An eye for movement quality: a phenomenological study of movement quality reflecting a group of physiotherapists' understanding of the phenomenon.
Movement quality is a phenomenon frequently used by physiotherapists in oral language, written text, and clinical practice, with little clarification. The purpose was to investigate the lived experiences of a group of expert physiotherapists, searching for essential features and characteristics of the phenomenon. A phenomenological study, using in-depth interviews was chosen. Ten copies of Fine Art were used to stimulate the description of the phenomenon. The informants were 15 peer-designated physiotherapists, five from each field of neurology, psychosomatic/psychiatry and primary health care. They were nominated by physical therapist leaders in the region. The interviews were audiotaped and transcribed. Giorgis' recommendation concerning analysis of the interview data was followed. Four main themes were developed, seeing movement quality as biomechanical, physiological, psycho-socio-cultural, and existential, all interacting processes. Each theme includes preconditions to movement quality and movement characteristics. Movement quality in general was seen as a unifying phenomenon, representing a synthesis of the four themes. The outcome of the study is the Movement Quality Model (MQM) illuminating essential features and characteristics of the phenomenon. Further research is needed for clarification and application in clinical practice.


Reducing Clostridium difficile in the Inpatient Setting: A Systematic Review of the Adherence to and Effectiveness of C. difficile Prevention Bundles.
BACKGROUND Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea, and its prevention is an urgent public health priority. However, reduction of CDI is challenging because of its complex pathogenesis, large reservoirs of colonized patients, and the persistence of infectious spores. The literature lacks high-quality evidence for evaluating interventions, and many hospitals have implemented bundled interventions to reduce CDI with variable results. Thus, we conducted a systematic review to examine the components of CDI bundles, their implementation processes, and their impact on CDI rates. METHODS We conducted a comprehensive literature search of multiple computerized databases from their date of inception through April 30, 2016. The protocol was registered in PROSPERO, an international prospective register of systematic reviews. Bundle effectiveness, adherence, and study quality were assessed for each study meeting our criteria for inclusion. RESULTS In the 26 studies that met the inclusion criteria for this review, implementation and adherence factors to interventions were variably and incompletely reported, making study reproducibility and replicability challenging. Despite contextual differences and the variety of bundle components utilized, all 26 studies reported an improvement in CDI rates. However, given the lack of randomized controlled trials in the literature, assessing a causal relationship between bundled interventions and CDI rates is currently impossible. CONCLUSION Cluster randomized trials that include a rigorous assessment of the implementation of bundled interventions are urgently needed to causally test the effect of intervention bundles on CDI rates. Infect Control Hosp Epidemiol 2017;38:639-650.


Genetic testing by cancer site: stomach.
Gastric cancer is a global public health concern, ranking as the fourth leading cause of cancer mortality, with a 5-year survival of only 20%. Approximately 10% of gastric cancers appear to have a familial predisposition, and about half of these can be attributed to hereditary germline mutations. We review the genetic syndromes and current standards for genetic counseling, testing, and medical management for screening and treatment of gastric cancer. Recently, germline mutations in the E-cadherin/CDH1 gene have been identified in families with an autosomal dominant inherited predisposition to gastric cancer of the diffuse type. The cumulative lifetime risk of developing gastric cancer in CDH1 mutation carriers is up to 80%, and women from these families also have an increased risk for developing lobular breast cancer. Prophylactic gastrectomies are recommended in unaffected CDH1 mutation carriers, because screening endoscopic examinations and blind biopsies have proven inadequate for surveillance. In addition to this syndrome, gastric cancer risk is elevated in Lynch syndrome associated with germline mutations in DNA mismatch repair genes and microsatellite instability, in hereditary breast and ovarian cancer syndrome due to germline BRCA1 and BRCA2 mutations, in familial adenomatous polyposis caused by germline APC mutations, in Li-Fraumeni syndrome due to germline p53 mutations, in Peutz-Jeghers syndrome associated with germline STK11 mutations, and in juvenile polyposis syndrome associated with germline mutations in the SMAD4 and BMPR1A genes. Guidelines for genetic testing, counseling, and management of individuals with hereditary diffuse gastric cancer are suggested. A raised awareness among the physician and genetic counseling communities regarding these syndromes may allow for increased detection and prevention of gastric cancers in these high-risk individuals.


[How relevant are calculations of mean intracompartmental pressure in functional compartment syndrome?].
The intracompartmental pressure in the anterior tibial compartment was documented under standardized conditions in 29 patients walking at a speed of 4.5 km/h, as well as heel-and-toe running at a speed of 8 km/h. All pressure curves were integrated and the resulting mean pressure was compared with the arithmetic mean pressure indicated in the literature. During walking, the difference between calculated and integrated pressures was between 80 and 140%. In the case of heel-and-toe running, the difference was between 80 and 165%. On the basis of these results, the calculation of the mean intracompartmental pressure recommended in the literature does not appear to be of any clinical relevance.


Current status and perspectives of nuclear cardiology.
Nuclear cardiology has long been used to identify myocardial ischemia for appropriate treatment strategies for stable coronary artery disease (CAD). After the Ischemia Trial, it is time to reevaluate the significance of ischemia assessment. Functional imaging continues to play pivotal role in detecting microcirculatory disturbances. PET provides a clear image of blood flow distribution and is useful for the quantitative evaluation of myocardial flow reserve (MFR), which plays an important role in predicting treatment strategies and improving prognosis in CAD. Heart failure has become a major area of focus in cardiovascular medicine. Radionuclide imaging has been widely applied in this field. FDG PET is useful in identifying cardiac sarcoidosis and active inflammation. Clinical values of I-123 MIBG and BMIPP SPECT have been reported worldwide from Japan. Additionally, clinical experiences of Tc-99m pyrophosphate imaging have recently gained attention for assessing cardiac amyloidosis. Cardiac PET/CT and PET/MR imaging permit combined assessment of metabolic/functional/structural analyses of various cardiac diseases. While other non-invasive imaging modalities have rapidly been developed, the roles of radionuclide imaging remain to be valuable for early and accurate diagnosis and patient management in most cases of chronic CAD and various cardiovascular diseases.


Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications.
Local tissue renin-angiotensin systems have recently been discovered in various organs, and evidence is accumulating that inhibition of these local renin-angiotensin systems may contribute to the actions of converting enzyme (CE) inhibitors. Measurements of CE activity and angiotensin II concentrations revealed that after oral administration of CE inhibitors, CE was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. The functional significance of tissue CE inhibition is suggested first by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, second by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after long-term oral CE inhibitor treatment and third by ex vivo experiments demonstrating marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may be an important factor involved in the beneficial effects of CE inhibitors in such cardiovascular diseases as arterial hypertension, congestive heart failure and cardiac arrhythmias.


Analysis of DNA regulatory elements required for expression of the Legionella pneumophila icm and dot virulence genes.
To investigate the regulation of the Legionella pneumophila icm and dot genes required for intracellular growth, a series of nine icm::lacZ fusions were constructed. These icm::lacZ fusions were found to have different levels of expression in L. pneumophila, and five of them were more highly expressed at stationary phase than at exponential phase. When the expression of these fusions in Escherichia coli was tested, all of them were found to be expressed but three of them had dramatic changes in their levels of expression in comparison to those in L. pneumophila. Site-directed and PCR random mutagenesis with these icm::lacZ fusions was used to identify DNA regulatory elements of icm genes. Four icm genes (icmT, icmP, icmQ, and icmM) that had low levels of expression in L. pneumophila were found to contain a 6-bp sequence (TATACT) essential for their expression. This sequence was shown by primer extension to serve as their -10 promoter elements. A similar sequence, which constitutes the -10 promoter elements of the icmV, icmW, and icmR genes which had high levels of expression in L. pneumophila, was also identified. In addition, regulatory elements that probably serve as binding sites for transcription regulators were found in these genes. Altogether, 12 regulatory elements, 7 of which constitute the -10 promoter elements of the icm genes, were found. Even though all the icm and dot genes are part of one system required for L. pneumophila intracellular growth and even though their promoters are probably recognized by the vegetative sigma factor, it seems that they are subjected to different regulation mediated by several regulatory factors.


Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML.
Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.


BEHAVIOR STABILITY AND RESPONSE RATE AS FUNCTIONS OF REINFORCEMENT PROBABILITY ON "RANDOM RATIO" SCHEDULES.
A random ratio schedule is one under which every ordinally specified response has the same probability of reinforcement as any other. Data have been gathered at several values of this type of schedule, using a separate group of pigeons for each schedule value and giving prolonged exposure to each value. No simple relationship was found between response rate and reinforcement probability. In general aspect group data from the present experiment agree with those from a single organism study cited. It was shown that 40 to 50 days of exposure to random ratio schedules yields fairly asymptotic response rate data. The tabulated raw data, and the results of some statistical manipulations, have been deposited with the American Documentation Institute.


