In vivo acylation of proteolipid protein and DM-20 in myelin and myelin subfractions of developing rat brain: immunoblot identification of acylated PLP and DM-20.
The acylation of proteolipid protein (PLP) was examined in myelin and myelin subfractions from rat brain during the active period of myelination. Proteolipid protein and DM-20 in myelin and myelin subfractions were readily acylated in developing rat brain 22 hours after intracerebral injection of [3H]palmitic acid. No differences in the relative specific activity of PLP in myelin from 9-, 15-, and 30-day-old rat brains was observed; however, the relative specific activity of PLP in the heavy myelin subfraction tended to be higher than that in the light myelin subfraction. The acylation of PLP was confirmed by fluorography of immuno-stained cellulose nitrate sheets, clearly establishing that the acylated protein is in fact the oligodendroglial cell- and myelin-specific protein, PLP. Since PLP is acylated in the 9-day-old animal, when little compact myelin is present, it is possible that the acylation of PLP is a prerequisite for the incorporation of this protein into the myelin membrane.


Obstetric and perinatal complications associated with assisted reproductive treatment in Spain.
Although most newborns conceived through assisted reproductive treatments are healthy, there are concerns about the safety of reproductive techniques and their effect on foetal/maternal well-being. This study aims to describe the incidence of obstetric and perinatal complications in women undergoing assisted reproductive treatments in the Spanish Health System. This is a cross-sectional observational study aimed at women who have been mothers between 2013 and 2018 in Spain. The data was collected through an online survey of 42 items that was distributed through lactation associations and postpartum support groups. In the data analysis, crude odds ratios (OR) and adjusted odds ratios (AOR) were calculated, through a multivariate analysis with binary logistic regression and multinomial logistic regression. Five thousand nine hundred forty-two women participated, 2.3% (139) through artificial insemination and 8.2% (486) through in vitro fertilisation (IVF) techniques. Women who underwent IVF had a higher likelihood of suffering problems during pregnancy (OR = 1.71; 95% confidence intervals (95% CI), 1.37-2.13), delivery (OR = 1.43; 95% CI, 1.01-2.02), and postpartum (OR = 1.94; 95% CI, 1.40-2.69) than women with spontaneous pregnancy. No increased likelihood of neonatal problems was observed in this group except for twin pregnancy (OR = 9.17; 95% CI, 6.02-13.96) and prematurity (OR = 1.43; 95% CI, 1.01-2.02). No differences were observed between spontaneous pregnancies and those achieved by artificial insemination. Pregnancies achieved through IVF present a higher risk of complications before, during and after delivery. However, there is no increased risk of neonatal problems except for a higher likelihood of twin pregnancy and prematurity.


Cadmium induces apoptotic cell death through p38 MAPK in brain microvessel endothelial cells.
Cadmium (Cd), an ubiquitous heavy metal, is known to be accumulated outside of the blood-brain barrier. In this study, we investigated whether Cd has cytotoxicity in mouse brain microvascular endothelial cells (bEnd.3). Results from the cell viability assay showed that Cd caused a remarkable decrease in cell viability in a dose-dependent manner. The cell death induced by Cd appeared to involve apoptosis, based on our results from annexin V staining, electron microscopy and TUNEL staining. And the cell death induced by Cd was inhibited by caspase inhibitor ZVAD-fmk. To further investigate the mechanism of the Cd-induced cell death, we examined the effects of selective inhibitors for mitogen activated protein kinase (MAPK) pathways on the cell death. The Cd-induced cell death was significantly inhibited by p38 MAPK inhibitor SB202190, but not by either, c-Jun N-terminal kinase (JNK) inhibitor SP600125 or extracellular signal-regulated kinase (ERK) inhibitor U0126. Phosphorylations of p38 MAPK, JNK and ERK were stimulated by treatment with CdCl(2). In summary, our results suggest that Cd can induce apoptotic cell death, at least in part, through the p38 MAPK pathway in brain microvascular endothelial cells.


Note on Thorson and Powell: undertakers' sense of humor.
Recently Thorson and Powell reported in this journal that morticians scored significantly lower on a multidimensional sense of humor scale than another group of similarly aged men from other occupations. These findings differ markedly with some in 1991 from a 2-yr. ethnographic study conducted with morticians and funeral directors in four states regarding how they managed the stigma associated with their occupation.


Interoceptive and integrative contributions of forebrain and brainstem to energy balance control.
An anatomically distributed model of energy balance control contrasts with the widely held hypothalamic center model. The distributionist model is recommended by the observations that the caudal brainstem contains critical interoceptive, integrative and neurochemical mediating functions. A prominent example of interoceptive function is sensitivity to the adipose tissue-derived hormone, leptin. To complement the well established focus on hypothalamic leptin receptors (Ob-Rb), we describe an extensive distribution of Ob-Rb in the brainstem. These receptors, moreover, are functionally relevant given the intake suppressive effects of fourth-intracerebroventricular (i.c.v) and brainstem intraparenchymal (in dorsal vagal complex) delivery. A wide variety of intake relevant peptides receptors are found in hypothalamus, but these receptors are also widely distributed in the caudal brainstem. As an example of the functional relevance of these neurochemical mediators, we describe ingestive effects of ligands for melanocortin 3/4 and corticotrophin-releasing hormone receptors obtained with brainstem ventricular and parenchymal (dorsal vagal complex and parabrachial nucleus) delivery. It is clear that responses obtained from hypothalamic treatments can arise independently from stimulation of caudal brainstem receptors. We have used the chronic decerebrate preparation to ask whether the brainstem contains integrative substrates sufficient to mediate behavioral responses to variations in physiological state. The experiments reveal that the brainstem is indeed sufficient for the integration of taste and gastrointestinal signals that co-determine the size of meals in the short term. Decerebrate rats, however, do not respond to food deprivation or to reductions in the number of daily feeding opportunities. These results suggest that the brainstem in neural isolation from forebrain influence is not sufficient for ingestive response to systemic/metabolic signals that affect intake over the long term. The relative contribution of brainstem and forebrain substrates to long-term intake and body weight control in the neurologically intact animal, remains unclear. The data reviewed support a distributed anatomical model of energy balance and recommend increased attention to specific responses (behavioral, autonomic and endocrine) that are mediated by local (brainstem or forebrain) interoceptive and integrative processes, and those requiring bi-directional interactions.


Synthesis and biological evaluation of a fluorine-18-labeled nonsteroidal androgen receptor antagonist, N-(3-[18F]fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide.
Androgen receptor (AR), which is overexpressed in most prostate cancers, is the target of androgen ablation and antiandrogen therapies: it is also the target for the receptor-mediated imaging of AR-positive prostate cancer using radiolabeled ligands. Previous AR imaging agents were based on a steroidal core labeled with fluorine. To develop a novel class of nonsteroidal imaging agents, with binding and pharmacological characteristics that are more similar to those of clinically used AR antagonists, we synthesized N-(3-fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide (3-F-NNDI), an analog of recently reported AR antagonist ligands. 3-F-NNDI was synthesized in six steps starting with 1-nitronaphthalene, with fluorine incorporation as the final step. The labeling of 3-F-NNDI with fluorine-18 was achieved through a novel, extremely mild, S(N)Ar displacement reaction of an o-nitro-activated arene trimethylammonium salt, and 3-[(18)F]F-NNDI was prepared in high specific activity. 3-F-NNDI was found to have an AR-binding affinity similar to that of its parent compound. In vitro assays demonstrated high stability of the labeled compound under physiological conditions in buffer and in the blood. Androgen target tissue uptake in diethylstilbestrol-pretreated male rats, however, was minimal, probably because of extensive metabolic defluorination the radiolabeled ligand. This study is part of our first look at a novel class of nonsteroidal AR antagonists as positron emission tomography (PET) imaging agents that are alternatives to steroidal AR agonist-based imaging agents. Although 3-[(18)F]F-NNDI has significant affinity for AR, it showed limited promise as a PET imaging agent because of its poor target tissue distribution properties.


Image quality in conventional lumbar spine radiography: evaluation using the post-processing tool Diamond View.
Conventional radiography contributes for the majority of examinations in radiology departments. Based on the European Commission Quality Criteria we evaluated the effects on image quality when applying the new post-processing tool Diamond View (Siemens AG Medical Solutions, Germany) to conventional lumbar spine radiographs. 100 digital image pairs in two directions in two planes of lumbar spine radiographs were prospectively evaluated by two radiologists. Statistical analysis was performed with a p-value<.05 considered as significant. Images were evaluated on basis of the modified imaging Quality Criteria by the Commission of the European Communities, rated on a five-point scale. Statistical analysis showed an overall tendency for improved image quality of Diamond View (DV) for all criteria. Significant differences could be found in most of the criteria. Additional phantom analyses supported the advantage of DV. In conclusion DV improves image quality in conventional lumbar spine radiographs.


Establishing the follitropin delta dose that provides a comparable ovarian response to 150 IU/day follitropin alfa.
The objective of this investigation was to determine the daily follitropin delta dose (µg) providing a similar ovarian response to 150 IU/day follitropin alfa. The study was a post-hoc analysis of ovarian response in 1591 IVF/intracytoplasmic sperm injection (ICSI) patients undergoing ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol in two recent randomized, assessor-blind, controlled trials in the development programme for follitropin delta: a phase II dose-response trial with a reference arm of a fixed daily dose of 150 IU follitropin alfa throughout stimulation, and a phase III efficacy trial with a comparator arm of 150 IU/day follitropin alfa as a starting dose. Daily follitropin delta doses of 10.0 µg (95% confidence interval [CI] 7.9-12.8) and 10.3 µg (95% CI 9.7-10.8) yielded the same number of oocytes as 150 IU/day follitropin alfa for all patients participating in the phase II and III trials, respectively. When analysing patients with either normal or high ovarian reserve (based on serum anti-Mullerian hormone ≥15 pmol/l) and no dose changes, the same number of oocytes was obtained with 150 IU/day follitropin alfa and daily doses of follitropin delta of 9.7 µg (95% CI 7.5-12.4) and 9.3 µg (95% CI 8.6-10.1) in the two trials. Daily follitropin delta doses in the range 9.5-10.4 µg were consistently estimated to correspond to 150 IU/day follitropin alfa for serum oestradiol concentration and number of follicles ≥12 mm at the end of stimulation across analysis populations in the phase III trial. A daily follitropin delta dose of 10 µg provides a similar ovarian response to 150 IU/day follitropin alfa in IVF/ICSI patients.


