD-1, and HT-1080. Exogenous human CDKN2A gene expression was also introduced into DLD-1 and MCF-10A in a similar pattern by using AAV vectors bearing the human β-actin and the CMV promoters. The six constitutive promoters were subsequently placed upstream of the neomycin resistance gene within AAV vectors, and HCT116, DLD-1, and HT-1080 were infected with the resulting vectors. Of the six promoters, the CMV promoter produced the largest number of G418-resistant colonies in all three cell lines. Because AAV vectors have been frequently used as a platform to construct targeting vectors that permit gene editing in human cell lines, we lastly infected the three cell lines with AAV-based targeting vectors against the human PIGA gene in which one of the six promoters regulate the neomycin resistance gene. This assay revealed that the CMV promoter led to the lowest PIGA gene targeting efficiency in the investigated promoters. These results provide a clue to the identification of constitutive promoters suitable to express exogenous genes with AAV vectors, as well as those helpful to conduct efficient gene targeting using AAV-based targeting vectors in human cell lines.


Clinical correlates of atrial tachyarrhythmias after valve replacement for aortic stenosis.
One hundred eighteen consecutive patients undergoing valve replacement for aortic stenosis were analyzed to determine the incidence of and predisposing factors to postoperative atrial tachyarrhythmias. Univariate and multivariate analyses were performed on 70 clinical, hemodynamic, radiographic, electrocardiographic, operative, and postoperative variables. Forty-seven patients (40%) experienced atrial tachyarrhythmias at a median of 3 days after surgery (70% atrial fibrillation, 22% atrial flutter, and 6% junctional tachycardia). Preoperative descriptors associated with an increased prevalence of atrial tachyarrhythmias were age 70 years or older (p less than .02), mitral regurgitation (p less than .002), history of paroxysmal atrial fibrillation (p less than .03), or antiarrhythmic therapy (p less than .006), diabetes mellitus (p less than .01), and elevated pulmonary systolic, mean, and capillary wedge pressures (p less than .02, p less than .007, p less than .005). Postoperative descriptors were prolonged respirator therapy (p less than .001), use of catecholamines (p less than .01) or vasodilators (p less than .05), and prolonged stay in the intensive care unit (p less than .04). Multivariate analysis of these 12 variables showed advanced age, diabetes mellitus, and prolonged respirator use to be independently associated with atrial tachycardias and to predict them with a sensitivity of 62% and a specificity of 77%. Anticipation of atrial arrhythmias in patients with specific clinical descriptors may be used to guide prophylactic therapy.


Characterisation of diarrhoeagenic Escherichia coli clones by ribotyping and ERIC-PCR.
The ability of ribotyping and enterobacterial repetitive intergenic concensus-polymerase chain reaction (ERIC-PCR) to discriminate diarrhoeagenic Escherichia coli clones of 122 strains belonging to 26 distinct serotypes was evaluated. The 26 serotypes corresponded to 24 ribotypes and 25 ERIC-types. Correlation between multilocus enzyme electrophoresis, ERIC-PCR and ribotyping was c. 90% for the dominant ribotypes. Related clones such as O55:H7 and O157:H7 presented similar ribotypes and clustered together in a dendrogram, and the two divergent clonal groups of enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) were included in distinct branches. The results suggest the possibility of applying these two simpler techniques as tools to identify clones of diarrhoeagenic E. coli.