Chronic kidney disease in type 2 diabetes patients in France: prevalence, influence of glycaemic control and implications for the pharmacological management of diabetes.
Type 2 diabetes mellitus (T2DM) is often associated with chronic kidney disease. For this reason, this article reviews the relationship between treatment of T2DM and renal disease. The review presents the recent French data on the management of diabetes in patients with renal impairment, and discusses the implications of renal disease for the treatment of such patients. Prescribing data are presented for various antidiabetic treatments, and the use of the more commonly prescribed medications is discussed with reference to T2DM patients with renal disease. In France, it is estimated that 4-5% of the general population has T2DM and that almost 40% of patients with end-stage renal failure have diabetes. Diabetes and renal disease are both risk factors for cardiovascular morbidity and mortality. Glycaemic control is pivotal in T2DM patients for minimizing the risk of vascular complications and hypoglycaemic episodes, particularly in patients with renal disease who also have a higher risk of hypoglycaemia. Whereas poorly controlled glycaemia increases the risk of renal disease and its progression, the risk is diminished in patients treated intensively for diabetes and in those who achieve stable glycaemic control. Intensive multitargeted treatment can also help to decrease cardiovascular morbidity and mortality, especially if started early in patients who have not yet developed macrovascular complications. In recent years, considerable improvement has been observed in France regarding the follow-up of diabetic patients. Less extensive, but nonetheless significant, improvement has also been observed in glycaemic control. However, even though treatment decisions generally take renal function into account, some at-risk treatments are often still being used in patients with renal insufficiency.


Anterior interosseous nerve syndrome following supracondylar lesions of the median nerve: clinical findings and electrophysiological investigations.
Lesions at the volar aspect of the forearm may lead to isolated paralysis of the anterior interosseous nerve, which is a purely motor branch of the median nerve. The same syndrome may result from circumscribed damage at the level of the upper arm. Two patients are reported with the typical anterior interosseous nerve syndrome following supracondylar lesions of the median nerve and the literature is reviewed. In most cases this syndrome is a complication of supracondylar fractures of the humerus in children. A simple clinical test for the diagnosis, the pinch test, and the typical electromyographic findings are described. Whereas electroneurography has been considered to provide little help in diagnosis, a significantly lower nerve conduction velocity was found in the median nerve between the medial intermuscular spatium and the cubital fossa compared to the normal arm, and a prolonged response latency of the pronator quadratus of the injured arm following stimulation of the median nerve in the intermuscular medial spatium and the cubital fossa.


OMIP 071: A 31-Parameter Flow Cytometry Panel for In-Depth Immunophenotyping of Human T-Cell Subsets Using Surface Markers.
Dissecting the functional diversity of T cells is critical in elucidating mechanisms and in developing therapies for various diseases. Here, we designed a 31-parameter (29-color) panel to enable the characterization of T-cell subsets and immunophenotyping of the human peripheral blood and lymph nodes using cell surface staining. In addition to adaptive T-cell markers, TCR Vα24-Jα18, TCR γδ, TCR Vɑ7.2, and CD161 were included to identify iNKT, γδ T, and MAIT cells, respectively, which are innate-like T cells. C-X-C chemokine receptors (CXCR3, CXCR4, CXCR5, CXCR6) and C-C motif chemokine receptors (CCR4, CCR6, CCR7) were included to enable the identification of Th cell subsets (Th1, Th2, Th17), Tfh cell subsets (Tfh1, Tfh2, Tfh17), and Th cells with specific homing capacities. Furthermore, in this panel, we also used markers for assessing cell differentiation (CD45RO, CD7), activation (CD57, CD95, HLA-DR) and the expression of some cosignaling molecules (PD-1, NKG2D, CD28). Particularly, CD69 and CD103 were included for the further analysis of tissue resident memory T (Trm) cells. This panel would enable the in-depth immunophenotyping of human T-cell subsets, and may be applied in the monitoring, prognosis, and mechanistic studies of various immune-related diseases.


Comparison of the effects of NADH- and NADPH-perturbation stresses on the growth of Escherichia coli.
To better understand how the reducing power of either NADH or NADPH affects cell growth, Escherichia coli strains expressing either NADH-dependent or NADPH-dependent azoreductase (EC 188.8.131.52), which mediates the reduction of an azo dye, were cultured in glucose minimal medium in the presence of 200 muM methyl red. Growth rates in NADH-perturbed, NADPH-perturbed, and control cells were 0.05, 0.12, and 0.13 h(-1), respectively. In addition, glucose consumption in NADH-perturbed cells was 10.8 g glucose/g cell, while that of control and NADPH-perturbed cells was very similar (3.6 vs 3.8 g glucose/g cell) during the perturbation phase. Therefore, NADH perturbation had a larger effect than NADPH on cellular growth.


Primary percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with giant coronary aneurysm due to Kawasaki disease.
We report a case of acute myocardial infarction in an 8-year-old boy with a history of Kawasaki disease and giant coronary aneurysms in the right and left coronary arteries. We performed coronary angiography and percutaneous coronary intervention 4 hours after the onset of symptoms. This case suggests that primary percutaneous coronary intervention might be safe and effective in the long-term treatment of acute myocardial infarction due to coronary sequelae of Kawasaki.


Effects of 5-aminolevulinic acid-mediated photodynamic therapy on antibiotic-resistant staphylococcal biofilm: an in vitro study.
Treatments of infections are not always successful because of multi-antibiotic-resistant organisms. It is therefore particularly urgent to provide more effective anti-infective strategy against these organisms. 5-Aminolevulinic acid (ALA), with the chemical structure C5H9NO3, is the only photodynamic therapy agent that is a biochemical precursor of a photosensitizer (protoporphyrin IX [PpIX]), which is naturally produced by the body. 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has been shown to have a strong effect on the treatment of localized cancerous and precancerous lesions, and further study demonstrated its efficacy for gram-positive and gram-negative bacteria. However, its effect on biofilm formed by antibiotic-resistant strains has not been reported. In this study, we evaluated the effectiveness of ALA-PDT on biofilms formed by methicillin-resistant Staphylococcus aureus (ATCC 43300) and methicillin-resistant S epidermidis (MRSE 287). The strains were cultured with 40 mM of ALA in 24-well microtiter plates containing coverslips at 37°C for 24 h in the dark. PpIX fluorescence in biofilms formed by the two strains was observed by confocal laser scanning microscopy (CLSM). ALA-treated biofilms were irradiated at different doses (0, 100, 200, and 300 J/cm(2)) using a semiconductor laser. Biofilm exposed only to Tryptone Soy Broth or irradiation (300 J/cm(2)) was investigated. Viability determination, CLSM, and scanning electron microscopy were used to investigate the photodynamic inactivation of ALA-PDT. ALA was absorbed and converted to PpIX by both methicillin-resistant S aureus and methicillin-resistant S epidermidis. No cell inactivation was detectable in biofilms of either strain incubated with ALA without exposure to light, incubated with Tryptone Soy Broth only, or irradiated with red light only. However, a significant number of cells within biofilms were inactivated during irradiation with different doses of red light in the presence of 40 mM of ALA in a dose-dependent manner. The drastic reduction in cell survival within biofilms and the disruption of biofilms were confirmed by CLSM and scanning electron microscopy. ALA-PDT has the potential to eliminate the biofilm of Staphylococcus, especially antibiotic-resistant strains, effectively. It will be suitable for the treatment of superficial local infections such as surface wounds, burns, oral and dental infections, dermatologic infections such as acne and rosacea, and soft tissue and bone infections with bone exposure.


Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing.
Community-acquired bacterial meningitis causes substantial morbidity and mortality in adults. To create and test a prognostic model for persons with community-acquired bacterial meningitis and to determine whether antibiotic timing influences clinical outcome. Retrospective cohort study; patients were divided into derivation and validation samples. Four hospitals in Connecticut. 269 persons who, between 1970 and 1995, had community-acquired bacterial meningitis microbiologically proven by a lumbar puncture done within 24 hours of presentation in the emergency department. Baseline clinical and laboratory features and times of arrival in the emergency department, performance of lumbar puncture, and administration of antibiotics. The target end point was the development of an adverse clinical outcome (death or neurologic deficit at discharge). For the total group, the hospital mortality rate was 27%. Fifty-six of 269 patients (21 %) developed a neurologic deficit, and in 9% the neurologic deficit persisted at discharge. Three baseline clinical features (hypotension, altered mental status, and seizures) were independently associated with adverse clinical outcome and were used to create a prognostic model from the derivation sample. The prediction accuracy of the model was determined by using the concordance index (c-index). For both the derivation sample (c-index, 0.73 [95% CI, 0.65 to 0.81]) and the validation sample (c-index, 0.81 [CI, 0.71 to 0.92]), the model predicted adverse clinical outcome significantly better than chance. For the total group, the model stratified patients into three prognostic stages: low risk for adverse clinical outcome (9%; stage I), intermediate risk (33%; stage II), and high risk (56%; stage III) (P=0.001). Adverse clinical outcome was more common for patients in whom the prognostic stage advanced from low risk (P=0.008) or intermediate risk (P=0.003) at arrival in the emergency department to high risk before administration of antibiotics. In persons with community-acquired bacterial meningitis, three baseline clinical features of disease severity predicted adverse clinical outcome and stratified patients into three stages of prognostic severity. Delay in therapy after arrival in the emergency department was associated with adverse clinical outcome when the patient's condition advanced to the highest stage of prognostic severity before the initial antibiotic dose was given.


Sirtuin 1 evaluation with a novel immunoassay approach based on TiO2-Au label and hyperbranched polymer hybrid.
Accurate and highly sensitive evaluation of the sirtuin 1 (SirT1) level is becoming increasingly important for understanding the contribution of SirT1 in metabolism pathways. Here, a novel electrochemical immunoassay of SirT1 based on crosslinked hyperbranched azo-polymer decorated with gold colloids (Au-HAP) as sensing platform and titanium dioxide (TiO2)-Au nanocomposites to immobilize secondary antibody-horseradish peroxidase (Ab2-HRP) as electrochemical labels has been designed. Greatly enhanced sensitivity was achieved by exploiting the excellent conductivity of Au nanoparticle, the amplification effect of Au-HAP and TiO2-Au, and the favorable catalytic ability of HRP. The nanocomposites of Au-HAP and TiO2-Au could attach numerous capture antibodies on the surface for significant immune recognition efficiency. Meanwhile, the TiO2-Au-labeled Ab2-HRP using an HRP-thionine-H2O2 (hydrogen peroxide) detection system could further induce signal readout. Under optimal conditions, the signal intensity was linearly related to the concentration of SirT1 in the range of 1-500 ng ml(-1), and the limit of detection was 0.28 ng ml(-1). The developed biosensor exhibits attractive performance for the analysis of SirT1, with rapid response, high sensitivity, and high accuracy, and could become a promising technique for protein detection.