Brain Development Includes Linear and Multiple Nonlinear Trajectories: A Cross-Sectional Resting-State Functional Magnetic Resonance Imaging Study.
Studies of brain structure have shown that the cortex matures in both a linear and nonlinear manner depending on the time window and specific region studied. In addition, it has been shown that socioeconomic status can impact brain development throughout childhood. However, very few studies have evaluated these patterns using functional measures. To this end, in this study we used cross-sectional resting-state functional magnetic resonance imaging data of 368 subjects, age 3-21 years, to examine the linear and nonlinear development of brain connectivity. We employed a clustering approach to characterize these developmental patterns into different linear and nonlinear groups. Our results showed that functional brain development exhibits multiple types of linear and nonlinear patterns, and assuming that brain connectivity values reach a stable state after a specific age might be misleading.


The mRNA stability of NCAPG2, a novel contributor to breast invasive carcinoma, is enhanced by the RNA-binding protein PCBP2.
Non-SMC condensin II complex subunit G2 (NCAPG2) is one of the three non-SMC subunits in condensin II, which plays a vital role in regulating chromosome condensation and segregation. Although the tumor-promoting role of NCAPG2 has been reported in several solid malignancies, its function in breast invasive carcinoma (BRCA) remains unknown. Data both from GEPIA and GSE36295 indicated that NCAPG2 mRNA expression was abnormally upregulated in cancer tissues, which was further verified in 40 paired BRCA and para-carcinoma samples. Kaplan-Meier Plotter further illustrated that BRCA patients with higher NCAPG2 expression have a poorer prognosis. Functional experiments carried out in two BRCA cell lines (MCF-7 and T-47D) showed that NCAPG2-silenced BRCA cells acquired less aggressive behavior - weakened growth and metastasis both in vitro and in vivo. Label-free proteomics quantified the protein expression patterns in MCF-7 cells, and the results revealed 684 differentially expressed proteins (|log2FC| > 1 and P < 0.05) downstream to NCAPG2. Interestingly, poly(C)-binding protein 2 (PCBP2), an RNA binding protein previously known to increase RNA stability of its target genes, was found to directly bind to and protect NCAPG2 mRNA from degradation-PCBP2 knockdown accelerated the degradation half-life time of NCAPG2 mRNA from approximately 8 h to 5 h. Taken together, our study indicates that NCAPG2 acts as a novel contributor to BRCA growth and metastasis under the regulation of PCBP2, providing insights into BRCA treatment.


Enzyme immunoassay of cortisol in human plasma using penicillinase as label.
An enzyme immunoassay for cortisol in human plasma using an antiserum raised against cortisol-3-O-carboxy-methyloxime bovine serum albumin and cortisol-21-hemisuccinate conjugated to penicillinase as tracer is described. Although employing immunoassay plates for separation of antigen-antibody complex from the free components was less time consuming, the slope and sensitivity of the standard curve were improved by the addition of goat anti-rabbit gamma globulin for precipitating the complex. There was good correlation between radioimmunoassay and enzyme immunoassay results obtained for cortisol levels present in normal human plasma.


Coronavirus infection in mink (Mustela vison). Serological evidence of infection with a coronavirus related to transmissible gastroenteritis virus and porcine epidemic diarrhea virus.
Antibodies to a transmissible gastroenteritis virus (TGEV)-related coronavirus have been demonstrated in mink sera by indirect immunofluorescence, peroxidase-linked antibody assays and immunoblotting. This is the first serological evidence of a specific coronavirus infection in mink. The putative mink coronavirus (MCV) seems to be widespread in the Danish mink population with a prevalence approaching 100%. Analysis by immunoblotting has shown that MCV is closely related to TGEV by the spike (S), matrix (M) and nucleoprotein (N) polypeptides. Furthermore, antibodies to MCV also cross-reacted with N and M polypeptides of porcine epidemic diarrhea virus (PEDV). Thus MCV may occupy an intermediate position between the TGEV group of coronavirus and PEDV. The possibility that MCV may be associated with syndromes of acute enteritis in preweaning mink is discussed.


Phenotypic and genetic patterns of resistance to the pathogen Phakopsora pachyrhizi in populations of Glycine canescens.
Phenotypic patterns of resistance to nine races of the pathogen Phakopsora pachyrhizi (soybean rust) in two natural populations of Glycine canescens were determined. In both populations there was considerable variability both within and between different host lines in their resistance or susceptibility to the nine different pathogen races. The genetic basis of these patterns of resistance was analyzed through an extensive series of crosses. In both host populations resistance was conditioned by single dominant genes with major phenotypic effects. One, two or three such genes were present in each host line. Using the principles of the gene-for-gene hypothesis, knowledge about the number of resistance genes present in each host line and by cross comparison of the phenotypic patterns of disease resistance detected in each line, estimates were made of the number of resistance genes or alleles present in each population of G. canescens. The two populations contained a minimum of 10 and 12 resistance genes. The relevance of these results to agriculture is discussed briefly.


How clonal are Trypanosoma and Leishmania?
The clonal theory of parasitic protozoa has been recently challenged by researchers stating that recombination in Kinetoplastida is much more frequent than previously believed, or that selfing and homogamy should be distinguished from 'strict' clonality. These researchers and many others show that the concept of clonality proposed by us is not correctly understood. A recapitulation of the clonal theory will thus be addressed herein. Comparisons with various other pathogens evidence general features among them and enhance our understanding of Trypanosoma and Leishmania population genetics. The relevance is considerable not only for our knowledge of the basic biology of these organisms but also for applied research: molecular epidemiology (strain-typing), clinical research, vaccine and drug design, and experimental evolution.


Zinc metabolism and homeostasis: the application of tracer techniques to human zinc physiology.
Tracer kinetic techniques based on zinc stable isotopes have a vital role in advancing knowledge of human zinc physiology and homeostasis. These techniques have demonstrated the complexity of zinc metabolism, and have been critical to estimating the size and interrelationships of those pools of zinc that exchange rapidly with zinc in plasma and which are likely to be especially important for zinc dependent biology. This paper presents findings from recent research linking a steady state compartmental model with non-steady state post-prandial sampling from the intestine, utilizing a combination of intestinal intubation/perfusion and stable isotope tracer kinetic techniques. The gastrointestinal tract has a central role in maintaining whole body zinc homeostasis. While the fractional absorption of zinc from a meal depends on the quantity of exogenous zinc and on such dietary factors as phytic acid, the fractional absorption does not appear to be dependent on the size of the rapidly exchanging pool of the host. In contrast, the quantity of endogenous zinc excreted via the intestine is positively correlated with both the amount of absorbed zinc and the zinc 'status' of the host, and thus this process has an equally critical role in maintaining zinc homeostasis. The observed alterations in zinc metabolism in some disease states can be understood in the context of known homeostatic processes. In other conditions, however, such alterations as inflammation-associated hyperzincuria and zinc redistribution, the links between homeostatic perturbation and cellular biology are yet to be explained. Thus the challenge remains for research at the whole body level to carefully characterize zinc distribution and exchange under diverse circumstances, while research at the cellular level must elucidate the regulatory processes and the factors to which they respond.


Trapezoidal Achilles Tendon Allograft Plug for Revision Quadriceps Tendon Repair With a Large Tendon Defect.
Revision quadriceps tendon repair presents a challenging problem for the treating surgeon because of associated anatomic defects such as large tendon-gap deficits and preexistent poor tissue quality. Current methods for revision quadriceps tendon repair use tendon autograft, which may predispose to additional morbidity because the repair relies only on soft tissue fixation. In this Technical Note, we describe a technique for revision of a failed quadriceps tendon repair with a large tendon gap using a trapezoidal plug Achilles tendon allograft. This technique constitutes a safe and effective approach to revising failed primary quadriceps tendon repairs, is suitable for large-gap defects, and has the ability to withstand large force transmissions.


Results of orthotopic heart transplantation with and without the use of maintenance steroids.
From March 1984 to June 1987, 51 patients underwent primary orthotopic heart transplantation at the Second University Department of Surgery, Vienna. Recipients were immunosuppressed with a combination of either ciclosporine and azathioprin (double drug regimen = DD, 10 patients), or ciclosporine, azathioprin and low-dose steroids (triple drug regimen = TD, 33 patients). Four patients who died intra- or perioperatively and 4 who were switched to conventional therapy were excluded from analysis. In both groups, ciclosporine was administered to obtain whole blood HPLC trough levels of 200-400 ng/ml in the 1st month, 150-250 ng/ml from the 2nd to the 6th and 100-150 ng/ml after the 6th month. Azathioprin 2 mg/kg per day was given, and in TD patients, an additional 0.2 mg/kg per day of prednisolon: all patients received prophylactic antithymocyte globulin for 7-10 days postoperatively. Five deaths from acute rejection in the DD group contrasted with none in the TD group. The high incidence of fatal rejection episodes was reflected in a 40% Kaplan-Meier 1-year survival for DD vs 84% for TD (p less than 0.0001). Analysis of endomyocardial biopsies (DD vs TD) demonstrated 20.4% vs 57.0% absent, 46.0% vs 29.5% mild, 31.2% vs 12.4% moderate and 2.4% vs 1.1% severe rejection. Fatal and nonfatal infections and toxic side effects occurred with the same frequency in both protocols. Calculation of mean ciclosporine levels resulted in 249.7 ng/ml (TD) and 206.0 ng/ml (DD) in the 1st month (p less than 0.05). Consequently, adjunctive maintenance low-dose steroids combined with increased ciclosporine levels in the early posttransplant course are considered responsible for the improved results.