DEET occurrence in wastewaters: Seasonal, spatial and diurnal variability - mismatches between consumption data and environmental detection.
DEET (N, N-diethyl-m-toluamide) is one of the most frequently detected trace organic contaminants (TOrC) in wastewaters and is used primarily as an insect repellent. It was introduced for use in the general public in 1957. It is ubiquitously present in the environment and DEET concentrations are usually among the highest reported for TOrCs. Due to recent concerns about possible analytical interferences in detection methods being reported, this study focused on possible artifacts caused by seasonal, spatial, and diurnal variations in wastewater influent concentration of DEET. We also compared usage data to observed wastewater concentrations of seven wastewater treatment plants (WWTPs) in four different regions in the US monitored from November 2014 to November 2016. Consumption data obtained reveal patterns of consumption according to climatic regions and season. During the summer DEET usage accounts for almost 60% of all usage during a year, while during the winter months DEET usage accounts for <5%. Concerning spatial distribution, while per capita consumption of DEET in Florida is three times higher than the one observed in Arizona (44 g vs 14 g), DEET concentrations in wastewater tend to be much higher in Arizona. Regardless of WWTPs or monitoring period, concentrations as high as 15,200 ng/L were observed during the month of October 2016. While DEET has a diurnal variation in the wastewater influent, with a maximum at 18:00, the diurnal variability is not enough to explain the great discrepancies between consumption of DEET versus occurrence in wastewaters. Although LC-MS/MS analysis of isobaric and structural mimics suggests some possibility of interferences, NMR spectroscopy analysis of environmental samples does not support the presence of such mimics in real samples.


The cross-cultural generalizability of the Psychopathy Checklist: Youth version for adjudicated indigenous youth.
There is a paucity of Indigenous-specific research examining the reliability and validity of assessment tools routinely utilized within the justice system. Evaluating the cross-cultural reliability and validity of such tools is important for establishing generalizability as part of ethical practices; this is particularly important to address within Canada's Indigenous youth population because of longstanding effects of colonization, structural adversities, and overrepresentation in the youth justice system and the possible long-term impact of improper assessment on adult outcomes. A step toward this aim was undertaken in the current study by comparing scale reliability, structural validity, measurement invariance, and predictive validity of the Psychopathy Checklist: Youth Version (PCL:YV) across Indigenous (n = 137) and White (n = 312) adjudicated youth. Polychoric ordinal alpha values indicated that PCL:YV test score scale reliability was high for both Indigenous and White youth. Confirmatory factor analyses demonstrated that a 3-factor and 4-factor model provided acceptable-to-good fit for the full sample, and an examination of configural, metric, and scalar measurement invariance illustrated that both factor structures fit the subsamples equally well. PCL:YV test scores were also moderately associated with measures of different offending outcomes and performed similarly across White and Indigenous participants. Overall, support was found for the use of the PCL:YV within Indigenous youth, including its use in conjunction with other risk factors and assessment tools to guide risk assessment decisions for this group. The importance of cross-cultural research and directions for future research are discussed. (PsycINFO Database Record


On-demand spin-state manipulation of single-photon emission from quantum dot integrated with metasurface.
The semiconductor quantum dot (QD) has been successfully demonstrated as a potentially scalable and on-chip integration technology to generate the triggered photon streams that have many important applications in quantum information science. However, the randomicity of these photon streams emitted from the QD seriously compromises its use and especially hinders the on-demand manipulation of the spin states. Here, by accurately integrating a QD and its mirror image onto the two foci of a bifocal metalens, we demonstrate the on-demand generation and separation of the spin states of the emitted single photons. The photon streams with different spin states emitted from the QD can be flexibly manipulated to propagate along arbitrarily designed directions with high collimation of the smallest measured beaming divergence angle of 3.17°. Our work presents an effectively integrated quantum method for the simultaneously on-demand manipulation of the polarization, propagation, and collimation of the emitted photon streams.


Pharmacoeconomic analyses using discrete event simulation.
To date, decision trees and Markov models have been the most common methods used in pharmacoeconomic evaluations. Both of these techniques lack the flexibility required to appropriately represent clinical reality. In this paper an alternative, more natural, way to model clinical reality--discrete event simulation--is presented and its application is illustrated with a real world example.A discrete event simulation represents the course of disease very naturally, with few restrictions. Neither mutually exclusive branches nor states are required, nor is a fixed cycle. All relevant aspects can be incorporated explicitly and efficiently. Flexibility in handling perspectives and carrying out sensitivity analyses, including structural variations, is incorporated and the entire model can be presented very transparently. The main limitations are imposed by lack of data to fit realistic models. Discrete event simulation, though rarely employed in pharmacoeconomics today, should be strongly considered when carrying out economic evaluations, particularly those aimed at informing policy makers and at estimating the budget impact of a pharmaceutical intervention.


Doxazosin Attenuates Liver Fibrosis by Inhibiting Autophagy in Hepatic Stellate Cells via Activation of the PI3K/Akt/mTOR Signaling Pathway.
To investigate the effect of doxazosin on autophagy and the activation of hepatic stellate cells (HSCs) in vivo and in vitro and determine the underlying mechanism. In vivo, a mouse liver fibrosis model was induced by the intraperitoneal injection of carbon tetrachloride (CCl4). Doxazosin was administered at doses of 2.5, 5 and 10 mg/(kg*day) by gavage. After 20 weeks, blood and liver tissues were collected for serological and histological analysis, respectively. Blood analysis, hematoxylin and eosin (HE) staining, Masson's trichrome staining, immunohistochemistry and immunofluorescence staining were used to measure the extent of liver fibrosis in model and control mice. In vitro, the human HSC cell line LX-2 was cultured and treated with different doses of doxazosin for the indicated times. The effects of doxazosin on LX-2 cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The number of autophagosomes in LX-2 cells was observed by transmission electron microscopy (TEM). Infection with green fluorescent protein (GFP)-LC3B adenovirus, GFP-red fluorescent protein (RFP)-LC3B adenovirus and mCherry-EGFP-LC3 adeno-associated virus was performed to examine changes in autophagic flux in vitro and in vivo. Cell apoptosis was measured by flow cytometry in vitro and by TUNEL assays both in vitro and in vivo. Immunoblotting was performed to evaluate the expression levels of proteins related to fibrosis, autophagy, apoptosis, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). Doxazosin inhibited HSC proliferation and migration. HSC activation was attenuated by doxazosin in a concentration-dependent manner in vivo and in vitro. Doxazosin also blocked autophagic flux and induced apoptosis in HSCs. In addition, the PI3K/Akt/mTOR pathway was activated by doxazosin and regulated fibrosis, autophagy and apoptosis in HSCs. The study confirmed that doxazosin could inhibit autophagy by activating the PI3K/Akt/mTOR signaling pathway and attenuate liver fibrosis.


Nickel contact hypersensitivity in children.
Nickel allergic contact dermatitis is the most prevalent allergy in North America, with an incidence of 14.3%. It is on the rise from 10 years ago, when the incidence was 10%. This has been presumed to represent an increased exposure to nickel in the environment-especially in costume jewelry and belt buckles. We examined a group of 30 pediatric patients who had either a personal history of umbilical or wrist dermatitis, or a family history of nickel allergic contact dermatitis. All of these patients had a positive patch test to nickel sulfate 5%. Moreover, 50% of patients had an id reaction; all of these patients had positive patch tests that were papular in nature, similar to their papular id reaction. We posit that the presence of a positive family history may be a positive predictor of nickel allergic contact dermatitis, requiring nickel avoidance, especially in atopic children. Based on the high level of positive reactions in patients with umbilical dermatitis and an id reaction, patch testing to nickel in these patients is most likely to yield a useful result. Knowledge of reactivity to nickel would then allow parents and patients to initiate nickel avoidance earlier in life.


Comparative changes of lipid levels in treatment-naive, HIV-1-infected adults treated with dolutegravir vs. efavirenz, raltegravir, and ritonavir-boosted darunavir-based regimens over 48 weeks.
Long-term use of antiretroviral therapy (ART) to treat HIV infection has been associated with dyslipidemia and metabolic and cardiovascular complications. Available options for patients at risk of cardiovascular disease include antiretroviral drugs with improved lipid profiles. Dolutegravir is one of a new generation of HIV integrase inhibitors recently incorporated into the US Department of Health and Human Services, German, Spanish, and Italian HIV treatment guidelines as a preferred first-line third agent in combination with dual nucleoside reverse transcriptase inhibitor (NRTI) backbone therapies. To understand the lipid profile of dolutegravir in the context of combination ART, we analyzed the lipid outcomes at 48 weeks in ART-naive participants in four phase IIb-IIIb clinical trials. Variables included in this analysis were total cholesterol (TC), low-density lipoprotein (LDL) cholesterol (LDL-C), high-density lipoprotein (HDL) cholesterol (HDL-C), TC/HDL ratio, and triglycerides at baseline and week 48. In a comparative analysis, dolutegravir demonstrated a broadly neutral effect on lipids versus efavirenz or ritonavir-boosted darunavir; in both comparisons, patients taking dolutegravir exhibited smaller increases in TC, LDL-C, and triglyceride levels. In comparison with raltegravir, dolutegravir exhibited a similar lipid profile, including small increases in TC, LDL-C, and triglyceride levels for both agents. In the pooled dolutegravir analysis, minimal increases in LDL-C and triglycerides were observed but mean values at 48 weeks remained below National Cholesterol Education Program target levels. HDL-C levels increased at 48 weeks, and the mean TC/HDL-C ratio was 0.6 at 48 weeks; these values are associated with a lower risk of cardiovascular disease. Together, these data show that dolutegravir has a safer lipid profile in combination ART and provides an important treatment option for older patients who may have other risk factors for metabolic syndrome or cardiovascular disease.