The impact of radiotherapy on quality of life for cancer patients: a longitudinal study.
The aim of this study was to assess for changes in quality of life (QOL) among cancer patients who undergo radiotherapy (RT) and to identify factors that influence QOL in this group. Three hundred sixty-seven cancer patients who received curative RT were investigated using the EORTC QLQ-C30 questionnaire at the start of RT, end of RT, and 1 and 6 months post-RT. The patients were 49 % women, 51 % men, and median age at diagnosis was 57 years (range, 16-86 years). Compared to pre-RT, at the end of RT, the global health status score (p < 0.001), nausea/vomiting (p < 0.001), and apetite loss scores (p < 0.001) were significantly poorer. Compared to the end of RT, at 1 and 6 months post-RT, global health status, all functional, and all symptom scores were significantly improved (p < 0.001). Patient sex influenced scores for pain (p = 0.036), appetite loss (p = 0.027), and financial difficulty (p = 0.003). Performance status influenced scores for global health status (p = 0.006), physical functioning (p < 0.001), cognitive functioning (p = 0.001), and role functioning (p = 0.021). Comorbidity influenced fatigue score (p < 0.001). Cancer stage influenced scores for physical functioning (p = 0.001), role functioning (p = 0.010), and fatigue (p < 0.001). Treatment modality (chemoRT vs. RT alone) influenced scores for physical functioning (p = 0.016), fatigue (p < 0.001), nausea/vomiting (p = 0.009), and appetite loss (p < 0.001); and RT field influenced scores for nausea/vomiting (p = 0.001), appetite loss (p = 0.003), and diarrhea (p = 0.037). Radiotherapy dose functioning (p < 0.001), cognitive functioning (p < 0.001), social functioning (p < 0.001), fatigue (p < 0.001), and pain (<60 vs ≥60 Gy) had an effect on scores for physical functioning (p < 0.001), role functioning (p < 0.001), emotional (p < 0.001), insomnia (p < 0.001), constipation (p < 0.001). While RT negatively affects cancer patients' QOL, restoration tends to be rapid and patients report significant improvement by 1 month post-RT. Various patient- and disease-specific factors and RT modality affect QOL in this patient group. We advocate measuring cancer patients' QOL regularly as part of routine patient management.


Ghana's National Health Insurance Scheme: a national level investigation of members' perceptions of service provision.
Ghana's National Health Insurance Scheme (NHIS), established into law in 2003 and implemented in 2005 as a 'pro-poor' method of health financing, has made great progress in enrolling members of the general population. While many studies have focused on predictors of enrolment this study offers a novel analysis of NHIS members' perceptions of service provision at the national level. Using data from the 2008 Ghana Demographic Health Survey we analyzed the perceptions of service provision as indicated by members enrolled in the NHIS at the time of the survey (n = 3468; m = 1422; f = 2046). Ordinal Logistic Regression was applied to examine the relationship between perceptions of service provision and theoretically relevant socioeconomic and demographic variables. Results demonstrate that wealth, gender and ethnicity all play a role in influencing members' perceptions of NHIS service provision, distinctive from its influence on enrolment. Notably, although wealth predicted enrolment in other studies, our study found that compared to the poorest men and uneducated women, wealthy men and educated women were less likely to perceive their service provision as better/same (more likely to report it was worse). Wealth was not an important factor for women, suggesting that household gender dynamics supersede household wealth status in influencing perceptions. As well, when compared to Akan women, women from all other ethnic groups were about half as likely to perceive the service provision to be better/same. Findings of this study suggest there is an important difference between originally enrolling in the NHIS because one believes it is potentially beneficial, and using the NHIS and perceiving it to be of benefit. We conclude that understanding the nature of this relationship is essential for Ghana's NHIS to ensure its longevity and meet its pro-poor mandate. As national health insurance systems are a relatively new phenomenon in sub-Saharan Africa little is known about their long term viability; understanding user perceptions of service provision is an important piece of that puzzle.


Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell.
Efaroxan induces membrane depolarization by interaction with the pore forming subunit of the ATP-sensitive potassium channel, Kir6.2. However, this effect is not responsible for its full secretory activity. In this study we have used an anti-idiotypic approach to generate antibodies that recognize additional proteins that may be regulated by efaroxan in pancreatic beta-cells. Using these antisera in an expression cloning strategy we have identified a monomeric GTP-binding protein, Rhes, as a potential target for regulation by imidazoline ligands. Rhes is shown to be expressed in beta-cells and its expression is regulated by efaroxan under conditions when a structurally related molecule, KU14R, is ineffective. The results reveal that beta-cells express Rhes and suggest that changes in the expression of this molecule may regulate the sensitivity of beta-cells to imidazoline secretagogues.


Correlation of BRAF Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials.
Tumor-derived circulating cell-free DNA (cfDNA) is a potential alternative source from which to derive tumor mutation status. cfDNA data from four clinical studies of the BRAF inhibitor (BRAFi) dabrafenib or the MEK inhibitor (MEKi) trametinib were analyzed to determine the association between BRAF mutation status in cfDNA and tumor tissue, and the association of BRAF cfDNA mutation status with baseline factors and clinical outcome. Patients with BRAF V600 mutation-positive melanoma were enrolled in each study after central confirmation of BRAF status in tumor using a PCR-based assay. BRAF mutation status in cfDNA from patient plasma collected at baseline, 732 of 836 (88%) enrolled patients in total, was determined. BRAF mutations were detectable in cfDNA in 76% and 81% of patients with BRAF V600E/V600K-positive tumors, respectively. Patients negative for BRAF mutations in cfDNA had longer progression-free survival (PFS) and overall survival in each of the four studies, compared with patients with detectable cfDNA BRAF mutations. The presence of BRAF-mutant cfDNA was an independent prognostic factor for PFS after multivariate adjustment for baseline factors in three of four studies. Patients negative for BRAF mutation-positive cfDNA in plasma had higher response rates to dabrafenib and trametinib. BRAF mutations in cfDNA are detectable in >75% of late-stage melanoma patients with BRAF mutation-positive tumors. The lack of circulating, BRAF mutation-positive cfDNA is clinically significant for metastatic melanoma patients, and may be a prognostic marker for better disease outcome.


TCF/Lef regulates the Gsx ParaHox gene in central nervous system development in chordates.
The ParaHox genes play an integral role in the anterior-posterior (A-P) patterning of the nervous system and gut of most animals. The ParaHox cluster is an ideal system in which to study the evolution and regulation of developmental genes and gene clusters, as it displays similar regulatory phenomena to its sister cluster, the Hox cluster, but offers a much simpler system with only three genes. Using Ciona intestinalis transgenics, we isolated a regulatory element upstream of Branchiostoma floridae Gsx that drives expression within the central nervous system of Ciona embryos. The minimal amphioxus enhancer region required to drive CNS expression has been identified, along with surrounding sequence that increases the efficiency of reporter expression throughout the Ciona CNS. TCF/Lef binding sites were identified and mutagenized and found to be required to drive the CNS expression. Also, individual contributions of TCF/Lef sites varied across the regulatory region, revealing a partial division of function across the Bf-Gsx-Up regulatory element. Finally, when all TCF/Lef binding sites are mutated CNS expression is not only abolished, but a latent repressive function is also unmasked. We have identified a B. floridae Gsx upstream regulatory element that drives CNS expression within transgenic Ciona intestinalis, and have shown that this CNS expression is dependent upon TCF/Lef binding sites. We examine the evolutionary and developmental implications of these results, and discuss the possibility of TCF/Lef not only as a regulator of chordate Gsx, but as a deeply conserved regulatory factor controlling all three ParaHox genes across the Metazoa.


In vitro, release of cholecystokinin from hypothalamus and frontal cortex of Sprague-Dawley, Zucker lean (Fa/-) and obese (fa/fa) rats.
Cholecystokinin (CCK) has been suggested as a putative satiety factor, whose site of action is in the hypothalamus. The genetically obese (fa/fa) Zucker rat has been proposed as a model of human obesity. Though hypothalamic tissue levels of CCK did not vary between the fa/fa rat and age-matched lean littermates (25.5 +/- 5.7 vs. 27.6 +/- 5.2 pmoles/g tissue) we sought to determine if the releasability of hypothalamic and cortical CCK was the same in lean and obese rats. The in vitro superfusion paradigm was used to study the release of CCK and substance P (sP) from hypothalamus, and CCK and vasoactive intestinal polypeptide (VIP) from frontal cortex. The potassium stimulated release of CCK from obese rat hypothalamic tissue was significantly higher than from lean rat hypothalamus (3.62 +/- 0.3 vs. 1.91 +/- 0.3 fmole equivalents CCK-8/mg tissue/10 min). Similarly, sP release was exaggerated in obese rats in a parallel fashion (5.56 +/- 0.44 vs. 2.761 +/- 0.46 fmoles/mg tissue/10 min). However, the potassium stimulated release of CCK and VIP from cortical tissue was the same in all three groups of rats. The obese Zucker rat thus, may have an anomalous release of CCK and sP from the hypothalamus, but not from the frontal cortex, an area not presumably associated with satiety.


The pulmonary physician in critical care * 2: oxygen delivery and consumption in the critically ill.
Early detection and correction of tissue hypoxia is essential if progressive organ dysfunction and death are to be avoided. However, hypoxia in individual tissues or organs caused by disordered regional distribution of oxygen delivery or disruption of the processes of cellular oxygen uptake and utilisation cannot be identified from global measurements. Regional oxygen transport and cellular utilisation have an important role in maintaining tissue function. When tissue hypoxia is recognised, treatment must be aimed at the primary cause. Supplemental oxygen may be life saving in some situations but cannot correct inadequate oxygen delivery caused by a low cardiac output or impaired ventilation. Recent innovations include artificial oxygen carrying proteins and "haemoglobin" molecules designed to improve tissue blood flow by reducing viscosity. Regulating cell metabolism using different substrates or drugs has so far been poorly explored but is an exciting area for further research. A minimum level of global oxygen delivery and perfusion pressure must be maintained in the critically ill patient with established "shock", but advances in the understanding and control of regional distribution and other "downstream" factors in the oxygen cascade are needed to improve outcome in these patients.


