Use of the passive lower lingual arch in the management of anterior mandibular crowding in the mixed dentition.
Leeway space preservation in the mixed dentition is a well-documented method of space management. In the mandibular arch it may be saved for utilisation in the correction of minor anterior crowding by the placement of a passive lower lingual arch (LLA) during the transition from the mixed dentition to the permanent dentition.


Evaluation of interrater reliability of different muscle segmentation techniques in diffusion tensor imaging.
Muscle diffusion tensor imaging (mDTI) is a quantitative MRI technique that can provide information about muscular microstructure and integrity. Ultrasound and DTI studies have shown intramuscular differences, and therefore separation of different muscles for analysis is essential. The commonly used methods to assess DTI metrics in muscles are manual segmentation and tract-based analysis. Recently methods such as volume-based tractography have been applied to optimize muscle architecture estimation, but can also be used to assess DTI metrics. To evaluate diffusion metrics obtained using three different methods-volume-based tractography, manual segmentation-based analysis and tract-based analysis-with respect to their interrater reliability and their ability to detect intramuscular variance. 30 volunteers underwent an MRI examination in a 3 T scanner using a 16-channel Torso XL coil. Diffusion-weighted images were acquired to obtain DTI metrics. These metrics were evaluated in six thigh muscles using volume-based tractography, manual segmentation and standard tractography. All three methods were performed by two independent raters to assess interrater reliability by ICC analysis and Bland-Altman plots. Ability to assess intramuscular variance was compared using an ANOVA with muscle as a between-subjects factor. Interrater reliability for all methods was found to be excellent. The highest interrater reliability was found for volume-based tractography (ICC ≥ 0.967). Significant differences for the factor muscle in all examined diffusion parameters were shown in muscles using all methods (main effect p < 0.001). Diffusion data can be assessed by volume tractography, standard tractography and manual segmentation with high interrater reliability. Each method produces different results for the investigated DTI parameters. Volume-based tractography was superior to conventional manual segmentation and tractography regarding interrater reliability and detection of intramuscular variance, while tract-based analysis showed the lowest coefficients of variation.


Clinical Features of Primary and Systemic Metastatic Intraocular Lymphomas in Spanish Patients.
To describe and compare clinical findings in different subtypes of biopsy-proven intraocular lymphomas (IOLs). Retrospective, observational case series. The clinical and pathologic features in IOLs at the Hospital Clinic of Barcelona from 1995 to 2018 were retrospectively studied. Twenty-one patients, 12 men (57%), median age 60 (interquartile range, IQR: 18 years), and a median follow-up of 30 (IQR 60) months were included. Eleven patients had primary vitreo-retinal lymphoma (PVRL, 52%), 4 had primary uveal lymphoma (PUL, 19%), and 6 had systemic metastatic retinal lymphomas (SMRLs, 28%). Diffuse large B-cell lymphoma was the main IOL subset in PVRL (91%) and in SMRL (83%), whereas extranodal marginal zone lymphoma was the only type in PUL (100%). Survival rate was 44% in PVRL and 20% in SMRL at 5 years (p=0.047). One patient had flow cytometry of two different vitreous humour samples. With them, flow cytometry was performed in a total of 11 samples, yielding 7 positive samples. Even though PVRL is the most frequent IOL subtype, our findings suggest that PUL and SMRL should be considered as potential IOL causes. Overall survival was poor in PVRL and even shorter in SMRL patients.


Posterior interosseous nerve syndrome caused by a bursa in the vicinity of the elbow.
A case of posterior interosseous nerve syndrome presented with difficulty in extending the metacarpophalangeal joint of the little finger. Compression was caused by a bicipital bursa. Surgical decompression led to a complete recovery.


The human milk microbiome aligns with lactation stage and not birth mode.
We analysed the human milk microbiome in a cohort of 80 lactating women and followed the dynamics in taxa over the course of lactation from birth to 6 months. Two hundred and thirty one milk samples were collected from full-term lactating women at 1, 4, 8 and 24 weeks following birth and analysed for microbiota composition using 16S rRNA sequencing. A significant decrease in milk microbiota diversity was observed throughout the first 6 months of lactation, with the greatest difference seen between week 8 and week 24. Nine genera predominated in milk over lactation from week 1 to week 24, comprising of Staphylococcus, Streptococcus, Pseudomonas, Acinetobacter, Bifidobacterium, Mesorhizobium, Brevundimonas, Flavobacterium, and Rhodococcus; however, fluctuations in these core genera were apparent over time. There was a significant effect of stage of lactation on the microbiome, while no effect of birth mode, infant sex and maternal BMI was observed throughout lactation. Streptococcus had the highest mean relative abundance at week 1 and 24 (17.3% and 24% respectively), whereas Pseudomonas predominated at week 4 (22%) and week 8 (19%). Bifidobacterium and Lactobacillus had the highest mean relative abundance at week 4 (5% and 1.4% respectively), and occurred at a relative abundance of ≤ 1% at all other time points. A decrease in milk microbiota diversity throughout lactation was also observed. This study concluded that lactation stage was the primary driving factor in milk microbiota compositional changes over lactation from birth to 6 months, while mode of delivery was not a factor driving compositional changes throughout human lactation.


Impact of land acquisition for large-scale agricultural investments on income and asset possession of displaced households in Ethiopia.
Displacement due to Large-Scale Agricultural Investments (LSAIs) is on the rise globally and in Africa. However, the impact of such displacement on the income and asset holding status of the displaced smallholders is not well explored. This study, therefore, empirically analyzed such impact taking Ethiopia as a case. A household survey covering different aspects of rural income sources and assets was collected from 255 displaced farmers and 266 non-displaced farmers in Adamitulu and Dugda districts. Propensity score matching technique (PSM) was applied to assess the impacts. The study findings indicated a significant reduction of income and assets among the displaced households. The mean annual income of the displaced households has declined by 72% (97,000 Ethiopian Birr (ETB)) compared to that of the income of the non-displaced households. Moreover, the livestock and productive assets holding of the displaced smallholders declined by 2.4 tropical livestock units (TLU) and 5219.6 ETB (69%) respectively compared to the non-displaced households. This implies displacement due to the LSAIs has worsened the income and asset condition of the displaced households in Ethiopia. Therefore, policymakers should put in place specific interventions to protect the income and asset holding of displaced smallholders. Empirical analysis of the impacts of LSAIs on livestock and productive asset possession of the displaced households is a key contribution of this study, and not well researched before.


Epilepsy and consanguinity in Shiraz, Iran.
The importance of consanguinity and its association with epilepsy has been suggested in some studies, but in one study the risk contributed to consanguinity for childhood epilepsy was not significanta. In the present study, there was an attempt to determine if consanguinity has any important association with epilepsy. All the epileptic children and adolescents up to the age of 18 years, who had been referred to Motahary Clinic in Shiraz, Iran, during a six-month period, were included in this cross-sectional study. The percentage of consanguinity in parents of the epileptic patients was compared to a sample of the general population in the same geographical area. In total, 181 unrelated epileptic children were included in this study. The mean age of these children was 7+/-4.6 years. The male/female ratio in these patients was 1.29. Overall, 61(33.7%) of the parents were first cousins (OR=2.264, 95%-CI: 1.618-3.169 in comparison to the general population), 37 (20.4%) were second cousins (OR=3.557, 95%-CI: 2.389-5.296), and 83 (45.9%) were not related. The percentage of consanguinity in parents of the epileptic patients was significantly higher in comparison to a sample of the general population (OR=2.612, 95%-CI: 1.929-3.536, P<0.0001) which signifies the importance of consanguinity as a potential risk factor for epilepsy. In this regard, more education and awareness of young individuals about the increased risk of epilepsy after familial marriages (at least by 2.2 folds), as well as pre-marriage counseling for couples who have a family history of epilepsy are necessary as an effective preventive program.


Visual pigments and retinoids in the Mongolian jird.
The visual cells, visual pigments and major retinoids of the Mongolian jird (Meriones unguiculatus) were examined. Light and electron microscope analyses show that these jirds had mainly rod photoreceptors. Octylglucoside extracts prepared from their retinas contained only rhodopsin with a maximum absorption at 497 nm and a concentration of 0.51 nmol per retina. Employing a standard method of high performance liquid chromatography (HPLC), the pigment epithelium from each eye was found to possess 0.52 nmol of retinyl palmitate (the most abundant form of retinyl ester) along with a small amount of retinol (0.02 nmol). Most of the retinoids in the body of these animals are stored in the liver, in the form of retinyl palmitate (1228.80 nmol per gram liver). As the Mongolian jird is small, inexpensive and readily available, this animal is a mammalian species suitable for the research of the biochemistry of retinoids and vision.


[Effects of hydrogen peroxide on intracellular free Ca2+ content in rat liver oval cells].
To study the effects and mechanism of hydrogen peroxide (H2O2) of low concentration on dynamic changes of intracellular free calcium contents ([Ca2+]i) in cultural rat liver oval cells (WB-F344 cells). Using Fluo-3/Am as fluorescent indicator of [Ca2+]i and it was measured by laser scanning confocal microscope system. The results showed that: (1) A rapid transient spiking of [Ca2+]i occurred after the stimulation of H2O2 of low concentration (800 nmol/L). (2) The [Ca2+]i increase was abolished by pretreated with catalase (CAT) or by incubated in D-Hank's solution containing EGTA, the chelate of extracellular Ca2+. (3) The [Ca2+]i increase was not inhibited by pretreated nifedipine, Ca2+ channel blocker, but was abolished by pretreated with anthracere-9-cardoxylic acid (A9C), the Cl-channel blocker and which also blocked calcium activated non-selective cation channel (CAN). These results suggest that the increase of [Ca2+]i induced by H2O2 of low concentration may be due to the influx of extracellular Ca2+ through CAN.