Relating divergence in polychaete musculature to different burrowing behaviors: a study using opheliidae (Annelida).
Divergent morphologies among related species are often correlated with distinct behaviors and habitat uses. Considerable morphological and behavioral differences are found between two major clades within the polychaete family Opheliidae. For instance, Thoracophelia mucronata burrows by peristalsis, whereas Armandia brevis exhibits undulatory burrowing. We investigate the anatomical differences that allow for these distinct burrowing behaviors, then interpret these differences in an evolutionary context using broader phylogenetic (DNA-based) and morphological analyses of Opheliidae and taxa, such as Scalibregmatidae and Polygordiidae. Histological three-dimensional-reconstruction of A. brevis reveals bilateral longitudinal muscle bands as the prominent musculature of the body. Circular muscles are absent; instead oblique muscles act with unilateral contraction of longitudinal muscles to bend the body during undulation. The angle of helical fibers in the cuticle is consistent with the fibers supporting turgidity of the body rather than resisting radial expansion from longitudinal muscle contraction. Circular muscles are present in the anterior of T. mucronata, and they branch away from the body wall to form oblique muscles. Helical fibers in the cuticle are more axially oriented than those in undulatory burrowers, facilitating radial expansion during peristalsis. A transition in musculature accompanies the change in external morphology from the thorax to the abdomen, which has oblique muscles similar to A. brevis. Muscles in the muscular septum, which extends posteriorly to form the injector organ, act in synchrony with the body wall musculature during peristalsis: they contract to push fluid anteriorly and expand the head region following a direct peristaltic wave of the body wall muscles. The septum of A. brevis is much thinner and is presumably used for eversion of a nonmuscular pharynx. Mapping of morphological characters onto the molecular-based phylogeny shows close links between musculature and behavior, but less correlation with habitat.


[Adolescence and parental authority].
Family crisis induced by a crisis of adolescence creates a drama involving 7 characters (adolescent, two parents and four grandparents), not counting family Ancestors and Phantoms. The author underlines the positive aspects of this crisis, for the adolescent himself as well as for his close relations. This crisis, indeed, may be maturative for all concerned, if the parents know how to construct and defend a family framework and an intergeneration-boundary. The author then describes three types of family structures (derived from the parent's families origin, or created by the parents, or re-created by the adolescent) which can impede the establishment of this intergenerational boundary; preventing the crisis from occurring; preventing its development and resolution. This leads to recurrent or chronic crisis. Finally, the author indicates precautions which general practitioners should take when dealing with family or adolescent crises.


Susceptibility of Dog, Hamster, and Mouse Cells to the Replication-Competent Adenovirus 11p E1/E3 Green Fluorescence Protein Vector Has Implications for the Selection of Animal Vaccine Models.
Human adenovirus (Ad)-vectored vaccines require viruses that can internalize into host cells and express the vaccine antigen. Evaluation of the expressed antigen in animal cells is a critical step in preclinical trials of viral vaccines. Due to the species specificity of Ads, it is difficult to find a suitable animal model. Thus, in this study, we compared the efficacy of Ad 11 prototype (Ad11p)-mediated green fluorescence protein (GFP) expression in cell lines of dog (MDCK), hamster (CHO), and mouse (McCoy and C127). Although these cell lines did not express the known primary cellular receptors for Ad11p virus infection (i.e., CD46), Ad11pE1GFP could infect and express GFP with various efficacies. For instance, it manifested relatively higher GFP expression in MDCK than in CHO, McCoy, and C127. However, infection leading to efficient viral release was not observed in any of the studied cell lines. The apparent differences were attributed to particularities of mouse and hamster cell lines, which might have led to the repression of viral DNA synthesis and to the low level of GFP expression mediated by Ad11pe3GFP. Moreover, our results revealed that undetectable hexon protein hampered the assembly of virus particles in CHO and MDCK cells. Ad11p differed from Ad5 in the ability for viral DNA synthesis when infecting CHO cells. Although a defective Ad has been successfully developed for SARS-CoV-2 vaccines in clinical applications, it has been difficult to generate one that can be used as an oral SARS-CoV-2 vaccine. Fortunately, our replication-competent Ad 11p vector might solve this problem. Regarding the use of Ad-vector candidates for vaccine purposes, this study demonstrates the selection of animal cell lines and determination of suitable virus doses in in vitro experiments.


A comparison of Golytely and standard preparation for barium enema.
A randomized prospective trial was performed comparing Golytely (with bisacodyl) with our standard two-day catharsis and bowel washout regimen as colon preparation for double-contrast barium enema examinations. Of the 107 patients who participated, 50 received the standard preparation and 57 Golytely. Two radiologists reviewed the enema films without knowledge of which preparation had been used. No significant difference was detected either in the number of failed preparations or in the quality. We conclude that routine use of Golytely is preferable to methods involving catharsis and standard tap water enemas for barium enema examination, on the grounds that it is equally effective, yet more convenient for patients and for the radiology department, and reduces total costs.


Interplay of vibrational wavepackets during an ultrafast electron transfer reaction.
Electron transfer reactions facilitate energy transduction and photoredox processes in biology and chemistry. Recent findings show that molecular vibrations can enable the dramatic acceleration of some electron transfer reactions, and control it by suppressing and enhancing reaction paths. Here, we report ultrafast spectroscopy experiments and quantum dynamics simulations that resolve how quantum vibrations participate in an electron transfer reaction. We observe ballistic electron transfer (~30 fs) along a reaction coordinate comprising high-frequency promoting vibrations. Along another vibrational coordinate, the system becomes impulsively out of equilibrium as a result of the electron transfer reaction. This leads to the generation (by the electron transfer reaction, not the laser pulse) of a new vibrational coherence along this second reaction coordinate in a mode associated with the reaction product. These results resolve a complex reaction trajectory composed of multiple vibrational coordinates that, like a sequence of ratchets, progressively diminish the recurrence of the reactant state.


Psychometric properties of the Chinese version of the Swanson, Nolan, and Pelham, version IV scale - parent form.
This study aimed to establish the psychometric properties of parent ratings on the Chinese version of the Swanson, Nolan, and Pelham IV scale (SNAP-IV) in a school-based sample of 3534 students in grades 1 to 8 from two cities and two suburbs in Taiwan and 189 children diagnosed with attention deficit/hyperactivity disorder (ADHD) (aged 6 to 15) consecutively recruited from a medical center in Taipei. Parents completed the Chinese versions of the SNAP-IV, Strengths and Difficulties Questionnaire, and Child Behavior Checklist. The Chinese SNAP-IV demonstrated similar three factor structure (Inattention, Hyperactivity/Impulsivity, and Oppositional) as its English version, and satisfactory test-retest reliability (intraclass correlation = 0.59 approximately 0.72), internal consistency (alpha = 0.88 approximately 0.90), concurrent validity (Pearson correlations = 0.56 approximately 0.72), and discriminant validity. Boys scored higher than girls across the eight school grade levels. The SNAP-IV clearly distinguished children with ADHD from school-based participants. Comorbidity with oppositional defiant disorder/conduct disorder predicted higher SNAP-IV scores among children with ADHD. Our findings suggest that the Chinese SNAP-IV is a reliable and valid instrument for rating ADHD-related symptoms in both clinical and community settings in Taiwan.


Genetic predisposition to Helicobacter pylori-induced gastric precancerous conditions.
Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helicobacter pylori (H. pylori) infection (e.g. TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epidemiological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymorphisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.


Lipid-Modified Aminoglycosides for mRNA Delivery to the Liver.
Cationic lipid nanoparticles (LNPs) are widely used as carriers for delivery of nucleic acids. Most synthetic routes toward cationic lipids have derived from simple amine cores. Greater chemical diversity can be obtained through starting with natural products containing basic nitrogen atoms, which offers routes to more complex molecules. Natural building blocks are not extensively explored, such as aminoglycosides, which are both structurally and functionally interesting for developing new carriers for nucleic acid delivery. Herein, cationic lipid-modified aminoglycosides (CLAs) are explored as a family of vehicles for messenger RNA (mRNA) delivery. CLAs are synthesized from natural existing aminoglycosides coupling with alkyl epoxides and acrylates. The top hit (GT-EP10) is able to deliver Luc mRNA to C57BL/6 mice at a dose of 0.05 mg kg-1 to achieve a 107 average luminescence intensity in the liver. The Lox-Stop-Lox tdTomato mouse model is used to further demonstrate that this efficient mRNA delivery system can be potentially used for gene editing. Successful delivery of human erythropoietin mRNA shows that CLA-based LNPs have promising opportunities for delivery of therapeutic nucleic acids in the future.


[Respiratory disorders in acquired heart valve defects with various degrees of heart failure].
The respiratory disorders with various degrees of cardiac insufficiency were studied in 226 patients with acquired heart defects. The indices characterizing the external respiration, alveolar ventilation, alveolar-capillary diffusion, functional and real intrapulmonary shunts and acid-base state were followed up. The results from the numerous indices followed up significantly express the progressive intensification of respiratory disorders with the advancement of cardiac insufficiency. In stage I of cardiac insufficiency, prior to the manifestation of clinical signs of pulmonary stasis, distinct disturbances were established in DLCO, Qs/Qt, PaO2, which, to a great extent, characterize the early respiratory disorders and have a definite importance for the diagnostic and therapeutic behaviour. Most severe are the functional disorders in respiratory system in stage II B of cardiac insufficiency.