Bibliometric evaluation of orthopaedics and traumatology publications from France: 20-year trends (1998-2017) and international positioning.
Little is known about the scientific publication output for individual countries and medical specialties. The contribution of French authors to the currently expanding volume of publications on orthopaedics and traumatology (OT) is unclear. Orthopaedics & Traumatology: Surgery & Research (OTSR) is an English-language version of a preexisting French journal that was launched in 2009 to increase the dissemination of research done in France. The objective of this study was to use Web of Science (WoS) data from 1998 to 2017 to determine (i) the contribution of OT publications to the total worldwide volume of scientific publications, (ii) the contribution of OT publications from France to the total worldwide volume of OT publications, and (iii) changes over time in the proportion of OT publications from France with special attention to potential effects of the creation of OTSR. The proportion of OT publications from France increased after 2010-2012, indicating a positive effect of OTSR. WoS data were used to identify original studies and review articles written by at least one French author, published between 1998 and 2017, and dealing with OT (defined as orthopaedics and/or traumatology in adult and/or paediatric patients). The worldwide volumes of publications in OT and other specialties were compared. Within worldwide OT publications, the proportion from France was determined. Indicators of impact were evaluated during successive 5-year periods. Finally, the position of OT in worldwide research was assessed and OT journals were analysed. Among worldwide scientific medical publications, the proportion dealing with OT increased year on year from 1.93% in 1998 to 2.65% in 2017. Among annual publications from France, the proportion dealing with OT rose similarly, from 1.32% to 2.40%. Over the 20-year study period, France moved from the sixth to the ninth position, chiefly due to a large increase in publications from Asia. However, France remained in third position among European countries and increased its OT production 3-fold between 1998 and 2017. The proportion of OT articles from France that ranked among the top 1% most cited articles increased by 65% from 2008-2012 (20 articles) to 2013-2017 (33 articles), and the proportion in the top 10% increased by 31.8% (211 in 2008-2012 and 278 in 2013-2017). This rate of progression was faster than in any of the other western countries. Between 1998-2011 and 2012-2017, the contribution of French OT to publication output showed a 1.56-fold greater increase than did the contribution of OT to the worldwide volume of scientific medical publications. OT publications from France have kept pace with the steady increase seen worldwide over the last 20years. Although the US and UK remain in the lead, and despite the considerable growth in the output of Asian countries, France occupies a prominent position on the international OT scene. The creation of OTSR has elevated the international profile of French OT centres. IV, retrospective study with no control group.


Cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver. A fraction of adenosine bound is converted to adenine.
1. Adenosine bound to the cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver was partly converted to a product which was identified as adenine in four chromatographic systems. Ribose was formed in equivalent amounts. 2. The time course of the reaction was characterized by an initial burst phase lasting for less than one second followed by a slow progressive phase. The reaction was partly reversed by prolonged incubation, slow denaturation of the protein, dilution of the incubation mixture and removal of adenosine by converting it to inosine by the enzyme adenosine deaminase. 3. Both the ATP-treated (Ueland, P.M. and Døskeland, S.O. (1978) Arch. Biochem. Biophys. 185, 195--203) and the non-treated protein were subjected to polyacrylamide gel electrophoresis at pH 8.8. The adenosine-adenine, the cyclic AMP binding activities and the conversion activity comigrated with the main protein band, indicating that these properties reside on the same protein molecule. 4. Adenine generated by hydrolysis of adenosine was mainly bound to the protein as judged by nearly complete reversion of the conversion upon dilution in the presence of excess unlabelled adenine and by Sephadex G-25 chromatography. 5. The conversion of adenosine to inosine by the enzyme adenosine deaminase was decreased in the presence of the binding protein. 6. Adenine formation could also be demonstrated under condition of enzymic formation of S-adenosylhomocysteine, i.e. in the presence of hymocysteine.


Precipitated abstinence in the diazepam-dependent rat.
Physical dependence was produced in the rat by exposure to continuous release of diazepam from silastic capsule implants (recrystallized diazepam) or by dosing through a gastric fistula. The precipitated abstinence syndrome induced by the IV infusion of flumazenil was characterized by clonic and tonic-clonic seizures, retropulsion, digging, rearing, head, limb and body tremors, twitches and jerks of the body, and ear twitches. This abstinence syndrome differed both qualitatively and quantitatively from the milder syndrome induced in previous experiments by the intragastric administration of flumazenil in the diazepam-dependent gastric fistula rat. Capsule-implanted rats had free plasma and extraneuronal brain levels of diazepam, oxazepam, and nordiazepam in the 10(-3) and 10(-4) mg/ml range, and their brain: plasma ratios were not significantly different from 1. The diazepam capsules had a sustained release of over 28 days. These studies show that the capsule implantation technique is an efficacious way of maintaining plasma levels of diazepam and its metabolites, and producing a high level of physical dependence in the rat.


A novel method to investigate the heterocliticity of antibodies.
Monoclonal and anti-dinitrophenyl and anti-trinitrophenyl IgE antibodies were used to measure heterocliticity using competitive inhibition assays with homologous and heterologous haptens. The antibodies or antibody-containing ascites fluids were diluted to give 50% of the maximum binding to wells of antigen-coated microtiter plates. The % inhibition of binding of the antibody to the antigen by various concentrations of homologous and heterologous haptens at a standard dilution of antibody can then be compared. The advantages of this method of determination of heterocliticity are that it is fast, simple, quantitative and does not need radiolabeled reagents.


Efferents to the labyrinth of the river lamprey (Lampetra fluviatilis) as revealed with retrograde tracing techniques.
The cells of origin of centrifugal fibres to the labyrinth were examined in a jawless vertebrate, the lamprey, with several retrograde tracers (horseradish peroxidase (HRP), fluorescein isothiocyanate (FITC) and rhodamine coupled dextran-amines (FDA and RDA), and cobalt-lysine) that had been applied to the eighth nerve. With all 3 techniques, up to 20 cells were consistently labelled ipsilaterally, adjacent to the Mauthner cell; none were labelled on the contralateral side. The axons of the efferent cells emanate either from lateral dendrites or the perikaryon and course laterally towards the ipsilateral eighth nerve root. The dendrites ramify widely in the basal plate and may thus receive diverse inputs. The same tracers were applied to the lateral-line nerve and afferent fibres were labelled but no efferent cells, thus confirming previous reports. These data suggest that lampreys have an efferent innervation to the labyrinth but not to the lateral line.


Risks involved in selective decontamination in immunocompromised patients.
Selective oral and systemic decontamination are widely discussed when it comes to the prophylaxis of bacterial and fungal infections in immunocompromised patients. The number of such patients is clearly rising due to the aggressiveness of modern medicine. Host defence is based on a variety of factors including the barrier function of mucosal surfaces as well as the phagocytic system provided by the blood. It seems helpful to distinguish between three different stages of immunodeficiency: "Minor immunodeficiency", "immunodeficiency" (in a stricter sense), "major immunodeficiency". When it comes to the choice of measures to be taken to protect the host, it is not only needed to consider the microbes already present but also the present state of defence mechanisms. When invasive fungal infections in particular have to be prevented, several drugs have to be discussed. As conventional antifungals have not met all expectations there is clear need for new drugs such as itraconazole.


A developmental study of proverb comprehension.
Growth in proverb comprehension was hypothesized to result from the gradual emergence of cognitive abilities reflected in a sequence of increasingly complex abilities: story matching, transfer of relations, desymbolization, proverb matching, and paraphrase. Items for these abilities for each of 10 proverbs of two structural types were administered in three test sessions to 438 students in grades three to seven. An analogy subtest was used to measure general intelligence. ANOVA yielded significant main effects for grade, tasks, and proverbs (all p's less than .01). A significant task x proverb interaction (p less than .01) revealed the difficulty of precise control over the language of the items. Proverb structure had no measurable impact on difficulty. Analogy score was a significant factor in performance (p less than .01) but not as potent as age (p less than .01). The sequential order of abilities received only weak confirmation, though tasks did correlate among themselves with medium strength (r's = .50-.70). Individual interviews added a qualitative dimension to the findings. The suitability of cognitive hierarchical models for proverb comprehension was questioned.


The effects of dopamine, noradrenaline and serotonin in the visual cortex of the cat.
The predominant effect of dopamine, norepinephrine and serotonin on the photically-evoked urinary activity was a prolonged inhibition of firing. These amines were also able to block acetylcholine-induced excitations and for longer periods of time than GABA.


Pathologic states associated with activation of eosinophils and with eosinophilia.
Eosinophils are involved in cytotoxicity against helminths and tumor cells and effect both tissue damage and tissue protection in hypersensitivity reactions. Their migratory patterns and oxidative mechanisms are most similar to those of neutrophils, but their tissue longevity and functional variation are more similar to those of monocytes and macrophages. Their enzyme components and behaviors are only now beginning to be defined, and their biologic functions in pathologic states remain a topic of considerable discussion.


Physicians' values and experience during adolescence. Their effect on adolescent health care.
The values and experience of physicians as adolescents can effect their care of adolescent patients. Eighty residents were studied using extensive personal data gathered from a structured interview, a questionnaire of perceived clinical skills, and a videotape with a simulated patient. A "values" and "risk-taking during adolescence" score was constructed and related to the resident's perceived skills for and attitudes about adolescent health care. Residents with higher values scores (more conservative) were more likely to be pediatric than internal medicine residents and less likely to prescribe birth control pills to an adolescent. Residents with higher risk-taking scores considered themselves more skilled in dealing with substance abuse and sexually transmitted diseases and in recognizing psychologic problems. Values or risk-taking scores were not related to the resident's perceived skill in areas such as evaluating hypertension or performing Tanner staging. These data suggest that certain values and experiences may be influential in the physician's ability and approach to dealing with certain issues related to adolescent health care.