Doctors' prescription behaviour regarding dosage recommendations for preparations of kava extracts.
There are many publications on the use of kava extracts as a treatment alternative to tricyclic antidepressants and benzodiazepines, but little has been done to investigate the potential adverse effects that may be associated with prolonged or high-dose usage. To investigate the extent to which physicians comply with the recommended daily dose (RDD) of an antidepressant such as kava and the consequences of this behaviour with regard to the safety and efficacy of frequently prescribed kava extracts (Trade names: Antares, Laitan and Kavasporal forte). The analysis was carried out using the patient database MediPlus, which provides anonymous access to a representative and valid panel of physicians and patients in Germany. Prescriptions for Antares showed that the RDD of 1 tablet per day was exceeded in 58.2% of the cases, while those for Laitan showed that the RDD of 1 capsule per day was significantly exceeded in 75.6% of the cases; a one-off prescription was issued in 66% of the cases. As a result, the required effect diminished very quickly. Prescriptions for Kavasporal forte showed that the daily dosage of 2 capsules per day complied with the recommendations in only 49.1% of the cases; in 38.8% of the cases, the dosage dropped below the respective recommendation. As a consequence, the lower-dosed Kavasporal forte was prescribed for longer periods than the higher-dosed Antares and Laitan. In the case of a low-dosage recommendation, we saw a trend to over-dose in prescribing behaviour, which increases the risk of undesirable adverse reactions. On the other hand, we saw a trend to under-dose in the case of a higher dosage recommendation. This fact may explain the unexpected inefficacy of the therapy. These trends affected the duration of therapy, whereby a dosage lower than the RDD was prescribed for a longer period than a dosage higher than the RDD.


End Group Functionalization of PFpP Macromolecules Via Fp Migration Insertion Reactions.
PFpP macromolecules, synthesized via migration insertion polymerization of CpFe(CO)2 (CH2)3 PPh2 (FpP), exhibit reactive Fp end groups for further migration insertion reactions in the presence of phosphines. A number of alkyl diphenylphosphines with varied alkyl length, Ph2PCn (n = 6, 10, 18), have been prepared for the reaction, resulting in PFpP-PPh2Cn (n = 6, 10, 18) amphiphiles. The phosphines with longer alkyl chains impose steric hindrance for the reaction and therefore require longer reaction times and excess phosphines relative to PFpP.


Macrophage-lymphocyte cluster formation in the medullary sinus of lymph node after immunization with sheep red blood cells (SRBC).
Normally the lymphatic sinuses of the lymph node are loosely packed with lymphocytes and free macrophages as well as with macrophages adhering to the fibrocellular trabeculae. After immunization with SRBC cluster formation occurs in the medullary sinuses of rats between a central macrophage and peripherally located lymphocytes. These rosette-like clusters are nearly identical with the clusters found during primary and secondary immune response against SRBC in vitro and seem to be the in vivo equivalent for the same immune response.


Determination of ultra trace amounts of metronidazole by 3-phenyl-N-[4-(10,15,20-triphenyl-porphyrin-5-yl)-phenyl]- acrylamide as the fluorescence spectral probe in CTAB microemulsion.
In this work, 3-Phenyl-N-[4-(10,15,20-triphenyl-porphyrin-5-yl)-phenyl]- acrylamide (TPPCA) was synthesized for the determination of metronidazole (MTZ). It was found that the type of fluorescence quenching was static quenching determined by Stern-Volmer plot and UV absorption spectroscopy, and thermodynamic related parameters were also obtained. Furthermore, the corresponding measurement conditions: the acidity of the system, the type of surfactant, the concentration of TPPCA and the sequence of reagent addition were optimized. Under the optimal experimental conditions, the linear range of MTZ was determined to be 0.01-0.20 μg mL-1, and the limit of detection (LOD) was 0.004 μg mL-1. Importantly, this report provides a simple, fast, and sensitive probe for the determination of MTZ in pharmaceutical practice.


Occurrence of periodontal bacteria in healthy children: a 2-year longitudinal study.
To examine the occurrence of specific periodontal bacteria in children and adolescents. Ten putative periodontal bacteria were longitudinally examined in plaque and saliva samples from 119 periodontally healthy children (2-15 years old) using a polymerase chain reaction method. Capnocytophaga ochracea, C. sputigena, and Actinobacillus actinomycetemcomitans were frequently found in saliva, and tended to persist in saliva for the remainder of the study, whereas Porphyromonas gingivalis, Treponema denticola, and Prevotella intermedia were rarely detected. P. nigrescens was more frequently detected in plaque and its prevalence increased with age. Eikenella corrodens and Campylobacter rectus were sometimes detected in both plaque and saliva, while Tannerella forsythensis was occasionally detected in saliva. A. actinomycetemcomitans, C. ochracea, C. sputigena, P. nigrescens, C. rectus, and E. corrodens are common members of the oral microbial flora of healthy children, whereas P. gingivalis, P. intermedia, and T. denticola appear to be transient organisms.


Concordance of dietary sodium intake and concomitant phosphate load: Implications for sodium interventions.
Both a high dietary sodium and high phosphate load are associated with an increased cardiovascular risk in patients with chronic kidney disease (CKD), and possibly also in non-CKD populations. Sodium and phosphate are abundantly present in processed food. We hypothesized that (modulation of) dietary sodium is accompanied by changes in phosphate load across populations with normal and impaired renal function. We first investigated the association between sodium and phosphate load in 24-h urine samples from healthy controls (n = 252), patients with type 2 diabetes mellitus (DM, n = 255) and renal transplant recipients (RTR, n = 705). Secondly, we assessed the effect of sodium restriction on phosphate excretion in a nondiabetic CKD cohort (ND-CKD: n = 43) and a diabetic CKD cohort (D-CKD: n = 39). Sodium excretion correlated with phosphate excretion in healthy controls (R = 0.386, P < 0.001), DM (R = 0.490, P < 0.001), and RTR (R = 0.519, P < 0.001). This correlation was also present during regular sodium intake in the intervention studies (ND-CKD: R = 0.491, P < 0.001; D-CKD: R = 0.729, P < 0.001). In multivariable regression analysis, sodium excretion remained significantly correlated with phosphate excretion after adjustment for age, gender, BMI, and eGFR in all observational cohorts. In ND-CKD and D-CKD moderate sodium restriction reduced phosphate excretion (31 ± 10 to 28 ± 10 mmol/d; P = 0.04 and 26 ± 11 to 23 ± 9 mmol/d; P = 0.02 respectively). Dietary exposure to sodium and phosphate are correlated across the spectrum of renal function impairment. The concomitant reduction in phosphate intake accompanying sodium restriction underlines the off-target effects on other nutritional components, which may contribute to the beneficial cardiovascular effects of sodium restriction. (f) Registration numbers: Dutch Trial Register NTR675, NTR2366.


Cascade polycyclization: exploration of a convergent route to access various tricyclic and tetracyclic products related to sterols.
The expedient synthesis of tricyclic and tetracyclic compounds via a cascade polycyclization methodology is described. Nazarov substrates (II) containing two Michael acceptors and a cyclohexenone ester (I) underwent cycloaddition followed by intramolecular 1,4-addition to furnish, in a highly stereoselective manner, tricyclic and tetracyclic products (III). Such compounds are interesting intermediates for the synthesis of polycyclic natural and unnatural products.


Transient use of a systemic adenosine kinase inhibitor attenuates epilepsy development in mice.
Over one-third of all patients with epilepsy are refractory to treatment and there is an urgent need to develop new drugs that can prevent the development and progression of epilepsy. Epileptogenesis is characterized by distinct histopathologic and biochemical changes, which include astrogliosis and increased expression of the adenosine-metabolizing enzyme adenosine kinase (ADK; EC 126.96.36.199). Increased expression of ADK contributes to epileptogenesis and is therefore a target for therapeutic intervention. We tested the prediction that the transient use of an ADK inhibitor administered during the latent phase of epileptogenesis can mitigate the development of epilepsy. We used the intrahippocampal kainic acid (KA) mouse model of temporal lobe epilepsy, which is characterized by ipsilateral hippocampal sclerosis with granule cell dispersion and the development of recurrent hippocampal paroxysmal discharges (HPDs). KA-injected mice were treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 1.6 mg/kg, b.i.d., i.p.) during the latent phase of epileptogenesis from day 3-8 after injury; the period when gradual increases in hippocampal ADK expression begin to manifest. HPDs were assessed at 6 and 9 weeks after KA administration followed by epilepsy histopathology including assessment of granule cell dispersion, astrogliosis, and ADK expression. 5-ITU significantly reduced the percent time in seizures by at least 80% in 56% of mice at 6 weeks post-KA. This reduction in seizure activity was maintained in 40% of 5-ITU-treated mice at 9 weeks. 5-ITU also suppressed granule cell dispersion and prevented maladaptive ADK increases in these protected mice. Our results show that the transient use of a small-molecule ADK inhibitor, given during the early stages of epileptogenesis, has antiepileptogenic disease-modifying properties, which provides the rationale for further investigation into the development of a novel class of antiepileptogenic ADK inhibitors with increased efficacy for epilepsy prevention.


Investigating Betrixaban Maleate drug degradation profiles, isolation and characterization of unknown degradation products by mass-triggered preparative HPLC, HRMS, and NMR.
Betrixaban Maleate, a novel oral, once-daily factor Xa inhibitor drug substance, was subjected to stress testing under a wide range of degradation conditions, including acidic hydrolysis, alkaline hydrolysis, oxidative, thermal, and photolytic, to determine its inherent stability. The drug was biodegradable in acidic and alkaline environments, and three new degradation products were identified. Two degraded products are formed in an acidic environment, while the third is in alkaline conditions. The three degradants were identified using UPLC-ESI/MS and isolated using mass-triggered preparative HPLC, and their structures were unambiguously elucidated using HRMS and 2D NMR techniques. Based on spectral and chromatographic data, it was firmly proven that these distinct degradation products were the betrixaban chemical's hydrolysis components. The formation of the degradants has been hypothesized through several possible mechanisms.