Calmodulin and insulin secretion: use of naphthalenesulfonamide compounds.
Studies have been performed on the involvement of calmodulin in the control of stimulated insulin secretion. The W-compounds, which are sulfonamide-derivative calmodulin inhibitors, were used in analogue pairs to control for hydrophobic and nonspecific effects. N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide HCl (W-13) inhibited glucose-stimulated insulin secretion from rat pancreatic islets over the concentration range appropriate for an action involving calmodulin. The control compound N-(4-aminobutyl)-2-naphthalenesulfonamide HCl (W-12) inhibited slightly only at higher concentrations. Similar differential inhibition by the analogue pairs was found using W-13 and W-12 and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide HCl (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide HCl (W-5) against depolarization-induced insulin secretion in the RINm5F clonal beta-cell line. A sufficient explanation for the inhibition of insulin release was found in the differential inhibition of depolarization-induced Ca2+ uptake, which located the action of the W-compounds at the voltage-dependent Ca2+ channels. These data suggest an action of the W-compounds at a point before elevation of intracellular Ca2+ concentration [( Ca2+]i) in stimulus-secretion coupling. In subsequent studies, with the voltage-dependent Ca2(+)-channel agonist BAY K 8644, which increases Ca2+ uptake and the rate of insulin secretion, it was demonstrated that the W-compounds had no effect on the stimulation of 45Ca2+ uptake or insulin secretion. Thus the W-compounds inhibit stimulus-secretion coupling before the elevation of [Ca2+]i but appear to have no action subsequently. These data cast doubt on the hypothesis that calmodulin is involved in stimulus-secretion coupling.


Hog barn dust extract increases macromolecular efflux from the hamster cheek pouch.
The purpose of this study was to determine whether short-term exposure to an aqueous extract of hog barn dust increases macromolecular efflux from the intact hamster cheek pouch and, if so, to begin to determine the mechanism(s) underlying this response. By using intravital microscopy, we found that suffusion of hog barn dust extract onto the intact hamster cheek pouch for 60 min elicited a significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (molecular mass, 70 kDa). This response was significantly attenuated by suffusion of catalase (60 U/ml), but not by heat-inactivated catalase, and by pretreatment with dexamethasone (10 mg/kg iv) (P < 0.05). Catalase had no significant effects on adenosine-induced increase in macromolecular efflux from the cheek pouch. Suffusion of hog barn dust extract had no significant effects on arteriolar diameter in the cheek pouch. Taken together, these data indicate that hog barn dust extract increases macromolecular efflux from the in situ hamster cheek pouch, in part, through local elaboration of reactive oxygen species that are inactivated by catalase. This response is specific and attenuated by corticosteroids. We suggest that plasma exudation plays an important role in the genesis of upper airway dysfunction evoked by short-term exposure to hog barn dust.


α-Lipoic acid protects against arsenic trioxide-induced acute QT prolongation in anesthetized guinea pigs.
Clinical use of arsenic trioxide (As₂O₃), which can induce the remission of relapsed or refractory acute promyelocytic leukemia, is often limited because of its cardiotoxicity. Symptoms of cardiotoxicity include acute cardiac conduction disturbances, such as QT prolongation. The present study was undertaken to evaluate the effects of α-lipoic acid (LA) on acute As₂O₃-induced ECG abnormalities (QTc interval prolongation) in anesthetized guinea pigs. Intravenous injection of As₂O₃ in guinea pigs caused QTc interval prolongation, which was significantly attenuated by co-treatment with LA (0.35, 3.5 and 35 mg/kg) in a dose-dependent manner. In isolated guinea pig cardiomyocytes, the decrease in IKs current induced by As₂O3 (1 μM) was rapidly restored to the basal level by the addition of LA (10 μM). Consistent with this finding, the As₂O₃-induced QTc interval prolongation was also improved rapidly by post-treatment with LA in guinea pigs. Electrospray ionization time-of-flight mass spectrometry analysis detected an expected peak of arsenic-LA complex in vitro, indicating that LA and As₂O3 form a new compound in vivo. In addition, pre-treatment with a chelating agent, British anti-Lewisite (BAL, 3.5 or 35 mg/kg), also attenuated the As₂O₃-induced QTc interval prolongation. In this study, co- and post-treatments with LA and pre-treatment with BAL ameliorated As₂O₃-induced acute QT prolongation in anesthetized guinea pigs. Because LA and probably BAL may bind to As₂O₃, these agents may exert protective effects through their chelating activity. Further studies are needed to determine whether LA is beneficial as a prophylactic or rescue agent for acute promyelocytic leukemia patients treated with As₂O₃.


Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward.
Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.


Ultrahigh Frequency Ultrasound Imaging of the Hand: A New Diagnostic Tool for Hand Surgery.
Ultrasonography is a cost-effective, noninvasive, and expedient imaging modality with numerous clinical applications. Conventional ultrasound uses transducers with frequencies that range from 5 to 12 MHz. However, ultrahigh frequency ultrasound (UHFUS) is capable of producing frequencies up to 70 MHz, which can achieve tissue resolution up to 30 μm. The purpose of our study is to present the capabilities of a novel technology and to describe its possible clinical applications for hand surgery. The Vevo 2100 (VisualSonics, Toronto, Canada) system was used to perform all ultrasound exams. Four unique linear array transducers were employed. All studies were performed by the authors, who have no formal training in ultrasound techniques, on 5 healthy resident volunteers and 1 clinical patient under institutional review board approval. A series of 10 static images per participant and dynamic, real-time videos were obtained at various locations within the hand and wrist. UHFUS is capable of quickly and reliably imaging larger structures such as foreign bodies, soft tissue masses, and the flexor tendons, and diagnosing an array of pathologies within these structures. In addition, UHFUS can identify much finer structures such as the intimal layer of the arteries in the hand and individual fascicles within the digital nerves to provide data about vessel quality and vascular and neural pathologies. UHFUS is a novel technology that shows multiple advantages over conventional ultrasound for imaging the fine superficial structures of the hand and wrist, and can be deployed by the surgeon at the point of care.


Exploring social accountability in Canadian medical schools: broader perspectives.
This article was migrated. The article was marked as recommended. This article is the second of a two-part series in a study that explores key drivers of social accountability in Canada's medical schools and offers examples of social accountability in action. The study gathered perspectives from medical school staff, students and faculty through focus group discussions, using an appreciative inquiry approach. Drivers of social accountability emerging from the focus groups largely corroborate what was discovered in the first part of the series during key informant interviews with senior leaders. These include the importance of accreditation, leadership, vision and mandate, and community engagement among others, and highlight the key role champions play in driving social accountability. This study builds on the first article in the series by recognizing leadership as an important driver for social accountability, but highlighting how leadership alone is not enough. The broader range of perspectives gathered through the focus group discussions uncovered the importance of social accountability 'champions' at all levels: formal leadership, faculty, student and staff. Focus group discussions also uncovered an additional key driver that was not found in key informant interviews - cultural humility, with participants noting that action towards social accountability requires shifts not only in organizational structure, but also organizational culture, to foster real, lasting change. This study demonstrates the utility of an appreciative inquiry approach for understanding how complex systems like medical education institutions are innovatively tackling challenges around health equity. The richness of the themes that emerged consistently across focus group sessions and key informant interviews support the utility of the approach in furthering our understanding as to what is working to drive social accountability in some Canadian medical schools.


Genetic interactions underlying the biosynthesis and inhibition of β-diketones in wheat and their impact on glaucousness and cuticle permeability.
Cuticular wax composition greatly impacts plant responses to dehydration. Two parallel pathways exist in Triticeae for manipulating wax composition: the acyl elongation, reduction, and decarbonylation pathway that is active at the vegetative stage and yields primary alcohols and alkanes, and the β-diketone pathway that predominates at the reproductive stage and synthesizes β-diketones. Variation in glaucousness during the reproductive stage of wheat is mainly controlled by the wax production genes, W1 and W2, and wax inhibitor genes, Iw1 and Iw2. Little is known about the metabolic and physiological effects of the genetic interactions among these genes and their roles in shifting wax composition during plant development. We characterized the effect of W1, W2, Iw1, and Iw2 and analyzed their interaction using a set of six near-isogenic lines (NILs) by metabolic, molecular and physiological approaches. Loss of functional alleles of both W genes or the presence of either Iw gene depletes β-diketones and results in the nonglaucous phenotype. Elimination of β-diketones is compensated for by an increase in aldehydes and primary alcohols in the Iw NILs. Accordingly, transcription of CER4-6, which encodes an alcohol-forming fatty acyl-CoA reductase, was elevated 120-fold in iw1Iw2. CER4-6 was transcribed at much higher levels in seedlings than in adult plants, and showed little difference between the glaucous and nonglaucous NILs, suggesting that Iw2 counteracts the developmental repression of CER4-6 at the reproductive stage. While W1 and W2 redundantly function in β-diketone biosynthesis, a combination of both functional alleles led to the β-diketone hydroxylation. Consistent with this, transcription of MAH1-9, which encodes a mid-chain alkane hydroxylase, increased seven-fold only in W1W2. In parallel with the hydroxyl-β-diketone production patterns, glaucousness was intensified and cuticle permeability was reduced significantly in W1W2 compared to the other NILs. This suggests that both W1 and W2 are required for enhancing drought tolerance.