The first metagenome of activated sludge from full-scale anaerobic/anoxic/oxic (A2O) nitrogen and phosphorus removal reactor using Illumina sequencing.
The anaerobic/anoxic/oxic (A2O) process is globally one of the widely used biological sewage treatment processes. This is the first report of a metagenomic analysis using Illumina sequencing of full-scale A2O sludge from a municipal sewage treatment plant. With more than 530,000 clean reads from different taxa and metabolic categories, the metagenome results allow us to gain insight into the functioning of the biological community of the A2O sludge. There are 51 phyla and nearly 900 genera identified from the A2O activated sludge ecosystem. Proteobacteria, Bacteroidetes, Nitrospirae and Chloroflexi are predominant phyla in the activated sludge, suggesting that these organisms play key roles in the biodegradation processes in the A2O sewage treatment system. Nitrospira, Thauera, Dechloromonas and Ignavibacterium, which have abilities to metabolize nitrogen and aromatic compounds, are most prevalent genera. The percent of nitrogen and phosphorus metabolism in the A2O sludge is 2.72% and 1.48%, respectively. In the current A2O sludge, the proportion of Candidatus Accumulibacter is 1.37%, which is several times more than that reported in a recent study of A2O sludge. Among the four processes of nitrogen metabolism, denitrification related genes had the highest number of sequences (76.74%), followed by ammonification (15.77%), nitrogen fixation (3.88%) and nitrification (3.61%). In phylum Planctomycetes, four genera (Planctomyces, Pirellula, Gemmata and Singulisphaera) are included in the top 30 abundant genera, suggesting the key role of ANAMMOX in nitrogen metabolism in the A2O sludge.


Management of tendon disorders in cattle.
This article describes tendon disorders in cattle and treatments for such disorders. Tendon injuries causing loss of a production animal or a decreased level of production result in significant economic loss to the cattle producer. Tendon disorders may be congenital or acquired. Congenital abnormalities may include tendon laxity, contracted tendons, or tendon displacement. Acquired tendon disorders may include tendon laxity, contracture, luxation, tendinitis, laceration, avulsion, rupture, and tenosynovitis.


Damage recognition in nucleotide excision DNA repair.
Nucleotide excision repair (NER) is a highly versatile DNA repair process. Its ability to repair a large number of different damages with the same subset of recognition factors requires structural tools for damage recognition that are both broad and very accurate. Over the past few years detailed structural information on damage recognition factors from eukaryotic and prokaryotic NER has emerged. These structures shed light on the toolkit utilized in the damage recognition process and help explain the broad substrate specificity of NER.


TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor.
Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.


Mitochondrial dysfunction in acute hyperammonemia.
Acute hyperammonemia resulting from congenital urea cycle disorders, Reye syndrome or acute liver failure results in severe neuronal dysfunction, seizures and death. Increasing evidence suggests that acute hyperammonemia results in alterations of mitochondrial and cellular energy function resulting from ammonia-induced inhibition of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase and by activation of the NMDA receptor. Antagonists of this receptor and NOS inhibitors prevent acute ammonia-induced seizures and mortality and prevent acute ammonia-induced changes in mitochondrial calcium homeostasis and cellular energy metabolism. Acute hyperammonemia also results in decreased activities of free radical scavenging enzymes and again, free radical formation due to ammonia exposure is prevented by either NMDA receptor antagonists or NOS inhibitors. Acute hyperammonemia also results in activation of "peripheral-type" benzodiazepine receptors and monoamine oxidase-B, enzymes which are localized on the mitochondrial membranes of astrocytes in the CNS. Activation of these receptors results in mitochondrial swelling and in increased degradation of monoamines, respectively. Alterations of mitochondrial function could contribute to the neuronal dysfunction characteristic of acute hyperammonemic syndromes.


Affinity purification of in vivo-assembled ribosomes for in vitro biochemical analysis.
As it has become increasingly clear that the RNA components of the ribosome are central to its function, the in vitro analysis of mutations in the ribosomal RNAs has become an important tool for understanding the molecular details of ribosome function. However, the frequent dominant lethal phenotypes of mutations at interesting rRNA residues has long presented a hurdle to this analysis, as their lethality has rendered it impossible to generate pure populations of in vivo-derived ribosomes for study. We present here the details of a method for affinity purification of ribosomes bearing any mutation in the 16S or 23S rRNA and demonstrate that ribosomes purified using this technology are highly active in the several steps of translation we have examined.


A puromycin-dependent activity-based sensing probe for histochemical staining of hydrogen peroxide in cells and animal tissues.
Hydrogen peroxide (H2O2) is a key member of the reactive oxygen species family of transient small molecules that has broad contributions to oxidative stress and redox signaling. The development of selective and sensitive chemical probes can enable the study of H2O2 biology in cell, tissue and animal models. Peroxymycin-1 is a histochemical activity-based sensing probe that responds to H2O2 via chemoselective boronate oxidation to release puromycin, which is then covalently incorporated into nascent proteins by the ribosome and can be detected by antibody staining. Here, we describe an optimized two-step, one-pot protocol for synthesizing Peroxymycin-1 with improved yields over our originally reported procedure. We also present detailed procedures for applying Peroxymycin-1 to a broad range of biological samples spanning cells to animal tissues for profiling H2O2 levels through histochemical detection by using commercially available anti-puromycin antibodies. The preparation of Peroxymycin-1 takes 9 h, the confocal imaging experiments of endogenous H2O2 levels across different cancer cell lines take 1 d, the dot blot analysis of mouse liver tissues takes 1 d and the confocal imaging of mouse liver tissues takes 3-4 d.


Close linkage of PUM and SPTA within chromosome band 1q21.
Nine families were examined for linkage on chromosome 1 between the hypervariable gene PUM and the alpha-spectrin (SPTA) gene using DNA probes. Close linkage was found with a maximum lod score of 5.98 at theta = 0.05. Hybridization to DNA from somatic cell hybrids made from a parent line carrying a balanced X:1 translocation showed both genes to lie proximal to the breakpoint at 1q23. DNA hybridization to cell lines carrying deletions of 1q21-25 showed the presence of two polymorphic alleles for both loci. These results, combined with existing in situ hybridization data, suggest PUM and SPTA both lie within 1q21. Linkage analysis between PUM and the Duffy blood group (FY) gave a maximum lod of 2.15 at theta = 0.15. These data combined with data from another laboratory give a maximum lod of 5.21 for linkage between PUM and FY at theta = 0.10.


Network-building by community actors to develop capacities for coproduction of health services following reforms: A case study.
Responsive, integrated and sustainable health systems require that communities take an active role in service design and delivery. Much of the current literature focuses on provider-led initiatives to gain community input, raising concerns about power imbalances inherent in invited forms of participation. This paper provides an alternate view, exploring how, in a period following reforms, community actors forge network alliances to (re)gain legitimacy and capacities to coproduce health services with system providers. A longitudinal case study traced the network-building efforts over 3 years of a working group formed by citizens and community actors working with seniors, minorities, recent immigrants, youth and people with disabilities. The group came together over concerns about reforms that impacted access to health services and the ability of community groups to mediate access for vulnerable community residents. Data were collected from observation of the group's meetings and activities, documents circulated within and by the group, and semi-directed interviews. The first stage of analysis used social network mapping to reveal the network development achieved by the working group; a second traced network maturation, based on actor-network theory. Network mapping revealed how the working group mobilized existing links and created new links with health system actors to explore access issues. Problematization appeared as an especially important stage in network development in the context of reforms that disrupted existing collaborative relationships and introduced new structures and processes. Network-building strategies enable community actors to enhance their capacity for coproduction. A key contribution lies in the creation of 'organizational infrastructure'. The lead researcher was embedded over 3 years in the activities of the community groups and community residents. Several group members provided comments on an initial draft of this paper. To preserve the anonymity of the group, their names do not appear in the acknowledgements section.


H1-Receptor Antagonist Olopatadine Inhibits MUC5AC Secretion by Conjunctival Goblet Cells.
The study examined the effect of H1-receptor antagonist olopatadine on the secretory function of cultured rat conjunctival goblet cells (CGC) assessed by enzyme-linked lectin assay employing UEA-I lectin. The level of mRNA for membrane-bound protein MUC16 in histaminestimulated CGC was assayed by reverse transcription PCR in the control and after preliminary application of olopatadine. The intracellular calcium concentration [Ca2+]i was measured by the calcium colorimetric method using GENMED kits. The effects of histamine and olopatadine on p-ERK level were assessed by Western blotting. Histamine up-regulated secretion of mucin MUC5AC and expression of membrane-bound protein MUC16 in CGC. In addition, it increased both [Ca2+]i and the level of phosphorylated ERK. These effects were diminished by preliminary application of olopatadine that probably acted via the ERK signaling pathway. Thus, olopatadine reduced [Ca2+]i and down-regulated ERK phosphorylation by binding to H1-receptors, thereby inhibiting secretion of mucin from histamine-stimulated CGC.


Determination of Tr1 cell populations correlating with distinct activation states in acute IAV infection.
Type I regulatory (Tr1) cells are defined as FOXP3-IL-10-secreting clusters of differentiation (CD4+) T cells that contribute to immune suppression and typically express the markers LAG-3 and CD49b and other co-inhibitory receptors. These cells have not been studied in detail in the context of the resolution of acute infection in the lung. Here, we identify FOXP3- interleukin (IL)-10+ CD4+ T cells transiently accumulating in the lung parenchyma during resolution of the response to sublethal influenza A virus (IAV) infection in mice. These cells were dependent on IL-27Rα, which was required for timely recovery from IAV-induced weight loss. LAG-3 and CD49b were not generally co-expressed by FOXP3- IL-10+ CD4+ T cells in this model and four populations of these cells based on LAG-3 and CD49b co-expression were apparent [LAG-3-CD49b- (double negative), LAG-3+CD49b+ (double positive), LAG-3+CD49b- (LAG-3+), LAG-3-CD49b+ (CD49b+)]. However, each population exhibited suppressive potential consistent with the definition of Tr1 cells. Notably, differences between these populations of Tr1 cells were apparent including differential dependence on IL-10 to mediate suppression and expression of markers indicative of different activation states and terminal differentiation. Sort-transfer experiments indicated that LAG-3+ Tr1 cells exhibited the capacity to convert to double negative and double positive Tr1 cells, indicative of plasticity between these populations. Together, these data determine the features and suppressive potential of Tr1 cells in the resolution of IAV infection and identify four populations delineated by LAG-3 and CD49b, which likely correspond to different Tr1 cell activation states.


