Mapping of neuronal and glial primary cilia contactome and connectome in the human cerebral cortex.
Primary cilia act as antenna receivers of environmental signals and enable effective neuronal or glial responses. Disruption of their function is associated with circuit disorders. To understand the signals these cilia receive, we comprehensively mapped cilia's contacts within the human cortical connectome using serial-section EM reconstruction of a 1 mm3 cortical volume, spanning the entire cortical thickness. We mapped the "contactome" of cilia emerging from neurons and astrocytes in every cortical layer. Depending on the layer and cell type, cilia make distinct patterns of contact. Primary cilia display cell-type- and layer-specific variations in size, shape, and microtubule axoneme core, which may affect their signaling competencies. Neuronal cilia are intrinsic components of a subset of cortical synapses and thus a part of the connectome. This diversity in the structure, contactome, and connectome of primary cilia endows each neuron or glial cell with a unique barcode of access to the surrounding neural circuitry.


Unguided percutaneous transthoracic fine needle aspiration cytology in the diagnosis of the peripheral lung lesions.
Percutaneous transthoracic fine needle aspiration cytology (PTFNAC) of lung was done in 614 cases at the department of Pathology of Institute of Diseases of Chest and Hospital (IDCH), Dhaka, during the period from July 1994 to July 1996. A definite diagnosis was possible in 417 cases (78.83%). More than half (57.65%) of the cases were proved to have malignant diseases. PTFNAC detected malignant lesion in these patients for the first time as because no other investigation was able to establish the diagnosis. Diagnostic accuracy was 74%. Only 12 (1.95%) patients developed pneumothorax and mild haemoptysis occurred in 23 (3.74%) patients. So unguided PTFNAC is a simple, time saving, safe and inexpensive method of diagnosis of peripheral lung lesions.


Atorvastatin reduces calcification in rat arteries and vascular smooth muscle cells.
To examine the in vivo effects of atorvastatin (AT) on arterial calcification in rats, arterial calcification was established by subcutaneous injection of vitamin D3 and Warfarin. Intragastric administration of AT began 4 days before establishment of arterial calcification in the AT group (n=6). Blood samples were taken and abdominal aortas were collected and stained. After induction of calcification, plasma Ca(2+) levels in the CA and AT groups were significantly higher than those before treatment and in the untreated controls. Plasma Ca(2+) levels in the AT group were significantly lower than in the CA group. The relative calcification area in aortic specimens from the AT group was significantly smaller than in the CA group. Rat aortic vascular smooth muscle cells (VMSC) were isolated from abdominal aortic segments and pre-treated with AT (1, 5, or 10 μM) for 24 hr. Cells in the calcification (CA) group and the AT group were cultured with β-glycerophosphate, insulin and vitamin C for 14 days to induce cell calcification. Calcium deposition and alkaline phosphatase activity were significantly increased in the CA group compared to untreated controls (p<0.01). This effect was ameliorated by AT (all p<0.01). In vivo administration of AT reduced arterial calcification and plasma Ca(2+) concentration. In vitro, AT reduced calcification markers in rat aortic vascular smooth muscle cells.


Neuronal morphology alterations in autism and possible role of oxytocin.
Current understanding of the neuroanatomical abnormalities in autism includes gross anatomical changes in several brain areas and microstructural alterations in neuronal cells as well. There are many controversies in the interpretation of the imaging data, evaluation of volume and size of particular brain areas, and their functional translation into a broad autism phenotype. Critical questions of neuronal pathology in autism include the concept of the reversible plasticity of morphological changes, volume alterations of brain areas, and both short- and long-term consequences of adverse events present during the brain development. At the cellular level, remodeling of the actin cytoskeleton is considered as one of the critical factors associated with the autism spectrum disorders. Alterations in the composition of the neuronal cytoskeleton, in particular abnormalities in the polymerization of actin filaments and their associated proteins underlie the functional consequences in behavior resulting in symptoms and clinical correlates of autism spectrum disorder. In the present review, a special attention is devoted to the role of oxytocin in experimental models of neurodevelopmental disorders manifesting alterations in neuronal morphology.


[Role of Delta-like 1 in differentiation and antigen presentation of mouse bone marrow-derived dendritic cells].
The aim of this study was to investigate the role of Delta-like 1 (Dll1) in differentiation and antigen pre-sensation of mouse bone marrow-derived dendritic cells (DCs). In the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4), mouse bone marrow cells were co-cultured with OP9-Dll1 and OP9-GFP cell lines respectively. After 8 days, the immature DCs were stimulated with tumor antigen. The surface molecules of the activated DCs including MHC II, CD80 and CD86 were analyzed by flow cytometry. Levels of IL-12 and IL-10 in the culture supernatant were detected by ELISA. In addition, the proliferation of T-cells co-cultured with DCs was analyzed by FACS through mixed T-lymphocyte reaction. The results showed that compared with OP9-GFP, the bone marrow cells co-cultured with OP9-Dll1 produced significantly more CD11c(+) DCs (p < 0.05), and possessed higher levels of surface molecule expression including MHC II, CD80 and CD86 after tumor antigen stimulation. The DCs secreted higher level of IL-12 (p < 0.05) and less IL-10 (p < 0.01). They also resulted in significantly stronger T-cell proliferation response. It is concluded that Dll1 can promote the differentiation of DCs from mouse bone marrow cells and enhance their antigen presentation capacity.


Distribution of cyclosporine in blood of a renal-transplant recipient with type V hyperlipoproteinemia.
A patient with severe type V hyperlipoproteinemia and chronic end-stage renal disease received a renal transplant and therapy with cyclosporine. Concentrations of the drug in plasma as determined by liquid chromatography appeared extraordinarily high for the dose ingested. When we measured the drug in the plasma, plasma cleared by ultracentrifugation, leukocytes, erythrocytes, and whole blood, we found that the high concentrations of cyclosporine were associated with the chylomicrons that always were present in this patient's blood. Cyclosporine added directly to this patient's plasma was less associated with the plasma lipids. Isolated lymphocytes and kidney slices incubated with plasma from this patient bound no more drug than when incubated with nonhyperlipemic plasma containing cyclosporine at a normal therapeutic concentration. We conclude that the cyclosporine associated with the chylomicrons in this patient was not biologically available to either lymphocytes or kidney tissue. We strongly recommend the use of chylomicron-cleared plasma for therapeutic drug monitoring of cyclosporine in type V hyperlipoproteinemic patients.


Seven up acts as a temporal factor during two different stages of neuroblast 5-6 development.
Drosophila embryonic neuroblasts generate different cell types at different time points. This is controlled by a temporal cascade of Hb→Kr→Pdm→Cas→Grh, which acts to dictate distinct competence windows sequentially. In addition, Seven up (Svp), a member of the nuclear hormone receptor family, acts early in the temporal cascade, to ensure the transition from Hb to Kr, and has been referred to as a 'switching factor'. However, Svp is also expressed in a second wave within the developing CNS, but here, the possible role of Svp has not been previously addressed. In a genetic screen for mutants affecting the last-born cell in the embryonic NB5-6T lineage, the Ap4/FMRFamide neuron, we have isolated a novel allele of svp. Expression analysis shows that Svp is expressed in two distinct pulses in NB5-6T, and mutant analysis reveals that svp plays two distinct roles. In the first pulse, svp acts to ensure proper downregulation of Hb. In the second pulse, which occurs in a Cas/Grh double-positive window, svp acts to ensure proper sub-division of this window. These studies show that a temporal factor may play dual roles, acting at two different stages during the development of one neural lineage.


Models of Inflammation: Carrageenan Air Pouch.
The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs.


Genetic map of the powdery mildew resistance gene in soybean PI 243540.
Powdery mildew (caused by Microsphaera diffusa Cooke & Peck) is a common disease of soybean in many soybean-growing regions of the world and under greenhouse conditions. The previously reported Rmd locus of soybean for resistance to powdery mildew was mapped on soybean molecular linkage group J (chromosome 16). We have discovered a single dominant gene in PI 243540 that provides season-long resistance to powdery mildew. The objective of this study was to map the powdery mildew resistance gene in PI 243540 with PCR-based molecular markers. One hundred eighty-four F2 plants and their F(2:3) families from a cross between the powdery mildew susceptible cultivar 'Wyandot' and PI 243540 were screened with M. diffusa in greenhouses. Bulked segregant analysis (BSA) with SSR markers was used to identify the tentative genomic location of the gene. The BSA localized the gene to a genomic region in soybean chromosome 16. A linkage map with seven SSR and six SNP markers flanking the gene was constructed. We positioned the gene between SSR marker Sat_224 and SNP marker BARC-021875-04228 at distances of 9.6 and 1.3 cM from the markers, respectively. The map position of the gene was slightly different from previously reported map positions of the only known Rmd locus. We have mapped a single dominant gene, tentatively called Rmd_PI243540, near the previously known Rmd locus on chromosome 16. The molecular markers flanking the gene will be useful for marker-assisted selection of this gene.


Novel RNA viruses from the Atlantic Ocean: Ecogenomics, biogeography, and total virioplankton mass contribution from surface to the deep ocean.
Marine viruses play a major role in the energy and nutrient cycle and affect the evolution of their hosts. Despite their importance, there is still little knowledge about RNA viruses. Here, we have explored the Atlantic Ocean, from surface to deep (4.296 m), and used viromics and quantitative methods to unveil the genomics, biogeography, and the mass contribution of RNA viruses to the total viroplankton. A total of 2481 putative RNA viral contigs (>500 bp) and 107 larger bona fide RNA viral genomes (>2.5 kb) were identified; 88 of them representing novel viruses belonging mostly to two clades: Yangshan assemblage (sister clade to the class Alsuviricetes) and Nodaviridae. These viruses were highly endemic and locally abundant, with little or no presence in other oceans since only ≈15% of them were found in at least one of the Tara sampling metatranscriptomes. Quantitative data indicated that the abundance of RNA viruses in the surface and deep chlorophyll maximum zone was within ≈106 VLP/mL representing a potential contribution of 5.2%-24.4% to the total viroplankton community (DNA and RNA viruses), with DNA viruses being the predominant members (≈107 VLP/mL). However, for the deep sample, the observed trend was the opposite, although as further discussed, several biases should be considered. Together these results contribute to our understanding of the diversity, abundance, and distribution of RNA viruses in the oceans and provide a basis for further investigation into their ecological roles and biogeography.