Screening the possible anti-cancer constituents of Hibiscus rosa-sinensis flower to address mammalian target of rapamycin: an in silico molecular docking, HYDE scoring, dynamic studies, and pharmacokinetic prediction.
One of the most common malignancies diagnosed and the leading cause of death for cancer-stricken women globally is breast cancer. The molecular subtype affects therapy options because it is a complex disorder with multiple subtypes. By concentrating on receptor activation, mTOR (mammalian target of rapamycin) can be employed as a therapeutic target. The goal of this work was to screen a number of inhibitors produced from Hibiscus rosa-sinensis for possible target to inhibit the mTOR and to determine which has the greatest affinity for the receptor. Primarily, the ionization states of the chosen compounds were predicted using the ChemAxon web platform, and their pKa values were estimated. Given the significance of interactions between proteins in the development of drugs, structure-based virtual screening was done using AutoDock Vina. Approximately 120 Hibiscus components and ten approved anti-cancer drugs, including the mTOR inhibitor everolimus, were used in the comparative analysis. By using Lipinski's rule of five to the chosen compounds, the ADMET profile and drug-likeness characteristics were further examined to assess the anti-breast cancer activity. The compounds with the highest ranked binding poses were loaded using the SeeSAR tool and the HYDE scoring to give interactive, desolvation, and visual ΔG estimation for ligand binding affinity assessment. Following, the prospective candidates underwent three replicas of 100 ns long molecular dynamics simulations, preceded with MM-GBSA binding free energy calculation. The stability of the protein-ligand complex was determined using root mean square deviation (RMSD), root mean square fluctuation (RMSF), and protein-ligand interactions. The results demonstrated that the best mTOR binding affinities were found for stigmastadienol (107), lupeol (66), and taraxasterol acetate (111), which all performed well in comparison to the control compounds. Thus, bioactive compounds isolated from Hibiscus rosa-sinensis could serve as lead molecules for the creation of potent and effective mTOR inhibitors for the breast cancer therapy.


Significance of initial "performance status" in patients receiving halfbody radiation.
The excellent palliative value of halfbody radiation is well documented. The optimum time to use this modality for palliation of symptoms is unclear. Our department treated 44 evaluable patients with upper and lower halfbody radiation. Stratification according to a modified Karnofsky performance scale revealed an 86% response with a notable increase in median duration of survival in those patients exhibiting an initial performance scale of -1. The optimum benefit from halfbody irradiation is derived when administered at the earliest indicated time.


Peptidoglycan from Staphylococcus aureus induces T(H)2 immune response in mice.
Atopic dermatitis patients have an increased number of type 2 helper (T(H)2) cells in their peripheral blood and superficial Staphylococcus aureus colonization. The purpose of this study was to clarify the effects of peptidoglycan (PEG) from S aureus on the induction of the TH2 immune response in mice. Mice were primed with PEG- and ovalbumin (OVA)-pulsed Langerhans cells (LCs) and given a booster OVA injection 2 days later via the hind footpad. Five days later, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). IL-12 production from cultured LCs was detected by ELISA and Western blot analysis. Administration of PEG- and OVA-pulsed LCs into the hind footpads of the mice induced a T(H)2-prone immune response as represented by the enhanced interleukin (IL) 4 expression in the lymph nodes. We further showed that higher levels of IL-12 p40 production by PEG-stimulated LCs relative to IL-12 p70 (p35/p40) production were associated with the induction of the T(H)2 immune response.The LC-derived IL-12 p40 protein induced by PEG stimulation was detected mainly as monomeric and homodimeric IL-12 p40 subunits; other heterodimers including the L-12 p40 subunit, such as IL-23, were undetected. These results suggest that PEG may have the ability to induce the development of T(H)2 cells through insufficient production of IL-12 p70 and excessive production by LCs of homodimeric IL-12 p40, a known antagonist of bioactive IL-12 p70, offering a possible explanation for the role of S aureus colonization in patients with atopic dermatitis.


Distinct Defects in Synaptic Differentiation of Neocortical Neurons in Response to Prenatal Valproate Exposure.
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by impairments in social interactions and stereotyped behaviors. Valproic acid (VPA) is frequently used to treat epilepsy and bipolar disorders. When taken during pregnancy, VPA increases the risk of the unborn child to develop an ASD. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Therefore, such rodent models may allow for identification of synaptic pathophysiology underlying ASD risk. Here, we systematically probed alterations in synaptic proteins that might contribute to autism-related behavior in the offspring of in utero VPA-exposed mice. Moreover, we tested whether direct VPA exposure of cultured neocortical neurons may recapitulate the molecular alterations seen in vivo. VPA-exposed neurons in culture exhibit a significant increase in the number of glutamatergic synapses accompanied by a significant decrease in the number of GABAergic synapses. This shift in excitatory/inhibitory balance results in substantially increased spontaneous activity in neuronal networks arising from VPA-exposed neurons. Pharmacological experiments demonstrate that the alterations in GABAergic and glutamatergic synaptic proteins and structures are largely caused by inhibition of histone deacetylases. Therefore, our study highlights an epigenetic mechanism underlying the synaptic pathophysiology in this ASD model.


Roles for long non-coding RNAs in physiology and disease.
While the vast majority of the genome is transcribed into RNA, only a small fraction of these transcripts have protein-coding potential. A large fraction of the transcribed RNA belongs to the class known as long non-coding RNAs (lncRNAs). Several recent studies have shown that at least some of these lncRNA transcripts represent functional RNA molecules. LncRNAs can utilize a wide range of mechanisms to regulate the RNA and/or the protein content of a cell on the transcriptional and the post-transcriptional levels. So far, many studies have identified differentially expressed lncRNAs in various physiological contexts, genetic disorders and human diseases. A steadily increasing number of studies could establish functional roles for some of these lncRNAs in developmental processes, cancer and tissue homeostasis. Taken together, these functions provide an additional layer of gene regulation and contribute to the high complexity of physiological and disease-related phenotypes.


Community perspectives on primary health centers in rural Maharashtra: What can we learn for policy?
Primary Health Centers (PHCs) are intended to be the "backbone" of the Indian public health system. Yet, these do not get utilized as frontline institutions for basic curative care. As we embark on comprehensive primary health care initiatives, it is important to understand people's perceptions on PHCs; and design services that cater to their felt needs. In this paper, we examine explanations that communities give for the use or bypass of PHCs. From these perspectives, we derive some policy directions for improving basic curative care services at PHCs. This qualitative study is based on data from 14 Focus Group Discussions in a rural area in Maharashtra in the catchment area of 8 PHCs (total 91 community participants). The discussions were coded and analyzed thematically with the aid of a qualitative software. PHCs were not viewed as first-access points for health care, though these were valued for specific services. The limited use of PHCs was attributed to the lack of availability of drugs/services of perceived relevance to communities; prevalent healing norms that mismatched with PHC services; doctor-patient interactions that were colored with mistrust; and widespread poor opinions of public-sector services in health. Currently, there seems to be little in the design of PHC services- that appeals to the "felt" needs of communities. Thus, the proposed Health and Wellness Centers (HWC) initiative resonates with people's expectations. In addition, staff at the periphery must provide "attentive" care and be prepared to contend with pre-existing poor expectations of care.


Establishment of substance P modified affinity chromatography for specific detection and enrichment of Mas-related G protein-coupled receptor X2.
Mas-related G protein-coupled receptor X2 (MrgX2) has been identified to be critical in drug-induced pseudo-allergic reactions and allergic diseases. Herein, an affinity high-performance liquid chromatography was established for the specific detection and enrichment of MrgX2. Substance P was used as an affinity ligand and immobilized on a glutaraldehyde-modified amino silica gel. The successful grafting of substance P was characterized by infrared spectroscopy, elemental analysis, X-ray photoelectron spectroscopy, thermogravimetric analysis, and nitrogen adsorption and desorption analyzes. The prepared materials were then used as the stationary phase to investigate the retention behavior of MrgX2 recombinant protein on the affinity column. The results obtained with the analytical techniques show the specificity and selectivity of the MrgX2 recombinant protein on the affinity column. The repeatability and reproducibility for the analysis of MrgX2 on the NH2-Silico@GD@SP column show relative standard deviation (RSD) values lower than the acceptance criteria of 2 and 5% of retention time, and RSD of peak areas < 7%. The RSD value of the results obtained for the control of the activity of the prepared columns respond to the acceptance criteria of 5% and proves that the NH2-Silico@GD@SP column are stable until 48 h. The suitability of the NH2-Silico@GD@SP column offline SEC system has been tested by using MrgX2 as positive control. The results of this experiment indicate that the offline system may be used to analyze the retention fraction. MrgX2 extracted from human mast cells LAD2 was also verified. An obvious retention can be observed and the natural MrgX2 was concentrated 114.6 times compared with the original complex components by using the affinity column. These results may provide a new approach for the specific detection and enrichment of G-protein-coupled receptors.


Efficacy of pre-expanded forehead flap based on the superficial temporal artery in correction of cicatricial ectropion of the lower eyelid.
Lower eyelid retraction or ectropion bring suffering to the patients both physically and mentally. Efforts to explore pertinent surgical treatments are still needed. Here we have described our preferred surgical technique for lower eyelid ectropion repair with pre-expanded island forehead flaps or pedicled forehead flaps. Between July 2007 and March 2017, a retrospective review of 12 patients who suffered from cicatricial lower eyelid ectropion as a result of trauma, surgery, or infection was conducted. Forehead skin flap based on the superficial temporal artery was expanded depending on the area of defect of the lower eyelid. Tissue expansion, flap transfer, pedicle delaying and division were involved in this process. There were no major complications, such as expander exposure, infection, haematoma or large skin flap necrosis in all the 12 patients. Venous congestion was reported in two patients. No recurrent ectropion was noted in any patient. During the three-month to two-year follow-up all patients were satisfied with the results in terms of the skin texture, colour, and flexibility after the treatment with an expanded forehead skin flap. This study suggests that expanded forehead skin flaps are effective for correction of cicatricial lower eyelid ectropion.


Molecular and biological effects of Cisplatin in Drosophila.
Cisplatin is widely used in cancer treatment and is one of the best cytostatic agents available for antitumor therapy. Drosophila melanogaster has one of the best annotated genomes and one of the best characterized sets of transposable elements (TE) sequences. This model organism is useful for analyzing the mode of action of several compounds in vivo and evaluating the behavioral consequences of treatments. The aim of our study was to increase the knowledge about the effects of Cisplatin in Drosophila by joining RNA-seq and biological assays. RNA-seq was followed by analyses of differential expression of genes (DEGs) and TEs (DETEs), and of pathways and ontology terms. DETEs were confirmed by qPCR. Cisplatin was evaluated at 50 and 100 μg/mL in Drosophila culture medium for 24 h. The fly locomotor assay, survival analysis, oviposition and development were used as biological assays. Cisplatin induced DEGs in a dose-dependent fashion, and four TEs were up-regulated. Most DEGs are related to DNA damage and detoxification processes. Cisplatin increases Drosophila locomotor activity and interrupts development. Genes and processes related to the assays were also identified. This is the first study to evaluate the effects of Cisplatin in flies using RNA-seq. Gene alteration was almost limited to drug metabolism and DNA damage, and the drug did not vastly affect Drosophila on the molecular level. Contrary to the hypothesis that stress dramatically alters TEs mobilization, only four TEs were up-regulated. Our study, together with previous knowledge, asserts Drosophila as a valuable organism in the study of chemotherapy drugs.