Differential effects of synthetic indoloquinolizines on in vitro rat lymphocyte and macrophage functions.
Indoloquinolizines are natural alkaloid indole products grouped as beta-carbolines. These compounds are commonly associated with neurological activities, but little is known about their role as immunomodulating agents. The present study was undertaken to evaluate the effects of synthetic indoloquinolizines on in vitro parameters of rat lymphocyte and macrophage functions. It was observed that proliferation of thymic lymphocytes was significantly (p<0.05) increased (20-30% increase) by dihydro-indoloquinolizinium chloride (2). dihydro-indoloquinolizinyl-ethanone (3). and dimeric dihydro-indoloquinolizinium dichloride (6). whereas dimeric indoloquinolizine (7). caused up to 40% increase in lymphoproliferation at concentrations ranging from 10(-11) to 10(-5) M, compared with untreated control. In contrast, indoloquinolizinium chloride (4) and indoloquinolizine (5). were toxic for lymphocytes at concentrations from 10(-9) to 10(-5) M, and compounds 6 and 7 were toxic at 10(-5) M. In addition, nitric oxide production by LPS-treated peritoneal macrophages was significantly (p<0.05) increased (up to 30% increase) by compounds 4 and 5 at concentrations of 10(-11) to 10(-5) M, and 10(-5) M, respectively; however, compounds 6 and 7 were toxic for macrophages at all concentrations tested. Furthermore, TNF-alpha production was also significantly increased (p<0.01) by compounds 4 and 5 (up to 30-fold increase) compared with untreated control. These novel synthetic indoloquinolizines could serve as immunotherapeutic agents by selectively increasing the pool of activated T lymphocytes or stimulating macrophage functions, with potential use in the treatment of infectious diseases including AIDS and cancer.


Erector spinae plane block for surgery of esophageal atresia in a preterm neonate.
Pain management during and after thoracotomy is challenging in premature neonates. Ultrasound-guided fascial plane block techniques, such as the erector spinae plane block are a relatively new regional anesthesia technique and have emerged as an alternative to thoracic epidural due to its clinical effectiveness, ease of administration and theoretically being safer to perform. The relative ease of identifying anatomical landmarks compared to the paravertebral block, as well as its safety profile compared to an epidural, may have contributed to the erector spinae plane Bs growing popularity. Currently, however, the published evidence for the efficacy of regional anesthesia techniques in low birth weight newborns undergoing this surgery is limited to few isolated case reports. Herein we describe the use of unilateral erector spinae plane block as part of anesthesia and postoperative analgesia management of surgical correction of esophageal atresia in a preterm neonate.


Molecular targets and system biology approaches for drug repurposing against SARS-CoV-2.
COVID-19, a pandemic declared by WHO, has infected about 39.5 million and killed about 1.1 million people throughout the world. There is the urgent need of more studies to identify the novel drug targets and the drug candidates against it to handle the situation. To virtually screen various drugs against SARS-CoV-2, the scientists need the detail information about the various drug targets identified till date. The present review provides the information about almost all the drug targets, including structural and non-structural proteins of virus as well as host cell surface receptors, that can be used for virtual screening of drugs. Moreover, this review also focuses on the different network analysis tools that have been used for the identification of new drug targets and candidate repurposable drugs against SARS-CoV-2. This review provides important insights of various drug targets and the network analysis tools to young bioinformaticians and will help in creating pace to the drug repurposing strategy for COVID-19 disease.


Backbone and side-chain chemical shift assignments for the ribosome-inactivating protein trichobakin (TBK).
Trichobakin (TBK) is a type-I ribosome-inactivating protein (RIP-I), acting as an extremely potent inhibitor of protein synthesis in the cell-free translation system of rabbit reticulocyte lysate (IC50: 3.5 pM). In this respect, TBK surpasses the well-studied highly homologous RIP-I trichosanthin (IC50: 20-27 pM), therefore creation of recombinant toxins based on it is of great interest. TBK needs to penetrate into cytosol through the cell membrane and specifically bind to α-sarcin/ricin loop of 28S ribosome RNA to perform the function of specific RNA depurination. At the moment, there is no detailed structural-dynamic information in solution about diverse states RIP-I can adopt at different stages on the way to protein synthesis inhibition. In this work, we report a near-complete assignment of 1H, 13C, and 15N TBK (27.3 kDa) resonances and analysis of the secondary structure based on the experimental chemical shifts data. This work will serve as a basis for further investigations of the structure, dynamics and interactions of the TBK with its molecular partners using NMR techniques.


Antithrombosis activity of protocatechuic and shikimic acids from functional plant Pinus densiflora Sieb. et Zucc needles.
Pine needle extract (PE) and fermented pine needle extract (FPE) have been reported to show various biological and pharmacological activities such as antioxidant, anti-inflammatory, anti-bacterial, anti-cholesterol, gastrointestinal motility control, and fibrinolytic effect. The aims of our research were to isolate fibrinolytic compounds from PE and FPE and evaluate their antithrombotic activity in vitro and in vivo. Protocatechuic (1) and shikimic (2) acids were isolated and identified from FPE. 1 and 2 not only have fibrinolysis activity but also inhibit fibrin formation similar to aspirin. Lysis of fibrin clots by 1 and 2 occurred completely at pH 2-4. Results of SDS-PAGE showed that fibrin polypeptide chains (Aα, Bβ, γ) lysed by 1 and 2 were intact. The antithrombotic effects of 1 and 2 were confirmed by models of carrageenan-induced tail thrombosis, collagen and epinephrine-induced pulmonary thromboembolism in mice, and FeCl3-induced carotid arterial thrombus. Moreover, 1 and 2 did not induce hemorrhage in the tail veins of mice, unlike common antithrombotic compounds. We also measured changes in the quantities of 1 and 2 obtained from FPE. As fermentation progressed, we demonstrated that the quantity of 1 steadily increased, while the quantity of 2 did not significantly change. We therefore demonstrated that FPE is an excellent resource for 1 and 2 and can be produced inexpensively in sufficient quantities for industrial-scale extraction.


Good chemistry.
The subject matter in chemistry courses reflects almost nothing of the issues that chemists are interested in. It is important to formulate a set of topics--and a Medical College Admissions Test reflecting them--that would leave chemistry departments no choice but to change their teaching.


Early mobilization does not reduce the risk of deep venous thrombosis after Achilles tendon rupture: a randomized controlled trial.
The hypothesis was that early functional mobilization would reduce the incidence of deep venous thrombosis (DVT) during leg immobilization after Achilles tendon rupture surgery. A secondary aim was to evaluate if the amount of weightbearing and daily steps influenced the risk of sustaining a DVT. One-hundred and fifty patients with Achilles tendon rupture repair were randomized to treatment with early functional mobilization, encouraging full weightbearing and ankle motion in orthosis, or treatment-as-usual, i.e., 2 weeks of unloading in plaster cast followed by 4 weeks weightbearing in orthosis. At 2 and 6 weeks postoperatively, all patients were screened for DVT using compression duplex ultrasound. During the first 2 weeks postoperatively, patient-reported loading, pain and step counts were assessed. At 2 weeks, 28/96 (29%) of the patients in early functional mobilization group and 15/49 (31%) in the control group (n.s) had sustained a DVT. At 6 weeks, the DVT rate was 35/94 (37%) in the early functional mobilization and 14/49 (29%) in the control group (n.s). During the first postoperative week, the early functional mobilization group reported low loading and higher experience of pain vs. the control group (p = 0.001). Low patient-reported loading ≤ 50% (OR = 4.3; 95% CI 1.28-14.3) was found to be an independent risk factor for DVT, in addition to high BMI and higher age. Early functional mobilization does not prevent the high incidence of DVT during leg immobilization in patients with Achilles tendon rupture as compared to treatment-as-usual. The low efficacy of early functional mobilization is mainly explained by postoperative pain and subsequent low weightbearing. To minimize the risk of DVT, patients should be encouraged to load at least 50% of body weight on the injured leg 1 week after surgery. Therapeutic, level 1.


Synthesis and study of molecular interactions between phosphatidyl choline and two laminin derived peptides hydrophobically modified.
Two peptides based on the active SIKVAV sequence were synthesized and hydrophobically modified through attachment of a myristoyl residue to the amino terminal group. A comparative study was carried out on the physicochemical properties of both parent and hydrophobically modified structures. Properties studied were hydrophobicity, surface activity, spreadability on aqueous surfaces, penetration in lipid monolayers, aggregation and haemolytic activity. Results obtained indicate that myristoyl containing peptides form micelles at 10(-6) M concentration, whereas parent peptides start to aggregate at 10(-5) M. All of them are able to spread on aqueous surfaces forming stable monolayers. Concerning their haemolytic activity only one of the sequences promotes a partial lysis of erythrocytes after 30 min incubation at 37 degrees C and 10(-5) M concentration in the media.


Dual-lumen balloon to increase onyx venous penetration in the treatment of spinal dural arteriovenous fistulas.
Spinal dural arteriovenous fistulas (sDAVF) are the most common spinal vascular lesions. The arterialization of the recipient vein results in venous hypertension and chronic ischemia. Intravascular injection of acrylic glue in order to occlude the draining vein is the principle of endovascular treatment, but a significant portion of embolization procedures do not succeed. We present our initial experience of endovascular balloon augmented embolization of sDAVF using a dual-lumen balloon. Three patients harboring sDAVF were submitted to endovascular treatment by onyx injection assisted by a double-lumen balloon as the sole therapy. Control angiography demonstrated complete obliteration of the fistula in all cases with clinical improvement. Dual-lumen balloon onyx embolization of spinal dural arteriovenous fistulas appears to be an acceptable and feasible alternative.