Detection of trace hydrocarbons in flames using direct sampling mass spectrometry coupled with multilinear regression analysis.
A technique for the determination of species' concentrations from the molecular growth regions of flames is presented. Samples are obtained by microprobe extraction from a nitrogen-diluted, methane/air, nonpremixed laminar flame supported on a coannular burner. Quantification of measurements is accomplished by doping the flame's fuel flow with argon at a level to match that in the laboratory's air. A library of 70 eV fragmentation patterns for several flame species is used in conjunction with a simplex algorithm to analyze mass spectra obtained at each flame location. Each fragmentation pattern is normalized for its integrated intensity and its ionization cross-section relative to argon. This technique provided sub-part-per-million sensitivity of a large range of major and minor carbon-containing species ranging in size from C(2) to C(12) hydrocarbons. This flame can be acoustically forced to oscillate at a frequency emulating natural flame flickering behavior. Time-resolved measurements are obtained using a modified quartz microprobe synchronized to open and close with the flame oscillations. The near real-time sampling and analysis time and the relatively high sensitivity make this technique preferable to other extraction-based flame measurements.


Health Professional Shortage Areas, insurance status, and cardiovascular disease prevention in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.
Individuals with cardiovascular disease (CVD) living in Health Professional Shortage Areas (HPSA) may receive less preventive care than others. The Reasons for Geographic And Racial Differences in Stroke Study (REGARDS) surveyed 30,239 African American (AA) and White individuals older than 45 years of age between 2003-2007. We compared medication use for CVD prevention by HPSA and insurance status, adjusting for sociodemographic factors, health behaviors, and health status. Individuals residing in partial HPSA counties were excluded. Mean age was 64±9 years, 42% were AA, 55% were women, and 93% had health insurance; 2,545 resided in 340 complete HPSA counties and 17,427 in 1,145 non-HPSA counties. Aspirin, beta-blocker, and ACE-inhibitor use were similar by HPSA and insurance status. Compared with insured individuals living in non-HPSA counties, statin use was lower among uninsured participants living in non-HPSA and HPSA counties. Less medication use for CVD prevention was not associated with HPSA status, but less statin use was associated with lack of insurance.


Intensive cognitive therapy for post-traumatic stress disorder in routine clinical practice: A matched comparison audit.
Intensive cognitive therapy for post-traumatic stress disorder (PTSD) has been shown to be as effective as weekly treatment in controlled trials. In this study, outcome data comparing standard and intensive treatments delivered in routine clinical practice were analysed. A consecutive case series of intensive treatment cases were compared to matched control cases who had completed weekly treatment. Both groups showed significant improvements on PTSD and depression measures. The intensive group showed larger PTSD symptomatic improvement. There were differences between the groups in age and time since trauma, suggesting selection biases in who is offered, and/or who chooses intensive treatment. For some individuals, an intensive format may be more effective than weekly treatment.


In vitro bioactivity of asbestos for the human alveolar macrophage and its modification by IgG.
The alveolar macrophage (AM) is likely to play a central role in the initiation and development of the fibrosis associated with asbestos exposure due to its ability to produce factors that modulate cellular functions of the immune system of the lung. In this study, we examine the effects of IgG, albumin, and dipalmitoylphosphatidylcholine (DPPC), the major protein and lipid constituents of alveolar lining fluid, on the interaction between the human AM and chrysotile and crocidolite asbestos, silica, and aluminum beads. We show that both chrysotile and crocidolite asbestos, but not silica and aluminum beads, stimulate the human AM to produce superoxide anion. Preincubating chrysotile and crocidolite asbestos with IgG resulted in an enhancement of their ability to stimulate superoxide anion production. IgG subclasses were studied to determine the subclass specificity of this enhancing effect; on a molar basis, IgG1 was the most potent. After preincubation with IgG, both silica and aluminum also stimulated superoxide anion production to levels similar to the IgG-preincubated asbestos. When albumin and DPPC were included in the preincubation mixture, the IgG-mediated enhancement of superoxide anion production by asbestos was unaffected, while that of silica and aluminum was abolished. In summary, these results indicate that IgG can significantly enhance the bioactivity of particulates for human AM in vitro, and that chrysotile and crocidolite asbestos are unique in their ability to retain this enhancement in the presence of albumin and DPPC. These results are consistent with the suggestion that superoxide anion production by the AM may play an important role in the development of asbestosis.


Disparities in Patient Safety Voluntary Event Reporting: A Scoping Review.
Voluntary event reporting (VER) systems underestimate the incidence of safety events and often capture only serious events. A limited amount of data is collected through these systems, and they may be inadequate to characterize disparities in reported safety events. We conducted a scoping review of the literature to summarize the state of the evidence as it relates to differences in safety events and safety event reporting by age, gender, and race. Using a broad-based query, a systematic search for published, peer-reviewed literature that discusses patient safety event reporting and differences by age, gender, race, and socioeconomic status was conducted. Based on modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 283 studies underwent title and abstract review, yielding 56 studies for full text review. After full text review, 23 studies were carefully reviewed individually, grouped thematically, and summarized to highlight the most pertinent findings. The studies reviewed yielded important insights, particularly with regard to race, gender, and the ways events are identified. Patients from minoritized groups may be less likely to have events reported and more likely to suffer serious events. Some studies found differences in rates of reporting safety events for female vs. male providers. The rate of VER is consistently lower than the rate of events identified through identified using automated detection. The current literature describing VER data shows disparities by race, language, age, and gender for patients and providers. Further research and systematic change are needed to specifically study these disparities to guide health care institutions on ways to mitigate bias and deliver more equitable care.


[Changes in the pepsin activity of the gastric mucosa of rats in the early stages of carcinogenesis].
The paper discusses changes occurring in the enzymatic activity of pepsin in rat's gastric mucosa at early stages of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine treatment with drinking water. All doses (5, 15, 45, 75 and 150 mg/l) proved to be effective and inhibited pepsinogen biosynthesis considerably. Particularly sharp drops in the enzyme activity were observed with the concentrations of 45, 75 and 150 mg/l. The effect was reversible at early stages, particularly, at low concentrations of the agent. It is suggested that the critical point reached by pepsinogen synthesis in gastric mucosa carcinogenesis, which is manifested by the enzyme synthesis resumption on treatment being suspended, may be regarded as the check point in the course of neoplastic development.


Outcome of pregnancies at risk for neonatal hemochromatosis is improved by treatment with high-dose intravenous immunoglobulin.
Neonatal hemochromatosis is the result of severe fetal liver injury that seems to result from maternal-fetal alloimmunity. Women who have had an infant affected with neonatal hemochromatosis are at high risk in subsequent pregnancies for having another affected infant. This study was designed to determine whether therapy directed at limiting the severity of gestational alloimmunity can reduce the occurrence of severe neonatal hemochromatosis in infants of women at risk. A secondary objective was to use a prospectively collected data set to examine questions of vital interest about neonatal hemochromatosis. Women with a history of pregnancy ending in documented neonatal hemochromatosis were treated with intravenous immunoglobulin at 1 g/kg of body weight weekly from week 18 until the end of gestation. Extensive data were prospectively collected regarding the gestational histories of the subjects. The outcomes of treated pregnancies were compared with those of previous affected pregnancies, which were used as historical controls. Forty-eight women were enrolled to be treated during 53 pregnancies. The gestational histories of these women demonstrated the high risk of occurrence of neonatal hemochromatosis: 92% of pregnancies at risk resulted in intrauterine fetal demise, neonatal death, or liver failure necessitating transplant. In contrast, with gestational therapy, the 53 at-risk gestations resulted in 3 failures and 52 infants who survived intact with medical therapy alone. When compared on a per-woman or per-infant basis, the outcome of gestation at risk for neonatal hemochromatosis was improved by gestational therapy. Neonatal hemochromatosis seems to be the result of a gestational alloimmune disease, and occurrence of severe neonatal hemochromatosis in at-risk pregnancies can be significantly reduced by treatment with high-dose intravenous immunoglobulin during gestation.


Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy?
With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.


Dynamical characteristics and their applications of semiconductor lasers subject to both optical injection and optical feedback.
We experimentally investigate the dynamical characteristics of semiconductor lasers subject to both the optical injection (OI) and the optical feedback (OF). By coupling the OI and the OF lights into the same fiber before injecting into the slave laser (SL), the ratio between the two perturbations can be accurately determined and controlled. The frequency shifts in the cavity resonance frequency of the SL (νSL) induced by the OI and the OF lights are compared quantitatively. To study the competition between the OI and the OF in the SL, the mapping of the dynamical scenarios and states are plotted in the parameter space. This mapping serves as the guideline for choosing the appropriate operation conditions in various applications employing both the OI and the OF at the same time. In this paper, the suitable feedback strengths to narrow the linewidths of photonic microwave signals generated by the OI are studied. The limitation of using OI in enhancing the bandwidths of the chaos states generated by the OF is discussed. Moreover, to suppress the unwanted dynamics due to the feedback, the optimal injection parameters of the OI are shown.