Correlated gene expression encoding serotonin (5-HT) receptor 4 and 5-HT transporter in proximal colonic segments of mice across different colonization states and sexes.
The production and handling of serotonin (5-HT) is an important determinant of colonic motility and has been reported to be altered in gastrointestinal (GI) disorders such as irritable bowel syndrome (IBS). Recent studies suggest that the intestinal microbiota and sex of the host can influence expression of genes involved in 5-HT biosynthesis and signaling. While expression of genes in serotonergic pathways has been shown to be variable, it remains unclear whether genes within this pathway are coregulated. As a first step in that direction, we investigated potential correlations in relative mRNA expression of serotonergic genes, in the proximal colon isolated from male and female mice in different states of microbial association: germ-free (GF), humanized (ex-germ-free colonized with human gut microbiota, HM), and conventionally raised (CR) mice. Among the 10 pairwise comparisons conducted between five serotonergic transcripts, Tph1, Chga, Maoa, Slc6a4, and Htr4, we found a strong, positive correlation between colonic expression of Slc6a4 and Htr4 across different colonization states and sexes. We also identified a positive correlation between the expression of Tph1 and Chga; however, there were no correlations observed between any other tested pair of 5-HT-related transcripts. These data suggest that correlated expression of Slc6a4 and Htr4 likely involves coregulation of genes located on different chromosomes which modulate serotonergic activity in the gut. Further work will need to be done to understand the pathways and cell types responsible for this correlated expression, given the important role of 5-HT in gastrointestinal physiology.


Impact of Medicare Annual Wellness Visits on Uptake of Depression Screening.
Depression screening is a required part of an initial annual wellness visit (AWV), a benefit for Medicare Part B beneficiaries. It is uncertain whether AWVs will increase depression screening. This study assessed whether patients with an AWV were more likely to be screened for depression than those with a primary care visit. A cross-sectional analysis of electronic health record data was conducted for 4,245 Medicare patients who had at least one primary care visit at one of 34 practices within a large multisite provider network between September 2010 and August 2012. Quota sampling was used so that half of the participants had an AWV and half had a randomly selected primary care visit during the study period (the index visit). Multilevel logistic regressions were used to determine whether patients with an AWV had increased odds of depression screening compared with patients with a primary care visit, after adjustment for physician and clinic clustering. Fifteen percent of patients with non-AWVs and 10% of patients with AWVs received depression screening. After accounting for clustering, there was no statistically significant difference in depression screening by visit type. There was a strong site effect, with one site conducting screening during 78% of AWVs and 82% of non-AWVs. Six sites screened none of their patients. Overall, depression screening during the index AWV was uncommon. By itself, the AWV benefit does not appear to be a strong enough incentive to increase depression screening.


Pooled retrospective analysis of 70 mg erenumab in episodic and chronic migraine: a two tertiary headache centers experience during clinical practice.
Erenumab is a monoclonal antibody, targeted against the calcitonin gene-related peptide (CGRP) receptor. Clinical studies have demonstrated prophylactic efficacy in both episodic (EM) and chronic migraine (CM). The aim of the present study is to evaluate the efficacy of treatment in tertiary headache centers under real-life conditions. In a retrospective analysis, the period of 3 months before and after initiation of erenumab therapy was compared. Relevant parameters (headache days, headache intensity, headache duration, acute medication, previous prophylaxis treatments) were collected from medical charts of all migraine patients (N = 82) who started treatment with erenumab between November 1st 2018 and May 1st 2019 at two tertiary headache centers in Germany. The sample included 68 female (82.9%) and 14 male patients aged between 22 and 78 years (mean 51.1 years, SD 10.5 years). Of these patients, 57.3% met the criteria for CM and 56.9% overused acute medication. Under therapy with erenumab, a significant reduction of headache days was observed from the first month on. The effect was most pronounced in the third month with a decrease in monthly headache days from 16.6 to 11.6 days (p < 0.001). There was also a significant reduction in reported headache intensity (p = 0.004) and average duration of headache attacks (p = 0.016). The 50% responder rate in patients with CM was lower in the first month compared to EM but then increased similarly to EM. Patients with medication overuse (MO) also responded to the therapy. There was a reduction in medication overuse from 57% at baseline to 29% after therapy (p = 0.011). Overall, a positive result of treatment with erenumab can be shown in a highly selected sample with severely affected migraine patients and a refractory course prior to treatment. This re-confirms the clinical trial data also for this highly selected group.


Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix.
Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of 125I-labeled LDL, LDL transport across the monolayers was unchanged; but, at all concentrations of LDL tested (1-100 micrograms), LDL retention by the monolayers increased more than fourfold. 125I-labeled LDL binding to extracellular matrix increased when LPL was added directly to the matrix or was added to the basolateral side of the endothelial cell monolayers. Increased LDL binding required the presence of LPL and was not associated with LDL aggregation. LPL also increased VLDL, but not HDL, retention. Monoclonal anti-LPL IgG decreased both VLDL and LDL retention in the presence of LPL. Lipoprotein transport across the monolayers increased during hydrolysis of VLDL triglyceride (TG). In the presence of LPL and VLDL, VLDL transport across the monolayers increased 18% and LDL transport increased 37%. High molar concentrations of oleic acid to bovine serum albumin (3:1) in the medium increased VLDL transport approximately 30%. LDL transport increased 42% when oleic acid was added to the media. Therefore, LPL primarily increased retention of LDL and VLDL. A less remarkable increase in lipoprotein transport was found during hydrolysis of TG-containing lipoproteins. We hypothesize that LPL-mediated VLDL and LDL retention within the arterial wall potentiates conversion of these lipoproteins to more atherogenic forms.


Color priming in pop-out search depends on the relative color of the target.
In visual search for pop-out targets, search times are shorter when the target and non-target colors from the previous trial are repeated than when they change. This priming effect was originally attributed to a feature weighting mechanism that biases attention toward the target features, and away from the non-target features. However, more recent studies have shown that visual selection is strongly context-dependent: according to a relational account of feature priming, the target color is always encoded relative to the non-target color (e.g., as redder or greener). The present study provides a critical test of this hypothesis, by varying the colors of the search items such that either the relative color or the absolute color of the target always remained constant (or both). The results clearly show that color priming depends on the relative color of a target with respect to the non-targets but not on its absolute color value. Moreover, the observed priming effects did not change over the course of the experiment, suggesting that the visual system encodes colors in a relative manner from the start of the experiment. Taken together, these results strongly support a relational account of feature priming in visual search, and are inconsistent with the dominant feature-based views.


Magnetic resonance cholangiopancreatography of anatomic variants of the biliary tree in Taiwanese.
Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive method for evaluating the hepatobiliary system. This study investigated the anatomic variants of the biliary tree in Taiwanese using MRCP. 170 patients with abdominal or liver diseases underwent diagnostic MRCP over the 29-month study period. We identified the type of biliary tree variants in 130 patients. The imaging findings showed that the most common biliary tree variants were type I and type IIA, which together comprised 70% of all variants. Type I is a triple confluence, which is an anatomy characterized by simultaneous emptying of the right posterior segment duct, right anterior segment duct, and left hepatic duct into the common hepatic duct. Type IIA involves drainage of the right posterior segment duct into the right anterior segment duct to form the right hepatic duct, and then confluence with the left hepatic duct to form the common hepatic duct. There was a mean percentage of 10 to 20% among the 7 types of variants identified. Comparison of these findings with previous investigation indicates that biliary tract structure shows racial and ethnic variation.


Genomic imprinting and dermatological disease.
Imprinting is the process whereby genetic alleles responsible for a phenotype are derived from one parent only. It is an epigenetic phenomenon resulting from DNA methylation or modification of protruding histones. When imprinted genes are disrupted, syndromes with characteristic patterns of inheritance and multisystem phenotype occur. Those detailed in this article have some quite characteristic cutaneous features and patterns of inheritance. These diseases include Beckwith-Wiedmann, Silver-Russell, Prader-Willi, McCune-Albright and Angelman syndromes, Albright's hereditary osteodystrophy, and progressive osseous heteroplasia. In the case of Von Hippel-Lindau syndrome, hypomelanosis of Ito and dermatopathia pigmentosa reticularis, imprinting may play a part in the inheritance. With neurofibromatosis type 1, a nonimprinted condition, the expression of the phenotype could be affected by interaction with imprinted gene loci. Imprinted genes could also play a part in the polygenetic inheritance of more common diseases also, as atopic eczema and psoriasis may have predominantly maternal and paternal modes of transmission, respectively.


Stereocontrolled syntheses of alpha-C-mannosyltryptophan and its analogues.
The total synthesis of alpha-C-mannosyltryptophan (C-Man-Trp), a naturally occurring C-glycosylamino acid, was achieved from a commercially available alpha-methyl-D-mannoside in 10 steps including the following key steps: the C-glycosidation of a mannose derivative with a stannylacetylene, Castro indole synthesis, and Sc(ClO4)3-promoted coupling with L-serine-derived aziridine carboxylate. The glucose- and galactose-analogues of C-Man-Trp were also synthesized in a similar manner. Conformational analyses of the synthesized C-glycosyltryptophan and its synthetic intermediate are briefly discussed.


Nuclear speckles: molecular organization, biological function and role in disease.
The nucleoplasm is not homogenous; it consists of many types of nuclear bodies, also known as nuclear domains or nuclear subcompartments. These self-organizing structures gather machinery involved in various nuclear activities. Nuclear speckles (NSs) or splicing speckles, also called interchromatin granule clusters, were discovered as sites for splicing factor storage and modification. Further studies on transcription and mRNA maturation and export revealed a more general role for splicing speckles in RNA metabolism. Here, we discuss the functional implications of the localization of numerous proteins crucial for epigenetic regulation, chromatin organization, DNA repair and RNA modification to nuclear speckles. We highlight recent advances suggesting that NSs facilitate integrated regulation of gene expression. In addition, we consider the influence of abundant regulatory and signaling proteins, i.e. protein kinases and proteins involved in protein ubiquitination, phosphoinositide signaling and nucleoskeletal organization, on pre-mRNA synthesis and maturation. While many of these regulatory proteins act within NSs, direct evidence for mRNA metabolism events occurring in NSs is still lacking. NSs contribute to numerous human diseases, including cancers and viral infections. In addition, recent data have demonstrated close relationships between these structures and the development of neurological disorders.