A rare case report of paratesticular spindle cell tumor: Inflammatory myofibroblastic tumor.
Spindle cell tumors in the paratesticular region are infrequent. Accurate diagnosis requires clinical assessment, pathological analysis, and immunohistochemical (IHC) analysis. The present study reports a 33-year-old male who presented with a painless mass in his right testis. The mass grew from the size of a marble to that of a tennis ball in two years. Physical examination and ultrasonography revealed a solid mass in the right paratesticular area. The patient underwent a right paratesticular tumor excision, without interfering the right testis. Histopathologic analysis showed spindle cell tumor appearance referring to inflammatory myofibroblastic tumor (IMT). IMT, also known as inflammatory pseudotumor, is a rare and benign neoplasm that can occur anywhere. Diagnosis is challenging, because it mimics other neoplasms. Immunohistochemical profiles were decisive in concluding a definitive diagnosis. Treatment, on the other hand, depends on tumor burden and connectivity to other region. Spindle cell tumors are very rare and can be treated with simple excision if no organ adhesion is detected. Therefore, right orchidectomy was not required in our case.


Sexual dichronism and intersexual phoresy in gall-forming coccoids.
Coccoid gall-formers from the genus Cystococcus exhibit sexual dichronism, producing the males of a brood well before their sisters. This ensures the coexistence in the maternal gall of winged adult males and their first instar wingless sisters. Females disperse by clinging to the attenuate abdomens of their brothers, and the efficiency of this dispersal is reflected in an even dispersion on host trees. Evolution of this form of phoresy may be associated with the paternal genome loss prevalent in the Coccoidea.


[Digestive cystic duplications: contribution of ultrasonography in the neonatal period. Apropos of 3 cases].
Three cases of enteric duplication cysts in newborns are reported. The importance of the ultrasonographic exploration for the diagnosis is outlined.


Improved barrier function observed in cultured skin substitutes developed under anchored conditions.
The current method of producing cultured skin substitutes (CSS) is focused on providing treatments for severe skin wounds/burns. We have developed a modified growth method to make them more suitable for in vitro product-testing/toxicity-testing purposes. CSS grown in Petri dishes were either transferred to Franz diffusion cells on day 5 (modified method) or left in the Petri dish (standard method) and maintained in these environments for the remainder of the growth phase. Mitochondrial metabolism (MTT assay) was measured on days 5, 10 and 14 and histology was studied on days 5, 10 and 14. Barrier function for all tissues was evaluated by transferring them to Franz cells (standard method) and measuring transepidermal water loss (TEWL), 3H2O penetration and 14C-niacinamide permeability on days 7, 14 and 21. CSS grown by the standard and modified methods showed comparable cell viability and tissue morphology. Barrier function, however, was markedly improved in CSS grown by the modified method. The average improvement at days 7 and 14 was 1.3-fold for TEWL, 2.1-fold for 3H2O penetration and 6.4-fold for 14C-niacinamide permeability. The barrier function of CSS grown by the modified method was still significantly lower than that of human cadaver skin tested by the same methods. CSS developed using the anchored multi-cell system showed similar cell viability and morphology and improved barrier function compared with CSS produced by the standard Petri dish method, thereby improving its potential as an in vitro skin permeability and toxicity model.


Adolescent travel patterns: pilot data indicating distance from home varies by time of day and day of week.
We conducted a pilot study using new technology to track adolescent "place." Using Global Positioning System (GPS)-enabled cell phones, we recruited and tracked 15 female adolescents for a 1-week period. Distance away from home was greatest in the evenings on weekends or holidays. The greatest percentage of time spent more than 1 kilometer away from home was also during these times. Such GPS technology holds promise for future adolescent health research in allowing more specific and dynamic measurement of where adolescents spend time.


Response of the grapevine rootstock richter 110 to inoculation with native and selected arbuscular mycorrhizal fungi and growth performance in a replant vineyard.
Two indigenous arbuscular mycorrhizal (AM) fungi from the Mediterranean wine growing area in the Northeast of Spain were isolated and classified as Glomus intraradices Schenck & Smith. Both native fungi were found to increase the growth of the vine rootstock 110 Richter under greenhouse conditions compared with G. intraradices (BEG 72) and a phosphorus (P) fertilization treatment. The effectivity of field inoculation of Cabernet Sauvignon plants grafted on Richter 110 with the former native fungi and with G. intraradices BEG 72 in a replant vineyard severely infested by the root-rot fungus Armillaria mellea (Vahl ex Fr.) Kummer was assessed. The native fungi were not effective at enhancing plant development, and only G. intraradices BEG 72, resulted in a positive response. Field inoculation with this selected fungus increased plant shoot dry weight at the end of the first growing season.


Viral Vector Production: Adenovirus.
Adenoviral vectors have proven to be valuable resources in the development of novel therapies aimed at targeting pathological conditions of the central nervous system, including Alzheimer's disease and neoplastic brain lesions. Not only can some genetically engineered adenoviral vectors achieve remarkably efficient and specific gene delivery to target cells, but they also may act as anticancer agents by selectively replicating within cancer cells.Due to the great interest in using adenoviral vectors for various purposes, the need for a comprehensive protocol for viral vector production is especially apparent. Here, we describe the process of generating an adenoviral vector in its entirety, including the more complex process of adenoviral fiber modification to restrict viral tropism in order to achieve more efficient and specific gene delivery.


Transient lesion in the splenium related to antiepileptic drug: case report and new pathophysiological insights.
Transient focal lesions in the splenium of the corpus callosum (SCC) have been associated with antiepileptic drug (AED) treatment. However, the aetiology is widely unknown. We describe a transient SCC lesion in an epilepsy patient after abrupt AED reduction. Whole head high-field diffusion tensor imaging (DTI) including fully automated quantitative fractional anisotropy (FA) analysis was used to get insight into the pathophysiology of transient SCC lesions. Our results demonstrate that a reversible loss of directional fibre organisation in the splenium, likely due to intramyelinic oedema, is the morphological correlate of transient SCC lesions. We conclude that DTI provides a highly sensitive and quantitative tool to detect subtle and transient loss of fibre integrity associated with AED treatment.


MicroRNA-361-5p suppresses the tumorigenesis of hepatocellular carcinoma through targeting WT1 and suppressing WNT/β-cadherin pathway.
MicroRNA-361-5p (miR-361-5p) has been found to be involved in the pathogenesis of several human cancers. However, the specific role of miR-361-5p is still unclear in hepatocellular carcinoma (HCC). Therefore, this study was designed to elucidate the function of miR-361-5p in HCC. The expression levels of miR-361-5p and Wilms' tumor-1 (WT1) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Moreover, the function of miR-361-5p was examined through Cell Counting Kit-8 (CCK-8) and transwell assays. The protein expressions were examined via Western blot analysis and immunocytochemical assay. Tumor growth of HCC was observed via xenograft tumor formation assay. The relationship between miR-361-5p and WT1 was verified by the Dual-Luciferase assay. Downregulation of miR-361-5p was identified in HCC, which predicted a worse prognosis in HCC patients. Furthermore, it was found that miR-361-5p suppressed cell proliferation, migration, and invasion in HCC by inhibiting WT1. MiR-361-5p also inhibited tumor growth of HCC. Besides that, miR-361-5p suppressed EMT and negatively activated the WNT/β-cadherin pathway in HCC. MiR-361-5p suppressed tumorigenesis of HCC by targeting WT1 and inactivating the WNT/β-cadherin pathway.


Prothioconazole and prothioconazole-desthio induced different hepatotoxicities via interfering with glycolipid metabolism in mice.
Prothioconazole (PTA), a new triazole fungicide, has been widely used worldwide. A recent study has confirmed that PTA and its main metabolite prothioconazole-desthio (dPTA) interfere with the liver metabolism in reptiles. However, little is known about liver toxicity of these two pollutants in mammals. Here, female mice were orally exposed to PTA (1.5 mg/kg body weight/day) and dPTA (1.5 mg/kg body weight/day) for 30 days. Additionally, growth phenotype and indexes related to serum and liver function were examined. Using metabolomics and gene expression analysis, PTA- and dPTA-induced hepatotoxicity was studied to clarify its potential underlying mechanism of action. Together, the results indicated that PTA and dPTA exposure caused changes in growth phenotypes, including elevated blood glucose levels, triglyceride accumulation, and damage of liver function. Additionally, exposure to PTA and dPTA caused changes in genes and metabolites related to glycolipid metabolism in female mice, thereby interfering with the pyruvate metabolism and glycolysis/gluconeogenesis pathways, ultimately leading to hepatic metabolism disorders. In particular, the effect of dPTA on hepatotoxicity has been proven to be more significant than that of PTA. Thus, these findings help us understand the underlying mechanism of action of PTA and dPTA exposure-induced hepatotoxicity in mammals and possibly humans.


High density lipoproteins (HDL) and physical activity: the influence of physical exercise, age and smoking on HDL-cholesterol and the HDL-/total cholesterol ratio.
220 trained men, examined the day before participation in a cross country ski-race, had significantly higher HDL-cholesterol and HDL-/total cholesterol ratio than untrained men, but did not differ signficantly from untrained women. HDL-cholesterol was significantly higher in skiers above 60 years than in skiers of younger age. Tobacco smokers ahd lower HDL-cholesterol and HDL-/total cholesterol ratio than non-smokers, but the differences were only significant in skiers, not in controls. HDL-cholesterol was positively correlated to total cholesterol in skiers. The HDL-cholesterol level may possibly contribute to the lower morbidity of CHD in men who are physically active during leisure time.


Expanding the application range of the κ‑carrageenase OUC-FaKC16A when preparing oligosaccharides from κ-carrageenan and furcellaran.
Carrageenan oligosaccharides are important products that have demonstrated numerous bioactivities useful in the food, medicine, and cosmetics industries. However, the specific structure-function relationships of carrageenan oligosaccharides are not clearly described due to the deficiency of high specific carrageenases. Here, a truncated mutant OUC-FaKC16Q based on the reported κ-neocarratetrose (Nκ4)-producing κ-carrageenase OUC-FaKC16A from Flavobacterium algicola was constructed and further studied. After truncating the C-terminal Por_Secre_tail (PorS) domain (responsible for substrate binding), the catalytic efficiency and temperature stability decreased to a certain extent. Surprisingly, this truncation also enabled OUC-FaKC16Q to hydrolyze Nκ4 into κ-neocarrabiose (Nκ2). The offset of Arg265 residue in OUC-FaKC16Q may explain this change. Moreover, the high catalytic abilities, the main products, and the degradation modes of OUC-FaKC16A and OUC-FaKC16Q toward furcellaran were also demonstrated. Data suggested OUC-FaKC16A and OUC-FaKC16Q could hydrolyze furcellaran to produce mainly the desulfated oligosaccharides DA-G-(DA-G4S)2 and DA-G-DA-G4S, respectively. As a result, the spectrum of products of κ-carrageenase OUC-FaKC16A has been fully expanded in this study, indicating its promising potential for application in the biomanufacturing of carrageenan oligosaccharides with specific structures. The online version contains supplementary material available at 10.1007/s42995-023-00181-2.