Matrix metalloproteinases 2 and 9 increase permeability of sheep pleura in vitro.
Matrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been found elevated in exudative pleural effusions. In endothelial cells these MMPs increase paracellular permeability via the disruption of tight junction (TJ) proteins occludin and claudin. In the present study it was investigated if MMP2 and MMP9 alter permeability properties of the pleura tissue by degradation of TJ proteins in pleural mesothelium. In the present study the transmesothelial resistance (RTM) of sheep pleura tissue was recorded in Ussing chambers after the addition of MMP2 or MMP9. Both enzymes reduced RTM of the pleura, implying an increase in pleural permeability. The localization and expression of TJ proteins, occludin and claudin-1, were assessed after incubation with MMPs by indirect immunofluorescence and western blot analysis. Our results revealed that incubation with MMPs did not alter neither proteins localization at cell periphery nor their expression. MMP2 and MMP9 increase the permeability of sheep pleura and this finding suggests a role for MMPs in pleural fluid formation. Tight junction proteins remain intact after incubation with MMPs, contrary to previous studies which have shown TJ degradation by MMPs. Probably MMP2 and MMP9 augment pleural permeability via other mechanisms.


What is a task? An ideomotor perspective.
Although multitasking has been the subject of a large number of papers and experiments, the term task is still not well defined. In this opinion paper, we adopt the ideomotor perspective to define the term task and distinguish it from the terms goal and action. In our opinion, actions are movements executed by an actor to achieve a concrete goal. Concrete goals are represented as anticipated sensory consequences that are associated with an action in an ideomotor manner. Concrete goals are nested in a hierarchy of more and more abstract goals, which form the context of the corresponding action. Finally, tasks are depersonalized goals, i.e., goals that should be achieved by someone. However, tasks can be assigned to a specific person or group of persons, either by a third party or by the person or the group of persons themselves. By accepting this assignment, the depersonalized task becomes a personal goal. In our opinion, research on multitasking needs to confine its scope to the analysis of concrete tasks, which result in concrete goals as anticipated sensory consequences of the corresponding action. We further argue that the distinction between dual- and single-tasking is dependent on the subjective conception of the task assignment, the goal representation and previous experience. Finally, we conclude that it is not the tasks, but the performing of the tasks, i.e. the actions that cause costs in multitasking experiments.


Ca2+-activated Cl- current in retinal arteriolar smooth muscle.
To characterize the biophysical, pharmacologic, and functional properties of the Ca(2+)-activated Cl(-) current in retinal arteriolar myocytes. Whole-cell perforated patch-clamp recordings were made from myocytes within intact isolated arteriolar segments. Arteriolar tone was assessed using pressure myography. Depolarizing of voltage steps to -40 mV and greater activated an L-type Ca(2+) current (I(Ca(L))) that was followed by a sustained current. Large tail currents (I(tail)) were observed on stepping back to -80 mV. The sustained current and I(tail) reversed close to 0 mV in symmetrical Cl(-) concentrations. The ion selectivity sequence for I(tail) was I(-)> Cl(-)> glucuronate. Outward I(tail) was sensitive to the Cl(-) channel blockers 9-anthracene-carboxylic acid (9-AC; 1 mM), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS; 1 mM), and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS; 1 mM), but only DIDS produced a substantial (78%) block of inward tail currents at -100 mV. I(tail) was decreased in magnitude when the normal bathing medium was substituted with Ca(2+)-free solution or if I(Ca(L)) was inhibited by 1 microM nimodipine. Caffeine (10 mM) produced large transient currents that reversed close to the Cl(-) equilibrium potential and were blocked by 1 mM DIDS or 100 microM tetracaine. DIDS had no effect on basal vascular tone in pressurized arterioles but dramatically reduced the level of vasoconstriction observed in the presence of 10 nM endothelin-1. Retinal arteriolar myocytes have I(Cl(Ca)), which may be activated by Ca(2+) entry through L-type Ca(2+) channels or Ca(2+) release from intracellular stores. This current appears to contribute to agonist-induced retinal vasoconstriction.


[Distribution of biogenic amines and acetylcholinesterase in the mammillary nuclei of rabbits].
The distribution of biogenic amines (BA) and acetylcholinesterase (AChE) in mamillary nuclei of rabbits was studied by the methods of Falck, Karnovski and Roots. The general mass of BA was shown to localize in the terminals of the lateral mamillary nucleus and in the supramamillary area. The amount of BA-terminals in the medial nucleus is insignificant. Besides, the cells containing BA were found in the lateral part of the lateral nucleus. AChE is localized mainly in the neuropile and the cells of the medical nucleus and the cells of the lateral mamillary nucleus. The fornix and the mamillo-thalamic tract do not respond to AChE (poor activity in the mamillo-thalamic tract) and to BA. The obtained results suggest the afferents of the medial nucleus to be cholinergic, and those of the lateral nucleus - monoaminergic. Due to the presence of AChE-cells in the medial nucleus and BA-cells and AChE-cells in the lateral nucleus a supposition is possible that while the afferents of the nedial nucleus are cholinergic, the efferents of the lateral nucleus contain both AChE AND BA.


Oral health status, knowledge, attitudes and behaviours among marginalized children in Addis Ababa, Ethiopia.
Data on oral health status in Ethiopia are scarce. We assessed the prevalence of dental decay and gum disease and oral health practices and its barriers. We performed a cross-sectional study using comprehensive questionnaires and oral examination of 132 children aged 6-15 years in Addis Ababa. Mean age was 10 years and 50% were females. A significant number of children were HIV positive and orphaned. Forty-eight percent did not brush teeth and 43% brushed only once daily. The majority consumed sugary food despite knowing its relationship with dental decay. Seventy-four percent had between 1 and 13 dental caries and 52% showed evidence of bleeding upon brushing. Seventy-eight percent did not clean between teeth and were more likely to consume sugary food (p < 0.05) with oral pain within past six months (p < 0.01). In logistic regression, bleeding upon brushing and caries were not predicted by age or gender. We provided oral health trainings with illustrative flip-book, games and interactive discussions. Marginalized children suffer from poor oral health. We recommend national oral health strategies, targeted health education tailored towards Ethiopian societal norms and resources, improving access to local preventive tools and provision of oral care by training community health workers in the World Health Organization basic oral care package.


Absence of NMDA receptors in dopamine neurons attenuates dopamine release but not conditioned approach during Pavlovian conditioning.
During Pavlovian conditioning, phasic dopamine (DA) responses emerge to reward-predictive stimuli as the subject learns to anticipate reward delivery. This observation has led to the hypothesis that phasic dopamine signaling is important for learning. To assess the ability of mice to develop anticipatory behavior and to characterize the contribution of dopamine, we used a food-reinforced Pavlovian conditioning paradigm. As mice learned the cue-reward association, they increased their head entries to the food receptacle in a pattern that was consistent with conditioned anticipatory behavior. D1-receptor knockout (D1R-KO) mice had impaired acquisition, and systemic administration of a D1R antagonist blocked both the acquisition and expression of conditioned approach in wild-type mice. To assess the specific contribution of phasic dopamine transmission, we tested mice lacking NMDA-type glutamate receptors (NMDARs) exclusively in dopamine neurons (NR1-KO mice). Surprisingly, NR1-KO mice learned at the same rate as their littermate controls. To evaluate the contribution of NMDARs to phasic dopamine release in this paradigm, we performed fast-scan cyclic voltammetry in the nucleus accumbens of awake mice. Despite having significantly attenuated phasic dopamine release following reward delivery, KO mice developed cue-evoked dopamine release at the same rate as controls. We conclude that NMDARs in dopamine neurons enhance but are not critical for phasic dopamine release to behaviorally relevant stimuli; furthermore, their contribution to phasic dopamine signaling is not necessary for the development of cue-evoked dopamine or anticipatory activity in a D1R-dependent Pavlovian conditioning paradigm.


Adult adjustment of survivors of institutional child abuse in Ireland.
To document the adult adjustment of survivors of childhood institutional abuse. Two hundred and forty-seven adult survivors of institutional abuse with a mean age of 60 were interviewed with a protocol that included the Childhood Trauma Questionnaire, modules from the Structured Clinical Interview for Axis I Disorders of DSM IV and the Structured Clinical Interview for DSM IV Personality Disorders, the Trauma Symptom Inventory, and the Experiences in Close Relationships Inventory. The prevalence of psychological disorders among adult survivors of institutional abuse was over 80% and far higher than in the normal population, with anxiety, mood and substance use disorders being the most prevalent diagnoses. Survivors also had high rates of trauma symptoms and insecure adult attachment styles, and these were higher for those who had experienced both institutional and intrafamilial abuse. There was an association between the experience of institutional abuse in childhood and the prevalence of adult mental health problems, particularly anxiety, mood and substance use disorders. Policies, practices and procedures should be regularly reviewed and revised to maximize protection of young people in institutional care. Evidence-based psychological treatment should be made available to adult survivors of institutional abuse.


Debridement arthroscopy. 10-year followup.
The treatment of osteoarthritis of the knee is a difficult problem. In the senior author's opinion, nonaggressive arthroscopic debridement of the knee is an effective procedure to relieve pain and restore function in patients with osteoarthritis of the knee. A subjective telephone interview of patients done 10 or more years after arthroscopic debridement evaluated the long term results of this treatment in patients with osteoarthritis of the knee. The patients all were candidates for total knee replacement who selected arthroscopy as a temporizing procedure. Of the 191 knees in patients undergoing arthroscopic debridement, 77 patients (91 knees) were contacted for followup. Sixty-seven percent of the 91 knees did not have total knee arthroplasty at an average of 13.2 years followup. The Tegner activity score averaged 3.5 and patient satisfaction averaged 8.6 on a 0 to 10 scale. Twenty-one patients (30 knees) or (33%) had total knee arthroplasty at an average of 6.7 years. Seven of these had total knee arthroplasty within 2 years of arthroscopic debridement. Six of these seven knees had Outerbridge Grade 4 articular cartilage changes and clinically significant meniscus tears. Seven of the 19 knees (37%) with Outerbridge Grade 4 changes in 80% of one knee compartment did not require total knee arthroplasty after greater than 10 year followup. The difficulties in long term followup in this patient population is evident, yet the number of patients who had a functional lifestyle after arthroscopic debridement was notable.