Direct photoaffinity labeling of the primary region of the ouabain binding site of (Na+ + K+)-ATPase with [3H]ouabain, [3H]digitoxin and [3H]digitoxigenin.
The tritiated cardiotonic steroids, ouabain, digitoxin, and digitoxigenin are shown to photolabel the large polypeptide but not the glycoprotein or proteolipid component of the (Na+ + K+)-ATPase when they are bound to the inhibitory site and exposed to light of 220 or 254 nm. The extent of photolabeling is low, less than 1%, and is limited by photocross-linking of the enzyme. The mechanism of photoincorporation does not appear to be either photolysis of the lactone ring in ouabain or photolysis of tryptophan or tyrosine residues in the polypeptide.


Robotics in Pediatric Urology: Evolution and the Future.
Almost 30 years have passed since the inception of minimally invasive surgery in urology and specifically in pediatric urology. Laparoscopy has now become an essential tool in the pediatric urologic armamentarium. The application of robot-assisted surgery in pediatrics has allowed for widespread utilization for common reconstructive procedures such as pyeloplasty and ureteral reimplantation. Understanding the implementation, technical considerations, and outcomes are critical for continued success and adoption. This has allowed for increased use in more complex urologic procedures such as redo pyeloplasty, dismembered ureteral reimplantation, catheterizable channel creation, and bladder augmentation.


[Glycopyrronium bromide is a long-acting inhaled anticholinergic in the treatment of severe COPD].
Long-acting bronchodilators are central in the management of chronic obstructive pulmonary disease (COPD). This short review provides an overview of the studies evaluating the safety and efficacy of inhaled glycopyrronium, a long-acting muscarinic antagonist, in patients with COPD. Glycopyrronium has clinically important effects on the level of forced expiratory volume in the first second, use of rescue medication, daytime dyspnoea scores, and health status. Glycopyrronium also has beneficial effects on dynamic hyperinflation, exercise tolerance, and the rate of exacerbations. Glycopyrronium seems to have the potential for a significant role in the future management of COPD.


Dieting attitudes and behavior in urban high school students: implications for calcium intake.
Adolescence is a time of rapid gain in bone density which may be influenced by calcium intake. This study assessed whether dieting concerns, known to be prevalent in adolescent girls, were associated with the calcium intake of adolescents of varying ethnicity. Students (n = 856) completed an instrument which assessed current weight, desired weight, height, age, ethnicity, calcium intake using a food frequency questionnaire, dieting concerns using the Eating Attitudes Test dieting subscale (DS), taste enjoyment of dairy products, and type of milk consumed. Among 782 students with useable responses, most girls (69.1%) wanted to lose weight and most boys (54.2%) wanted to gain weight. Asian girls had lower body mass index (BMI) than Caucasians (19.3 +/- 2.1 vs 20.8 +/- 2.6 kg/m2, p < 0.05), but desired BMI did not vary by ethnicity in either girls or boys. Asian girls also had lower DS scores than Caucasians, but the difference was not significant with current BMI as a covariate. Girls' DS scores were higher than those of boys (6.3 +/- 6.5 vs 2.3 +/- 3.2, p < 0.001), and estimated calcium intakes were lower (815 +/- 528 vs 1149 +/- 701 mg/day, p < 0.001); however, DS scores were not associated with calcium intake for either sex. Especially among girls, dieting and body size concerns were associated with taste enjoyment of certain dairy products, and with the type, but not the amount, of milk consumed. Girls using skim milk had higher DS scores than those using low-fat or whole milk. In this non-clinical sample, greater concern about dieting and body size did not directly compromise calcium intake but was associated with the type of milk used.


Interrupting rituximab treatment in relapsing-remitting multiple sclerosis; no evidence of rebound disease activity.
Rituximab (RTX) and other anti-CD20 therapies are increasingly used as disease modifying treatments (DMTs) in MS. However, data on reasons to interrupt treatment, alternative DMTs after anti-CD20 therapy and potential rebound disease activity are limited. The objective here was therefore to determine the rate and cause of RTX treatment interruptions and responses to subsequent DMTs in a large single centre cohort addressing also the hypothesis that there would not be rebound activity after discontinuation of RTX, regardless of reason for discontinuation and irrespective of subsequent treatments. A retrospective observational study of all relapsing-remitting MS (RRMS) patients having received at least one dose of RTX at the Karolinska University Hospital from 2009 to 2018 and having either stopped treatment or had more than one year since last RTX infusion, as identified in the Swedish MS registry with additional data derived from clinical charts. As of February 2018, we identified 808 patients ever treated with RTX out of 1513 RRMS patients with current or previous DMT, 92 (11%) had terminated RTX; 27 (29%) stopped RTX due to pregnancy, 26 (28%) due to adverse events, 23 (25%) for other reasons, 9 (10%) due to stable disease and the remaining 7 (8%) due to lack of effect. The cohort of 92 patients was followed until April 2019, when 34 had restarted RTX, 27 switched DMT, 24 remained without DMT and 7 were lost to follow up. Of the 7 patients terminating RTX due to lack of effect, 4 started ofatumumab, 2 had autologous hematopoietic stem cell transplantation and 1 was lost to follow up. In all of the 92 patients, after initial RTX discontinuation, only 3 patients had relapses and 4 had new T2 lesions (one of which had both). Gadolinium was administered in 78% of follow up magnetic resonance imaging (MRI) with no enhancing lesions found (mean MRI follow up from RTX discontinuation 29 months, range 7-92 months, n = =77). Findings are consistent with a low rate of RTX interruptions, with pregnancy and adverse events as most frequent reasons. A small proportion of patients switched due to breakthrough disease in context of incomplete B-lymphocyte depletion. Signs of ongoing disease activity in the remaining group was low regardless of whether a new DMT was started. These findings are consistent with a long acting effect of RTX in RRMS and absence of rebound disease activity phenomena upon stopping therapy.


PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays.
The arginine methyltransferases CARM1 and PRMT1 associate with the p160 family of nuclear hormone receptor coactivators. This association enhances transcriptional activation by nuclear receptors. We describe a method for identifying arginine N-methyltransferase substrates using arrayed high-density protein membranes to perform solid-phase supported enzyme reactions in the presence of the methyl donor S-adenosyl-l-methionine. Using this screen, we identified distinct substrates for CARM1 and PRMT1. All PRMT1 substrates harbor the expected GGRGG methylation motif, whereas the peptide sequence comparisons of the CARM1 substrates revealed no such motif. The predominant CARM1 substrate identified in this screen was PABP1. We mapped the methylated region of this RNA binding molecule in vitro and demonstrate that PABP1 is indeed methylated in vivo. Prior to these findings, the only known substrate for CARM1 was histone H3. We broaden the number of CARM1 targets and suggest a role for CARM1 in regulating transcription/translation.


A new flap design for tongue reconstruction after total or subtotal glossectomy in thin patients.
For tongue reconstruction after total or subtotal glossectomy, a rectus abdominis musculocutaneous flap is often used to obtain sufficient flap volume. However, thin patients often have too little fat tissue to ensure adequate flap volume. For this reason we developed a new flap design to compensate for insufficient flap volume in thin patients. In this series, total or subtotal glossectomy was performed in 20 thin men with a mean age of 58.3 years. The patients had a mean body mass index of 18.22 kg/m(2) and most were considered emaciated. The defects were reconstructed using a rectus abdominis musculocutaneous flap with two skin islands. The first skin island was used to reconstruct the mucosal defect, and the second was de-epithelialised and used to increase flap volume. Flaps were transferred successfully in 19 out of 20 patients. Most patients could tolerate more than a soft diet without severe aspiration and could engage in conversation. However, four patients required total laryngectomy or a permanent stoma owing to severe aspiration. In this series, the larynx could be preserved in 80% of thin patients, and satisfactory postoperative oral function was obtained. The most important point for obtaining satisfactory oral function is to reconstruct a tongue with a protuberant shape and sufficient volume. We could maintain sufficient flap volume with the de-epithelialised skin island of a rectus abdominis musculocutaneous free flap. We believe our new flap design is effective for tongue reconstruction in thin patients.


Overview of toxicological studies.
Ofloxacin was tested in various toxicological test systems. In common with other 4-quinolone derivatives, ofloxacin caused erosions and eruption of blisters in articular cartilage of immature animals. Such effects have not occurred in adults, and monkeys have tolerated ofloxacin up to 40 mg/kg/day for up to 12 months. Administration of various doses of ofloxacin to rats, dogs and monkeys for 4 weeks or up to 12 months did not cause anaemia. Ofloxacin did not impair male fertility. Pefloxacin, in contrast, caused azoospermia and testicular damage in dogs, and enoxacin caused testicular atrophy in rats and reduced spermatogenesis in dogs. In tests for cataractogenesis, ofloxacin was inactive, and adverse hepatic and renal effects occurred only after doses which were greater than the equivalent therapeutic maximum. Mutagenicity studies were negative. Only a recently conducted unscheduled deoxyribonucleic acid synthesis (UDS) test showed some effects, again at therapeutically non-significant concentrations.