Induced osteogenesis using a new periosteal distractor.
We developed a new device mainly composed of a titanium mesh to distract the periosteum. The purpose of this study is to evaluate induced osteogenesis by periosteal distraction with the new device. We divided 12 Japanese male rabbits into 3 groups, with 4 rabbits in each. In all groups the calvarial periosteum was reflected, and 1 side of the titanium mesh was fixed to the bone surface with 2 micro-screws. In groups 1 and 2, an elevation screw was inserted into a serrated hole on the other side of the plate 7 days after surgery. Then the device was activated at a rate of 0.5 mm every 12 hours for 5 days. At 4 weeks of the consolidation period, group 1 was killed, followed by group 2 at 6 weeks. Group 3 (control) received no screws, and hence no activation was performed. In group 3, 2 animals were killed 4 weeks after titanium mesh insertion, followed by the other 2 animals at 6 weeks. The device was designed to simultaneously distract the periosteum at different rates along its inclined surface. Newly formed bone was histologically and radiographically evaluated. The new device effectively induced osteogenesis and successfully distracted the soft tissue after 6 weeks in a rabbit model. The new device is slim, and the procedure is straightforward. Thus, periosteal distraction with this device can potentially be used for vertical and horizontal ridge augmentation in the oral cavity. In addition, the results suggest that connective tissue growth in the distraction site might be controlled by reducing the speed of periosteal distraction.


IPDmada: An R Shiny tool for analyzing and visualizing individual patient data meta-analyses of diagnostic test accuracy.
Individual patient data meta-analyses (IPD-MA) are regarded as the gold standard for systematic reviews, which also applies to systematic reviews of diagnostic test accuracy (DTA) studies. An increasing number of DTA systematic reviews with IPD-MA have been published in recent years, but there is much variation in how these IPD-MA were performed. A number of existing methods were found, but there is no consensus as to which methods are preferred as the standard methods for statistical analysis in DTA IPD-MA. To create a web-based tool which integrates recommended statistical analyses for DTA IPD-MA, and allows researchers to analyse the data and visualize the results with interactive plots. A systematic methodological review was performed to identify statistical analyses and data visualization methods used in DTA IPD-MA. Methods were evaluated by the authors and recommended analyses were integrated into the IPDmada tool which is freely available online with the user interface developed with R Shiny package. IPDmada allows users to upload their own data, perform the meta-analysis with both continuous and dichotomized tests, and incorporate individual level covariate-adjusted analysis. All tables and figures can be exported as .csv or .pdf files. A hypothetical dataset was used to illustrate the application of IPDmada. IPDmada will be very helpful to researchers doing DTA IPD-MA, since it not only facilitates the statistical analysis but also provides a standard framework. The introduction of IPDmada will harmonize the methods used in DTA IPD-MA and ensure the quality of such analyses. IPDmada is a newly developed web-based tool for performing statistical analysis of individual patient data meta-analysis of diagnostic accuracy and visualizing the results. The tool is freely available to all the researchers, and requiring no installation of statistical software/packages. The tool has an user-friendly interface, and allows meta-analysis on both dichotomized and continuous test results. Researchers can easily use this tool to investigate the threshold effect and covariate effect on the summary accuracy. The introduction and implementation of IPDmada will serve as a useful tool for DTA IPD-MA and increase the quality of such studies.


Sleep and sleepiness during an ultra long-range flight operation between the Middle East and United States.
This study provides a practical example of fatigue risk management in aviation. The sleep and sleepiness of 44 pilots (11 trips × 4 pilot crew) working an ultra long-range (ULR; flight time >16 h) round-trip operation between Doha and Houston was assessed. Sleep was assessed using activity monitors and self-reported sleep diaries. Mean Karolinska Sleepiness Scores (KSS) for climb and descent did not exceed 5 ("neither alert nor sleepy"). Mean daily sleep duration was maintained above 6.3h throughout the operation. During in-flight rest periods, 98% of pilots obtained sleep and sleepiness was subsequently reduced. On layover (49.5h) crew were advised to sleep on Doha or Universal Co-ordinated Time (UTC), but 64% slept during the local (social) night time. Pilots originating from regions with a siesta culture were more likely to nap and made particularly effective use of their daytime in-flight rest periods. The results indicate that the operation is well designed from a fatigue management perspective.


Healthy lifestyle changes and mental health of healthcare workers during the COVID-19 pandemic in China.
This study investigated lifestyle changes in physical activity, sleep, and diet among healthcare workers and their impact on their mental health during the COVID-19 pandemic in China. Healthcare workers (N = 589) completed an online survey about demographic and personal characteristics, working experiences, COVID-19-related stressors, lifestyle changes, and mental health (anxiety and depression) about three months after the lift of the lockdown policy in China. Lifestyle Changes (including changes in physical activity, sleep, and diet), Generalized Anxiety Disorder (GAD-7), and Depression (PHQ-9) were used to measure main outcomes. Of the participants, 39.7% (N = 234) had less physical activity, 36.0% (N = 212) slept less, and 41.8% (N = 246) ate healthier than before pandemic. Lower educational level, working within original hospitals, less physical activity and less sleep time was associated with increased anxiety. Working within original hospitals, less physical activity and an unhealthier diet was associated with increased depression. In summary, healthcare workers who became less healthy in lifestyles experienced a higher level of anxiety and depression symptoms during the COVID-19 pandemic. Strategies to promote healthy living and improve mental health among healthcare workers should be developed and implemented both during the ongoing COVID-19 pandemic and beyond.


H3K36 trimethylation-mediated biological functions in cancer.
Histone modification is an important form of epigenetic regulation. Thereinto, histone methylation is a critical determination of chromatin states, participating in multiple cellular processes. As a conserved histone methylation mark, histone 3 lysine 36 trimethylation (H3K36me3) can mediate multiple transcriptional-related events, such as the regulation of transcriptional activity, transcription elongation, pre-mRNA alternative splicing, and RNA m6A methylation. Additionally, H3K36me3 also contributes to DNA damage repair. Given the crucial function of H3K36me3 in genome regulation, the roles of H3K36me3 and its sole methyltransferase SETD2 in pathogenesis, especially malignancies, have been emphasized in many studies, and it is conceivable that disruption of histone methylation regulatory network composed of "writer", "eraser", "reader", and the mutation of H3K36me3 codes have the capacity of powerfully modulating cancer initiation and development. Here we review H3K36me3-mediated biological processes and summarize the latest findings regarding its role in cancers. We highlight the significance of epigenetic combination therapies in cancers.


Immunoglobulin producing cells in the rat dental pulp after unilateral sympathectomy.
Recent studies show that sympathetic nerves participate in immunomodulation. We investigated the effects of unilateral sympathectomy on recruitment of cells expressing kappa and lambda (kappa and lambda) light chains in the rat dental pulp. Superior cervical ganglion was removed in experimental rats (n=10) while control rats (n=8) received sham surgery. Following perfusion 18 days later, mandibular jaws were processed for immunohistochemistry and electron microscopy. Sympathectomy results in recruitment of cells expressing kappa and lambda light chains into the dental pulp (P=0.005). Electron microscopy revealed these cells to be mainly plasma cells and Mott cells. We conclude that neural imbalance caused by unilateral sympathectomy recruits immunoglobulin producing cells in the dental pulp. Our results are in agreement with a model of immune regulation in which the sympathetic nervous system exerts a tonic regulatory effect over lymphocyte proliferation and migration.


Novel approach of processing electrical bioimpedance data using differential impedance analysis.
The goal of this manuscript is to present a new methodology for real time analysis of time-varying electrical bioimpedance data. The approach assumes that the Fricke-Morse model of living tissues is meaningful and valid within the measured frequency range (10 kHz to 1 MHz). The parameters of this model are estimated in the whole frequency range with the presented method based on differential impedance analysis (DIA). The numerical accuracy of the developed approach has been validated and compared to complex nonlinear least square (CNLS) approach through simulations and also with experimental data from in vivo time-varying human lung tissue bioimpedance. The new developed method has demonstrated a promising performance for fast and easily interpretable information in real time.


The Evolution of Ultrasound in Medicine: A Case Report of Point-of-care Ultrasound in the Self-diagnosis of Acute Appendicitis.
Point-of-care ultrasound (POCUS) education during medical school develops physicians who are properly prepared for the next generation of medicine. The authors present the case of a first-year medical student who self-diagnosed appendicitis using POCUS. A 25-year-old, first-year medical student presented to the emergency department with lower abdominal pain. What seemed like a straightforward appendicitis presentation came with a twist; the student brought self-performed ultrasound imaging of his appendix. The student's ultrasound skill set reflects favorably on the rapid evolution of ultrasound teaching in medical education.


Reviewing maternal deaths to make pregnancy safer.
Every year, some eight million women around the world suffer pregnancy-related complications; over half a million of these women die. Although most of these deaths could be averted at little or no extra cost, even where resources are limited, if we are to take action and develop and implement changes to maternity services to save the lives of mothers and newborns, we need the right kind of information. This more in-depth information might not be available through national statistics on maternal mortality rates or death certificate data; what is required is a detailed understanding of the clinical, social, cultural and other underlying factors that result in a mother's death. The World Health Organization's programme and philosophy for such maternal death or disability reviews is called Beyond the numbers. It outlines the five key methodologies for reviewing maternal deaths or disabilities that are now being introduced in a number of countries around the world.