Cultural Immersion as a Strategy for Empowerment.
Cultural immersion experiences offered through study abroad opportunities for nursing students have been increasing in recent years. Examining the impact of these experiences has largely focused on students and not on the faculty leading the experiences. It is important to understand the impact of these experiences on all participants. Exploring the literature on empowerment provides some clarity on the relationship between studying abroad and its impact on participants. Further research linking cultural immersion experiences with empowerment is needed to better understand this relationship and the possibilities of empowering both students and faculty engaged in these exciting opportunities.


Genetic syndromic immunodeficiencies with antibody defects.
This article reviews the major syndromic immunodeficiencies with significant antibody defects, many of which may require intravenous immunogammaglobulin therapy. The authors define syndromic immunodeficiency as an illness associated with a characteristic group of phenotypic abnormalities or laboratory features that comprise a recognizable syndrome. Many are familial with a defined inheritance pattern. Immunodeficiency may not be a major part of the illness and may not be present in all patients; thus, these conditions differ from primary immunodeficiency syndromes, in which immune abnormalities are a consistent and prominent feature of their disease.


[Home return Assistance Program for Chronic heart failure in-hospitalized patients (PRADO-IC) : Description, evaluations, perspectives].
Return to home after discharge for congestive heart failure (CHF) is associated with prolonged and recurrent hospitalizations, the prognosis remains poor. Since 2013, the Caisse Nationale d'Assurance Maladie (CNAM) with the Société Française de Cardiologie (SFC) has set up a support program PRADO-IC (support program for returning home after hospitalization for heart failure). was to describe the program, to present epidemiologic data, and the evaluations by the CNAM, and by clinical studies, then to expose strengths limits and perspectives. After the inclusion a CPAM advisor organize the outcome, the care of the outpatient is based on his general practitioner (GP) and a private nurse trained in CHF care during a three-months program. Between 2017 and 2019, 20 264 patients per year were hospitalized in Ile de France, 8.8% were included in PRADO-IC. The retrospective CNAM evaluations were positive: follow up criteria were improved and mortality rate at 6 months was lower (10.3% vs. 14.1%). However, clinical retrospective study of Troyes hospital (n = 89), and Paris Saint Joseph Hospital (n = 633), did not confirm these results: rate mortality and/or re-hospitalization were not different between patients and control. Several prospective studies are underway; results will be soon available. Limits of PRADO-IC are discussed like the lack of inclusion criteria, lack of geriatric evaluation, or the pivotal role based on GP, and the short term of duration. Strengths are its existence, national reach, multi-disciplinary approach, educational contents. Clinical studies showed that the PRADO-IC program concerned to the most severe patients. Despite this, the one-year mortality and the HF readmission rate are the same than out-program patients. PRADO-IC is the one and the only national transition of care program for IC patients. First evaluations are positive but prospective evaluation studies are needed in order to limit methodologic bias.


Best nonsurgical managements of acute urinary retention: what's new?
To provide a comprehensive review of the nonsurgical management of acute urinary retention (AUR). A recent meta-analysis confirmed that α-blockers are associated with higher rates of successful trial without catheter (TWOC) compared with placebo, while combination therapies do not significantly reduce the rate of recatheterization. Compared with standard TWOC, bladder perfusion with physiological serum prior to catheter removal is a simple and cost-effective method to increase TWOC success rates (odds ratio 2.41, 95% confidence interval 1.53-3.8), and to reduce time-to-discharge (-89.68 min, 95% confidence interval -160.55, -18.88). Clean intermittent catheterization (CIC) is increasingly used for urinary retention in patients with benign prostatic hyperplasia as existing data suggest that it may decrease the risk of urinary tract infections, accelerate spontaneous voiding recovery and might be more cost-effective compared with indwelling urethral catheterization. Ongoing trials are examining whether office-placed prostate stent may be a promising solution in patients with AUR. The recent development of alternative approaches to traditional TWOC may lead to new therapies for treating patients with AUR. Further studies are needed as the level of evidence from published studies remains low.


Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.
To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).


Magnetic resonance imaging of the so-called cerebral cryptic angiomas.
Cerebral cryptic angiomas are vascular malformations with variable histological appearance, but with similar radiological features. Angiography does not usually visualize the lesion. Computer tomography often detects the malformation, but frequently fails to make classify correctly. With magnetic resonance imaging (MRI) the cryptic angioma is studied best on T2 weighted images. The pattern of signal intensities differs both among and within the lesions. Evidence of small hemorrhages of different ages and flow phenomena are seen in all malformations. A total of 51 angiomas were demonstrated in 38 patients by MRI (excluding one patient with a very large number of angiomas). Enhanced or plain CT scans depicted respectively 16 and 6 lesions. In one case angiography was the only way to detect an angioma. Currently, MRI is the most sensitive method for the detection of cerebral cryptic angiomas.


The crypt cycle. Crypt and villus production in the adult intestinal epithelium.
We propose a model for the growth of individual crypts that is able to account for the observed changes in the number of cells in crypts under normal conditions, after irradiation, and after 30% resection. Parameter values for this model are estimated both for mouse and man, and detailed predictions of crypt growth rates are made. This model does not predict a steady-state crypt size; rather it suggests that crypts grow until they bifurcate. We therefore propose a crypt cycle (analogous to the cell cycle) and present evidence that most if not all crypts in the adult mouse are cycling asynchronously and independently. This evidence consists of four experiments that indicate that branching crypts are randomly distributed over the intestinal epithelium, that the plane of bifurcation of branching crypts is randomly oriented with respect to the villus base, and that the size distribution of crypts is consistent with an expanding crypt population. We also report for the first time evidence of villus production in the adult mouse intestinal epithelium. We conclude that the crypt and villus populations in the adult mouse are not in a steady state.


Liver stiffness values in HIV-infected patients with isolated anti-hepatitis B core antibodies.
Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population. We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values. Fifty-one out of 69 patients (74%) had low LSV (≤7.1 kPa). In univariate analysis, high LSV (>7.1 kPa) were associated with HCV coinfection, the duration of HIV infection, the duration of antiretroviral therapy and lipodystrophy. In age-adjusted multivariate analysis, HCV coinfection (OR 11.5; 95% CI, 3.0-62.9; P=0.001) and lipodystrophy (OR 4.6; 95% CI, 1.1-20.7; P=0.031) remained associated with high liver stiffness values. Lipodystrophy was the only factor associated with high liver stiffness values in our population of HIV-infected patients with isolated anti-Hbc and extensive exposure to antiretroviral drugs active on HBV, apart from HCV coinfection Our study correlates to recent studies the results of which have shown that lipodystrophy, and more generally mitochondrial toxicity, was associated with advanced liver fibrosis in HIV/HCV co-infected patients.


Effects of endomycorrhizal infection, artificial herbivory, and parental cross on growth of Lotus corniculatus L.
We examined how combinations of parentage, fungicide application, and artificial herbivory influence growth and shoot phosphorus content in pre-reproductive Lotus corniculatus, using young offspring arising from three parental crosses, two of which had one parent in common. Soil with vesicular-arbuscular mycorrhizal (VAM) fungi was treated with either water or benomyl, an anti-VAM fungicide, and added to trays containing groups of four full siblings. There were two experiments; in the first no plants were clipped while in the second two of the four plants were clipped to simulate herbivory. In both experiments plants of the two related crosses accumulated more biomass and total shoot P than did plants of the third cross. Plants inoculated with watertreated soil had greater shoot mass and P concentration than did fungicide-treated replicates but the extent of increase in P concentration varied among crosses. In Experiment 2, clipping reduced root mass and resulted in higher shoot P concentration. In this experiment there was a significant interaction of fungicide application and clipping: both unclipped and clipped plants grew better in soil not treated with fungicide, but the increase in shoot mass, total mass, and total P was greater in unclipped plants. Significant interaction of fungicide treatment and clipping is most likely due to reduced availability of carbon to the roots of clipped plants, resulting in poorer symbiotic functioning.


An internal medicine interest group research program can improve scholarly productivity of medical students and foster mentoring relationships with internists.
Shortages in primary care careers such as internal medicine are projected in the future. Conducting research is an explicit requirement for graduate medical education and interest in research is growing in undergraduate medical education. We hypothesized that a medical student research initiative could increase student research productivity and foster mentoring relationships with internists. We compared the number of medical student presentations, awards, and peer-reviewed publications before and after a brief research initiative at a single institution and recorded comments from student participants; data collected before the initiative were retrospective, and data after the initiative were collected prospectively. Mann-Whitney U was used for statistical analysis. Twenty-seven students participated in our workshop initiative during the study period (2000-2005). Eighteen (67%) subsequently had presentations, research awards, and/or publications during the study period. Mann-Whitney U testing of groups (all pre-initiative Uniformed Services University students and initiative participants) showed a statistically significant increase in regional presentations (p = .003), research awards (p = .01), and publications (p = .02) after the research initiative. Student comments not only revealed research mentoring benefits but also commented on receiving career counseling advice from mentors. Our study findings support the feasibility of this initiative as well as produced significant outcomes in terms of quantified research productivity and student mentoring.


High resolution single particle refinement in EMAN2.1.
EMAN2.1 is a complete image processing suite for quantitative analysis of grayscale images, with a primary focus on transmission electron microscopy, with complete workflows for performing high resolution single particle reconstruction, 2-D and 3-D heterogeneity analysis, random conical tilt reconstruction and subtomogram averaging, among other tasks. In this manuscript we provide the first detailed description of the high resolution single particle analysis pipeline and the philosophy behind its approach to the reconstruction problem. High resolution refinement is a fully automated process, and involves an advanced set of heuristics to select optimal algorithms for each specific refinement task. A gold standard FSC is produced automatically as part of refinement, providing a robust resolution estimate for the final map, and this is used to optimally filter the final CTF phase and amplitude corrected structure. Additional methods are in-place to reduce model bias during refinement, and to permit cross-validation using other computational methods.