Synthesis and degradation of NAD in guinea pig cardiac muscle: I. Dependence upon the extracellular concentration of nicotinamide and nicotinic acid.
The NAD concentration as well as the 14C-incorporation in NAD and the disappearance of 14C-NAD were studied in spontaneously beating atria of guinea pigs at high and low concentrations of the precursors nicotinamide or nicotinic acid. Atria were incubated in Krebs-Henseleit solution containing 15 mM glucose and the appropriate precursors at 30 degrees C. The control NAD concentration (33 nMol/100 mg w.w.) remained unchanged during a 24-h-incubation time. -20 mM 14C-nicotinamide increased the total NAD about three-fold (90 nMol/100 mg w.w.) after an incubation period of 24 h, with positive effects on the performance. The incorporation rate in 14C-NAD was calculated to be 43.7 nMol/100 mg w.w. . 24 h. The ADPR moiety for the NAD synthesis stemmed from an endogenous pool. Between 5 and 20 mM nicotinamide the increase in the NAD concentration followed an apparent Michaelis-Menten kinetics with a Km of 6.1 mM nicotinamide and a Vmax of 70.92 nMol NAD/100 mg w.w. . 24 h. This can be explained as a new synthesis of NAD by a high concentration of nictoinamide and also by a decreased degradation of NAD, due to inhibition of the glycohydrolase by the high concentration of nicotinamide. The ratio of incorporation and disappearance of 14C-NAD during the 8th and 16th h incubation period was 2:1. After pre-incubation with 20 mM nicotinamide for an 8-h period the NAD concentration decreased to normal values after incubation for 8 h in a nicotinamide free medium. -20 mM 14C-nicotinic acid did not change the total NAD level and no significant incorporation in 14C-NAD could be detected, whereas negative effects on the performance occurred. -10 muM 14C-nicotinamide showed a slight increase in the total NAD concentration (39.7 nMol/100 mg w.w.) and in the 14C-incorporation (4.8 nMol/100 mg w.w.) within 24 h. -10 muM 14C-nicotinic acid seemed here to be the better precursor in this concentration. The NAD concentration increased to 49.8 nMol/100 mg w.w. after a 16 h incubation period and the incorporation in 14C-NAD was 12.1 nMol/100 mg w.w. after an incubation time of 24 h. As consequences of the observed different influences of each precursor on NAD turnover and NAD concentration the pathways of NAD synthesis and degradation must be studied. The importance of an increased NAD level for the energy metabolism of the cardiac muscle under aerobic and anaerobic conditions is discussed.


The surgical treatment of chronic interstitial cystitis.
Satisfactory relief of the symptoms of intolerable frequency and painful voiding due to interstitial cystitis has been attained by ileocystoplasty and colocystoplasty in eight patients.


Decreased dynorphin A (1-17) in the spinal cord of spastic rats after the compressive injury.
Spasticity in rat hindlimbs was induced by compressing cervical spinal cord with a wax ball. Ashworth score and H-reflex were measured 1 week after the surgery. The results showed that: (1) muscle spasm was detected in the hindlimbs a week after the operation and maintained at least 8 weeks, (2) in the spastic animals, dynorphin A (1-17)-ir decreased significantly in thoracic and lumbar segments of the spinal cord and (3) peripheral administration of kappa receptor agonist U50488H and electrical stimulation at 100 Hz effectively relieved the muscle spasm. Our data supported the note that the reduction of endogenous dynorphin A (1-17) might play an important role in the pathogenesis of spinally induced muscle spasticity and the replenishment of its shortage might relieve the spasticity.


Immunohistochemical localization of substance P-like immunoreactivity in the hypothalamus of the lizard, Podarcis sicula, R.
The distribution of substance P (SP) immunoreactivity was investigated in the hypothalamus (preoptic area included) of the lizard by single and double immunocytochemical procedures, SP-immunopositive cell bodies were seen in the paraventricular nucleus and periventricular hypothalamic gray (including the paraventricular organ) together with some more lateral elements. Extensive nerve fibers were seen in the white matter and surrounding the paraventricular and supraoptic neurons, and more caudally reaching the hypothalamic periventricular gray, suggesting a massive involvement of SP-like substance in the control of hypothalamic neuroendocrine areas.


Design and optimization of a cavitating device for Congo red decolorization: Experimental investigation and CFD simulation.
The aim of this work is to perform design and optimization of a cavitating device based on CFD simulation. A set of operational and geometrical parameters such as convergence angle, divergence angle, length of throat, and inlet pressure that can affect the hydrodynamic cavitation phenomenon generating in a Venturi are evaluated through CFD simulation and experimental approaches. Response surface methodology (RSM) was employed to achieve the optimum geometrical configuration. The CFD results show that the maximum cavitation zone in the Venturi can be obtained when half angle of the convergence section, throat length and half angle of the divergence section are 22.7°, 4 mm, and 6.5°, respectively. A maximum decolorization of 38.8% has been obtained using the designed Venturi at cavitation number (Cv) of 0.12. Additionally, the results were compared to that of various orifice plates. A decolorization of 26.2% using 33 holes orifice plate and 11.55% in one hole orifice plate approved the superiority of the designed Venturi.


Dual-emission carbon dots-stabilized copper nanoclusters for ratiometric and visual detection of Cr2O72- ions and Cd2+ ions.
The pollution of heavy metal increases greatly accompanying by the development of industries. So, it is very important to build up a quick and reliable technique for detection of heavy metal ions. In this work, we developed a simple and convenient method for ratiometric and visual detection of Cr2O72- ions and Cd2+ ions. We utilized glutathione as raw material to prepare cyan-emitting carbon dots (GSH@CDs). The GSH@CDs were further used as the template to prepare carbon dots-stabilized copper nanoclusters (GSH@CDs-Cu NCs) that displayed two well-separated emission peaks respectively at 450 nm and 750 nm. The GSH@CDs-Cu NCs can be applied for the ratiometric and visual detection of Cr2O72- and Cd2+ ions based on the fluorescence quenching or enhancement of GSH@CDs-Cu NCs at 750 nm. A linear range of 2-40 μmol L-1 with a detection limit of 0.9 μmol L-1 for Cr2O72- ions, and a linear range of 0-20 μmol L-1 with a detection limit of 0.6 μmol L-1 for Cd2+ ions were achieved based on this method. The fluorescent test strips for Cr2O72- ions were successfully prepared based on GSH@CDs-Cu NCs. Moreover, the GSH@CDs-Cu NCs were successfully applied to determine Cr2O72- and Cd2+ ions in real samples with promising results.


Antioxidant and Prooxidant Effects of Metal Dafonates on the NADPH-Dependent Lipid Peroxidation in the Murine Hepatic Microsomal System.
Dafone inhibits the lipid peroxidation significantly in a concentration dependent manner. The inhibition was found to be an uncompetitive type with the inhibition constant (Ki) of 62.5muM On the other hand complexation with metal ions results in a significant reversal from antioxidant to pro-oxidant properties for the resulting complexes which are cationic and with associated halometallate anions. The nature of the potentiation in case of the ferric compound was of competitive type with activation constant (Ka) having the value 32.5muM. The neutral copper-dafonate complex, however, inhibits lipid peroxidation with increase in concentration.


Proximal femoral anatomy and collared stems in hip arthroplasty: is a single collar size sufficient?
Even if the benefits of collars are unclear, they remain widely used, in several femoral stem designs. This study aimed to determine whether collar size should be proportional to hip dimensions and morphology. The hypothesis was that the collar should be larger for greater stem sizes and for varus femoral necks. Computed Tomography scans of 204 healthy hips were digitally analysed and manually templated to determine principle dimensions, appropriate stem size and model, as well as cortical distance at the femoral calcar (ideal collar size). Univariable analysis revealed that cortical distance was moderately correlated with mediolateral offset (r = 0.572; p < 0.0001) and stem model (r = 0.520; p < 0.0001). Cortical distance was weakly correlated with head diameter (r = 0.399; p < 0.0001), stem size (r = 0.200; p = 0.017), and patient gender (r = 0.361; p < 0.0001). Multivariable analysis confirmed that stem model (p < 0.0001) and head diameter (p = 0.0162) are directly correlated to cortical distance. We found that cortical distance along the femoral calcar is directly correlated with the model of the stem implanted ('standard' or 'varus') and with the head diameter. This cortical distance indicates optimal collar size, which would grant maximum calcar coverage without prosthetic overhang. Collar size should be proportional to the size of the operated hip, and should be larger for 'varus' stem models than for 'standard' stem models.


A symptom severity questionnaire for patients suffering from functional gastrointestinal disorder: FGI-Checklist.
A well-validated, comprehensive checklist of functional gastrointestinal (FGI) disorder (FGID) symptom severity for tracking symptom profile changes over time is lacking. We aim to develop and validate a comprehensive symptom severity checklist for FGID. A 20-item scale, including both upper and lower gastrointestinal symptoms, was generated to measure the symptom severity commonly found in FGID. Patients who experienced at least monthly symptoms of FGID with negative endoscopy findings were invited to complete the FGI-Checklist, Patient Health Questionaire-9 for assessing depressive symptoms, and Patient Health Questionnaire-15 for assessing somatic symptoms at baseline. A subset of patients who met Rome III diagnostic criteria of gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome received medication treatment for 8-12 weeks and completed the FGI-Checklist again at a follow-up visit. Exploratory factor analysis was performed for subscales formation and psychometric properties were measured. Six hundred and forty-one patients were recruited for current study and 108 (16.8%) of them completed the FGI-Checklist again at follow-up. Exploratory factor analysis identified a five-factor solution accounting for 66.8% of the total variance. The five factors are named esophageal syndrome, reflux syndrome, functional dyspepsia syndrome, nausea and vomiting syndrome, and abdominal and bowel syndrome. The FGI-Checklist total score correlated with Patient Health Questionaire-9 and Patient Health Questionnaire-15 (all P < 0.001), which demonstrated good construct validity. Good item-internal consistency was found (Cronbach's alphas: 0.69-0.87). Responsiveness for reflux syndrome subscale, functional dyspepsia syndrome subscale, and abdominal and bowel syndrome subscale after medication treatment was significant (paired-t-test: all P < 0.01). The instrument, Checklist, is valid and reliable.


Ontogeny of glucose homeostasis in low birth weight infants.
Suppression of the endogenous glucose production rate (Ra) is the adult response to glucose infusion. Persistent Ra (greater than or equal to 1 mg.kg-1min-1 or less than 80% decrease in basal Ra) in response to glucose infusion is evidence of a transitional homeostatic state in the neonate during the first days after birth. To determine whether postnatal development produces an adultlike response, Ra was measured in 11 infants (birth weight 1716 +/- 48 g, gestational age 33 +/- 0.3 weeks) at 2 to 5 weeks of age. In these paired studies, 4 micrograms.kg-1min-1 D-(U-13C)glucose tracer was infused by prime constant infusion to determine Ra, during infusion of either saline solution or glucose, the latter at a rate of 5.3 +/- 0.2 mg.kg-1min-1 (mean +/- SEM). When the results of the saline infusion turnover period were compared with those of the glucose infusion turnover period, plasma glucose concentration increased significantly, from 88 +/- 3 mg/dL to 101 +/- 4 mg/dL (P less than 0.001). Plasma insulin concentration remained unchanged (12 +/- 5 microU/mL vs 8 +/- 3 microU/mL). Ra was heterogenous during glucose infusion, and persistent Ra was present in six of 11 infants. Of the five infants who had decreased Ra during glucose infusion, three received glucose at a rate exceeding basal Ra. Of the remaining six infants who evidenced persistent Ra during glucose infusion, three received glucose at a rate equal to or in excess of basal Ra. We conclude that glucose homeostasis in low birth weight infants is transitional throughout the neonatal period.