[Complex diagnostic method of early forms of cancer of the uterine cervix].
A complex of diagnostic procedures including extended colposcopy, aiming biopsy, cytological examination and endocervical curettage was carried out in 110 patients for differential diagnosis between precancerous diseases and early forms of carcinoma of the uterine cervix. Application of the complex diagnostic method may be recommended for identification of early stages of malignancy in cervix uteri. Due to the findings obtained, it becomes possible to give a more accurate definition of pathologic process necessary for determination of therapy to be carried out in patients with cervical carcinoma in situ which has been detected without colposcopy. Cytological method appeared to provide much information on tissue specimens.


Prolonged cardiac allograft survival using iodine 131 after human sodium iodide symporter gene transfer in a rat model.
Radioiodine is efficiently concentrated by tissues expressing the human sodium iodide symporter (hNIS). To analyze the effects of iodine 131 on acute cardiac allograft rejection after ex vivo hNIS gene transfer in a rat model of cardiac allotransplantation. Hearts from Brown Norway rats were perfused ex vivo either with UW (University of Wisconsin) solution (n = 9) or UW solution containing 1 x 10(9) pfu/mL of adenovirus 5 plus NIS (Ad-NIS) (n = 18). Donor hearts were transplanted heterotopically into the abdomen of Lewis rats, and recipients were treated on postoperative day 3 with either 15,000 microCi of (131)I or saline solution. The hearts were explanted when no longer beating, and were evaluated histologically for evidence of rejection and other changes. Grafts perfused with the Ad-NIS vector survived significantly longer in recipients injected with (131)I (mean [SD], 11.3 [1.9] days) compared with control animals not treated with (131)I (5.7 [0.65] days) (P < .001). Treatment with (131)I did not prolong graft survival in recipients of hearts that were not perfused with Ad-NIS (5.5 [1.0] vs 5.3 [0.8] days). In Ad-NIS (131)I-treated transplants, the level of myocardial damage on day 6 after surgery, when control hearts were rejected, was significantly lower (60.8 [28.0] vs 99.7 [0.8]; P < .05). Our findings indicate that (131)I, after NIS gene transfer, can effectively prolong cardiac allograft survival. To our knowledge, this is the first report of the use of NIS-targeted (131)I therapy in cardiac transplantation. Further studies are required to determine the mechanism of this effect and its potential for clinical application.


TNF Receptor-Associated Factor (TRAF) Signaling Network in CD4(+) T-Lymphocytes.
CD4(+) T helper cells (TH cells), such as TH1, TH2, TH17, TFH, and Treg cells, play critical roles in host defense against infection and in the pathogenesis of immune-mediated diseases. Antigen-presenting cells, such as dendritic cells, deliver three kinds of signals essential for the activation, differentiation, and survival of naïve CD4(+) T cells: the first signal is transmitted through T-cell receptors (TCRs) providing the specificity of the immune response and initiating the earliest signals leading to T-cell activation, the second signal through costimulatory receptors promoting the survival and clonal expansion of the antigen-primed T cells, and the third signal through cytokine receptors directing the differentiation of naïve CD4(+) T cells into the various TH subsets. Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs), which are composed of six TRAF proteins (TRAF1-TRAF6) with a conserved C-terminal TRAF domain, are intracellular signaling adaptors that mediate the link between receptor-proximal activation events and intracellular signaling proteins. There is growing evidence that TRAFs recruited to TCRs, costimulatory TNFRs, and cytokine receptors play crucial roles in key signaling events in CD4(+) T cells and control the lineage commitment, functionality, and life-and-death decisions of different TH subsets. In this review, we summarize the TRAFs' physiological functions in T-cell immunity and the molecular mechanisms by which TRAFs regulate the three signals required for the activation, differentiation, and survival of CD4(+) T cells and other T-cell subsets.


Improving physical activity in daycare interventions.
The aim of the study was to objectively determine whether the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) program improved physical activity levels during the school day. The study compared the physical activity levels of subjects from 26 daycare centers, randomized into treatment (N=13) and control (N=13) groups. The subjects were 3 to 5 year olds (N=209, 104 males and 105 females; age [years]=3.85±0.8 [mean±standard deviation]), and accelerometry was used to determine the subjects' physical activity levels. Accelerometers were attached to each subject for 2 days before and immediately after a 6-month intervention. Height, mass, and waist were also measured. Regression analyses indicated that the treatment group demonstrated significant increases in moderate and vigorous physical activity, as compared to the control group (F(1, 207)=6.3, p<0.05, Cohen's d=0.30; F(1, 207)=4.7, p<0.05, Cohen's d=0.25, respectively). The treatment group also showed significant increases in total physical activity (F(1, 218)=12.4; p<0.05) from pre- to post-test with significant increases in moderate and vigorous intensity physical activity (F(1, 218)=18.6, p<0.05; F(1, 218)=23.3, p<0.05, respectively). Regression analyses revealed significant increases in height for both groups from pre- to post-tests, but no differences were noted between groups. Implementation of the NAP SACC program in treatment daycare facilities resulted in significant increases in objectively measured physical activity levels, compared to the control group, demonstrating physical activity improvement in the treatment daycare centers.


Novel application of pH-sensitive firefly luciferases as dual reporter genes for simultaneous ratiometric analysis of intracellular pH and gene expression/location.
Firefly luciferases are widely used as bioluminescent reporter genes for bioimaging and biosensors. Aiming at simultaneous analyses of different gene expression and cellular events, luciferases and GFPs that exhibit distinct bioluminescence and fluorescence colors have been coupled with each promoter, making dual and multicolor reporter systems. Despite their wide use, firefly luciferase bioluminescence spectra are pH-sensitive, resulting in a typical large red shift at acidic pH, a side-effect that may affect some bioanalytical purposes. Although some intracellular pH-indicators employ dual color and fluorescent dyes, none has been considered to benefit from the characteristic spectral pH-sensitivity of firefly luciferases to monitor intracellular pH-associated stress, an important indicator of cell homeostasis. Here we demonstrate a linear relationship between the ratio of intensities in the green and red regions of the bioluminescence spectra and pH using firefly luciferases cloned in our laboratory (Macrolampis sp2 and Cratomorphus distinctus), allowing estimation of E. coli intracellular pH, thus providing a new analytical method for ratiometric intracellular pH-sensing. This is the first dual reporter system that employs a single luciferase gene to simultaneously monitor intracellular pH using spectral changes, and gene expression and/or ATP concentration using the bioluminescence intensity, showing great potential for real time bioanalysis of intracellular processes associated with metabolic changes such as apoptosis, cell death, inflammation and tissue acidification, among the other physiological changes.


Use of the agar diffusion precipitation test in the diagnosis of hog cholera.
The application of the agar diffusion precipitation (ADP) test for diagnosing hog cholera was investigated. The test used as antigen, pancreatic tissue from 272 pigs that had been inoculated with hog cholera virus. The test was positive for 13.5% of the animals that were sick for 4 days or less, 40% of those sick for 5 days, and 77% of those sick for 6 days or more. The test was positive for 13.5% of all animals that had been vaccinated with crystal violet-glycerol hog cholera vaccine and had been sick for at least 6 days after challenge inoculation. Titration of the virus in ADP-test-negative and ADP-test-positive pancreatic suspensions did not show a direct correlation between the infective virus particle and the precipitating antigen.


Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis.
Delta-9-tetrahydrocannabinol (THC), an active component of cannabis, can cause anxiety in some users during intoxication. Cannabidiol (CBD), another constituent of cannabis, has anxiolytic properties suggesting that cannabis products containing CBD in addition to THC may produce less anxiety than THC-only products. Findings to date around this issue have been inconclusive and could conceivably depend on moderating factors such as baseline anxiety levels in users. The present study examined whether anxiety following single doses of vaporised THC, CBD and THC/CBD might be explained by state and trait anxiety levels at baseline. A placebo-controlled, randomised, within-subjects study including 26 healthy recreational cannabis users tested the effects of vaporised THC-dominant cannabis (13.75 mg THC), CBD-dominant cannabis (13.75 mg CBD), THC/CBD-equivalent cannabis (13.75 mg THC/13.75 mg CBD) and placebo cannabis on anxiety. Self-rated trait anxiety was assessed with the State-Trait Anxiety Inventory (STAI). State levels of anxiety were objectively assessed with a computer-based emotional Stroop task (EST) and subjectively rated with the STAI-state questionnaire and a visual analogue scale. Both THC and THC/CBD significantly increased self-rated state anxiety compared to placebo. State anxiety after THC/CBD was significantly lower than after THC alone. THC-induced anxiety was independent of anxiety at baseline. When baseline anxiety was low, CBD completely counteracted THC-induced anxiety; however, when baseline anxiety was high, CBD did not counteract THC-induced anxiety. There were no effects of any treatment condition on the EST. Overall, the study demonstrated that the THC/CBD-equivalent cannabis induces less state anxiety than THC-dominant cannabis.