Voluntary activation and central activation failure in the knee extensors in young women and men.
Quadriceps muscle weakness is common after knee injuries. This weakness is caused, in part, by reduced voluntary activation (VA) because of central activation failure (CAF). Superimposed electrical stimulation techniques are used to assess VA and to detect CAF. The aim of this study was to assess VA during knee extension in young healthy women and men, and to evaluate subjective discomfort from the electrical stimulation. The quadriceps muscle in six young healthy women (mean age 22 years) and six young healthy men (mean age 29 years) was stimulated during maximal voluntary contractions using a 100 Hz pulse train. Data were collected from two test sessions separated by 6-8 days and each session comprised of two trials. A visual analog scale for pain (VAS-pain) was used to evaluate subjective discomfort. Overall, young healthy, moderately active men and women did have the ability to fully activate their knee extensors isometrically, but they did not achieve full activation on every trial. In those trials where a CAF was detected, the degree was small (mean less than 2%), and did not vary between the two test sessions. Subjective discomfort was generally moderate and tolerable (mean VAS-pain score 35 mm). These results will assist the clinical assessment of muscle weakness following a knee injury and facilitate the design and evaluation of appropriate rehabilitation interventions.


High rates of adherence and treatment success in a public and public-private HIV clinic in India: potential benefits of standardized national care delivery systems.
The massive scale-up of antiretroviral treatment (ART) access worldwide has brought tremendous benefit to populations affected by HIV/AIDS. Optimising HIV care in countries with diverse medical systems is critical; however data on best practices for HIV healthcare delivery in resource-constrained settings are limited. This study aimed to understand patient characteristics and treatment outcomes from different HIV healthcare settings in Bangalore, India. Participants from public, private and public-private HIV healthcare settings were recruited between 2007 and 2009 and were administered structured interviews by trained staff. Self-reported adherence was measured using the visual analogue scale to capture adherence over the past month, and a history of treatment interruptions (defined as having missed medications for more than 48 hours in the past three months). In addition, CD4 count and viral load (VL) were measured; genotyping for drug resistance-associated mutations was performed on those who were in virological failure (VL > 1000 copies/ml). A total of 471 individuals were included in the analysis (263 from the public facility, 149 from the public-private facility and 59 from the private center). Private facility patients were more likely to be male, with higher education levels and incomes. More participants reported ≥ 95% adherence among public and public-private groups compared to private participants (public 97%; private 88%; public-private 93%, p < 0.05). Treatment interruptions were lowest among public participants (1%, 10%, 5% respectively, p < 0.001). Although longer clinic waiting times were experienced by more public participants (48%, compared to private 27%, public-private 19%, p < 0.001), adherence barriers were highest among private (31%) compared with public (10%) and public-private (17%, p < 0.001) participants. Viral load was detectable in 13% public, 22% private and 9% public-private participants (p < 0.05) suggesting fewer treatment failures among public and public-private settings. Drug resistance mutations were found more frequently among private facility patients (20%) compared to those from the public (9%) or public-private facility (8%, p < 0.05). Adherence and treatment success was significantly higher among patients from public and public-private settings compared with patients from private facilities. These results suggest a possible benefit of the standardized care delivery system established in public and public-private health facilities where counselling by a multi-disciplinary team of workers is integral to provision of ART. Strengthening and increasing public-private partnerships can enhance the success of national ART programs.


Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis.
Urinary tract infections (UTI), the most common infectious complications after kidney transplantation, are associated with poor allograft survival. Identifying its predisposing factors is therefore remarkably important in order to optimize prevention strategies. A retrospective study was performed in a cohort of patients who received kidney transplantation between June 2007 and June 2009. Factors associated with development of UTI were assessed. The population consisted of 301 patients, with majority receiving allograft from living donors (85%). A total of 101 patients (34%) developed at least one episode of UTI, and 25% of the episodes occurred during the first year after transplantation. Risk factors associated with increased risk of UTI were female gender, recurrent UTI prior to transplant, and presence of urological abnormalities. Trimethoprim-sulfamethoxazole (TMP-SMZ) use was associated with a lower risk of UTI, including a lower risk of recurrent UTI. In this cohort of predominantly living donor kidney transplant recipients, we report a high incidence of UTI, despite our practice of early ureteral and Foley catheter removal. Female gender and prior recurrent UTI or urological abnormalities were predisposing factors, while TMP-SMZ use had a protective role. These clinical relevant findings should guide clinicians in optimizing prevention strategies against UTI in kidney transplant recipients.


Guidelines for the management of patients with severe forms of dengue.
Dengue is the most common vector-borne viral infection worldwide. In Brazil, the incidence has increased with successive epidemics, and an increasing proportion of patients present with severe forms of the disease. The prognosis for these patients is directly influenced by the quality of medical care. These guidelines present the management of the severe forms of dengue, including the recognition of warning signs, the treatment for prompt re-establishment of euvolemia and the evaluation and appropriate care of potential complications, thus reducing morbidity and mortality of infected children and adults.


Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis.
The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide.


Gene expression profiles of hepatoma cell line HLE.
To investigate the global gene expression of cancer related genes in hepatoma cell line HLE using Atlas Human Cancer Array membranes with 588 well-characterized human genes related with cancer and tumor biology. Hybridization of cDNA blotting membrane was performed with (32)P-labeled cDNA probes synthesized from RNA isolated from Human hepatoma cell line HLE and non-cirrhotic normal liver which was liver transplantation donor. AtlasImage, a software specific to array, was used to analyze the result. The expression pattern of some genes identified by Atlas arrays hybridization was confirmed by reverse transcription polymerase chain reaction (RT-PCR) in 24 pairs of specimens and Northern blot of 4 pairs of specimens. The differential expression of cell cycle/growth regulator in hepatocellular carcinoma (HCC) showed a stronger tendency toward cell proliferation with more than 1.5-fold up-regulation of Cyclin C, ERK5, ERK6, E2F-3, TFDP-2 and CK4. The anti-apoptotic factors such as Akt-1 were up-regulated, whereas the promotive genes of apoptosis such as ABL2 were down-regulated. Among oncogene/tumors suppressors, SKY was down-regulated. Some genes such as Integrin beta 8, Integrin beta 7, DNA-PK, CSPCP, byglycan, Tenacin and DNA Topo were up-regulated. A number of genes, including LAR, MEK1, eps15, TDGF1, ARHGDIA were down-regulated. In general, expression of the cancer progression genes was up-regulated, while expression of anti-cancer progression genes was down-regulated. These differentially expressed genes tested with RT-PCR were in consistent with cDNA array findings. Investigation of these genes in HCC is helpful in disclosing molecular mechanism of pathogenesis and progression of HCC. For the first time few genes were discovered in HCC. Further study is required for the precise relationship between the altered genes and their correlation with the pathogenesis of HCC.


Membrane-permeable tenofovir-di- and monophosphate analogues.
The development of new antiviral agents such as nucleoside analogues or acyclic nucleotide analogues (ANPs) and prodrugs thereof is an ongoing task. We report on the synthesis of three types of lipophilic triphosphate analogues of (R)-PMPA and dialkylated diphosphate analogues of (R)-PMPA. A highly selective release of the different nucleotide analogues ((R)-PMPA-DP, (R)-PMPA-MP, and (R)-PMPA) from these compounds was achieved. All dialkylated (R)-PMPA-prodrugs proved to be very stable in PBS as well as in CEM/0 cell extracts and human plasma. In primer extension assays, both the monoalkylated and the dialkylated (R)-PMPA-DP derivatives acted as (R)-PMPA-DP as a substrate for HIV-RT. In contrast, no incorporation events were observed using human polymerase γ. The dialkylated (R)-PMPA-compounds exhibited significant anti-HIV efficacy in HIV-1/2 infected cells (CEM/0 and CEM/TK-). Remarkably, the dialkylated (R)-PMPA-MP derivative 9a showed a 326-fold improved activity as compared to (R)-PMPA in HIV-2 infected CEM/TK- cells as well as a very high SI of 14,000. We are convinced that this study may significantly contribute to advancing antiviral agents developed based on nucleotide analogues in the future.


Coupling efficiency evaluation of multimode fiber devices using GRIN rod lenses.
For an efficient analysis of the coupling characteristics of a multimode fiber device using GRIN rod lenses, it is important to consider both the third-order aberration effects of a GRIN rod lens and the actual source fiber optical power distribution. In this paper the ray tracing technique has been used with a set of point sources representing the extended source fiber core. Such a new representation is carried out according to the best agreement with measurable near-field and far-field source fiber distributions. In such a way we determined a set of results that show the relationships between coupling efficiency, lens length, and fiber lateral misalignments, as a function of the radial position of the input fiber. The results obtained pointed out, on the one hand, the poor reliability of the predictions based on a perfectly parabolic profile and, on the other, the dependence of the coupling efficiency vs lateral misalignment relationships on two different excitation distributions: uniform and steady state. The results of the experimental measurements carried out on a 0.5-pitch GRIN rod lens are consistent with the suggested model. Such an approach can be advantageously used in the design of microoptic devices based on GRIN rod lenses, such as multi/demultiplexers, directional couplers, and lens connectors.