Peer community health workers improve HIV testing and ART linkage among key populations in Zambia: retrospective observational results from the Z-CHECK project, 2019-2020.
Zambia has made tremendous progress towards HIV epidemic control; however, gaps remain among key populations (KPs), such as female sex workers (FSWs), men who have sex with men (MSM), people who inject drugs (PWID) and people in prisons and enclosed settings due to cultural, social and legal barriers. The University of Maryland, Baltimore Zambia Community HIV Epidemic Control for Key Populations (Z-CHECK) project aimed to improve HIV case-finding, linkage and treatment adherence at the community level for KPs in Zambia. We describe Z-CHECK strategies and examine HIV positivity yield and antiretroviral therapy (ART) linkage among KPs to inform ongoing programme improvement. Z-CHECK recruited, trained and deployed peer community health workers (CHWs) for KP groups, with ongoing mentorship in community engagement. CHWs offered HIV testing in safe spaces and escorted newly HIV-diagnosed clients for same-day ART initiation. Z-CHECK also reached out to KP community leaders and gatekeepers for KP mobilization and trained healthcare workers (HCWs) on KP services and sensitivity. We conducted a retrospective observational review of routinely collected aggregate data for KPs aged ≥15 years at high risk for HIV transmission across five districts in Zambia from January 2019 to December 2020. Z-CHECK provided HIV testing for 9211 KPs, of whom 2227 were HIV positive (positivity yield, 24%). Among these, 1901 (85%) were linked to ART; linkage for MSM, FSW, PWID and people in prisons and enclosed settings was 95%, 89%, 86% and 65%, respectively. Programme strategies that contributed to high positivity yield and linkage included the use of peer KP CHWs, social network testing strategies and opportunities for same-day ART initiation. Challenges to programme implementation included stigma and discrimination among HCWs, as well as KP CHW attrition, which may be explained by high mobility. Peer CHWs were highly effective at reaching KP communities, identifying persons living with HIV and linking them to care. Engaging KP community gatekeepers resulted in high diffusion of health messages and increased access to health resources. The mobility of CHWs and HCWs is a challenge for programme implementation. Innovative interventions are needed to support PWID and people in prisons and enclosed settings.


Breast cancer survival among Japanese individuals and US residents of Japanese and other origins: a comparative registry-based study.
Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US residents with Japanese origin (USJ), and US residents with other origins (USO). Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status. We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval [CI] 0.45-0.47 for Japanese and 0.66 [95% CI 0.59-0.74] for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 [95% CI 0.51-0.55] for Japanese and 0.53 [95% CI 0.52-0.74] for USJ). In stage I-III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.


Single-incision laparoscopic Heller myotomy and Dor fundoplication for achalasia: report of a case.
Our objective was to establish the efficiency of single-incision laparoscopic Heller myotomy and Dor fundoplication (SILHD) as treatment for esophageal achalasia. A 58-year-old man underwent SILHD for achalasia. The left triangular ligament was retracted using a suture thread and fixed to the body surface, providing a good operative field at the cardia. We performed a 7-cm long myotomy, extending 2 cm into the gastric wall, using a tissue-sealing device or L-shaped electrocautery. Oral intake resumed on postoperative day 1, and hospital stay was 4 days. No morbidity was observed. Based on our experience, we believe that the SILHD can be performed safely and seems to offer at least short-term benefits for selected patients with esophageal achalasia, when performed by surgeons experienced in laparoscopic and esophageal surgery.


Coccidioidomycosis Resulting in a Prosthetic Joint Infection in an Immunocompetent Patient after a Total Hip Arthroplasty: A Case Report and Review of the Literature.
Coccidioidomycosis is a fungal infection that is a rare cause of prosthetic joint infection (PJI) in patients. This case report describes an immunocompetent patient who had a right total hip arthroplasty (THA) complicated with Coccidioidomycosis. This patient is the 9th reported case of Coccidioidomycosis, causing a PJI and only the second case to be reported in a THA. Once progressed, it can be difficult to treat, often reoccurring and requiring repeat surgical and prolonged therapy. This study discusses the clinical presentation in this patient and reviews the literature on the currently published cases.


An efficient synthesis of the C-23 deoxy, 17 alpha-hydroxy South 1 hemisphere and its cephalostatin 1 analog.
[reaction: see text] Methods for functionalization of the D ring of diene 1 were investigated. This study led to efficient syntheses of 3 and the subsequent 23'-deoxy,17'alpha-hydroxy cephalostatin 1 analog (4). The bioactivity data of 2 and 4 are in the low nanomolar range for a 10-cell-line minipanel.


Impaired glucocorticoid receptor expression in liver disrupts feeding-induced gene expression, glucose uptake, and glycogen storage.
The transition from a fasted to a fed state is associated with extensive transcriptional remodeling in hepatocytes facilitated by hormonal- and nutritional-regulated transcription factors. Here, we use a liver-specific glucocorticoid receptor (GR) knockout (L-GRKO) model to investigate the temporal hepatic expression of GR target genes in response to feeding. Interestingly, in addition to the well-described fasting-regulated genes, we identify a subset of hepatic feeding-induced genes that requires GR for full expression. This includes Gck, which is important for hepatic glucose uptake, utilization, and storage. We show that insulin and glucocorticoids cooperatively regulate hepatic Gck expression in a direct GR-dependent manner by a 4.6 kb upstream GR binding site operating as a Gck enhancer. L-GRKO blunts preprandial and early postprandial Gck expression, which ultimately affects early postprandial hepatic glucose uptake, phosphorylation, and glycogen storage. Thus, GR is positively involved in feeding-induced gene expression and important for postprandial glucose metabolism in the liver.


Immunohistochemical study of A2B5-positive ganglioside in postmortem human brain tissue of Alzheimer disease, amyotrophic lateral sclerosis, progressive supranuclear palsy and control cases.
Localization of gangliosides positively stained by the monoclonal antibody A2B5 was investigated in postmortem brain tissue of Alzheimer disease, amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP) and control cases. In control cases, A2B5-staining was granular, appearing in selective neuronal populations. In the neocortex, the A2B5-positive neurons were distributed mainly in deep cortical layers. In the cerebellum, A2B5-positive structures were detected in processes extending from the Purkinje cell layer into the molecular layer. In Alzheimer cases, many neurofibrillary tangles, neuropil threads and dystrophic neurites were strongly A2B5-positive. In addition, aggregations of A2B5-positive granules were detected in some neurons lacking neurofibrillary tangles. Alterations of A2B5-positive gangliosides were also detected in ALS and PSP cases. In ALS cases, A2B5-positive granules were aggregated in Betz cells of the precentral gyrus. In PSP cases, globose-type neurofibrillary tangles were also strongly A2B5-positive. The results indicate that A2B5-positive gangliosides are widely but selectively distributed in human brain and may be involved in several neuropathological processes.


The relationship between negative life events and non-suicidal self-injury (NSSI) among Chinese junior high school students: the mediating role of emotions.
Adolescent non-suicidal self-injury (NSSI) is common and adolescence is the most common period of first self-injury, and the occurrence of NSSI is influenced by negative life events and emotional symptoms. The mediating role of emotional symptoms in the interaction between negative life events and NSSI has not been carefully investigated yet. For middle school students in three schools in a Chinese province, the Adolescents Self-Harm Scale was used to investigate NSSI, the Adolescent Self-Rating Life Events Check List was used to investigate adolescent negative life events, and the Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to assess their emotional symptoms. After the description of general data and the test for differences between groups, the relationship between negative life events, emotional symptoms and NSSI was analyzed using Pearson correlation analysis. Structural equation modeling was used to analyze the mediating role of emotions in negative life events and NSSI. A total of 2376 junior high school students completed this survey, which revealed an annual NSSI prevalence of 37.1% (n = 881) and a higher prevalence of NSSI among girls and rural adolescents. Among adolescents who developed NSSI, 67.4% (N = 594) used multiple means of self-injury. The most common means of self-injury was hair pulling (51.0%), and the most common NSSI purpose and external factors/events were venting bad emotions or feelings (57.5%) and poor academic performance (44.9%), respectively. Negative life events, emotional symptoms and NSSI were positively associated (P < 0.05). Structural equation modeling with negative life events, emotional symptoms and NSSI as variables showed that the model-fit index matched the data well, with RMSEA = 0.073, AGFI = 0.945, GFI = 0.980, CFI = 0.985, NFI = 0.982, TLI = 0.968, IFI = 0.985, and negative life events, emotional symptoms (anxiety, depression) and NSSI all had direct effects with standardized path coefficients of 0.16, 0.19, and 0.23, respectively, with negative life events playing an indirect role in NSSI through emotional symptoms and emotional symptoms playing an incomplete mediating role in negative life events and NSSI. The prevalence of NSSI was higher among Chinese junior high school students. Both negative life events and emotional symptoms were direct risk factors for NSSI. In addition, negative life events were also indirect risk factors for NSSI, and emotional symptoms played an incomplete mediating role in the relationship between the effects of negative life events and NSSI. This indicates that the combination of reducing the frequency of negative life events while maintaining individual emotional stability during adolescent development can effectively reduce the prevalence of NSSI in adolescents.


Developing a Prediction Model for Determination of Peanut Allergy Status in the Learning Early About Peanut Allergy (LEAP) Studies.
The Learning Early About Peanut Allergy (LEAP) study team developed a protocol-specific algorithm using dietary history, peanut-specific IgE, and skin prick test (SPT) to determine peanut allergy status if the oral food challenge (OFC) could not be administered or did not provide a determinant result. To investigate how well the algorithm determined allergy status in LEAP; to develop a new prediction model to determine peanut allergy status when OFC results are not available in LEAP Trio, a follow-up study of LEAP participants and their families; and to compare the new prediction model with the algorithm. The algorithm was developed for the LEAP protocol before the analysis of the primary outcome. Subsequently, a prediction model was developed using logistic regression. Using the protocol-specified algorithm, 73% (453/617) of allergy determinations matched the OFC, 0.6% (4/617) were mismatched, and 26% (160/617) participants were nonevaluable. The prediction model included SPT, peanut-specific IgE, Ara h 1, Ara h 2, and Ara h 3. The model inaccurately predicted 1 of 266 participants as allergic who were not allergic by OFC and 8 of 57 participants as not allergic who were allergic by OFC. The overall error rate was 9 of 323 (2.8%) with an area under the curve of 0.99. The prediction model additionally performed well in an external validation cohort. The prediction model performed with high sensitivity and accuracy, eliminated the problem of nonevaluable outcomes, and can be used to estimate peanut allergy status in the LEAP Trio study when OFC is not available.