Failure to Thrive: A Prospective Study in a Pediatric Gastroenterology Clinic.
We aimed to describe the clinical characteristics, diagnostic work-up, interventions, and outcomes of children referred to a pediatric gastroenterology clinic with the diagnosis of failure to thrive (FTT). We prospectively enrolled 110 children seen for the first time in our pediatric gastroenterology clinic for FTT. Standard demographic information, history, and anthropometric data were collected at initial and follow-up visits. We also obtained data about diagnostic workup, therapeutic interventions, and growth outcomes. Seventy patients (63.6%) were boys with a median age of 0.79 years (interquartile range 0.36-1.98). Of the 91 children with follow-up data, 81 (89%) were found to have nonorganic etiologies of their FTT. The majority of children (56.4%) underwent laboratory evaluation. Imaging and endoscopic evaluations were performed in fewer patients (29.6 and 10.2%, respectively). Endoscopic intervention yielded a diagnosis in 16.7% of patients while the positive result rates for laboratory testing and imaging were 3.2% and 3.1%, respectively. The most common therapeutic interventions included increasing calories (71.8%), avoiding grazing (71.8%), and structuring meals and snacks (67.3%). Compared with nonadherent children, children who were adherent with standard behavioral and nutritional interventions showed a higher positive change in z scores for weight (0.36 vs -0.01, P = 0.001) and body mass index (0.58 vs -0.18, P = 0.031). The majority of children in a pediatric gastroenterology clinic with FTT have nonorganic etiologies of their failure to thrive. Laboratory, imaging, and endoscopic evaluation are rarely positive and should be judiciously performed. Adherence to standardized interventions leads to improved growth.


Optimisation of methods for bacterial skin microbiome investigation: primer selection and comparison of the 454 versus MiSeq platform.
The composition of the skin microbiome is predicted to play a role in the development of conditions such as atopic eczema and psoriasis. 16S rRNA gene sequencing allows the investigation of bacterial microbiota. A significant challenge in this field is development of cost effective high throughput methodologies for the robust interrogation of the skin microbiota, where biomass is low. Here we describe validation of methodologies for 16S rRNA (ribosomal ribonucleic acid) gene sequencing from the skin microbiome, using the Illumina MiSeq platform, the selection of primer to amplify regions for sequencing and we compare results with the current standard protocols.. DNA was obtained from two low density mock communities of 11 diverse bacterial strains (with and without human DNA supplementation) and from swabs taken from the skin of healthy volunteers. This was amplified using primer pairs covering hypervariable regions of the 16S rRNA gene: primers 63F and 519R (V1-V3); and 347F and 803R (V3-V4). The resultant libraries were indexed for the MiSeq and Roche454 and sequenced. Both data sets were denoised, cleaned of chimeras and analysed using QIIME. There was no significant difference in the diversity indices at the phylum and the genus level observed between the platforms. The capture of diversity using the low density mock community samples demonstrated that the primer pair spanning the V3-V4 hypervariable region had better capture when compared to the primer pair for the V1-V3 region and was robust to spiking with human DNA. The pilot data generated using the V3-V4 region from the skin of healthy volunteers was consistent with these results, even at the genus level (Staphylococcus, Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, Enhydrobacter and Deinococcus identified at similar abundances on both platforms). The results suggest that the bacterial community diversity captured using the V3-V4 16S rRNA hypervariable region from sequencing using the MiSeq platform is comparable to the Roche454 GS Junior platform. These findings provide evidence that the optimised method can be used in human clinical samples of low bacterial biomass such as the investigation of the skin microbiota.


Step Activity Monitor: accuracy and test-retest reliability in persons with incomplete spinal cord injury.
Recovery of walking after incomplete spinal cord injury (iSCI) is a common focus of rehabilitation, but few measurement tools capture walking performance outside the clinic or laboratory. This study determined the accuracy and test-retest reliability of the Step Activity Monitor (SAM), a microprocessor-driven accelerometer that measures walking activity. We evaluated 11 individuals with iSCI during replicate 6-minute walk tests (6MWTs) and 10-meter walk tests (10mWTs) scheduled <1 week apart. The SAM was 97% accurate compared with hand-tallied step counts. SAM values were stable across repeated walking performances (intraclass correlation coefficient = 0.97-0.99). Standard error of measurement values were 6.0 steps and 0.8 steps for the 6MWT and 10mWT, respectively. Ninety-five percent confidence intervals were 203.7 to 177.0 steps for the 6MWT and 16.1 to 12.7 steps for the 10mWT. The SAM is an accurate and reliable device for capturing walking activity in individuals with iSCI.


Cardioprotective O-GlcNAc signaling is elevated in murine female hearts via enhanced O-GlcNAc transferase activity.
The post-translational modification of intracellular proteins by O-linked β-GlcNAc (O-GlcNAc) has emerged as a critical regulator of cardiac function. Enhanced O-GlcNAcylation activates cytoprotective pathways in cardiac models of ischemia-reperfusion (I/R) injury; however, the mechanisms underpinning O-GlcNAc cycling in response to I/R injury have not been comprehensively assessed. The cycling of O-GlcNAc is regulated by the collective efforts of two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which catalyze the addition and hydrolysis of O-GlcNAc, respectively. It has previously been shown that baseline heart physiology and pathophysiology are impacted by sex. Here, we hypothesized that sex differences in molecular signaling may target protein O-GlcNAcylation both basally and in ischemic hearts. To address this question, we subjected male and female WT murine hearts to ex vivo ischemia or I/R injury. We assessed hearts for protein O-GlcNAcylation, abundance of OGT, OGA, and glutamine:fructose-6-phosphate aminotransferase (GFAT2), activity of OGT and OGA, and UDP-GlcNAc levels. Our data demonstrate elevated O-GlcNAcylation in female hearts both basally and during ischemia. We show that OGT activity was enhanced in female hearts in all treatments, suggesting a mechanism for these observations. Furthermore, we found that ischemia led to reduced O-GlcNAcylation and OGT-specific activity. Our findings provide a foundation for understanding molecular mechanisms that regulate O-GlcNAcylation in the heart and highlight the importance of sex as a significant factor when assessing key regulatory events that control O-GlcNAc cycling. These data suggest the intriguing possibility that elevated O-GlcNAcylation in females contributes to reduced ischemic susceptibility.


Field validation of an antibiotic-free hoof spray to effectively treat ovine footrot by eliminating virulent Dichelobacter nodosus.
Ovine footrot caused by Dichelobacter nodosus is a highly contagious hoof disease negatively impacting animal welfare and causing major economic losses to the sheep industry. Bactericidal footbaths have shown to be an efficient treatment option and will be used in the national footrot control program in Switzerland. However, the application of footbaths is laborious and economically not sound for small flock holders. We therefore tested in a field study the Intra Repiderma spray for its applicability and efficacy to treat ovine footrot. Ten independent flocks fulfilling defined parameters (e.g. clinical signs, positive for D. nodosus, flock size) could be identified and were included in the study. Farms were visited weekly to fortnightly and clinical scores and swabs for D. nodosus real-time (rt)PCR were taken. Treatment with the Intra Repiderma spray was started after initial claw trimming at the very first visit and was carried out three times within a week. Clearly visible clinical improvement was evident after one week of treatment. Virulent D. nodosus amounts on feet declined constantly during treatment which was continued until all sheep of a flock tested rtPCR-negative (1-10 weeks). Results indicate that a highly effective improvement of clinical signs and complete elimination of virulent D. nodosus can be achieved with the spray treatment. Therefore, it is a valuable alternative to cumbersome footbaths especially for small flocks. A sustainable control of footrot and its pathogen in a successfully treated flock can be maintained by strict biosecurity measures and continued treatment as far as necessary.


Isolation of a toxin B-deficient mutant strain of Clostridium difficile in a case of recurrent C. difficile-associated diarrhea.
Clostridium difficile-associated diarrhea (CDAD) recurs in approximately 15%-20% of patients after discontinuation of metronidazole or vancomycin therapy. Most recurrences are believed to be endogenous relapses due to the persistence of spores. However, there is evidence that reinfection with a different strain is a cause of recurrence. We report the case of a patient with a history of multiple episodes of C. difficile colitis. The patient, a 56-year-old female, has had 5 years of repeated recurrences, each shortly after discontinuing vancomycin therapy. During the course of these episodes, three isolates were cultured from her stools at different times. These isolates were analyzed for the presence of toxin A and B gene sequences and genotyped by means of arbitrarily primed polymerase chain reaction (AP-PCR). The original two isolates contained the toxin A and B genes, as determined by PCR, and were of the same AP-PCR type. During her last relapse, a C. difficile strain lacking at least a portion of the toxin B gene was isolated. AP-PCR analysis of this isolate showed a different DNA banding pattern from that of the previous isolates. A vancomycin susceptibility assay revealed a slight decrease in vancomycin activity as compared with that against the prior isolate. This case demonstrates two unique features: (1) recurrent infections can be due to reinfections and (2) toxin B mutants can possibly cause CDAD. This study also raises concerns about long-term vancomycin use and the development of resistance of C. difficile to vancomycin.


A therapeutic strategy to target distinct sources of IgE and durably reverse allergy.
Immunoglobulin E (IgE) is a key driver of type 1 hypersensitivity reactions and allergic disorders, which are globally increasing in number and severity. Although eliminating pathogenic IgE may be a powerful way to treat allergy, no therapeutic strategy reported to date can fully ablate IgE production. Interleukin-4 receptor α (IL-4Rα) signaling is required for IgE class switching, and IL-4Rα blockade gradually reduces, but does not eliminate, IgE. The persistence of IgE after IL-4Rα blockade may be due to long-lived IgE+ plasma cells that maintain serological memory to allergens and thus may be susceptible to plasma cell-targeted therapeutics. We demonstrate that transient administration of a B cell maturation antigen x CD3 (BCMAxCD3) bispecific antibody markedly depletes IgE, as well as other immunoglobulins, by ablating long-lived plasma cells, although IgE and other immunoglobulins rapidly rebound after treatment. Concomitant IL-4Rα blockade specifically and durably prevents the reemergence of IgE by blocking IgE class switching while allowing the restoration of other immunoglobulins. Moreover, this combination treatment prevented anaphylaxis in mice. Together with additional cynomolgus monkey and human data, our studies demonstrate that allergic memory is primarily maintained by both non-IgE+ memory B cells that require class switching and long-lived IgE+ plasma cells. Our combination approach to durably eliminate pathogenic IgE has potential to benefit allergy in humans while preserving antibody-mediated immunity.


Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors.
The basic helix-loop-helix (bHLH) class of transcription factors plays a pivotal role in tissue-specific determination and differentiation. Moreover, dysregulated expression or loss of function of these factors contributes to leukemogenesis and solid tumor development. Neurogenesis is regulated by genes of the NEUROD/atonal and ACHAETE SCUTE families. We analyzed expression of human NEUROD1, NEUROD2, NEUROD3, and ACHAETE SCUTE 1 (HASH1) in cerebellar and cerebral primitive neuroectodermal tumors (PNETs), gliomas, and cell lines derived from a variety of neuroectodermal tumors by Northern analysis and in situ hybridization. NEUROD1 was expressed in each of the 12 medulloblastoma specimens, whereas NEUROD2 and NEUROD3/neurogenin were expressed in partly overlapping subsets of medulloblastomas. All of the tumors that presented with distant metastases expressed NEUROD3. The only other NEUROD3-positive tumor progressed early in treatment. Human ACHAETE SCUTE homologue (HASH1) was not expressed in medulloblastomas (infratentorial PNETs) but was expressed in three of five supratentorial PNETs. Neuroectodermal tumor cell lines derived from other sites (e.g., neuroblastoma and retinoblastoma) expressed NeuroD and ACHAETE SCUTE family members. No NEUROD message was detected in glial tumors or cell lines. Neurogenic bHLH transcription factor expression patterns suggest that specific family members may contribute to or reflect biological differences that arise during malignant transformation.


Phylogenetic assessment reveals continuous evolution and circulation of pigeon-derived virulent avian avulaviruses 1 in Eastern Europe, Asia, and Africa.
The remarkable diversity and mobility of Newcastle disease viruses (NDV) includes virulent viruses of genotype VI. These viruses are often referred to as pigeon paramyxoviruses 1 because they are normally isolated and cause clinical disease in birds from the Columbidae family. Genotype VI viruses occasionally infect, and may also cause clinical disease in poultry. Thus, the evolution, current spread and detection of these viruses are relevant to avian health. Here, we describe the isolation and genomic characterization of six Egyptian (2015), four Pakistani (2015), and two Ukrainian (2007, 2013) recent pigeon-derived NDV isolates of sub-genotype VIg. These viruses are closely related to isolates from Kazakhstan, Nigeria and Russia. In addition, eight genetically related NDV isolates from Pakistan (2014-2016) that define a new sub-genotype (VIm) are described. All of these viruses, and the ancestral Bulgarian (n = 2) and South Korean (n = 2) viruses described here, have predicted virulent cleavage sites of the fusion protein, and those selected for further characterization have intracerebral pathogenicity index assay values characteristic of NDV of genotype VI (1.31 to 1.48). A validated matrix gene real-time RT-PCR (rRT-PCR) NDV test detect all tested isolates. However, the validated rRT-PCR test that is normally used to identify the virulent fusion gene fails to detect the Egyptian and Ukrainian viruses due to mismatches in primers and probe. A new rapid rRT-PCR test to determine the presence of virulent cleavage sites for viruses from sub-genotypes VIg was developed and evaluated on these and other viruses. We describe the almost simultaneous circulation and continuous evolution of genotype VI Newcastle disease viruses in distant locations, suggesting epidemiological connections among three continents. As pigeons are not migratory, this study suggests the need to understand the possible role of human activity in the dispersal of these viruses. Complete genomic characterization identified previously unrecognized genetic diversity that contributes to diagnostic failure and will facilitate future evolutionary studies. These results highlight the importance of conducting active surveillance on pigeons worldwide and the need to update existent rapid diagnostic protocols to detect emerging viral variants and help manage the disease in affected regions.


Partnership, knowledge translation, and substance abuse prevention with a First Nations community.
Having identified substance abuse as an issue of concern in their community, the Alexis Nakota Sioux Nation invited University of Alberta researchers to partner on the cultural adaptation, delivery, and evaluation of a school-based drug and alcohol abuse prevention program. Researchers conducted a literature review of available drug and alcohol prevention programs for children and youth, identifying the Life Skills Training (LST) program as a viable model for cultural adaptation. Four program objectives were developed: (1) Review and cultural adaptation of the elementary and junior high LST programs, (2) delivery of the adapted programs, (3) measurement of changes in students' knowledge of the negative effects of drug and alcohol use, attitudes toward drugs and alcohol, drug and alcohol refusal and life skills, and changes in self-esteem/self-concept, and (4) documentation of the community's experience of the project. Using the principles of community-based participatory research (CBPR), we employed both qualitative and quantitative methods to evaluate the impact of the project. Qualitative evaluation of the program adaptation and implementation were both positive. Qualitative measures of program impact on students revealed a positive effect, whereas results of the quantitative measures were mixed. Culturally adapted, evidence-based programs can have a positive effect on Aboriginal youth and their communities. Strategies to expand knowledge translation (KT) when working with Aboriginal communities include working to create an "ethical space" that draws on the strengths of both Western and Indigenous worldviews.


Efficient spectral control and tuning of a high-power narrow-linewidth Yb-doped fiber laser using a transversely chirped volume Bragg grating.
A transversely chirped volume Bragg grating (TCVBG) is used for flexible wavelength-tuning of a high-power (>100 W) tunable Yb-fiber laser oscillator. Continuous tuning over 2.5 THz of the narrow-band (13 GHz) signal was achieved by transversely translating the TCVBG during high-power operation without cavity realignment. The laser operated in a single polarization with a beam propagation factor (M(2)) of 1.2. Since the cavity losses remained constant, the high gain fiber laser exhibited excellent power stability (<0.6% relative deviation) over the investigated tuning range. The possibility of considerably increasing the output power and extending the tuning range while maintaining the power stability is discussed.


Electrical activity of the hippocampus during delayed responses and hypothalamic stimulation in the cat.
Electrical activity of hippocampus was investigated in cats in the delayed response situation by comparing spectral analysis and integration of electrohippocampogram rhythms in different stages of delayed response performance. In addition, electrical stimulation of lateral and ventromedial hypothalamic nuclei was used to observe changes in the hippocampal theta rhythm, as well as the behavioral effect during the delayed response performance. It is concluded that changes in the hippocampal theta rhythm are related to the changes in the drive level: high drive results in increasing the theta rhythm, whereas drive reduction results in its suppression. The activating role of hypothalamus in the dynamic changes occurring in the limbic circuit and their function in solving the delayed response problem are widely discussed.


Cross-Talk of NADPH Oxidases and Inflammation in Obesity.
Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and clinical studies have shown increased oxidative stress and inflammation linked to obesity. NADPH oxidases are major sources of reactive oxygen species in the cardiovascular system and in metabolically active cells and organs. An impaired balance due to the increased formation of reactive oxygen species and a reduced antioxidative capacity contributes to the pathophysiology of cardiovascular and metabolic diseases and is linked to inflammation as a major pathomechanism in cardiometabolic diseases. Non-alcoholic fatty liver disease is particularly characterized by increased oxidative stress and inflammation. In recent years, COVID-19 infections have also increased oxidative stress and inflammation in infected cells and tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications of cardiometabolic diseases after COVID-19. In this review, we discuss the role of oxidative stress and inflammation in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential therapeutic strategies.


Regulating the stemness of mesenchymal stem cells by tuning micropattern features.
There is increasing evidence that microstructures play an important role in the maintenance of the multipotency of stem cells. However, it is not clear how micropatterns affect the stemness of stem cells. We prepared micropatterns of different sizes, shapes and aspect ratios and used them for the culture of mesenchymal stem cells (MSCs) derived from human bone marrow to investigate their influence on the stemness of MSCs at the single cell level. The percentage of cells positively stained by stem cell markers decreased with increasing spreading area and aspect ratio. However, the cellular geometry controlled by the geometrical micropatterns had no significant influence on the expression of stem cell markers. The change in the stemness of stem cells was accompanied by changes in the nuclear activity and cytoskeleton. The nuclear activity increased with increasing spreading area and aspect ratio. The actin filament structure was significantly influenced by the spreading area and aspect ratio. The cells became stiffer when they had sufficient area to spread into or when they were elongated. These results suggest that controlling the cell morphology by micropatterns may be useful in varying the stemness of MSCs. This study will contribute to the design of materials for maintaining the multipotency of stem cells, enhancing their clinical application and helping to reveal the processes taking place under conditions of stem cell quiescence in vivo.


An update on molecular diagnostics of squamous and salivary gland tumors of the head and neck.
Molecular testing in anatomic pathology is becoming standardized and can contribute valuable diagnostic, therapeutic, and prognostic information for the clinical management of patients. In head and neck pathology, recent advances in molecular testing have provided important targets in several different diagnostic areas, with particular emerging clinical applications in squamous and salivary gland pathology. In squamous mucosal-derived lesions, human papilloma virus has emerged as an important pathogenic etiology in a subset of oropharyngeal squamous cell carcinomas. Within the category of salivary gland tumors, 3 tumors have recently been recognized that contain oncogenic translocations. To describe the current state of information about the molecular alterations in squamous lesions and in salivary gland tumors of the head and neck. Published literature on squamous and salivary gland tumors of the head and neck. The different approaches to identification of viral-associated tumors include assays using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Most mucoepidermoid carcinomas harbor MECT1-MAML2 gene rearrangement. The MYB-NFIB translocations have recently been identified in adenoid cystic carcinomas. Finally, a newly described tumor of salivary gland, mammary analogue secretory carcinoma, harbors the ETV6-NTRK3 translocation. Although these translocations are just emerging as diagnostic targets, future roles may evolve as potential therapeutic targets.