[Perfluorocarbon emulsions and other corpuscular systems influence on neutrophil activity].
Influence of perfluorodecalin, perfluoromethilcyclohexylpiperidine, perfluorotributylamine emulsions on active oxygen form (AOF) generation by neutrophils has been studied. All investigated emulsions stabilized both proxanol 268 and egg yolk phospholipids inhibited PMA-stimulated neutrophil activity. Castor oil emulsion also inhibited the neutrophil activity. Neutrophil response for chemotactic peptide, was unchanged in the presence of all tested emulsions. We suppose that fast hydrophobic attachment of inert submicrone emulsion particles to cell surface provokes alteration of neutrophil plasma membrane function resulting in a decrease of AOF generation.


Rainmakers: why bad weather means good productivity.
People believe that weather conditions influence their everyday work life, but to date, little is known about how weather affects individual productivity. Contrary to conventional wisdom, we predict and find that bad weather increases individual productivity and that it does so by eliminating potential cognitive distractions resulting from good weather. When the weather is bad, individuals appear to focus more on their work than on alternate outdoor activities. We investigate the proposed relationship between worse weather and higher productivity through 4 studies: (a) field data on employees' productivity from a bank in Japan, (b) 2 studies from an online labor market in the United States, and (c) a laboratory experiment. Our findings suggest that worker productivity is higher on bad-, rather than good-, weather days and that cognitive distractions associated with good weather may explain the relationship. We discuss the theoretical and practical implications of our research.


Different techniques of adenoidectomy and its impact on middle ear pressure: a randomized controlled study.
The aim of this work is to compare between different techniques of adenoidectomy: endoscopic microdebrider-assisted, coblation and conventional adenoidectomy and its effect on middle ear pressure. Adenoidectomy, either alone or with tonsillectomy, is considered among the most performed procedures in pediatric otorhinolaryngology. This procedure usually related to the Eustachian tube function and middle ear status. Eustachian tube dysfunction is mainly caused by mechanical obstruction of the tubal orifice, insufficient swallowing and inflammation in the nasopharyngeal mucosa. This prospective randomized study was conducted on 90 patients with symptomatic adenoid hypertrophy confirmed by nasopharyngeal X-ray and endoscopic grading preoperatively. Patients were admitted at Otorhinolaryngology department of our institute during the period from January 2022 to January 2023. They were divided into three groups that were operated either by conventional (Group I), endoscopic microdebrider (Group II), or coblation technique (Group III). Each group was assessed through the audiometric parameters plus postoperative bleeding, and VAS results for pain score and postoperative endoscopic grading for adenoid recurrence. Mean age in group A was 9.03 years and in group B was 8.99 years and was 8.99 years in group C with insignificant differences between three groups. There is significant improvement of tympanographic results comparing all groups of the patients at 6 months postoperatively. There is significant relation between the mean VAS comparing preoperative and postoperative results. There are better results in tympanographic data at conventional adenoidectomy versus other techniques. However, there are also better postoperative results after either coblation or endoscopic microdebrider adenoidectomy over the conventional technique.


Effect of an 8.0% arginine and calcium carbonate desensitizing toothpaste on shear dentin bond strength.
The objective of this study was to determine the effect of an 8.0% arginine and calcium carbonate desensitizing toothpaste (Colgate Sensitive Pro-Relief) on shear bond strength of composites to bovine incisor dentin. Bovine incisors were sectioned and prepared into 27 dentin specimens. The experimental group had 13 specimens treated for 10 sessions of two-minute brushing with an 8.0% arginine and calcium carbonate desensitizing toothpaste, followed by a 30-second agitated water wash. The control group had 14 specimens treated with flour of pumice only. Each specimen was dried, etched with 35% phosphoric acid for 15 seconds, and washed clean. A bonding agent was applied and polymerized. A 2.38 mm diameter column of Filtek Supreme A2 was bonded to the surface and polymerized as per manufacturer's instructions. Specimens were stored in water for at least 48 hours, subjected to a shear force at a crosshead speed of 0.5 mm/minute on an Instron mechanical testing device, and force at failure was recorded. A one-sided t-test was used to evaluate significant differences among the groups as measured by mean shear strength. Mean shear force was 19.6 +/- 9.4 (SD) for the experimental group and 15.4 +/- 6.0 for the control group with p = 0.0291. No significant differences were found for bond strength to dentin treated with an 8.0% arginine and calcium carbonate desensitizing toothpaste or pumice. Dentists can still achieve optimal dentin bonding results if a patient is using Colgate Sensitive Pro-Relief to manage dentin hypersensitivity.


The Big (Genetic) Sort? A Research Note on Migration Patterns and Their Genetic Imprint in the United Kingdom.
This research note reinvestigates Abdellaoui et al.'s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non-coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non-coal mining to non-coal mining) into "stay" categories, preventing them from distinguishing migrants from nonmigrants. We reinvestigate the question of genetically selective migration by examining migration patterns between places rather than place types and find genetic selectivity in whether people migrate and where. For example, we find evidence of positive selection: people with genetic variants correlated with better education moved from non-coal mining to coal mining places with our measure of migration. Such findings were obscured in earlier work that could not distinguish nonmigrants from migrants.


Rosmarinic acid: modes of action, medicinal values and health benefits.
The supplementation of livestock rations with herbs containing bioactive components, such as rosmarinic acid (RA), have shown promising results as a natural feed additive in promoting growth, productive and reproductive performance, feed utilization, fertility, anti-oxidant status and immunologic indices. Furthermore, RA reportedly reduces the risks of various animal diseases and mitigates side effects of chemical and synthetic drugs. RA is a natural polyphenol present in several Lamiaceae herbs like Perilla frutescens, and RA is becoming an integral component of animal nutrition as it counters the effect of reactive oxygen species induced in the body as a consequence of different kinds of stressors. Studies have further ascertained the capability of RA to work as an anti-microbial, immunomodulatory, anti-diabetic, anti-allergic, anti-inflammatory, hepato- and renal-protectant agent, as well as to have beneficial effects during skin afflictions. Additionally, RA is favored in meat industries due to enhancing the quality of meat products by reportedly improving shelf-life and imparting desirable flavor. This review describes the beneficial applications and recent findings with RA, including its natural sources, modes of action and various useful applications in safeguarding livestock health as well as important aspects of human health.


Biomaterial-Based Gene Delivery: Advanced Tools for Enhanced Cartilage Regeneration.
Gene therapy has emerged as a promising and innovative approach in cartilage regeneration. Integrating biomaterials into gene therapy offers a unique opportunity to enhance gene delivery efficiency, optimize gene expression dynamics, modulate immune responses, and promote tissue regeneration. Despite the rapid progress in biomaterial-based gene delivery, there remains a deficiency of comprehensive discussions on recent advances and their specific application in cartilage regeneration. Therefore, this review aims to provide a thorough overview of various categories of biomaterials employed in gene delivery, including both viral and non-viral vectors, with discussing their distinct advantages and limitations. Furthermore, the diverse strategies employed in gene therapy are discussed and summarized, such as the utilization of growth factors, anti-inflammatory cytokines, and chondrogenic genes. Additionally, we highlights the significant challenges that hinder biomaterial-based gene delivery in cartilage regeneration, including immune response modulation, gene delivery efficiency, and the sustainability of long-term gene expression. By elucidating the functional properties of biomaterials-based gene therapy and their pivotal roles in cartilage regeneration, this review aims to enhance further advances in the design of sophisticated gene delivery systems for improved cartilage regeneration outcomes.


Effects of membrane surface charge and calcium on the gating of rat brain sodium channels in planar bilayers.
The voltage-dependent gating of single, batrachotoxin-activated Na channels from rat brain was studied in planar lipid bilayers composed of negatively charged or neutral phospholipids. The relationship between the probability of finding the Na channel in the open state and the membrane potential (Po vs. Vm) was determined in symmetrical NaCl, both in the absence of free Ca2+ and after the addition of Ca2+ to the extracellular side of the channel, the intracellular side, or both. In the absence of Ca2+, neither the midpoint (V0.5) of the Po vs. Vm relation, nor the steepness of the gating curve, was affected by the charge on the bilayer lipid. The addition of 7.5 mM Ca2+ to the external side caused a depolarizing shift in V0.5. This depolarizing shift was approximately 17 mV in neutral bilayers and approximately 25 mV in negatively charged bilayers. The addition of the same concentration of Ca2+ to only the intracellular side caused hyperpolarizing shifts in V0.5 of approximately 7 mV (neutral bilayers) and approximately 14 mV (negatively charged bilayers). The symmetrical addition of Ca2+ caused a small depolarizing shift in Po vs. Vm. We conclude that: (a) the Na channel protein possesses negatively charged groups on both its inner and outer surfaces. Charges on both surfaces affect channel gating but those on the outer surface exert a stronger influence. (b) Negative surface charges on the membrane phospholipid are close enough to the channel's gating machinery to substantially affect its operation. Charges on the inner and outer surfaces of the membrane lipid affect gating symmetrically. (c) Effects on steady-state Na channel activation are consistent with a simple superposition of contributions to the local electrostatic potential from charges on the channel protein and the membrane lipid.