Patterns and variability in the microplastic contamination along the southwest coast of India with emphasis on submarine groundwater discharge sites.
Beach sediments of the southwest coast of India were analysed to estimate the microplastic contamination with emphasis on the submarine groundwater discharge (SGD) zones. Both SGD and non-SGD sites were assessed for abundance, morphotype and polymer type of microplastics. Microplastic load was 230.429 ± 62.87 particles per 100 g. Fibre, mainly blue, was the abundant morphotype, followed by fragment, foam and film. The polymer types were POLYETHYLENE (PE) (30.77 %), POLYPROPYLENE (PP) (26.92 %), POLYAMIDE (PA) (19.23 %), POLYSTYRENE (PS) (11.54 %), ETHYLENE VINYL ACETATE (EVA) (7.692 %) and POLYVINYL CHLORIDE (PVC) (3.846 %). The SGD zones exhibited higher microplastic contamination with statistically significant variations from non SGD sites. The study accounts the levels of microplastic contamination along the southwest coast of India, a major fishery zone. The higher abundance of microplastic in the SGD zones indicates the significance of subterranean groundwater through flow as a pathway of anthropogenic contaminants towards marine ecosystems.


Polydipsia-hyponatraemia syndrome : epidemiology, clinical features and treatment.
The polydipsia-hyponatraemia syndrome (PHS) occurs in about 5 to 10% of institutionalised, chronically psychotic patients, 80% of whom have schizophrenia. Major clinical features are polydipsia and dilutional hyponatraemia. Complications of PHS include delirium, generalised seizures, coma and death.Nonpharmacological interventions are fluid restriction, diurnal bodyweight monitoring, behavioural approaches, and supplemental oral sodium chloride administration. These interventions require an experienced and dedicated multidisciplinary staff.A number of pharmacological treatments have been assessed for PHS including the combination of lithium and phenytoin, demeclocycline, propranolol, ACE inhibitors, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, typical antipsychotic drugs, clozapine and risperidone. Of these agents, the most promising are the combination of lithium and phenytoin, and clozapine.Integrated treatment requires a highly informed multidisciplinary staff, meticulous monitoring of diurnal weight gain and serum sodium level, and careful record keeping. Acute interventions of observation by trained staff, fluid restriction, water-free areas and supplemental sodium chloride administration are based on diurnal weight gain employing a monthly weight chart and a base weight method. Intravenous hypertonic saline is used briefly and administered in a highly controlled manner when patients with PHS present with generalised seizures and coma. Long term strategies include behavioural interventions and the combination of lithium and phenytoin, and clozapine.


Crystal structure of Escherichia coli thymidylate synthase with FdUMP and 10-propargyl-5,8-dideazafolate.
The crystal structure of an E. coli TS ternary complex containing FdUMP and PDDF has been determined and refined at 2.3A resolution. Each of the two chemically identical subunits folds into a three-layer domain anchored by a large six-stranded mixed beta sheet. The backside of one sheet is juxtaposed against the corresponding face of the equivalent sheet in the second protomer creating a beta sandwich. In contrast to other proteins of known structure in which aligned beta sheets stack face to face with a counterclockwise rotation, sheets in the TS dimer are related by a clockwise twist. The substrate binding pocket is a large funnel-shaped cleft extending some 25A into the interior of each subunit and surrounded by 28 amino acids, 26 from one subunit and 2 from the other. FdUMP binds at the bottom of this pocket covalently linked through C6 to the sulfur of Cys-146. Up-pointing faces of the pyrimidine and ribose rings are exposed to provide a complementary docking surface for the quinazoline ring of PDDF. The quinazoline inhibitor binds in a partially folded conformation with its p-aminobenzoylglutamate tail exposed at the entrance to the active site cleft. Ternary complex formation is associated with a large conformational change involving 4 residues at the protein's carboxy-terminus that close down on the distal side of the inhibitor's quinazoline ring, capping the active site and sequestering the bound ligands from bulk solvent.


Changes in Addressing Patients' Smoking: Cross-Sectional Data from 2002 and 2014 among Physicians in Estonia.
For health professionals, personal and contextual factors influence addressing patients' smoking habits. The objective of the study was to describe frequency of addressing patients' smoking in 2002 and 2014 and to analyse factors related to addressing patients' smoking habits. Data of physicians from 2 postal cross-sectional surveys were used (n = 4140 in 2002, n = 5666 in 2014). The number of respondents was 2747 in 2002 and 2903 in 2014. The corrected response rate was 67.8% and 53.1%, respectively. Age-standardized frequency of addressing patients' smoking during the last 7 days was determined. Distribution of other variables along with confidence intervals (CI) was calculated. Logistic regression was used to analyse association of addressing patients' smoking with attitudes and perceived barriers regarding addressing patients' smoking and with background factors. Fully adjusted odds ratios (OR) with 95% CIs were calculated. The age-standardized prevalence of addressing patients' smoking habits among men was 84.4% (95% CI 80.3-88.5) in 2002 and 88.3% (95% CI (84.5-92.2) in 2014, among women 82.1% (95% CI 80.2-83.9) and 89.0% (95% CI 87.2-90.8), respectively. According to logistic regression analysis, in 2014, significantly more physicians agreed that it is doctors' responsibility to convince people to stop smoking (among men, OR 2.32; 95% CI 1.19-4.54, among women OR 1.41; 95% CI 1.06-1.88), that smoking prevention should form part of health professionals' training, that physicians should have smoking related hand-out materials, and that lack of time was a barrier to addressing patients' smoking. Addressing patients' smoking was significantly associated with attitudes and perceived barriers regarding addressing patients' smoking, age, and other background factors (among women only). Addressing patients' smoking habits was more common in 2014 than in 2002, but the change was significant among women only. Compared to 2002, in 2014 physicians' attitudes regarding addressing patients' smoking were more approving. Results of this study are useful for policymakers and institutions involved in organization and development of smoking prevention training and cessation services.


The effect of inhibition of leukotriene synthesis on the activity of interleukin-8 and granulocyte-macrophage colony-stimulating factor.
The cytokines interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the extracellular release of arachidonate metabolites from ionophore-stimulated neutrophils by 145 +/- 10% (mean +/- S.E.M., n = 13) and 182 +/- 11% (n = 16), respectively. To determine whether enhanced leukotriene production mediates the effects of these cytokines on neutrophil activity, two different specific arachidonate 5-lipoxygenase (5-LO) inhibitors, piriprost and MK-886, were used to inhibit leukotriene synthesis. Neither inhibitor affected the upregulation of CD11b beta(2)-integrin expression or priming of superoxide generation stimulated by IL-8 and GM-CSF. It is concluded that leukotrienes do not mediate either the direct or priming effects of these cytokines and that these classes of anti-inflammatory drugs are therefore unlikely to inhibit the effects of IL-8 and GM-CSF on neutrophil activation.


[Increasing mental performance by multistep oxygen therapy. Computer-assisted measurements of information processing capacity, intelligence, short-term memory and further parameters of cerebral performance].
Several basic characteristics of mental capacity were measured on 59 patients by means of computer-based-methods before and after oxygen multistep therapy (O2-MT) and compared with the results obtained from 14 volunteers serving as controls. Before and without O2-MT, an appreciable, age-dependent decline of the short-term memory capacity (general fluid intelligence) was found. O2-MT, completed by brain jogging, effected a significant increase in the presence duration by 0.4-0.7 secs, in the information flow by 1.4-1.9 bit/sec, resulting in an increase in the short-term memory capacity by 19-23% (in two experimental groups). The short-term memory itself was, however, not improved as compared to the controls. Moreover, the times needed for the accomplishment of perception, interference and reaction tests became significantly shorter by 12-18%. By using the screening test for cerebral insufficiency (CI), which is based on these parameters, the suspicion of CI could be excluded in 18 of 59 patients.


Maternal perception of excess weight in children: a survey conducted by paediatricians in the province of Milan.
To establish whether maternal perception of a child's body weight (BW) and food intake is related to the level of maternal education. Height and BW of 569 mother/child couples were measured, and mothers received a questionnaire regarding their perception of their own weight and their child's BW and food intake. Twenty-nine percent of mothers and 35% of children were overweight or obese. Only 10% of the mothers underestimated their own weight, while 37% overestimated it. In contrast, 28% of mothers underestimated their child's BW, while 9% overestimated it. Higher maternal instruction level was significantly associated to a lower weight class in both mothers and children, and to a correct perception of the child's weight. Fifty-seven per cent of the mothers who perceived their child to be overweight or obese were not concerned. Forty-four per cent of the mothers with overweight or obese children believed that their child was eating correctly. A better understanding of how mothers perceive the problem of excess weight in their children is relevant to the success of preventive interventions in childhood obesity.


Discovery of novel triazine derivatives as potent retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonists.
Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) has been exploited as a promising target for the new small molecule therapeutics to treat inflammatory and autoimmune diseases via modulating the interleukin-17 (IL-17) production by T helper 17 (Th17) cells. Herein, we reported a series of triazine-based derivatives as novel RORγt inverse agonists. By screening of our in-house compound library, the hit compound 1 was identified with weak RORγt inhibitory activity. Subsequently, we engineered detailed structural modifications to explore the structure-activity relationships (SARs) of triazines derivatives, which led to discovery of a number of potent RORγt inverse agonists with IC50 values in the range of 7 nM-50 nM in RORγt dual FRET assay. Among them, compound 14g displayed potent RORγt inverse agonistic activity with an IC50 value of 22.9 nM in dual FRET assay. In a cell-based reporter gene assay, compound 14g showed an IC50 value of 0.428 μM and maximum inhibition rate of 108.9%. Compound 14g also exhibited good metabolic stability and a decent pharmacokinetic profile with a low clearance (CL = 0.229 L/h/kg) and a reasonable oral exposure (AUC0-Last = 5058 ng/mL*h). Most importantly, 14g alleviated the severity of imiquimod-induced psoriasis in mice. Taken together, triazine-based derivatives represent a new chemical class of RORγt inverse agonists as potential therapeutic agents against autoimmune diseases.