[Botulinum toxin A after microvascular ALT flap in a patient with (corrected) squamous cell carcinoma of the tongue].
We report the case of a 23-year-old man presenting with a cT4 cN1 M0squamous cell carcinoma of the right tongue. After tumor resection and covering of the defect with a microvascular anterolateral thigh (ALT) flap, the patient showed distinct drooling without any substantial regression after anticholinergic therapy. For this reason 75 units of Botox® were injected into the submandibular and parotid glands. After the intraglandular injections, good reduction of saliva secretion was achieved. The treatment improved flap healing, aspiration and patient satisfaction. Injection of botulinum toxin A into the salivary glands is a sufficient therapy for postoperative hypersalivation.


A method for the determination of confidence limits for the P/2e- ratio for chosen values of ymaxatp form the results of continuous culture experiments.
A model is described, which allows the determination of 95% confidence limits for the maintenance coefficient and the efficiency of oxidative phosphorylation for chosen values of the growth yield for ATP corrected for energy maintenace (YmaxATP). As experimental data the specific rates of substrate consumption, product formation and oxygen uptake in chemostat cultures at various growth rates are use.


Quality of Life in Head and Neck Cancer Patients.
To assess the quality of life in head and neck cancer patients and the various factors which affect the quality of life in head and neck cancer patients was the main aim of the study. A prospective longitudinal study with a sample size of 130 patients was done within the time period of one and a half years. Patients with biopsy proven squamous cell carcinoma of the head and neck were treated as per their treatment protocol either by combined modality or single modality. Follow up at the completion of treatment was done and the quality of life questionnaire was filled out. QoL was assessed pre-treatment and at 4 times at different stages of follow up period. Demographic data was also taken into consideration for comparison which showed that head and neck cancer is more common in the males (80%) between the age group of 35-50 years, chronic tobacco chewers (45%) with most common site of cancer being the oral cavity (61%). Majority of the patients presented at Stage IV of their disease (35%) with largest HRQoL changes seen within the first three months after commencement of treatment. The most debilitating modality of treatment was Surgery + CTRT. Detailed assessment of the various factors which hamper the QoL in head and neck cancer patients should be done by which we can provide quality care and a completely new view into the health care experience and improving patient satisfaction.


Early electrophysiological study variants and their relationship with clinical presentation and outcomes of patients with Guillain-Barré syndrome.
This study compared the clinical outcomes of the two main neurophysiological types of Guillain-Barré Syndrome (GBS). Sixty-two GBS patients were examined clinically at onset using Medical Research Council (MRC), Hughes disability scales (HDS), and nerve conduction studies were evaluated in four limbs. The Modified Erasmus GBS outcome score (MEGOS) was assessed 2 weeks after onset. Outcomes were measured after 3 months using MRC and HDS scores. According to electrophysiological data two main groups identified acute inflammatory demyelinating polyneuropathy (AIDP = 31 cases) or acute axonal GBS including inexcitable forms (26 cases). The number of days between onset of weakness and admission was significantly shorter, and gastrointestinal symptoms were significantly higher among the axonal type than AIDP. MRC sum scores at onset and at nadir were significantly worse in the axonal type than in AIDP. Neck muscle weakness, impaired cough reflex, the need for mechanical ventilation, hypoalbuminemia, and hypernatremia were more common in the axonal type. At outcome, 74% of the AIDP were healthy/minor symptoms versus 38.46% of the axonal type. There was a high prevalence of the axonal variant (41.9%) compared with European and North American populations. The axonal type had a significantly worse outcome than AIDP type.


Surgical management of failed pyeloplasty in children: single-center experience.
To evaluate the outcome of secondary surgical procedures for the management of failed pyeloplasty in children. Between 1996 and 2007, 590 cases of primary ureteropelvic junction (UPJ) obstruction underwent open dismembered pyeloplasty at our center. Of these patients, 18 (3%) with recurrent UPJ obstruction (14 males, 4 females; age range: 2-15 years) have undergone management of failed pyeloplasty. Secondary intervention was by open operative procedure in all cases. Clinical and radiological outcomes were assessed. Success was defined as both symptomatic relief and radiographic resolution of obstruction at last follow up. Follow up ranged from 8 to 41 months (mean 28). The overall salvage rate was 89%. Secondary reoperative surgery was successful in 16 patients: dismembered pyeloplasty in 14 patients (78%) and ureterocalyceal anastomosis in 2 (11%). Nephrectomy was necessitated in 2 patients (11%). No perioperative complications were encountered. All patients showed stability of renal function on radiological follow up without evidence of obstruction and with no further symptoms. Persistent UPJ obstruction after pyeloplasty is an uncommon complication. Secondary procedures have a very high success rate with excellent functional results. Nephrectomy is indicated in rare cases of severely deteriorated renal function.


Unsedated colonoscopy: an option for some but not for all.
The increasing request for colonoscopy in clinical practice, coupled with the lack of time, has led to a renewed interest in unsedated procedures. To evaluate the acceptability of unsedated colonoscopy and to characterize the subset of patients more likely to undergo and complete the procedure without sedation and/or analgesia. Prospective, population study. Nonacademic community hospital, 6-month observation period. Adult outpatients referred for colonoscopy were offered unsedated procedure, with the possibility of on-demand sedation. Demographics, clinical features, and endoscopy outcomes were recorded. Data were analyzed by stepwise logistic regression analysis, and odds ratio (OR) and 95% confidence interval (CI) are given for significant variables. Unsedated colonoscopy acceptance rate. Factors significantly associated with acceptance and completion of unsedated procedures. The acceptance rate for unsedated colonoscopy was 56.2% of 964 consecutive evaluated patients. The cecal intubation rate in unsedated patients was 81.6% and increased to 97.3% with the option of on-demand sedation. At multivariate analysis, factors significantly associated with the acceptance were no previous colonoscopy (OR 1.52; 95% CI, 1.10-2.11), absent/low level of anxiety (OR 3.82; 95% CI, 2.71-5.38), and no concern about the examination (OR 1.80; 95% CI, 1.17-2.77). Fear of procedure-related pain was inversely associated with acceptance (OR 0.28; 95% CI, 0.17-0.35). Factors associated to drug-free colonoscopy completion were absence of preprocedure anxiety (OR 1.87; 95% CI, 1.08-3.21) and male sex (OR 3.59; 95% CI, 2.13-6.05). Single-center study. The acceptance rate of unsedated colonoscopy is clinically relevant, and the procedure can be completed without sedation in the majority of patients. Subject-related factors may help to identify patients willing to undergo and potentially complete unsedated procedures.


A genetic study of two French Guiana Amerindian populations. II. Rare electrophoretic variants.
Two Amerindian populations of French Guiana were investigated for plasma proteins and red-cell enzymes. In the Wayampi tribe, rare variants were identified in 4 systems. The corresponding alleles are designated AK1 3 Wayampi, PGM1 (4/10) Wayampi, PGM2 6 Wayampi, and TfD. In the Emerillon tribe, a variant allele of PGM2, designated PGM2 6 Emerillon, was identified. For three of the systems, PGM1, PGM2, Tf, similar isozymes have been described in other Amerindian populations. These findings suggest that the corresponding alleles may have the same origin.


Xanthogranuloma of the intrasellar region presenting in pituitary dysfunction: a case report.
Differentiation of cystic mass lesions of the sellar and parasellar regions may pose a diagnostic dilemma for physicians, neurosurgeons, radiologists and pathologists involved in treating patients with these entities. A considerable number of tumors previously identified as craniopharyngiomas may, in fact, have been xanthogranulomas. We report a case of pituitary dysfunction caused by xanthogranuloma of the intrasellar region. A 47-year-old man of Japanese descent presented to our institution with a tumor located exclusively in the intrasellar region which manifested as severe hypopituitarism. MRI revealed a clearly defined intrasellar mass that was heterogeneously hyperintense on T1-weighted images and markedly hypointense on T2-weighted images. We preoperatively diagnosed the patient with Rathke's cleft cyst or non-functioning pituitary adenoma. Although the tumor was completely removed using a transsphenoidal approach, the improvement of the patient's endocrine function was marginal, and continued endocrine replacement therapy was needed. Postoperatively, a histological examination revealed the tumor to be a xanthogranuloma of the intrasellar region. His visual field defects and headache improved. Because diagnosis depends on surgical intervention and xanthogranulomas of the intrasellar region are very rare, the natural history of xanthogranuloma is still unknown. Therefore, this entity is difficult to diagnose preoperatively. We suggest that xanthogranuloma should be included in the differential diagnosis, even in the case of sellar lesions, to formulate appropriate postoperative management and improve endocrine outcomes.


Practical applications of neuronal tissue culture in in vitro toxicology.
1. Primary chick embryo forebrain neurones are relatively easy to culture and are quite resilient to treatment manipulation. These characteristics have allowed application in a surprisingly diverse number of areas. 2. These cultures have been used to investigate the anticholinesterase potencies of many organophosphate (OP) nerve agents and insecticides. 3. These cultures have been used to quantitate levels of OP in 'spiked' unknowns and in OP-contaminated soil samples. 4. These cells have also been used to test a variety of compounds using the MTT and neutral red cytotoxicity assays.