Approach to newborn priapism: a rare entity.
Priapism is a rare entity with a different aetiology in newborns than in childhood and adult life. Due to its rarity, management can be challenging. The possible consequences of improper treatment make management of this condition clinically relevant. Preservation of normal erection is the major goal. Although the majority of cases are idiopathic, prolonged erection may be associated with polycythemia. As spontaneous detumescence occurs in the majority of cases, conservative non-surgical treatment is advocated initially. We report the case of a newborn presenting with priapism on the 1st day of life. Detumescence was achieved on the 4th day of life with conservative management.


EBIO, an agent causing maintained epithelial chloride secretion by co-ordinate actions at both apical and basolateral membranes.
The effect of 1-ethyl-2-benzimidazolone (EBIO) on electrogenic chloride secretion in murine colonic and nasal epithelium was investigated by the short-circuit technique. In the colon, EBIO produces a sustained current increase in the presence of amiloride, which is sensitive to furosemide. In nasal epithelium EBIO causes only a small, transient current increase. Sustained increases in current were obtained in response to forskolin in both epithelia. To examine the mechanisms by which EBIO increases chloride secretion, the effects on intracellular mediators were measured in colonic crypts. There was no effect on [Ca(2+)]i but cAMP content was increased, more so in the presence of IBMX, indicating a direct effect on adenylate cyclase. In colonic epithelia in which the apical surface was permeabilized by nystatin, and the tissue subjected to an apical to basolateral K(+) gradient, EBIO caused a current increase that was entirely sensitive to charybdotoxin (ChTX). In similarly permeabilized colons Br-cAMP caused a current increase that was entirely sensitive to 293B. Thus EBIO increases chloride secretion in the colon by coordinated actions at both the apical and basolateral faces of the cells. These include direct and indirect actions on Ca(2+)-sensitive and cAMP-sensitive K(+) channels respectively, and indirect actions on the basolateral cotransporter and apical CFTR chloride channels via cAMP. In CF colonic epithelia EBIO did not evoke chloride secretion. It is not clear why the nasal epithelium responds poorly to EBIO whereas it gives a sustained response to the related compound chlorzoxazone.


Exploratory analysis of the human breast DNA methylation profile upon soymilk exposure.
Upon soy consumption, isoflavone metabolites attain bioactive concentrations in breast tissue possibly affecting health. Though in vitro epigenetic activity of soy metabolites has been described, the in vivo impact on the epigenome is largely unknown. Therefore, in this case-control study, the breast glandular tissue DNA methylome was explored in women undergoing an aesthetic breast reduction. After a run-in phase, 10 generally healthy Belgian or Dutch women received soymilk for 5 days. MethylCap-seq methylation profiles were compared with those of 10 matched controls. Isoflavones and their microbial metabolites were quantified in urine, serum, and glandular breast tissue (liquid chromatography-mass spectrometry) and 17β-estradiol in glandular breast tissue (immunoassay). Global DNA methylation levels were obtained for 6 cases and 5 controls using liquid chromatography-mass spectrometry. Although lower MethylCap-seq coverages were observed, mass spectrometry results and computational LINE-1 methylation analysis did not provide evidence supporting global methylation alterations upon treatment. At a false discovery rate of 0.05, no differentially methylated loci were identified. Moreover, a set of previously identified loci was specifically tested, but earlier reported results could not be validated. In conclusion, after a 5-day soymilk treatment, no major general epigenetic reprogramming in breast tissue could be found in this exploratory study.


Self-perception of dietary quality and adherence to food groups dietary recommendations among Mexican adults.
Mexicans' adherence to food group's dietary recommendations is low and an inaccurate self-perception of dietary quality might perpetuate this low adherence. Our aim was to compare the intake and the adherence to the dietary recommendations for several food groups, subgroups, and to an overall Mexican Diet Quality Index (MxDQI), among those that perceived their diet as healthy vs. those that did not. We analyzed data from 989 subjects 20-59 y old from the nationally representative Mexican National Health and Nutrition Survey 2016. Dietary intake was collected with one 24-h recall and a repeated recall in 82 subjects. Self-perception of dietary quality was evaluated with the following question "Do you consider that your diet is healthy? (yes/no)". We used the National Cancer Institute method to estimate the usual intake. We compared the mean intake adjusted by sociodemographic variables and the percentage of adherence according to the self-perception of dietary quality among the whole sample and in sociodemographic subpopulations. Sixty percent perceived their diet as healthy, and their adherence to recommendations was low [20% for fruits and vegetables, < 8% for legumes, seafood and SSBs, and ~ 50% for processed meats and high in saturated fat and/or added sugar (HSFAS) products]. The mean number of recommendations they met was 2.8 (out of 7) vs. 2.6 among the rest of the population (p > 0.05), and the MxDQI score was 40 vs. 37 (out of 100 points). The only food groups and subgroups with a statistically significant difference between those that perceived their diet as healthy vs. unhealthy were fruits [38 g/d (95% CI 3, 73)], fruit juices [27 g/d (95% CI 2, 52)], industrialized SSBs [- 35 kcal/d (- 70, - 1)] and salty snacks [- 40 kcal/d (- 79, - 1)]. Other differences were small or inconsistent across subgroups of the population. Those that perceived their diet as healthy only had a slightly healthier diet than the rest of the population, moreover, their adherence to recommendations was very low. Hence, it is necessary to improve their nutrition knowledge.


Production of cyclodextrins in ultrafiltration membrane reactor containing cyclodextrin glycosyltransferase from Bacillus macerans.
An enzyme reactor installed with ultrafiltration membrane was developed to produce alpha-, beta-, and gamma-cyclodextrins (CDs) from soluble starch by Bacillus macerans cyclodextrin glycosyltransferase (CGTase) tagged with 10 lysines at its C-terminus (CGTK10ase). Ultrafiltration membrane YM10 with 10,000 of molecular cutoff was chosen for membrane modification and CD production. A repeated-batch type of the enzyme reaction with free CGTK10ase resulted in a alpha-CD yield of 24.0 (+/-1.5)% and a productivity of 4.68 (+/-0.88) g/l-h, which were 7 times higher that those for CGTK10ase immobilized on modified YM10 membrane. Addition of 1- nonanol increased CD yields by 30% relative to the control, which might be due to prevention of the reversible hydrolysis of CDs.


Determination of perfluorocarboxylic acids in water by ion-pair dispersive liquid-liquid microextraction and gas chromatography-tandem mass spectrometry with injection port derivatization.
A novel technique for derivatization in a gas chromatograph injection port after a one-step extraction of trace perfluorocarboxylic acids (PFCAs) in water with ion pair formation during dispersive liquid-liquid microextraction (DLLME) was investigated. Tetrabutylammonium hydrogen sulfate (TBAHS) was used as the ion pair reagent. PFCA butyl ester derivatives were formed in the GC injection port and then analyzed using gas chromatography coupled to tandem mass spectrometry with negative chemical ionization. According to our analysis, the operative linear range for PFCA detection from 250 pg mL(-1) to 2 μg mL(-1) with a relative standard derivation (RSD) below 13%. Detection limits were achieved at the level of 37-51 pg mL(-1). This method was successfully applied for the analyzing of PFCAs in river water samples from urban and industrial areas without tedious pretreatment. The concentration range over which PFCAs were detected is from 0.6 ng mL(-1) to 604.9 ng mL(-1).


Reliability of Doppler ultrasound in the diagnosis of acute venous thrombosis both above and below the knee.
We have found the Doppler examination to be accurate in 92% of limbs with suspected iliofemoral thrombosis and in 86% of limbs with suspected calf vein thrombosis. Above the knee, the sensitivity was 94% and the specificity, 90%. Below the knee, the sensitivity was 91% and the specificity, 84%. In the hands of a skilled examiner, Doppler ultrasound is a reliable noninvasive technique for evaluating patients with suspected deep venous thrombosis and one on which therapy can safely be based.


Off-On-Off fluorescence behavior of an intramolecular charge transfer probe toward anions and CO2.
The photophysical behavior of a newly developed fluorescent probe, tricyanoethylphenyl phenanthroimidazole (TCPPI) has been studied. Upon interaction of different class of anions TCPPI displayed naked-eye sensitive fluorescence "turn-on" response to detect selectively F(-) (0.98μM, 18.62ppb) and CN(-) (1.12μM, 29.12ppb) anions in acetonitrile (MeCN). Job's plot analysis revealed a 1:1 binding stoichiometry between probe and anions. The spectral data analysis and 1H NMR titration studies suggested about the affinity of F(-) and CN(-) anions with moderately acidic -NH fragment of imidazolyl unit of probe through deprotonation and H-bonding interaction. Moreover, the anion activated probe upon interaction with CO2 revived photophysical properties of probe, "On-Off-On" type fluorescence and enabled anion-induced CO2 sensing in the medium.


'Yes, we have bananas!'.
This paper takes as its starting point 'identifying markers of Latin American psychoanalysis'. The authors see this theme as a compromise between two diverging approaches. On one hand, the conference at which the content was presented provided the opportunity for Latin American psychoanalytical thinking to be discussed and, as a reward to the best papers, to be published. On the other, both the conference and the reward are more indicative of the observer's biases than of the object's peculiarities. The authors consider that the conference mistakenly focused on the search for minor differences (secondary identifications) instead of looking for invariances (identities). Considering that uncertainty, pluralism and complexity are issues relevant to the whole of psychoanalysis in its current stage of development as a scientific discipline, the authors think that treating these elements as 'identifying markers of Latin American psychoanalysis' is evidence of prejudice brought about by a coloniser-colonised relationship. To develop their argument, the authors discuss a paper on editorial criteria by Tuckett as a clinical case, and use an episode of Brazilian history as further illustration. They address issues such as conformity to cultural patterns; the search for certainties and proofs; the domination of some groups over others; and editorial power-more specifically, its influence on the acceptance or rejection of scientific ideas. These issues have distracted attention away from the fundamentals of psychoanalysis by introducing other, extraneous aims. Publication plays a key role in feeding a possibly vicious circle wherein only a small proportion of scientific contributions manages to reach a wide audience--exactly those contributions that conform to established patterns. The act of publication turns that portion into official knowledge, while unpublished ideas become increasingly excluded.


Hearing impairment in children.
This article describes the current standard for infant hearing loss identification and intervention. Since the standard of care was driven by the recommendations made by the Joint Committee on Infant Hearing, a summary of the most recent recommendations is provided, followed by illustrative case studies that highlight how implementation of these guidelines allow access to the critical window for auditory and speech-language development.