With Bare Feet in the Soil: Podoconiosis, a Neglected Cause of Tropical Lymphoedema.
Podoconiosis is a form of lymphoedema that occurs in tropical highland areas in genetically susceptible individuals who are exposed to irritant volcanic soils. The disease is preventable through consistent use of footwear and attention to foot hygiene; however, in endemic areas there is a strong barefoot tradition, and many cannot afford shoes. Patients with podoconiosis face significant physical disability, psychological comorbidity, reduced quality of life and experience frequent episodes of systemic illness due to acute dermatolymphangioadenitis. This review provides an overview of this important and neglected tropical skin disease and summarizes the latest research findings.


miR-190a-5p participates in the regulation of hypoxia-induced pulmonary hypertension by targeting KLF15 and can serve as a biomarker of diagnosis and prognosis in chronic obstructive pulmonary disease complicated with pulmonary hypertension.
miR-190a-5p expression alters dynamically in response to hypoxia. However, the role of miR-190a-5p expression in hypoxia-induced pulmonary hypertension (PH) remains unclear. We sought to correlate the miR-190a-5p expression levels with the severity, diagnosis, and prognosis of PH in relation to chronic obstructive pulmonary disease (COPD-PH). Additionally, we evaluated the effect of miR-190a-5p through in vitro experiments on human pulmonary endothelial cells (HPECs) that were exposed to hypoxia and in vivo experiments using an animal model of hypoxia-induced PH. Circulating miR-190a-5p levels were measured from 73 patients with PH and 32 healthy controls through quantitative real-time PCR. The levels of miR-190a-5p and the expression of Krüppel-like factor 15 (KLF15) were analyzed in HPECs that were exposed to hypoxia, and the effects of antagomir-190a-5p in mice with chronic hypoxia-induced PH were tested. Target gene analysis was performed by Western blot and luciferase assay. The miR-190a-5p level was significantly higher in patients with COPD-PH than in the healthy controls. Higher miR-190a-5p levels were associated with a greater severity of COPD-PH. In vitro experiments on HPECs showed that exposure to hypoxia increased the miR-190a-5p levels significantly. KLF15 was validated as a target of miR-190a-5p. Transfection with miR-190a-5p mimicked inhibition of KLF15 expression in HPECs. In the mouse model of PH, antagomir-190a-5p reduced right ventricular systolic pressure and enhanced the KLF15 expression levels in lung tissue. miR-190a-5p regulates hypoxia-induced PH by targeting KLF15. The circulating levels of miR-190a-5p correlate with the severity of COPD-PH, thereby confirming the diagnostic and prognostic value of this parameter in COPD-PH.


Soybean oligosaccharides. Potential as new ingredients in functional food.
The effects of maturity degree and culture type on oligosaccharide content were studied in soybean seed, a rich source of non-digestible galactooligosaccharides (GOS). Therefore, two commercial cultivars of yellow soybeans (ripe seeds) and two of green soybeans (unripe seeds) were chosen. One yellow and one green soybean seed were from intensive culture, while one yellow and one green soybean seed were biologically grown. Low molecular weight carbohydrates (LMWC) in soybean seeds were extracted with 85% ethanol and determined spectrophotometrically and by high performance liquid chromatography. LWC in soybean seeds were mainly: stachyose, raffinose and sucrose. Oligosaccharide content was not affected significantly, either by biological or intensive culture technique. On the contrary, significant differences in GOS content were found depending on ripeness degree of soybean seeds. Ripe yellow soybean seeds showed a higher oligosaccharide content (1.84-1.95%), than unripe green seeds (1.43-1.61%). Other LMWC content was also affected by ripeness degree, thus making that the relative percentage of GOS was higher in immature (47-53%) than in matured soybean seeds (21-34%). Moreover, in order to purify soybean GOS, biologically grown yellow soybean seeds with a higher GOS content were selected and a previously reported method was followed. Although the GOS containing fraction was enriched, the yield obtained was low and an effective purification was not achieved. According to these results, yellow soybean seeds seem to be a good source of GOS but, in order to improve their purification, simple methods must be further developed and evaluated.


Transcriptome profiling of granulosa and theca cells during dominant follicle development in the horse.
Several aspects of equine ovarian physiology are unique among domestic species. Moreover, follicular growth patterns are very similar between horses and humans. This study aimed to characterize, for the first time, global gene expression profiles associated with growth and preovulatory (PO) maturation of equine dominant follicles. Granulosa cells (GCs) and theca interna cells (TCs) were harvested from follicles (n = 5) at different stages of an ovulatory wave in mares corresponding to early dominance (ED; diameter ≥22 mm), late dominance (LD; ≥33 mm) and PO stage (34 h after administration of crude equine gonadotropins at LD stage), and separately analyzed on a horse gene expression microarray, followed by validation using quantitative PCR and immunoblotting/immunohistochemistry. Numbers of differentially expressed transcripts (DETs; ≥2-fold; P < 0.05) during the ED-LD and LD-PO transitions were 546 and 2419 in GCs and 5 and 582 in TCs. The most prominent change in GCs was the down-regulation of transcripts associated with cell division during both ED-LD and LD-PO. In addition, DET sets during LD-PO in GCs were enriched for genes involved in cell communication/adhesion, antioxidation/detoxification, immunity/inflammation, and cholesterol biosynthesis. In contrast, the largest change in TCs during the LD-PO transition was an up-regulation of genes involved in immune activation, with other DET sets mapping to GPCR/cAMP signaling, lipid/amino acid metabolism, and cell proliferation/survival and differentiation. In conclusion, distinct expression profiles were identified between growing and PO follicles and, particularly, between GCs and TCs within each stage. Several DETs were identified that have not been associated with follicle development in other species.


Bicarbonate transport by isolated perfused rat collecting ducts.
Previously, bicarbonate transport was measured in isolated perfused rabbit cortical collecting ducts (CCD) and outer medullary collecting ducts (OMCD). Rabbit CCD either absorbed or secreted bicarbonate in vitro, depending on whether the animals were treated with NH4Cl or NaHCO3, but the OMCD absorbed bicarbonate regardless of the treatment. The general significance of these findings (particularly the bicarbonate secretion) was questioned because rabbits are herbivores that normally excrete alkaline urine. Therefore, we have now studied rats, an omnivorous species, that normally excrete acid urine. The overall pattern of bicarbonate transport in rats was similar to that previously found in rabbits. CCD from rats given NaHCO3 initially secreted bicarbonate, but those from rats given NH4Cl absorbed bicarbonate. Rat OMCD all absorbed bicarbonate, regardless of the treatment. The significant differences between the results with rats and rabbits were 1) a marked shift in bicarbonate transport in control and bicarbonate-loaded rat (but not rabbit) CCD with time of perfusion in vitro from secretion toward absorption; this implies an additional regulatory mechanism in rats; and 2) rat OMCDs absorbing bicarbonate more than three times faster than rabbit OMCD. These results provide additional evidence that conditioned changes in cortical collecting duct bicarbonate transport, now observed in two different species, play a significant role in the control of net acid excretion.


Anaerobically expressed Escherichia coli genes identified by operon fusion techniques.
Genes that are expressed under anaerobic conditions were identified by operon fusion techniques with a hybrid bacteriophage of lambda and Mu, lambda placMu53, which creates transcriptional fusions to lacZY. Cells were screened for anaerobic expression on XG medium. Nine strains were selected, and the insertion point of the hybrid phage in each strain was mapped on the Escherichia coli chromosome linkage map. The anaerobic and aerobic expression levels of these genes were measured by beta-galactosidase assays in different medium conditions and in the presence of three regulatory mutations (fnr, narL, and rpoN). The anaerobically expressed genes (aeg) located at minute 99 (aeg-99) and 75 (aeg-75) appeared to be partially regulated by fnr, and aeg-93 is tightly regulated by fnr. aeg-60 requires a functional rpoN gene for its anaerobic expression. aeg-46.5 is repressed by narL. aeg-65A and aeg-65C are partially controlled by fnr but only in media containing nitrate or fumarate. aeg-47.5 and aeg-48.5 were found to be anaerobically induced only in rich media. The effects of a narL mutation on aeg-46.5 expression were observed in all medium conditions regardless of the presence or absence of nitrate. This suggests that narL has a regulatory function in the absence of exogenously added nitrate.


Metaplastic breast carcinoma: a heterogeneous disease.
The aim of this study is to evaluate clinicopathologic characteristics and the multi-disciplinary treatment results of metaplastic breast cancer (MBC) patients treated in a single institute. Seventeen female patients with MBC treated in our department between June 2000 and January 2012 were identified and retrospectively evaluated. The median age at diagnosis was 46 years (range, 26-66 years). The median tumor size at diagnosis was 3.5 cm (range 1.5-12 cm). Six (35%) patients underwent breast conservation surgery and 11 (65%) mastectomy. Axillary lymph node metastasis was found in 6 (35%) patients. Twelve (71%) had triple negative tumors. Postoperative RT and systemic adjuvant treatment was given to all patients accordingly to stage and biological characteristics. Median follow-up time was 27 months (range, 12-151 months). At the time of this analysis, 14 (82%) patients were alive with no evidence of disease, and 1 (6%) was alive with disease. The 3-year OS was 91% and 5-year 80%, and DFS rates were 76% and 76%, respectively. Despite the young age of our patients with mostly high grade tumors, larger tumor size and higher rates of lymph node metastasis, the survival outcomes in our study are favorable in comparison with previously reported series.