The C2 domains of dysferlin: roles in membrane localization, Ca2+ signalling and sarcolemmal repair.
Dysferlin is an integral membrane protein of the transverse tubules of skeletal muscle that is mutated or absent in limb girdle muscular dystrophy 2B and Miyoshi myopathy. Here we examine the role of dysferlin's seven C2 domains, C2A through C2G, in membrane repair and Ca2+ release, as well as in targeting dysferlin to the transverse tubules of skeletal muscle. We report that deletion of either domain C2A or C2B inhibits membrane repair completely, whereas deletion of C2C, C2D, C2E, C2F or C2G causes partial loss of membrane repair that is exacerbated in the absence of extracellular Ca2+ . Deletion of C2C, C2D, C2E, C2F or C2G also causes significant changes in Ca2+ release, measured as the amplitude of the Ca2+ transient before or after hypo-osmotic shock and the appearance of Ca2+ waves. Most deletants accumulate in endoplasmic reticulum. Only the C2A domain can be deleted without affecting dysferlin trafficking to transverse tubules, but Dysf-ΔC2A fails to support normal Ca2+ signalling after hypo-osmotic shock. Our data suggest that (i) every C2 domain contributes to repair; (ii) all C2 domains except C2B regulate Ca2+ signalling; (iii) transverse tubule localization is insufficient for normal Ca2+ signalling; and (iv) Ca2+ dependence of repair is mediated by C2C through C2G. Thus, dysferlin's C2 domains have distinct functions in Ca2+ signalling and sarcolemmal membrane repair and may play distinct roles in skeletal muscle. KEY POINTS: Dysferlin, a transmembrane protein containing seven C2 domains, C2A through C2G, concentrates in transverse tubules of skeletal muscle, where it stabilizes voltage-induced Ca2+ transients and participates in sarcolemmal membrane repair. Each of dysferlin's C2 domains except C2B regulate Ca2+ signalling. Localization of dysferlin variants to the transverse tubules is not sufficient to support normal Ca2+ signalling or membrane repair. Each of dysferlin's C2 domains contributes to sarcolemmal membrane repair. The Ca2+ dependence of membrane repair is mediated by C2C through C2G. Dysferlin's C2 domains therefore have distinct functions in Ca2+ signalling and sarcolemmal membrane repair.


Zebrafish mast cells possess an FcɛRI-like receptor and participate in innate and adaptive immune responses.
We previously identified a zebrafish mast cell (MC) lineage and now aim to determine if these cells function analogously in innate and adaptive immunity like their mammalian counterparts. Intraperitoneal (IP) injection of compound 48/80 or live Aeromonas salmonicida resulted in significant MC degranulation evident histologically and by increased plasma tryptase compared with saline-injected controls (p=0.0006, 0.005, respectively). Pre-treatment with ketotifen abrogated these responses (p=0.0004, 0.005, respectively). Cross-reactivity was observed in zebrafish to anti-human high-affinity IgE receptor gamma (FcɛRIγ) and IgE heavy chain-directed antibodies. Whole mount in situ hybridization on 7-day embryos demonstrated co-localization of cpa5, a MC-specific marker, with myd88, a toll-like receptor adaptor, and zebrafish FcɛRI subunit homologs. Zebrafish injected IP with matched dinitrophenyl-sensitized mouse (anti-DNP) IgE and DNP-BSA or trinitrophenyl-sensitized mouse (anti-TNP) IgE and TNP-BSA demonstrated increased plasma tryptase compared with mismatched controls (p=0.03, 0.010, respectively). These results confirm functional conservation and validate the zebrafish model as an in vivo screening tool for novel MC modulating agents.


Airway management for anaesthesia in the ambulatory setting.
The number of anaesthetic procedures in the ambulatory setting is steadily increasing. During the last years, more and more patients with complex medical conditions undergo ambulatory interventions. This review will focus on airway management practices, but especially on techniques used in the ambulatory setting. It will highlight recent literature published in the focus of ambulatory anaesthesia and will discuss relevant findings of the last year. Literature search and analysis performed independently by two reviewers. Practical points to improve success of anaesthesia and to avoid complications in the ambulatory setting are provided. In addition to concepts for the (un)expected difficult airway, new supraglottic devices, and modern concepts for teleconsultation, are discussed. There are several points which should be considered for ambulatory anaesthesia. Selected patient groups (e.g., obstructive sleep apnoea, obesity) may have a higher anaesthesia-related risk. To handle the more and more complex conditions in a growing number of ambulatory patients, straightforward concepts, especially for the (un)expected difficult airway, are required.


Scanning electron microscopic investigations on the morphology and phase conversions of uroliths.
The most frequent structures of the majority of possible urolith components are assessed by scanning electron microscopic investigations. Typical examples of the conversion of uric acid dihydrate into uric acid, weddellite into whewellite and MgHN4PO4 . 6 H20 into MgNH4PO4 . H2O are given.


CD44-high neural crest stem-like cells are associated with tumour aggressiveness and poor survival in neuroblastoma tumours.
Neuroblastoma is a paediatric tumour originated from sympathoadrenal precursors and characterized by its heterogeneity and poor outcome in advanced stages. Intra-tumoral cellular heterogeneity has emerged as an important feature in neuroblastoma, with a potential major impact on tumour aggressiveness and response to therapy. CD44 is an adhesion protein involved in tumour progression, metastasis and stemness in different cancers; however, there has been controversies about the significance of CD44 expression in neuroblastoma and its relationship with tumour progression. We have performed transcriptomic analysis on patient tumour samples studying the outcome of patients with high CD44 expression. Adhesion, invasion and proliferation assays were performed in sorted CD44high neuroblastoma cells. Tumoursphere cultures have been used to enrich in undifferentiated stem-like cells and to asses self-renewal and differentiation potential. We have finally performed in vivo tumorigenic assays on cell line-derived or Patient-derived xenografts. We show that high CD44 expression is associated with low survival in high-grade human neuroblastoma, independently of MYCN amplification. CD44 is expressed in a cell population with neural crest stem-like features, and with the capacity to generate multipotent, undifferentiated tumourspheres in culture. These cells are more invasive and proliferative in vitro. CD44 positive cells obtained from tumours are more tumorigenic and metastatic, giving rise to aggressive neuroblastic tumours at high frequency upon transplantation. We describe an unexpected intra-tumoural heterogeneity within cellular entities expressing CD44 in neuroblastoma, and propose that CD44 has a role in neural crest stem-like undifferentiated cells, which can contribute to tumorigenesis and malignancy in this type of cancer. Research supported by grants from the "Asociación Española contra el Cáncer" (AECC), the Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P), and the European Research Council (ERC Starting Grant to RP).


Evaluation of different diagnostic modalities of minimal hepatic encephalopathy in cirrhotic patients: case-control study.
Minimal hepatic encephalopathy (MHE) represents one of the most overlooked complications of liver cirrhosis. To compare the utility and efficacy of different MHE diagnostic modalities. This case-control study was conducted on hepatitis C virus (HCV)-related compensated cirrhotic patients. The Psychometric Hepatic Encephalopathy Score (PHES) was used to assign patients to MHE and controls. All patients were subjected to plasma ammonia, serum 3-nitrotyrosine (3-NT), critical flicker frequency (CFF), and the modified inhibitory control test (ICT). CFF was significantly lower in the control group (38.5, 40 Hz, p = 0.003). The unweighted lures on ICT were 8.7, 4.9 in MHE and controls (p < 0.001). Moreover, ammonia was higher in the MHE group (89, 61.5 µmol/l, p < 0.001). 3-NT was also higher in the MHE group (31.5, 13.7 nmol/l, p < 0.001) respectively. CFF at cutoff < 39 Hz had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 57.5%, 77.5%, 71.9% and 64.6%, respectively; in modified ICT, at cutoff > 5 unweighted lures the values were 87.5%, 80%, 81.4% and 86.5%, respectively; in ammonia, at cutoff ≥ 76.45 µmol/l the values were 65%, 72.5%, 70.3% and 67.4%, respectively; for 3-NT at cutoff ≥ 14.15 nmol/l the values were 85%, 82.5%, 82.9% and 84.6%, respectively. The accuracy for MHE diagnosis was 67.5%, 83.3%, 68.8%, 83.8% relying on CFF, 3-NT, ammonia, and ICT respectively. On multivariate analysis, CFF < 39 Hz (OR = 10.2, p = 0.04), modified ICT > 5 unweighted lures (OR = 43.2, p = 0.002), and serum 3-NT levels ≥ 14.15 nmol/l (OR = 50.4, p < 0.001) were independent predictors of MHE. 3-NT and ICT are advantageous to reveal MHE in compensated liver cirrhosis, while CFF can be only used as adjuncts, with humble merits of ammonia.


PEGylated Fluorescent Anti-carcinoembryonic Antigen Antibody Labels Colorectal Cancer Tumors in Orthotopic Mouse Models.
Colorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a humanized anti-carcinoembryonic antigen monoclonal antibody conjugated to a PEGylated near-infrared dye, that targets and brightly labels human CRC tumors in metastatic orthotopic mouse models. The hT84.66-M5A (M5A) monoclonal antibody was conjugated with a polyethylene glycol (PEG) chain that incorporated a near infrared (NIR) IR800 dye to establish M5A-IR800 Sidewinder (M5A-IR800-SW). Nude mice with CRC orthotopic primary tumors and liver metastasis both developed from a human CRC cell line, were injected with M5A-IR800-SW and imaged with the Pearl Trilogy Imaging System. M5A-IR800-SW targeted and brightly labeled CRC tumors, both in primary-tumor and liver-metastasis models. M5A-IR800-SW at 75 μg exhibited highly-specific tumor labeling in a primary-tumor orthotopic model with a median tumor-to-background ratio of 9.77 and in a liver-metastasis orthotopic model with a median tumor-to-background ratio of 7.23 at 96 h. The precise labeling of the liver metastasis was due to lack of hepatic accumulation of M5A-IR800-SW in the liver. M5A-IR800-SW provided bright and targeted NIR images of human CRC in orthotopic primary-tumor and liver-metastasis mouse models. The results of the present study suggest the clinical potential of M5A-IR800-SW for fluorescence-guided surgery including metastasectomies for CRC. The lack of hepatic NIR signal is of critical importance to allow for precise labeling of liver tumors.


Sonohysterosalpingography: a suitable choice in infertility workup.
To evaluate the efficacy, compliance, and cost effectiveness of sonohysterosalpingography (HyCoSy) compared with hysteroscopy for uterine cavity evaluation and compared with RX-hysterosalpingography (RX-HSG) for tubal patency determination. Three hundred and eight infertile patients underwent HyCoSy, hysteroscopy, and RX-HSG. We compared sensitivity, specificity, positive and negative predictive values (PPV and NPV), discomfort level, and cost of all three procedures. Sensitivity, specificity, PPV, and NPV were higher for HyCoSy than for hysteroscopy but the differences were not significant. HyCoSy also has the same accuracy as RX-HSG. Pain perception and cost were higher for RX-HSG and hysteroscopy than for HyCoSy. HyCoSy can be regarded as a procedure for initial evaluation of the uterine cavity and of tubal patency in infertile patients.