Intrarenal reflux: anatomical, dynamic and radiological studies-part I.
The radiographic appearances and dynamics of intrarenal reflux have been defined in an experimental study of the pig's kidney. Intrarenal reflux occurs only with "refluxing" papillae and is an "all-or-none" phenomenon when the threshold figure of 10-15 mm Hg is exceeded. Increasing intrapelvic pressure leads to increasing density of the radiographic shadow but new areas of intrarenal reflux are not produced.


High-dose ifosfamide and mesna in advanced breast cancer. A phase II study.
Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (including anthracyclines). They were included in a trial to receive 6 g/m3 ifosfamide, mixed with 6 g/m2 mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2-8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation.


Congenital neuroblastoma presenting as a paratesticular tumor.
A 1-month-old male newborn was operated upon for a scrotal tumor that was localized outside of the testis. Histological diagnosis was neuroblastoma. Although neuroblastoma often may present as metastatic disease when first seen, this case is unique in that an undetected adrenal neuroblastoma presented as a paratesticular tumor immediately after birth.


Association of RANTES -403 G/A, -28 C/G and In1.1 T/C polymorphism with HIV-1 transmission and progression among North Indians.
The relationships between host immune factors and HIV-1 disease progression are still in dispute. The RANTES SNPs exhibit distinct ethnic distribution and are associated with different effects on the course of HIV infection. Therefore, impact of RANTES gene polymorphism on HIV-1 transmission and progression needs to be evaluated. The RANTES genotypes were identified by PCR-RFLP method and confirmed by sequencing in HIV-1 seronegative (HSN; n=315), HIV-1 exposed seronegative (HES; n=47) and HIV-1 seropositive (HSP; n=196) patients classified into different clinical stages (i.e. Stages I, II, III). Fisher exact test was used for statistical analysis and Arlequin software for haplotype analysis. RANTES allele -403G, -28C and In1.1 T were the predominant allele in the subject studied. HSP group have higher frequency of RANTES In1.1 T allele compared with HSN (91.32% vs. 86.19%; P=0.013) and HES (91.32% vs. 78.72%; P=0.001). Higher frequency of RANTES In1.1 C allele in Stage III was observed, compared with Stage I (14.28% vs. 6.39%) and was significantly associated with high risk (P=0.047, OR=2.439, C.I.=1.061-5.609). Haplotype II (ACT) was significantly higher in HSP compared with HSN (9.69% vs. 1.58%) and associated with high risk (P<0.001, OR=6.655, C.I.=2.443-18.132). There were no significant differences in RANTES -403 A/G and -28 C/G genotype and allele distribution in all the groups compared. Our results implicate that RANTES In1.1 T allele and haplotype II (ACT) may be a risk factor for HIV-1 transmission while RANTES In1.1 C allele may be risk factor for disease progression among North Indians.


Retrievable vena cava filters: a clinical review.
Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE), is a major cause of morbidity and mortality. Parenteral anticoagulant treatment with full-dose unfractioned heparin, low-molecular-weight-heparin, or fondaparinux, followed by oral treatment with the vitamin K antagonists, is recommended for the majority of patients. However, in the presence of contraindications to anticoagulant treatment, bleeding complications during antithrombotic treatment, or VTE recurrences despite optimal anticoagulation, interruption of the inferior vena cava with a filter is a potential option aimed to prevent life-threatening PE. Currently, the vast majority of filters implanted worldwide are of the permanent type, but their use is associated with a number of long term complications. Non-permanent filters represent an important alternative, and in particular retrievable filters are an attractive option because they may be either left in place permanently or safely retrieved after a quite long period when they become unnecessary. In this review, we summarize the currently available literature regarding retrievable vena cava filters and we discuss current evidences on their efficacy and safety. Moreover, the appropriate indications for their use in daily clinical practice are reviewed.


Comparison of oxygen kinetics in young and old subjects.
Five older men (aged 60-69 yr) and five young men (aged 21-29 yr) with approximately equal levels of age-corrected VO2 max were compared with respect to oxygen kinetics at equal absolute workloads (100 watts) and at equal relative workloads (45% VO2 max) on a cycle ergometer. At 45% VO2 max, half times for VO2 response to instantaneous transition from unloaded pedalling were 30.0 s and 27.4 s for old and young respectively (t = 0.260, p less than 0.80). No significant differences were found in the VE response and by inference none existed in O2 extraction. Mean half times for heart rate responses at a workload of 100 W were 24.2 s and 20.6 s for old and young groups respectively (t = 0.722, p less than 0.49). Mechanical efficiency estimated from steady state data at 100 W was 19.8% and 20.5% for old and young groups respectively (t = 0.574). The close similarity in responses to submaximal work in old and young subjects of equivalent fitness suggests caution in the interpretation of agewise decrements observed in physiological variables which may be sensitive to physical fitness status.


An efficient LC-MS method for isomer separation and detection of sugars, phosphorylated sugars, and organic acids.
Assessing central carbon metabolism in plants can be challenging due to the dynamic range in pool sizes, with low levels of important phosphorylated sugars relative to more abundant sugars and organic acids. Here, we report a sensitive liquid chromatography-mass spectrometry method for analysing central metabolites on a hybrid column, where both anion-exchange and hydrophilic interaction chromatography (HILIC) ligands are embedded in the stationary phase. The liquid chromatography method was developed for enhanced selectivity of 27 central metabolites in a single run with sensitivity at femtomole levels observed for most phosphorylated sugars. The method resolved phosphorylated hexose, pentose, and triose isomers that are otherwise challenging. Compared with a standard HILIC approach, these metabolites had improved peak areas using our approach due to ion enhancement or low ion suppression in the biological sample matrix. The approach was applied to investigate metabolism in high lipid-producing tobacco leaves that exhibited increased levels of acetyl-CoA, a precursor for oil biosynthesis. The application of the method to isotopologue detection and quantification was considered through evaluating 13C-labeled seeds from Camelina sativa. The method provides a means to analyse intermediates more comprehensively in central metabolism of plant tissues.


Plasmapheresis, Photopheresis, and Endovenous Immunoglobulin in Acute Antibody-mediated Rejection in Kidney Transplantation.
Acute antibody-mediated rejection (AAMR) is the subject of much research. It is diagnosed by C4d staining at biopsy and circulating donor-specific antibodies (DSA). The combination of intensive plasmapheresis and intravenous immunoglobulin (IVIG) has been recognized as an effective treatment for AAMR. We report our single-center experience on AAMR treatment. We treated 23 transplanted patients (group A) with protein-A immunoadsorption (IA) and 7 patients (group B) with double-filtration plasmapheresis. All patients were treated with IVIG (400 mg/kg/d). Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). A subgroup of 3 patients (3/7; group B1) was treated with photopheresis. In both groups, the mean number of extracorporeal procedures was 7.3 ± 4.5 and 5.5, respectively; the mean duration of treatment was 12.3 ± 10.2 and 14.5 days, respectively. In group A, we observed negative cross-matching in 96% after mean of 18 days; 1 patient died from sepsis, and 6 lost their grafts. In group B, negative circulating DSA were observed in all patients after a mean of 25 days, and 1 patient lost their allograft. In our observation, the 2 extracorporeal procedures had similar effects in terms of graft survival, DSA removal, and cross-match negativity (group A 74% vs 86%; 95.6% vs 100%). IA was faster for DSA removal. In our opinion, the higher costs of IA suggests its use just in high-risk cases, such as in hyperimmune or sensitized patients. Further studies are necessary to improve our knowledge.


Borax exerts protective effect against ferrocene-induced neurotoxicity in Oncorhynchus mykiss.
In recent years, therapeutic targets and the development of new drugs have shifted research towards inflammatory and oxidative stress pathways. Ferrocene (FcH) is a stable, small molecule that exhibits immunostimulatory and anti-tumor properties by a different mechanism and is effective at low doses in oral administration. However, it was surprising that there has been no performed investigation using FcH on aquaculture. On the other hand, recent papers reveal the key biological functions and health benefits due to daily boron intake in animals and humans. Therefore, we investigated the neurotoxic damage potential of FcH and its related neurotoxicity action mechanism in aquatic environments. In addition, the protective potential of borax (BX, or sodium borate) were evaluated againt in vivo neurotoxicity by FcH. Neurotoxicity assessment was performed in rainbow trout brain tissue, acutely under semi-static conditions via determining a vide range of parameters including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities as well as glutathione (GSH), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA levels), DNA damage (8-OHdG), apoptosis (caspase 3), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), nuclear factor erythroid-2 (Nrf-2), acetylcholinesterase (AChE) and brain-derived neurotrophic factor (BDNF) levels. In addition, the LC50 96 h level of FcH was determined for the first time in rainbow trout in this study. In the obtained results, while FcH caused inhibition in enzyme activities, it showed an inducing effect on MDA, MPO, BDNF, Nrf2, TNF-α and IL-6 levels. It was determined that this oxidative damage related alterations were significantly different (p < 0.05) in comparison between FcH treated and controls. Again, the LC50 96 h value in rainbow trout was determined as 11.73 mg/L, which is approximately 5% less than the value given for freshwater fish (12.3 mg/L). On the contrary, it was observed that BX has a mitigating effect on FcH-induced neurotoxicity. The present study suggests that borax may be useful for preventing or alleviating neurotoxicity induced by environmental contaminants or toxic chemicals.


Water absorption of methacrylate soft lining materials.
The water absorption of soft methacrylate prosthetic materials is very high compared with rigid methacrylates and is not at an equilibrium value even after 6 yr. This very high and prolonged uptake can be explained qualitatively in terms of the presence of water soluble impurities which form sites for the formation of water droplets. These droplets grow until the osmotic and elastic forces balance; this mechanism can be accompanied by creep or even rupture under the osmotic pressure. Desorption on the other hand, is rapid and obeys diffusion laws, giving diffusion coefficients of 5-7 X 10(-8) cm2 s-1.


Metabolic rearrangement of fluorenone oxime to phenanthridinone.
Fluorenone oxime is metabolized in vivo in the rat to phenanthrifinone which is excreted in the urine. The structure of the metabolite has been determined by comparison of chromatographic and spectral properties of the metabolites with authentic phenanthridinone.