Aberrant wound healing and TGF-beta production in the autoimmune-prone MRL/+ mouse.
Wound healing is a complex process that involves inflammation, apoptosis, growth, and tissue remodeling. The autoimmune-prone inbred mouse strain MRL/+ manifests accelerated and extensive healing to ear punch wounds, suggesting a link between immune defects and wound healing. Prior studies with lupus-prone mice have shown that hematopoietic cells of lupus-prone strains can transfer disease to otherwise non-autoimmune-prone recipients. In this study we performed reciprocal bone marrow transfers between MRL and the control strain B10.BR and found that radioresistant MRL/+ host cells, rather than hematopoietic cells, are required for the healing response. We have also made the novel observations that, compared to normal controls, MRL/+ hematopoietic cells overproduce TGF-beta1 and manifest impaired inflammatory responses to lipopolysaccharide challenge. These features suggest that the aberrant wound healing phenotype of MRL mice is independent of their propensity to develop autoimmunity.


NF-κB-inducing kinase in thymic stroma establishes central tolerance by orchestrating cross-talk with not only thymocytes but also dendritic cells.
Essential roles of NF-κB-inducing kinase (NIK) for the development of medullary thymic epithelial cells (mTECs) and regulatory T cells have been highlighted by studies using a strain of mouse bearing a natural mutation of the NIK gene (aly mice). However, the exact mechanisms underlying the defect in thymic cross-talk leading to the breakdown of self-tolerance in aly mice remain elusive. In this study, we demonstrated that production of regulatory T cells and the final maturation process of positively selected conventional αβ T cells are impaired in aly mice, partly because of a lack of mature mTECs. Of note, numbers of thymic dendritic cells and their expression of costimulatory molecules were also affected in aly mice in a thymic stroma-dependent manner. The results suggest a pivotal role of NIK in the thymic stroma in establishing self-tolerance by orchestrating cross-talk between mTECs and dendritic cells as well as thymocytes. In addition, we showed that negative selection was impaired in aly mice as a result of the stromal defect, which accounts for the development of organ-specific autoimmunity through a lack of normal NIK.


Brand variation in oxidant production in mainstream cigarette smoke: Carbonyls and free radicals.
Oxidative stress/damage resulting from exposure to cigarette smoke plays a critical role in the development of tobacco-caused diseases. Carbonyls and free radicals are two major classes of oxidants in tobacco smoke. There is little information on the combined delivery of these oxidants across different cigarette brands; thus, we set out to measure and compare their levels in mainstream smoke from popular US cigarettes. Mainstream smoke from 28 different cigarette brands produced by smoking (FTC protocol) was analyzed for five important, abundant carbonyls, and levels were compared to previously determined free radical for the same brands. Overall, there were large variations (3- to 6-fold) in carbonyl levels across brands with total carbonyl levels ranging from 275 to 804 μg/cigarette, which persisted even after adjusting for ventilation. Individual carbonyl levels were highly correlated with each other (r2: 0.40-0.95, P < 0.003) except for formaldehyde. Both gas-phase (r2: 0.37, P = 0.006) and particulate-phase (r2: 0.27, P = 0.005) free radicals were correlated to total carbonyl content; however, this correlation disappeared after adjusting for ventilation. These data show that overall oxidant production varies widely by cigarette brand and the resulting difference in oxidant burden could potentially lead to differences in disease risk.


Practice management guidelines for the diagnosis and management of injury in the pregnant patient: the EAST Practice Management Guidelines Work Group.
Trauma during pregnancy has presented very unique challenges over the centuries. From the first report of Ambrose Pare of a gunshot wound to the uterus in the 1600s to the present, there have existed controversies and inconsistencies in diagnosis, management, prognostics, and outcome. Anxiety is heightened by the addition of another, smaller patient. Trauma affects 7% of all pregnancies and requires admission in 4 of 1000 pregnancies. The incidence increases with advancing gestational age. Just over half of trauma during pregnancy occurs in the third trimester. Motor vehicle crashes comprise 50% of these traumas, and falls and assaults account for 22% each. These data were considered to be underestimates because many injured pregnant patients are not seen at trauma centers. Trauma during pregnancy is the leading cause of nonobstetric death and has an overall 6% to 7% maternal mortality. Fetal mortality has been quoted as high as 61% in major trauma and 80% if maternal shock is present. The anatomy and physiology of pregnancy make diagnosis and treatment difficult.


Preclinical and Toxicology Studies of BRD5529, a Selective Inhibitor of CARD9.
The caspase recruitment domain-containing protein 9 (CARD9) inhibitor BRD5529 has been shown to be an effective in vitro inhibitor of Pneumocystis β-glucan-induced proinflammatory signaling, suggesting its viability as a candidate for preliminary anti-Pneumocystis drug testing in the rodent Pneumocystis pneumonia (PCP) model. Mice were injected intraperitoneally (IP) daily with either vehicle or BRD5529 at 0.1 or 1.0 mg/kg for 2 weeks. Mouse weights were taken daily. At day 14, mice were euthanized, weighed, and analyzed by flexiVent™ for lung stiffness. Lungs, liver, and kidney were then harvested for hematoxylin and eosin (H&E) staining and pathology scoring. Lung samples were further analyzed for proinflammatory cytokines via enzyme-linked immunosorbent assay (ELISA) and extracellular matrix generation via quantitative polymerase chain reaction (qPCR). Blood collection postmortem was performed for blood chemistry analysis. Furthermore, administration of BRD5529 prior to the intratracheal inoculation of fungal β-glucans, which are known proinflammatory mediators via the Dectin-1-CARD9 pathway, resulted in significant reductions in lung tissue interleukin-6 and tumor necrosis factor-α, suggesting the exciting possibility of the use of this CARD9 inhibitor as an additional therapeutic tool in fungal infections. BRD5529 at both IP doses resulted in no significant changes in daily or final weight gain, and analysis of lung stiffness by flexiVent™ showed no significant differences between the groups. Furthermore, ELISA results of proinflammatory cytokines showed no major differences in the respective groups. qPCR analysis of extracellular matrix transcripts were statistically similar. Examination and pathology scoring of H&E slides from lung, liver, and kidney in all groups, as well as subsequent pathology scoring, showed no significant change. Blood chemistry analysis revealed similar, non-significant patterns. In our initial general safety and toxicology assessments, BRD5529 displayed no inherent safety concerns in the analyzed parameters. These data support broader in vivo testing of the inhibitor as a timed adjunct therapy to the deleterious proinflammatory host immune response often associated with anti-Pneumocystis therapy.


Cardiac surgery in adult patients with remitted or active malignancies: a review of preoperative screening, surgical management and short- and long-term postoperative results.
Candidate patients for cardiac surgery procedures with a history of malignancies and antitumour therapy or with an active cancer and on antineoplastic treatment are increasingly common in daily practice. Oncological therapy can lead to cardiovascular injury and, therefore, has the potential for impacting operative risks and surgical strategies. This means that a number of considerations are essential to take into account prior to cardiac surgery. These include the type of cancer, previous cardiotoxicity or concomitant antitumour therapy, reversibility or irreversibility of such complications, the interaction between cancer disease course and extracorporeal circulation, the need for associated surgery and the impact of cancer on early and long-term outcomes. Adequate preoperative evaluation of cardiovascular abnormalities potentially related to antineoplastic therapy and proper diagnostic workup of other conditions linked to the type of cancer (e.g. haematological disorders and lung dysfunction) are therefore of paramount importance for appropriate surgical decision-making. Careful evaluation of the association of cardiovascular disease to be treated and the prognosis of remitted or active cancer should be established to enhance the prediction of early, medium and long-term outcomes and for a more correctly informed patient. Furthermore, if the prognosis of operated patients appears unfavourable, then alternative therapeutic strategies can be applied without significant delay. The aim of this review is to give an overview of factors that should be considered in adult patients who are undergoing, or have undergone, treatment for oncological indications who are candidates for cardiac surgery.


Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by migraine with aura.
We previously showed paradoxical facilitatory effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of patients suffering migraine with aura. In this study we evaluated the effects of 1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor cortex to explore whether the abnormal pattern of excitability extends beyond the sensory cortex also involving motor areas in migraine with aura. Nine patients affected by migraine with aura and eight healthy controls entered into the study. The hot spot for activation of the right abductor pollicis brevis (APB) was checked by means of a figure-of-eight coil and motor threshold (MT) recorded on this point. Nine hundred magnetic stimuli at 1 Hz frequency and 90% MT intensity were delivered at the hot spot. Before and after rTMS, intracortical inhibitory and facilitatory circuit excitability was assessed by means of a paired pulse paradigm (conditioning stimulus 80% MT and test stimulus 120% MT) with two different interstimulus intervals: 2 ms (inhibitory) and 10 ms (facilitatory). Amplitude of the responses was expressed as the percentage of motor evoked potential (MEP) to test stimulus alone. Results showed that in basal condition migraineurs present significantly reduced levels of intracortical inhibition (ICI) compared to controls. More importantly, opposite results were obtained in migraineurs with respect to controls when 1 Hz rTMS was applied. Specifically, whereas intracortical facilitation (ICF) significantly decreased in controls, it significantly increased in migraineurs. ICI levels were not significantly affected by low-frequency stimulation. Our results showed that motor as well as sensory cortex of migraine patients present an abnormal modulation of cortical excitability, where a relevant role is likely played by the inefficiency of inhibitory circuits.