Injectable long acting chitosan/tripolyphosphate microspheres for the intra-articular delivery of lornoxicam: Optimization and in vivo evaluation.
Chitosan microspheres were formulated for the intra-articular delivery of lornoxicam in knee osteoarthritis, to minimize associated side-effects after prolonged oral administration. Ionotropic-gelation technique was employed using tripolyphosphate as anionic cross-linker. Full-factorial design experiment was conducted to optimize lornoxicam entrapment-efficiency%. Formulations were assessed for their particle size, in-vitro drug release, Scanning electron microscopy, Differential-scanning-calorimetry and Fourier transform infra-red spectroscopy studies. Changing independent variables, chitosan pH, TPP pH and lornoxicam concentration resulted in different values of entrapment-efficiency% ranging from 13.5%±0.35 to 59.5%±2.2. Particle size ranged from 3.57μm±0.02 to 6.12μm±0.00 and lornoxicam%release was prolonged for up to 8days. SEM results showed spherical shape of the microspheres. FTIR and DSC studies confirmed the crosslinking of chitosan with tripolyphosphate. In-vivo therapeutic effect of lornoxicam microspheres was investigated using Monosodiumiodoacetate (MIA) induced osteoarthritis model in rats. Optimized formula showed long-term in-vivo anti-inflammatory effect relative to lornoxicam solution injected intra-articularly with significant reduction of histological, inflammatory and biochemical parameters of osteoarthritis.


A light and transmission electron microscope study of hepatic portal tracts in the rhesus monkey (Macacus rhesus).
This study reports on morphological features of hepatic portal tracts in the liver of a rhesus monkey. The light microscope shows that the number of each type of principal component comprising a portal tract varies but that there are usually one to five lymphatics, one bile ductule, one bile duct, one arteriolar and one arterial branch of the hepatic artery, and one hepatic portal vein. Bile ductules, in cross section, have 6-10 cells (mostly low pyramidal, but with a few cuboidal) bordering the lumen, an outside diameter of from about 20 to 25 microm, and a luminal diameter of from 2 to 10 microm. Bile ducts, in cross section, have more than 10 cells (about equal numbers of low pyramidal and cuboidal) bordering the lumen, an outside diameter greater than 25 microm and a luminal diameter of greater than 10 microm. The term "pyramidal" has not previously been applied to the cells of the ductules and ducts. The monkey tracts show several cytological features previously undescribed, viz., abortive cilia and basal bodies in the duct cells, abortive cilia in the ductule cells, and an occasional aggregation of ribosomes in arterial endothelial cells. They also show a major histological feature previously mentioned but not illustrated, viz., bundles of nerve processes which exhibit a preferential location, i.e., proximity to the arterioles and arteries.


Human papillomavirus type 16 P670 promoter is negatively regulated by CCAAT displacement protein.
HPV16 late gene transcription from P670 is suppressed in undifferentiated keratinocytes. To identify DNA sites involved in the negative regulation, we examined the effect of a series of substitutions in the P670 promoter region (nucleotide (nt) 106-855) on the transcription, using an expression plasmid having the promoter fragment placed to drive the firefly-luciferase gene. Twenty-base pair-long segments covering the entire promoter region were replaced with a sequence lacking any so far known factor-binding motifs to produce 38 mutants. These plasmids were introduced by transfecton into undifferentiated or partially differentiated human HaCaT and HeLa cells, and transient expression of the reporter was examined with the cell extracts. The reporter expression from the wild-type promoter region was lower, half to one-third, in the undifferentiated cells than in the partially differentiated cells, which expressed hSkn-1a, a keratinocyte specific transcription factor that activates P670, and CCAAT displacement protein (CDP), a transcriptional repressor involved in cell differentiation. Two mutants with substitutions including the putative CDP-binding sites, one from nt 562 to 567 and the other from nt 673 to 678, induced markedly enhanced reporter expression particularly in the partially differentiated cells. Electrophoretic mobility shift analysis demonstrated that bacterially produced GST-CDP bound to the two sites in a sequence-specific manner. The data strongly suggest that CDP acts as a major suppressor for P670 transcription by binding to the promoter region in the undifferentiated cells and even in the partially differentiated cells that express the activator hSkn-1a.


Percutaneous bunionette correction.
Treatment of tailor's bunion is largely conservative. For severe or refractory cases surgical intervention is necessary. The aim of this study is to evaluate a percutaneous technique for correcting such bunionette deformities. Twenty-one procedures were performed on 20 patients using a percutaneous technique. Patients were scored using the American Orthopaedic Foot & Ankle Society (AOFAS) Lesser Toe Metatarsophalangeal-Interphalangeal Scale. No wound healing problems, infections, non-unions or mal-unions occurred. Functional assessments revealed very good results. Radiographic evaluation confirmed good average correction of the fourth-fifth intermetatarsal angle and metatarsophalangeal angle. This percutaneous technique is a reliable and effective approach for the treatment of bunionette deformity. The results obtained were comparable to those reported using traditional open techniques, but major complications due to soft tissue damage were averted. This technique can be adapted depending on the type of deformity, and does not require internal fixation.


Association between intimate partner violence and nutritional status among Indian women: a latent class analysis approach.
Intimate partner violence (IPV) is an unabating public health issue that has numerous negative repercussions for women's health. Its detrimental impact on women's nutritional outcomes has been documented in a few studies from low- and middle-income countries; however, there is a lack of granular understanding in terms of the typology of IPV experiences and their association with nutritional outcomes. This study explores the distinct classes of IPV experience among women in India and examines how these classes are associated with their nutritional outcomes. Using data of 60,622 ever-married women aged 15-49 years from the 2019-21 National Family Health Survey (NFHS-5), latent class analysis (LCA) was performed to identify distinct groups of women based on their IPV experiences. BMI was used to assess women's nutritional status, and it was classified as: <18.5 kg/m2 (underweight), 18.5-24.9 kg/m2 (normal) and ≥ 25.0 kg/m2 (overweight). Further, multinomial logistic regression analyses were used to estimate the odds of being underweight or overweight by latent classes of IPV experiences. LCA model identified four distinct IPV experience groups of women: Low Physical and Low Sexual IPV (LPLS-IPV) class (72%); High Physical and Low Sexual IPV (HPLS-IPV) (12.5%); High Sexual and Low Physical IPV (HSLP-IPV) (12%); and High Physical and High Sexual (HPHS-IPV) class (3.5%). The likelihood of being underweight was higher among women in the HPHS-IPV class (aOR: 1.24, 95% CI: 1.08-1.44), followed by those in the HPLS-IPV class (aOR: 1.11, 95% CI: 1.04-1.20). The latent class groups found that high physical IPV experiences were associated with women's nutritional outcomes. The experiences of women having both high physical and sexual violence affect women's nutritional outcomes to a greater extent and they are more likely to be undernourished.


Environmental pseudotargeted metabolomics: A high throughput and wide coverage method for metabolic profiling of 1000-year paddy soil chronosequences.
Pseudotargeted metabolomics is achieved by introducing an algorithm designed to choose ions for selected ion monitoring from identified metabolites. This method integrates the advantages of both untargeted and targeted metabolomics. In this study, environmental pseudotargeted metabolomics was established to analyze the soil metabolites, based on microwave assisted derivatization followed by gas chromatography-mass spectrometry analysis. The method development included the optimization of extraction factors and derivatization conditions, evaluation of silylation reagent types and matrix-dependent behaviors. Under the optimal conditions, the microwave oximation and silylation were completed in 5 min and 9 min. A total of 184 metabolites from 26 chemical classifications were identified in soil matrices. The method validation demonstrated excellent performance in terms of linearity (correlation coefficient > 0.99), repeatability (relative standard deviation (RSD) < 20 %), reproducibility (RSD < 25 %), stability (relative difference < 10 % within 18 h), and sensitivity (16-110 times higher signal-to-noise ratio). This developed method was applied to characterize the metabolite compositions and metabolic profiling in a 1000-year paddy soil chronosequence. The relative abundance of trehalose was highest in 6-(40.3 %), 60-(55.8 %), 300-(67.7 %)and 1000-(61.7 %)years paddy soil, respectively, but long-chain fatty acids were most abundant in marine sediment (57.4 %). Forty-two characteristic metabolites were considered as primarily responsible for discriminating and characterizing the paddy soil chronosequences development and seven major metabolic pathways were altered. In addition, GC-MS metabolite profile presented better discriminating power in paddy soil ecosystem changes than phospholipid fatty acids (PLFAs). Overall, environmental pseudotargeted metabolomics can provide a high throughout and wide coverage approach for performing metabolic profiling in the soil research.


Associations between 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population.
Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28-2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86-2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09-0.81) and rectal cancer (OR = 0.43, 95% CI 0.23-0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09-0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86-6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73-3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram-years) may be also associated with colon or rectal cancer risk.


Who should nurse children requiring emergency care?
There are constant challenges in developing a workforce fit to deliver care to children and young people requiring emergency or urgent care. These challenges are often compounded when the care setting for children and young people is within a general Emergency Department. This paper will review contemporary issues around who should deliver emergency care to children in these settings; reasoned debate is required to ensure that we have a workforce fit for purpose.


Optimized quantitative PCR analysis of random DNA aptamer libraries.
The quantitative polymerase chain reaction (qPCR) with detection of duplex DNA yield by intercalator fluorescence is a common and essential technique in nucleic acid analysis. We encountered unexpected results when applying standard qPCR methods to the quantitation of random DNA libraries flanked by regions of fixed sequence, a configuration essential for in vitro selection experiments. Here we describe the results of experiments revealing why conventional qPCR methods can fail to allow automated analysis in such cases, and simple solutions to this problem. In particular we show that renaturation of PCR products containing random regions is incomplete in late PCR cycles when extension fails due to reagent depletion. Intercalator fluorescence can then be lost at standard interrogation temperatures. We show that qPCR analysis of random DNA libraries can be achieved simply by adjusting the step at which intercalator fluorescence is monitored so that the yield of annealed constant regions is detected rather than the yield of full duplex DNA products.


Infective popliteal artery aneurysm by Streptococcus equi: An unusual pathogen.
We report the case of a 63-year-old man who presented with a 2-week complaint of lower extremity pain, swelling, and low-grade fever after an episode of septic arthritis in the ipsilateral knee. The investigation showed a rapidly expanding popliteal artery aneurysm (PAA). The rare clinical entity of an infective PAA was suspected and was confirmed by the cultures obtained at the right femoropopliteal bypass with an autologous vein graft and subtotal resection of the aneurysm sac. Streptococcus equi was identified as the primary pathogen, which, to the best of our knowledge, has not been previously described for an infective PAA.