In vitro protein synthesis capacities in a cold stenothermal and a temperate eurythermal pectinid.
The translational system was isolated from the gills of the Antarctic scallop Adamussium colbecki (Smith) and the European scallop Aequipecten opercularis (Linnaeus) for in vitro protein synthesis capacities microg protein mg FW(-1) day(-1)) and the translational capacities of RNA (k(RNA in vitro) mg protein mg RNA(-1) day(-1)). In vitro protein synthesis capacity in the cold-adapted pectinid at 0 degrees C was similar to the one found in the temperate scallop at 25 degrees C. These findings might reflect cold compensated rates in Adamussium colbecki, partly explainable by high tissue levels of RNA. Cold-compensated in vitro protein synthesis capacities may further result from increments in the translational capacity of RNA. The thermal sensitivity of the translation machinery was slightly different in the two species, with significantly lower levels of Arrhenius activation energies E(a) and Q(10) in Adamussium colbecki in the temperature range 0-15 degrees C. Reduced protein synthesis and translational capacities were found in vitro in gills of long-term aquarium-maintained Adamussium colbecki and were accounted for by a loss of protein synthesis machinery, i.e. a reduction in RNA levels, as well as a decrease in the amount of protein synthesized per milligram of RNA (RNA translational capacity, k(RNA in vitro)). Such changes may involve food uptake or mirror metabolic depression strategies, like those occurring during winter. Consequences of high in vitro RNA translational capacities found in the permanently cold-adapted species are discussed in the context of seasonal food availability and growth rates at high latitudes.


Functional effects of a monoclonal antibody on mechanoelectrical transduction in outer hair cells.
The functional effect of a monoclonal antibody, RA6.3, on mechanoelectrical transduction (MET) of outer hair cells (OHCs) isolated from the adult guinea-pig cochlea was investigated. This antibody was raised by an antiidiotypic approach against amiloride binding sites. RA6.3 irreversibly reduced the receptor current, independent of membrane potential. The time course of the functional block was independent of dilution (1:100, 50 and 10), beginning 1.2+/-0.5 min after the start of application and decreasing exponentially with a time constant of 0.29+/-0.18 min to 53+/-8% of the control current. The residual current was reversibly blocked by amiloride (300 microM), mainly at negative membrane potentials. Block of control current by amiloride was competitively inhibited by simultaneous application of RA6.3. These results suggest that RA6.3 binds to or in close proximity to amiloride receptor sites associated with the MET channels. Irreversibility, incompleteness, independence of membrane potential and independence of antibody dilution of the functional block can all be explained by irreversible binding of one antibody molecule to a receptor site, yielding a non-blocked state, followed by a relatively slow, reversible transition to a blocked state. It is proposed that the reversible transition might represent intramolecular binding of the second antibody combining site to the second receptor site.


Whole-genome resequencing of common bean elite breeding lines.
The expansion of bean genome technologies has prompted new perspectives on generating resources and knowledge essential to research and implementing biotechnological tools for the practical operations of plant breeding programs. This study aimed to resequence the entire genome (whole genome sequencing-WGS) of 40 bean genotypes selected based on their significance in breeding programs worldwide, with the objective of generating an extensive database for the identification of single nucleotide polymorphisms (SNPs). Over 6 million SNPs were identified, distributed across the 11 bean chromosomes. After quality variant filtering, 420,509 high-quality SNPs were established, with an average of 38,228 SNPs per chromosome. These variants were categorized based on their predicted effects, revealing that the majority exerted a modifier impact on non-coding genome regions (94.68%). Notably, a significant proportion of SNPs occurred in intergenic regions (62.89%) and at least one SNP was identified in 58.63% of the genes annotated in the bean genome. Of particular interest, 7841 SNPs were identified in 85% of the putative plant disease defense-related genes, presenting a valuable resource for crop breeding efforts. These findings provide a foundation for the development of innovative and broadly applicable technologies for the routine selection of superior genotypes in global bean improvement and germplasm characterization programs.


Characterization of T cell clones derived from lymph nodes and lungs of Pseudomonas aeruginosa-susceptible and resistant mice following immunization with heat-killed bacteria.
Pseudomonas aeruginosa-resistant BALB/c and susceptible C57Bl/6 (B6) mice were immunized with heat-killed Pseudomonas either in the foot pad or via the trachea, and panels of Pseudomonas-specific T cell clones were developed from lymph nodes and lungs. All clones from either strain, whether of lymph node or lung origin, were CD3+CD4+CD8-TCRalphabeta+. The efficacy of cloning from lymph node cells was comparable between BALB/c and B6 mice. All lymph node BALB/c clones proliferated in response to Pseudomonas antigen in a dose-dependent manner, and this response was MHC class II-restricted. Vigorous proliferation by a considerable proportion of B6 T cell clones occurred in the absence of specific antigen. Lymph node clones from either strain could be categorized as either Th1 or Th0 on the basis of interferon-gamma (IFN-gamma)/IL-4 production. In either mouse strain the efficacy of cloning from lung tissue was substantially lower than from lymph nodes, but the efficacy of cloning from BALB/c compared with B6 lungs was higher. Four lung T cell clones from BALB/c and two from B6 mice were expanded for further analyses, and an interstrain difference was observed in cytokine production. Both B6 lung T cell clones were Th1-like and produced IFN-gamma but not IL-4 and IL-10, whereas four BALB/c lung T cell clones were Th2-like and produced IL-4 and IL-10 but not IFN-gamma. These observations suggest that differences in the CD4+ Th response in the lung may contribute to differences among inbred mouse strains in the level of resistance to bronchopulmonary Pseudomonas infection.


All roads lead to FoxO.
Stress-activated kinases control metabolism by antagonizing the early steps of insulin signal transduction. Two papers now demonstrate that Jnk, the prototypical stress-activated kinase, controls life span in Drosophila and C. elegans by promoting phosphorylation of the forkhead protein FoxO (Oh et al., 2005; Wang et al., 2005). The findings provide yet another mechanism by which metabolic and stress responses are integrated via phosphorylation of FoxO proteins.


Dermoscopy in the Diagnosis of Palmoplantar Eczema and Palmoplantar Psoriasis: A Cross-Sectional, Comparative Study from a Tertiary Care Centre in North India.
Palmoplantar hyperkeratotic lesions pose a diagnostic difficulty when differentiating clinically between palmoplantar psoriasis (PPP) and palmoplantar eczema (PPE). Dermoscopy can provide valuable clues in reaching the final diagnosis. To identify and compare dermoscopic findings seen in PPP and PPE. This was a cross-sectional, comparative study carried out prospectively between March 2019 and June 2020. All adult, consenting patients visiting the dermatology outpatient department who were clinically diagnosed and histopathologically confirmed as PPP and PPE were recruited into two groups. The dermoscopic examination was done, and images were taken from the representative area. The findings were analysed by two dermatologists who were unaware of the diagnosis. The sensitivity, specificity, positive predictive value and negative predictive value of these findings were assessed. A total of 81 patients were recruited (39 patients of PPP and 42 patients of PPE). Significant findings seen in psoriatic plaques were the presence of regular vessels (84.6%, P < 0.001), with diffuse scales (87.2%) over a dull red/pink background (69.2%, P < 0.001). Dermoscopy of PPE displayed a significant presence of yellowish scales (76.2%, P < 0.001), with focal (61.9%) or absent vessels (35.7%), brown/orange-brown dots and/or globules (66.7%), yellow/yellow-orange crusts (57.1%) over a yellow/yellow-brown background (88.1%). Distribution of vessels, distribution of scales and the colour of scales, presence of brown/orange-brown dots and/or globules, yellow/yellow-orange crust and background colour (dull red vs. yellow/yellow-brown) of the plaques can be useful clues in the diagnosis of PPP and PPE.


What's for Lunch? Investigating the Experiences, Perceptions, and Habits of Parents and School Lunches: A Scoping Review.
Research indicates home-packed school lunches are lower in nutritional value compared with school-provided meals. Due to the lack of a school lunch program, most of what Canadian children consume during the school day is determined by parents and caregivers through packed lunches. Despite this, little research has focused on the school lunch packing habits and attitudes of parents. The purpose of this scoping review was to improve understanding of parental perceptions, experiences, and habits with respect to home-packed school lunches. We conducted a scoping review of peer-reviewed and gray literature. We reviewed only studies published from January 2000 to January 2019 with a focus on parents' lunch packing habits for their school-aged children. The review included 7 studies, with articles from the United Kingdom, Australia, and Canada. The studies identified 6 themes influencing parental decisions regarding what to pack in their child's lunch-school environment, food as fuel, convenience, child's influence, cost, and the lunch experience. The decisions that influence what is packed in a school lunch are complex and indicate the need for support. Parents, schools, districts, and government policymakers need to work collaboratively to improve the healthiness of home-packed school lunches.


Aberrant anterior branch of segment V traveling ventrally across the gallbladder: a case of critical anatomy.
This paper presents a case of critical anatomic variation in laparoscopic cholecystectomy, as an anterior segmental branch of segment V from the left hepatic artery passing anterior to the fundus of the gallbladder and coursing to the anterior hepatic segment. A 46-year-old man was admitted to our hospital complaining of hypochondralgia attributed to gallbladder stones. An aberrant artery crossed the ventral side of the neck of the gallbladder and ran into the right liver Glissonean sheath of segment V. During laparoscopic cholecystectomy, this artery was taped and exposed from proximal to distal ends, revealing an origin from the left hepatic artery with the vessel acting as the anterior branch of segment V to the liver. The cystic artery branching from the aberrant artery was found on the left side of the gallbladder. Laparoscopic cholecystectomy was performed with no injury to the hepatic arteries and the patient was discharged 3 days postoperatively. In general laparoscopic cholecystectomy, we expose only the area inside Calot's triangle. With such an approach, this type of aberrant hepatic artery may be injured intraoperatively without consequences. Detailed preoperative evaluation using modalities such as 3-dimensional reconstruction of CT and knowledge of variations in the hepatic artery will help avoid vessel injury.