Removal of scleral buckling elements. Causes and complications.
Fifty-three patients underwent removal of their scleral buckling elements in our operating rooms during a 25-year period. Of these, 18 patients suffered a retinal redetachment and two went on to phthisis. "Life-table" (survival) analysis showed that the risk of redetachment was 23% within the first 30 days after buckling element removal and 33% within 90 days. The cumulative risk of redetachment during a four-year period gradually increased to 47%. Factors that had a statistically significant association with redetachment included the degree of vitreous traction at the time of the original retinal detachment and the extent of the original detachment. Age, race, sex, preoperative condition, type of buckling element, and cause of buckling element removal did not have a statistically significant association with redetachment.


Dermal Fillers in the Treatment of Acne Scars: A Review.
Acne vulgaris (AV) is the eighth most common disease in the world. This condition can impair the affected patients' social and psychological functioning and lower their quality of life. In general, scar reduction, rather than complete scar removal, is the aim of AV treatment. Dermal abrasion, chemical peeling, laser resurfacing, subcision, punch methods, tissue-improving substances, and dermal fillers are the currently available therapeutic options. In this study, we focused on the rapidly developing field of dermal fillers used alone or in combination with other therapies to reconstruct skin affected by acne scars and to evaluate the improvement of facial appearance after using different types of dermal fillers.


Electrocardiographic surrogates of structural myocardial alterations in the Dorper sheep heart.
In this study we evaluated the validity of well-known human electrocardiographic markers of myocardial pathology in Dorper sheep. These markers include: the duration of the QRS complex of premature ventricular complexes (PVCs), the presence of notching of the QRS complex of PVCs and change of the ST-segment of PVCs. It was shown that these three electrocardiographic phenomena correlate with myocardial pathology in the hearts of Dorper sheep. We also describe a new electrocardiographic indicator of myocardial pathology, namely an increase in the frequency of cardiac memory T waves as a new electrocardiographic surrogate for myocardial pathology in the hearts of Dorper sheep.


The intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria.
Nitric oxide (NO) is a diffusible radical gas produced from the activity of nitric oxide synthase (NOS). NOS activity in murine macrophages has a protective role against mycobacteria through generation of reactive nitrogen intermediates (RNIs). However, the production of NO by human macrophages has remained unclear due to the lack of sensitive reagents to detect NO directly. The purpose of this study was to investigate NO production and the consequence to mycobacteria in primary human macrophages. We found that Mycobacterium bovis BCG or Mycobacterium tuberculosis infection of human macrophages induced expression of NOS2 and NOS3 that resulted in detectable production of NO. Treatment with gamma interferon (IFN-γ), l-arginine, and tetrahydrobiopterin enhanced expression of NOS2 and NOS3 isoforms, as well as NO production. Both of these enzymes were shown to contribute to NO production. The maximal level of NO produced by human macrophages was not bactericidal or bacteriostatic to M. tuberculosis or BCG. The number of viable mycobacteria was increased in macrophages that produced NO, and this requires expression of nitrate reductase. An narG mutant of M. tuberculosis persisted but was unable to grow in human macrophages. Taken together, these data (i) enhance our understanding of primary human macrophage potential to produce NO, (ii) demonstrate that the level of RNIs produced in response to IFN-γ in vitro is not sufficient to limit intracellular mycobacterial growth, and (iii) suggest that mycobacteria may use RNIs to enhance their survival in human macrophages.


Coping, mood, and aspects of personality in Spanish translation and evidence of convergence with English versions.
Research on stress and its influence on health and well-being has flourished for several decades, examining as predictors such psychosocial variables as personality and coping. This work now often targets multiethnic samples. Because many potential participants lack facility in English, a need exists for translations of measures into other languages. We translated 6 instruments into Spanish and studied their characteristics. Of these, 3 were measures of personality qualities: the Life Orientation Test--Revised (Scheier, Carver, & Bridges, 1994), the Behavioral Inhibition/Behavioral Activation Scales (Carver & White, 1994), and the Measure of Body Apperception (Carver et al., 1998). The others were the Brief COPE (Carver, 1997), the Center for Epidemiological Studies--Depression Scale (Radloff, 1977), and an abbreviated version of the Profile of Mood States (McNair, Lorr, & Droppelman, 1971). Correlations between English and Spanish versions in bilingual samples were all above. 72, except for the COPE's Behavioral Disengagement scale. Alpha reliabilities of the Spanish versions were comparable to those of the English versions. Correlations among measures in a sample of cancer patients were similar across languages.


Thymus: the next (re)generation.
As the primary site of T-cell development, the thymus plays a key role in the generation of a strong yet self-tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. As the importance of the role of the thymus has grown, so too has the understanding that it is extremely sensitive to both acute and chronic injury. The thymus undergoes rapid degeneration following a range of toxic insults, and also involutes as part of the aging process, albeit at a faster rate than many other tissues. The thymus is, however, capable of regenerating, restoring its function to a degree. Potential mechanisms for this endogenous thymic regeneration include keratinocyte growth factor (KGF) signaling, and a more recently described pathway in which innate lymphoid cells produce interleukin-22 (IL-22) in response to loss of double positive thymocytes and upregulation of IL-23 by dendritic cells. Endogenous repair is unable to fully restore the thymus, particularly in the aged population, and this paves the way toward the need for exogenous strategies to help regenerate or even replace thymic function. Therapies currently in clinical trials include KGF, use of the cytokines IL-7 and IL-22, and hormonal modulation including growth hormone administration and sex steroid inhibition. Further novel strategies are emerging in the preclinical setting, including the use of precursor T cells and thymus bioengineering. The use of such strategies offers hope that for many patients, the next regeneration of their thymus is a step closer.


Inoculum size influences bacterial cross contamination between surfaces.
Many factors have been shown to influence bacterial transfer between surfaces, including surface type, bacterial species, moisture level, pressure, and friction, but the effect of inoculum size on bacterial transfer has not yet been established. Bacterial cross contamination rates during performance of common food service tasks were previously determined in our laboratory using nalidixic acid-resistant Enterobacter aerogenes. Eight different transfer rates were determined, each involving a minimum of 30 volunteers. The influence of source inoculum level on the percentage of bacteria transferred (percent transfer rates) and log10 CFU per recipient surface was determined using statistical analysis. The effect of inoculum size on transfer rate was highly statistically significant (P < 0.0001) for all transfer rate data combined (352 observations) and for each individual cross contamination rate, except for data on contamination via transfer from chicken to hand through a glove barrier (P = 0.1643). Where inoculum size on the source was greater, transfer rates were lower, and where inoculum size on the source was less, transfer rates were higher. The negative linear trend was more obvious for activities that had a larger range of inoculum sizes on the source surface. This phenomenon has serious implications for research seeking to determine bacterial cross contamination rates, since the different transfer efficiencies that were previously shown to be associated with certain activities may actually be the result of differing initial inoculum levels. The initial inoculum size on the source and the amount of bacteria transferred must both be considered to accurately determine bacterial transfer rates.


LY53857, a selective and potent serotonergic (5-HT2) receptor antagonist, does not lower blood pressure in the spontaneously hypertensive rat.
LY53857 was a potent antagonist of vascular contraction to serotonin, which is mediated by serotonergic (5-HT2) receptors, with a dissociation constant in vitro of 5.4 X 10(-11) M. Unlike several other serotonin antagonists, LY53857 showed minimal affinity for vascular alpha adrenergic receptors (dissociation constant of 1.4 X 10(-5) M). Thus, LY53857 was a highly potent and selective antagonist at 5-HT2 receptors. In vivo activity paralleled the in vitro observations. In pithed spontaneously hypertensive rats (SHR), LY53857 at 0.1 and 3.0 mg/kg i.p. produced a 22-and 480-fold shift, respectively, in the pressor response to serotonin whereas LY53857 at 10 mg/kg did not alter the pressor response to the alpha receptor agonist, methoxamine. Furthermore, LY53857 administered peripherally also inhibited central serotonin receptors, as evidenced by blockade of the serum corticosterone increase produced by the central actions of the serotonin agonist, quipazine, and by antagonism of tryptamine-induced convulsions in rats. LY53857 in doses that blocked the pressor response to serotonin and that blocked central serotonin receptors did not lower mean arterial blood pressure in the SHR. Thus, the lack of effectiveness of LY53857 to lower blood pressure in the SHR indicates that blockade of both central and vascular serotonin receptors is not a sufficient mechanism to lower blood pressure in this model of hypertension.


The behavioral context of visual displays in common marmosets (Callithrix jacchus).
Communication is important in social species, and may occur with the use of visual, olfactory or auditory signals. However, visual communication may be hampered in species that are arboreal have elaborate facial coloring and live in small groups. The common marmoset fits these criteria and may have limited visual communication. Nonetheless, some (contradictive) propositions concerning visual displays in the common marmoset have been made, yet quantitative data are lacking. The aim of this study was to assign a behavioral context to different visual displays using pre-post-event-analyses. Focal observations were conducted on 16 captive adult and sub-adult marmosets in three different family groups. Based on behavioral elements with an unambiguous meaning, four different behavioral contexts were distinguished: aggression, fear, affiliation, and play behavior. Visual displays concerned behavior that included facial expressions, body postures, and pilo-erection of the fur. Visual displays related to aggression, fear, and play/affiliation were consistent with the literature. We propose that the visual display "pilo-erection tip of tail" is related to fear. Individuals receiving these fear signals showed a higher rate of affiliative behavior. This study indicates that several visual displays may provide cues or signals of particular social contexts. Since the three displays of fear elicited an affiliative response, they may communicate a request of anxiety reduction or signal an external referent. Concluding, common marmosets, despite being arboreal and living in small groups, use several visual displays to communicate with conspecifics and their facial coloration may not hamper, but actually promote the visibility of visual displays.


Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women's Healthy Eating and Living Study.
The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes (⁻x, SE) of 3.1 ± 0.05 and 0.5 ± 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55-0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41-0.77 for total vegetables and 0.65, 95% CI 0.47-0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32-0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.