The crystal structure of a complex of p11 with the annexin II N-terminal peptide.
The aggregation and membrane fusion properties of annexin II are modulated by the association with a regulatory light chain called p11.p11 is a member of the S100 EF-hand protein family, which is unique in having lost its calcium-binding properties. We report the first structure of a complex between p11 and its cognate peptide, the N-terminus of annexin II, as well as that of p11 alone. The basic unit for p11 is a tight, non-covalent dimer. In the complex, each annexin II peptide forms hydrophobic interactions with both p11 monomers, thus providing a structural basis for high affinity interactions between an S100 protein and its target sequence. Finally, p11 forms a disulfide-linked tetramer in both types of crystals thus suggesting a model for an oxidized form of other S100 proteins that have been found in the extracellular milieu.


Evaluation of Organochlorine Compounds (PCDDs, PCDFs, PCBs and DDTs) in Two Raptor Species Inhabiting a Mediterranean Island in Spain (8 pp).
-: DOI: http://dx.doi.org/10.1065/espr2006.01.015 Species that are at high levels of the food web have often been used as bioindicators to evaluate the presence of persistent contaminants in ecosystems. Most of these species are long-lived, so pollutant burdens may be integrated in some complex way over time. This makes them particularly sensitive to deleterious effects of Persistent Organic Pollutants (POPs). Birds have been suggested as useful organisms for monitoring pollutant levels. Traditionally such studies have been carried out with raptors such as osprey (Pandion haliaetus), peregrine falcon (Falco peregrinus), bald eagle (Haliaetus leucocephalus), etc. In this paper we present the results of a monitoring study conducted on two raptor species, osprey (Pandion haliaetus) and red kite (Milvus milvus), inhabiting a Mediterranean island (Menorca, Spain). These two species have different feeding habits; ospreys prey on fish and red kites feed on terrestrial species. This study constitutes a good opportunity to investigate if differences in feeding habits (aquatic vs. terrestrial) influences the contaminants pattern in two species inhabiting the same area. The study was conducted in a non-destructive way, using only failed eggs, to avoid the damage of the population stability. Eggs were collected during the period 1994-2000. The contaminants examined were dichlorodiphenyltrichloroethanes (DDTs, including DDT and its main metabolite, DDE), polychlorinated biphenyls (PCBs), including ortho PCBs (PCBs with at least one Chlorine atom in the ortho position): #28, 52, 95, 101, 123+149, 118, 114, 153, 132+105, 138, 167, 156, 157, 180, 170, 189, 194; and non ortho PCBs (PCBs with no Chlorine atom in the ortho position): #77, 126, 169 and all the polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) with Chlorine atoms at the 2,3,7 and 8 position (2,3,7,8-substituted PCDDs and PCDFs). The analysis of organochlorine compounds was performed using a sample treatment based on a Solid Phase Matrix Dispersion procedure. Ortho PCBs and DDTs were determined by HRGC-µECD; non ortho PCBs and PCDD/Fs were determined by HRGC-HRMS. The sum of the ortho PCB congeners analysed ranged from 0.94 to 15.03 µg/g wet weight (ww) for ospreys and from 1.0 to 11.2 µg/g ww for red kites. In both species, PCB congeners #153, #138 and #180 accounted about 75% to total ortho PCB concentrations. Regarding non ortho PCBs, for ospreys, concentrations ranged from 0.16 to 1.39 ng/g wet weight (ww) and for red kites from 0.12 to 0.51 ng/g ww, being congener #126 the most abundant. Concerning DDTs, concentration for ospreys ranged from 0.07 to 1.03 µg/g ww; and for red kites ranged from 0.90 to 2.10 µg/g ww, representing DDE more than 95% of the total DDTs, which proves a past use of DDT in the study area. Differences in contaminant levels between species are probably associated to feeding habits. The fish-eating species presents the highest PCB levels, whereas the terrestrial species exhibits the highest DDT levels. PCDD/Fs in ospreys were in the range 2.6-14.2 pg/g ww, while in red kites the range was slightly wider (22.2-43.2 pg/g ww), being PCDDs the major contributors in black kites. Ospreys had PCDDs similar to PCDF concentrations. PCDD/F profiles were mostly influenced by OCDD in both species. Non ortho PCBs were the major contributors to calculated Toxic Equivalent Quantity (TEQs) in both species. In both species studied, ortho-PCBs could represent a problem of concern since 57% of the eggs exhibited levels higher than 4 µg/g ww, reported as the level that could cause reduced hatchability, embryo mortality, and deformities in birds. Results found in this study suggest that a more detailed study to clear up possible deleterious effects of PCBs on the bird populations studied here should be done.


Insomnia Symptoms among African-American Older Adults in Economically Disadvantaged Areas of South Los Angeles.
Although psychosocial and health factors impact insomnia symptoms, less is known about these effects in economically disadvantaged African-American older adults. This study investigated social and health determinants of insomnia symptoms among economically disadvantaged African-American older adults. This survey enrolled 398 African-American older adults (age ≥ 65 years) from economically disadvantaged areas of South Los Angeles. Gender, age, educational attainment, financial difficulty, number of chronic diseases, self-rated health, pain intensity, and depression were covariates. Total insomnia, insomnia symptoms, and insomnia impact were our outcomes. Linear regression was applied for data analysis. Based on linear regression, higher financial difficulty (B = 0.48, 95% CI = 0.35-0.61), smoking status (B = 1.64, 95% CI = 0.13-3.16), higher pain intensity (B = 0.39, 95% CI = 0.11-0.67), higher number of chronic diseases (B = 0.34, 95% CI = 0.05-0.64), and more depressive symptoms (B = 0.35, 95% CI = 0.12-0.57) were associated with a higher frequency of insomnia symptoms. Based on a logistic regression model, lower age (B = 0.91, 95% CI = 0.91-1.00) and high financial difficulty (OR = 1.15, 95% CI = 1.08-1.24), pain (OR = 2.08, 95% CI = 1.14-3.80), chronic disease (OR = 1.27, 95% CI = 1.07-1.51) and depression (OR = 2.38, 95% CI = 1.22-4.65) were associated with higher odds of possible clinical insomnia. We also found specific predictors for insomnia symptoms and insomnia impact. Among African-American older adults in economically disadvantaged areas of South Los Angeles, insomnia symptoms co-occur with other economic, physical, and mental health challenges such as financial difficulty, smoking, multimorbidity, pain, and depression. There is a need to address sleep as a component of care of economically disadvantaged African-American older adults who have multiple social and health challenges.


A randomized controlled trial comparing prevention and promotion cognitive strategies in a behavioral weight-loss intervention.
Two approaches may shift attention from short-term rewards to longer-term weight-loss goals: focusing on long-term consequences of unhealthy choices (prevention) or benefits of healthy choices (promotion). This randomized controlled trial tested the impact of prevention- versus promotion-focused strategies in an internet-delivered behavioral weight-loss intervention (iBWL). A total of 95 participants with overweight/obesity were randomized to one of three 12-week iBWLs: (1) STANDARD (n = 31), (2) PREVENT (standard iBWL+prevention-focused training; n = 32), or (3) PROMOTE (standard iBWL+promotion-focused training; n = 32). Participants in the two enhanced arms were trained in their assigned strategy, and lessons and weekly feedback featured arm-specific content and reminders. Intent-to-treat analysis revealed significant differences in weight loss and self-control use at 12 weeks (weight loss p = 0.002, self-control p = 0.0006). PREVENT was associated with 6.6% (±4.5%) weight loss and a 20.3% (±26.5%) increase in self-control, STANDARD and PROMOTE were associated with 4.4% (±4.2%) and 3.1% (±3.1%) weight losses, respectively, and neither STANDARD nor PROMOTE participants exhibited significant changes in self-control. Across arms, increased self-control was associated with greater weight loss (p = 0.0005). Cognitive strategies to focus on preventing negative consequences of unhealthy choices led to greater weight loss and self-control compared with both standard iBWL and promotion-focused iBWL. Prevention strategies should be given further attention for overweight/obesity treatment.


New insights on the role of nitrogen in the resistance to environmental stress in an endosymbiotic dinoflagellate.
Endosymbiotic dinoflagellates provide the nutritional basis for marine invertebrates, especially reef-building corals. These dinoflagellates are sensitive to environmental changes, and understanding the factors that can increase the resistance of the symbionts is crucial for the elucidation of the mechanisms involved with coral bleaching. Here, we demonstrate how the endosymbiotic dinoflagellate Durusdinium glynnii is affected by concentration (1760 vs 440 µM) and source (sodium nitrate vs urea) of nitrogen after light and thermal stress exposure. The effectiveness in the use of the two nitrogen forms was proven by the nitrogen isotopic signature. Overall, high nitrogen concentrations, regardless of source, increased D. glynnii growth, chlorophyll-a, and peridinin levels. During the pre-stress period, the use of urea accelerated the growth of D. glynnii compared to cells grown using sodium nitrate. During the luminous stress, high nitrate conditions increased cell growth, but no changes in pigments composition was observed. On the other hand, during thermal stress, a steep and steady decline in cell densities over time was observed, except for high urea condition, where there is cellular division and peridinin accumulation 72 h after the thermal shock. Our findings suggest peridinin has a protective role during the thermal stress, and the uptake of urea by D. glynnii can alleviate thermal stress responses, eventually mitigating coral bleaching events.


Microsatellite-based deletion bin system for the establishment of genetic-physical map relationships in wheat (Triticum aestivum L.).
Because of polyploidy and large genome size, deletion stocks of bread wheat are an ideal material for physically allocating ESTs and genes to small chromosomal regions for targeted mapping. To enhance the utility of deletion stocks for chromosome bin mapping, we characterized a set of 84 deletion lines covering the 21 chromosomes of wheat using 725 microsatellites. We localized these microsatellite loci to 94 breakpoints in a homozygous state (88 distal deletions, 6 interstitial), and 5 in a heterozygous state representing 159 deletion bins. Chromosomes from homoeologous groups 2 and 5 were the best covered (126 and 125 microsatellites, respectively) while the coverage for group 4 was lower (80 microsatellites). We assigned at least one microsatellite in up to 92% of the bins (mean 4.97 SSR/bin). Only a few discrepancies concerning marker order were observed. The cytogenetic maps revealed small genetic distances over large physical regions around the centromeres and large genetic to physical map ratios close to the telomeres. As SSRs are the markers of choice for many genetic and breeding studies, the mapped microsatellite loci will be useful not only for deletion stock verifications but also for allocating associated QTLs to deletion bins where numerous ESTs that could be potential candidate genes are currently assigned.